How much design is there in asymmetric catalysis ? and ... · How much design is there in...

How much design is there in asymmetric catalysis and

what makes a ligand to a privileged ligand

A Togni Department of Chemistry and Applied Biosciences

1

Introductionndash Privileged ligandsndash C1 vs C2 Symmetric ligands

TADDOLs in the Ti-Catalyzed Enantioselective Fluorination of 13-Dicarbonyl Compoundsndash Understanding the origin of enantioselectivity

Ferrocenyl Derivatives as Prototypes for C1 Symmetric Ligandsndash Modular synthesis and applicationsndash Conformational aspectsndash Steric bulk shape and sizendash Electronic effects by peripheral substituents

2

Privileged Ligands and Catalysts

TP Yoon EN Jacobsen Science 2003 299 1691

[] certain classes of synthetic catalysts are enantioselective over a wide range of different reactions Such catalysts may be called ldquoprivileged structuresrdquo in much the same manner that the term has been applied in pharmaceutical research to compound classes that are active against a number of different biological targets Privileged chiral catalysts offer much more than one might have imagined creating effective asymmetric environments for mechanistically unrelated reactions

Jacobsens definition

3

Examples of privileged ligands and catalysts given in the original Jaconsens paper

Hydrogenationhydroamination

hydrophosphinationhydrosilylation

allylic substitution conjugate additionco-polymerization

4




5

Non Catalytic Asymmetric Electrophilic Fluorination of Enolates Using N-F Reagents mdash The State of the Art up to 2001

SO2

NF

RR

1 (R=H) 2 (R=Cl)

NS

O O

Me

F

O

Ph1) LDA THF

2) 3

OPh

F

79 yield 88 ee

3

SO2

N

O2S

F

4

NO

Me Ph

O

RO

NO

Me Ph

O

RO1) Base

F

80-90 yield 86-99 de

N

N

OHH

ClO

OMe

2)

NN

Cl

F

+

+2 BF4

ndash

5

Bn

OSiMe3

Bn

O

F4 5

MeCN -20degC

86-99 yield up to 91 ee

Pioneering workbull E Differding RW Lang Tetrahedron Lett 1988 29 6087

Recent reviewsbull H Ibrahim A Togni Chem Comm 2004 1147 (Feature Article)bull K Muntildeiz Angew Chem Int Ed 2001 40 1653 (Highlight)bull SC Taylor et al Tetrahedron 1999 55 12431bull GG Furin in Houben-WeylVol E10 pp 432-499 1999

Recent examplesbull Y Takeuchi et al J Org Chem 1999 64 5708bull FA Davis PVN KasuTetrahedron Lett 1998 39 6135bull N Shibata et al J Am Chem Soc 2001 123 7001bull D Cahard et al Org Lett 2000 2 3699Tetrahedron Lett 2001 42 1867Angew Chem Int Ed 2001 40 4214

6

C2 Symmetric Ligands in Transition-Metal-Catalyzed Enantioselective Electrophilic Fluorinations

up to 99 yieldup to 88 ee

O

COOtBu

OCOOtBu

F

(PhSO2)2NF EtOH rt5 mol Pd catalyst


P

PR2

Pd

HO

OH

PdP

PR2

R2 R2

(BF4)2

R = 35-Me2Ph

O

COOtBu

OCOOtBu

F

(PhSO2)2NF Et2O HFIP rt1 mol Cu catalyst


N

O

N

O

PhPh CuTfO OTf

P

PPh2

NiCl

Cl

Ph2

N S

OO

Ph N S

OO

Ph

F

5-10 mol Ni catalyst15 equiv (PhSO2)2NF

Et3SiOTf toluene ndash20degC

26-lutidine

T Suzuki Y Hamashima M Sodeoka Angew Chem Int Ed 2007 46 5435J-A Ma D Cahard Tetrahedron Asymmetry 2004 15 1007 Y Hamashima K Yagi H Takano L Tamas M Sodeoka J Am Chem Soc 2002 124 14530For a recent reviews see a) H Ibrahim A Togni Chem Comm 2004 1147 (Feature Article) b) PM Pihko Angew Chem Int Ed 2006 45 544 c) M Oestreich Angew Chem Int Ed 2005 44 2324 d) GKS Prakash P Beier Angew Chem Int Ed 2006 45 2172 e) VA Brunet D OHagan Angew Chem Int Ed 2008 47 1179 Organocatalytic approaches by Barbas Enders Joslashrgensen MacMillan etc

7

Structure of Crystalline Stable Ti(TADDOLato) Complexes Used as Catalyst Precursors in the First Catalytic Asymmetric Fluorination

Preparation and structure L Hintermann D Broggini A Togni Helv Chim Acta 2002 85 1597For a review on TADDOLs see D Seebach et al Angew Chem Int Ed 2001 40 93

Ar=PhenylL2 =DME

Ar=1-NaphthylL=NCMe

These isolated reagents are more reliable than when generated in situ

OO

Ar

ArOAr

ArO

Ti

Cl

ClL L TADDOLs are derivatives of

tartaric acid

In C2 symmetric complexes the aryl groups will pairwise adopt an edge-on and a face-on orientation

1-Naphthyl substituents are crucial for selectivity in the fluorination of β-keto esters (empirical finding)

8

TiCl2(TADDOLato)-Catalyzed Fluorination of Various 13-Dicarbonyl Compounds With Selectfluorreg

General conditions 5 mol catalyst (isolated complex) room temperature MeCN solvent 15min-2d 80-90 isolated yield

L Hintermann A Togni Angew Chem Int Ed 2000 39 4359

OO 1-Naph

1-NaphO

1-Naph

1-NaphO

Ti

Cl

ClMeCN NCMe

O

O O

90 ee

FO

O O

88 ee

FS

O O

91 ee

F

O

O O

82 ee

F

N

O O

F

84 ee

O

O O

F

86 ee

O

O O

F

dr = 965 35

O

ON

O O

F

59 ee

Problem The enol form of a 13-dicarbonyl compound undergoes uncatalyzed fluorination with N-F reagents

N N CH2ClF

2 BF4ndash

++

9

A Simple Mechanistic HypothesisThe catalyst is a cationic Ti monochloro complex

An SN2 processat the F atom

RR Cl

Ti

Cl

OO

NCMeMeCN

OO

Np

Np

Np

Np

R OR

O O

Me

Cl

Ti

O

OOO

OR

MeR

MeCN

OO

Np

Np

Np

Np

F

R OR

O O

MeF

N N FCl

S

Cl

Ti

O

OOO

OR

MeR

MeCN

OO

Np

Np

Np

Np

ndash H+

ndash Clndash ndash MeCN

++

+

+

Cl

Ti

O

OOO

OR

MeR

MeCN

OO

Np

Np

Np

Structure type has precedent in the literature

H-M Gau et al Inorg Chim Acta 2001 314 105

A postulated mechanism reflects a typical implicit situation and sequence Find a ligand andor catalyst first optimize the reaction (and publish) understand the reaction and the efficacy of the catalyst (if you have time)

10

A Model Enolato Complex and Its Fluorination

77 ee (71 ee in the catalytic reaction)

Re-side attack forSS-TADDOL

A C2-symmetric complexin solution (by 2D NMR)Major product (ca 75) in a mixture of three clearly detectable diastereoisomers

SS

Cl

Ti

Cl

O O

MeCN NCMe

OO

Np

Np

Np

Np Et OBn

O O

Me

Et OBn

O O

MeF

N N F

Cl

R

O

Ti

O

O O

OBnO

Me Et

O

OONp

Np

Np

Np

OBn

Et

Me++

Nandash

C6H6 rt 80-90

M Perseghini M Massaccesi Y Liu A Togni Tetrahedron 2006 62 7180

11

Possible Diastereoisomeric Forms of [Ti(TADDOLato)(carbonylenolato)]2 Complexes

OTiO

OOO

O

R

O

O ONp

NpNp

O

R

R

R

OTiO

OOO

R

O

O

O ONp

NpNp

R

OR

R

OTiO

OOO

R

O

O

O ONp

NpNp

O

R

RR

TiOO

O ONp

NpNp

O

OO

R

R

OO

O

R

R

TiOO

O ONp

NpNp

O

OR

OOO

R

O

TiOO

O ONp

NpNp

O

OR

OOO

O

R

R

RR R

A Face-on ReFace-on Re (C2)

D Edge-on ReEdge-on Re (C2)

B Face-on SiFace-on Si (C2)

E Edge-on SiEdge-on Si (C2)

C Face-on ReFace-on Si (C1)

G Edge-on ReEdge-on Si (C1)


12

The Four Most Stable Octahedral Ti Enolate Adducts Containing Cl in Axial Position ndash QMMM Models

00 (63) kcalmolS-product

(Face-on Re)


(Edge-on Re)

13 (75) kcalmolR-product

(Face-on Si)

28 ( 61) kcalmolR-product

(Edge-on Si)

13

The Origin of Enantioselectivity as From the QMMM Computational Model

Cl

Ti

O

OOO

O

Me

MeCN

OO

Np

Np

Np

The face-on naphthyl group in RR-TADDOL shields the Re enantioface of the chelating enolate

Interplanar distance of ca 36 Aring

The attack of the electrophile is only possible from the Si-side

14

The Origin of Enantioselectivity as From the Crystal Structure of a Bis(enolato) Complex

O

Ti

O

OOO

OBnO

OO

Np

NpNp

BnO

A C₂ symmetric bis(carbonylenolato) complex displays the same local structural features in the solid state as the computed model

The average distance of the enolato ligand from the naphthyl plane is 36 Aring and the interplanar angle is 5deg

RR-TADDOL leads to preferential Si-side attack

15

Mechanistic DescriptionStructural and kinetics studies confirm postulated mechanism

kHkD = 098 plusmn 005 for

Me O

O O

Me HDF

RR Cl

Ti

Cl

OO

THFTHF

OO

Np

Np

Np

Np

R OR

O O

Me

Cl

Ti

O

OOO

OR

MeR

THF

OO

Np

Np

Np

Np

F

R OR

O O

MeF

S

Cl

Ti

O

OOO

OR

MeR

THF

OO

Np

Np

Np

Np

ndash H+

ndash Clndash ndash THF

+

+

Cl

Ti

O

OOO

OR

MeR

THF

OO

Np

Np

Np

HD

HD

N FPhSO2

PhSO2

rate = k [catalyst][NFSI]

[THF]+ k [substrate][NFSI]

Mihai Viciu to be published

16

Free Energy Profile and Spin Density From Constrained Molecular Dynamics Simulations of the F-Transfer Step

S Piana I Devillers A Togni U Roumlthlisberger Angew Chem Int Ed 2002 41 979

CPMD simulation with the system immersed in a 46 times 49 times 44 Aring box of 557 acetonitrile molecules

Total simulation time 48 ps for T = 300 K

ΔG kcalsdotmol-1 ρpol

17

The Actual Fluorination Step Involves a (Concerted)Dissociative Electron-Transfer Process

A singlet diradical(EPR silent)

For reviews on electron-transfer chemistry see 1) J-M Saveacuteant Adv Phys Org Chem 2000 35 117 2) R Rathore JK Kochi Adv Phys Org Chem 2000 35 193

ClTi

O

OOO

OR

MeR

MeCN

OO

Np

Np

NpNp

NN

F

Cl

N NCl

ClTi

O

OOO

OR

MeR

MeCN

OO

Np

Np

NpNp

ClTi

O

OOO

OR

MeR

MeCN

OO

Np

NpNp

Np

F

N N FCl

++

+

+

SET

Fluorine atom transfer(radical recombination)

+

18

Frontier Orbital Considerations

LUMO of [F-TEDA]2+

σ(N-F) ndash9531 eV N-F 1390 Aring (exp 137(2) Aring)

SOMO of [F-TEDA]+

ndash10144 eV N-F 1974 Aring

RE Banks et al Acta Cryst C 1993 49 492 For previous frontier-orbital considerations on N-F reagents see K Sudlow AA Woolf J Fluorine Chem 1994 66 9

HOMO

of enolato complex

ndash endash

B3LYP6-31G level

19

Simple Frontier Orbital Requirement for Electrophilic Atom-Transfer Reactions to (Potentially) Occur

SET

R

ORO

O

E ERn

Rm

LUMO (σEndashE)HOMO

-

R

ORO

O

ERn

+ RmEndash

O O

MeMe

O N

HMe

Me

ICl

MeS

Me

SMe

N

O

O

Cl

SCl

All orbitals at the B3LYP6-31G level

20

Summary Various Hetero Functionalizations of 13-Dicarbonyl Compounds Using One and the Same Catalyst

absolute configuration known for at least one derivative

F L Hintermann A Togni Angew Chem Int Ed 2000 39 4359Cl L Hintermann A Togni Helv Chim Acta 2000 83 2425FCl R Frantz L Hintermann M Perseghini D Broggini A Togni Org Lett 2003 5 1709OH P Toullec C Bonaccorsi A Mezzetti A Togni Proc Natl Acad Sci 2004 101 5810SPh M Jereb A Togni Org Lett 2005 7 4041

R1 OR3

O O

R2

R1 OR3

O O

R2SPh

R1 OR3

O O

R2F

R1 OR3

O O

R2Cl

R1 OR3

O O

FCl

R1 OR3

O O

R2HO

NCS

Selectfluor

SelectfluorNCS(R2=H)

N SO2PhO2N

H

O

RR Cl

Ti

Cl

OO

NCMeMeCN

OO

Np

Np

Np

Np

Catalyst precursor(Np = 1-naphthyl)

up to 90 ee up to 93 ee

up to 88 ee


PhSCl (F5C6SCl) toluene rt

Problem The enol form of a 13-dicarbonyl compound may undergo uncatalyzed reaction with the electrophile

21




22

The Modularity of Classical Ferrocenyl LigandsPrototypes for C1 Symmetric Ligands

Me Ferrocene fragment(carrier of the chiral information)Fe

Ligand fragment 2(achiral nucleophilicsynthon)

L1 L2Ligand fragment 1(achiral electrophilic synthon)

The assembly of the three components occursin two consecutive stereoselective (-specific) synthetic steps

Step 12 Step 21

Synthetic scheme allows the preparation of ligands containing PP PN PO PS NN combinations of donor atoms

Ligand libraries become accessible (and are partly commercially available)

23

Josiphos and Pigiphos Are Readily Available

A Togni C Breutel A Schnyder F Spindler H Landert A Tijani J Am Chem Soc 1994116 4062

See also EP 0 564 406 A1 (Priority 02041992 CH)

Pierluigi (Pigi) Barbaro A Togni Organometallics 1995 14 3570

Combination of a bulky trialiphatic phosphine with one or two triaryl phosphines

Josiphos Steric and electronic differentiation between the two P donors

Pigiphos is a rare example of a chiral triphosphineFlexible coordination geometry facial and equatorial (d6) distorted planar (d8) tetrahedral (d10)

Josiphos

Pigiphos

Fe

NMe2

MeFe PPh2

NMe2

Me

Fe PPh2

PCy2

Me

PFe PPh2

Fe

Ph2PUgis amine

24

A Togni et al Organometallics 1995 14 5415

Regioselectivity R1 is bulky andorelectron-withdrawing

Synthesis of Pyrazole-Containing Ferrocenyl Ligands

NMe2

MePAr2

R1 R3

OO

R2

H2NNH2

NNH

R3R2

R1

Fe Fe

NMe

NR3

R2

R1

PAr2

Several combinations of Ar R1 R2 and R3

AcOH 70-90 degC

80-90 yield

+

25

Ph2PCy2P

Ph2P

PCy2

Ph2PCy2P

Ph2P

Cy2P

PPh2PCy2

Ph2P

PCy2

Si

O

O

HN

O

NH

Si

Si

O

OHN

O

HN

Si

NP N P

NP

NP Si

O

OHN

ONH

Si

Si

OO

HNO NH

Si

Si

O

ONH

O

HN

Si

Si

O

ONH

ONH Si

SiO

ONH

OHN

Si

Si

OO

NH O

HN

Si

PPh2Cy2P

Ph2PCy2P

PPh2

PCy2

PPh2PCy2

Ph2PPCy2

PPh2

Cy2P

PPh2PCy2

PPh2

PCy2

Ph2P

Cy2P

Fe

PPh2Cy2P

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Incorporation of Josiphos Into Dendrimers

C Koumlllner B Pugin A Togni J Am Chem Soc 1998120 10274

C Koumlllner A Togni Can J Chem 200179 1762

26

For recent reviews see a) H-U Blaser B Pugin F Spindler M Thommen Acc Chem Res 2007 40 1240-1250b) H-U Blaser W Brieden B Pugin F Spindler M Studer A Togni Topics in Catalysis 200219 3-16See also A Togni Angew Chem Int Ed Engl 1996 35 1475-1477

Examples of Past and Present Production-Scale Applications of Josiphos Ligands in Catalytic Asymmetric Hydrogenations

NH3C

CH3

OCH3

CH3OCl

H

P

MeFe

PPh2

S-Metolachlor(Syngenta)

2

Ir

S

NHHN

O

H H

P(t-Bu)2

MeFe

PPh2

COOH

(+)-Biotin(LONZA)

Rh

Sitagliptin(Merck)

Rh

F

FF

NN

NN

ONH2

CF3

PtBu2

MeFe P(4-F3CPh)2

27

Rh(Josiphos)-Catalyzed Hydrogenation of Tetrahydropyrazine Derivatives Intermediates in the Synthesis of Indinavir

Pilot scale at LONZA

H NN

ONHO

O

H NN

ONHO

O[Rh(COD)2]BF4Josiphos ligand

SC=2000

MeOH 90degC 50 bar H2

96 ee

P(t-Bu)2

MeFe PPh2

N NN

OH

O

NH

ONH OH

Indinavir (Crixivan Merck Sharp amp Dohmeantiviral HIV-1-protease inhibitor)

JF McGarrity W Brieden R Fuchs H-P Mettler B Schmidt O Werbitzky in Large Scale Asymmetric Catalysis HU Blaser E Schmidt (Eds) Wiley-VCH Weinheim 2003 p 283

28

CS Shultz SD Dreher N Ikemoto JM Williams EJJ Grabowski SW Krska Y Sun

PG Dormer L DiMichele Org Lett 2005 7 3405 (Merck amp Co)

Ru-Catalyzed Hydrogenation of N-Sulfonylated-α-dehydroamino Acids Synthesis of an Anthrax Lethal Factor Inhibitor

P(t-Bu)2

MeFe PPh2

O

HOOCHN

S

F

O O

O

HOOCHN

S

F

O O

RuCl2(P-P)LnNEt3

H2 EtOH

O

HN

S

F

O O

O

HOHNP-P =

97 ee

29

Asymmetric Hydrogenation of Unprotected Enamines(Collaboration Merck - Solvias)

1) Y Hsiao et al J Am Chem Soc 2004 126 9918See also 2) N Ikemoto et al J Am Chem Soc 2004 126 3048 3) KB Hansen et al J Am Chem Soc 2009 131 8798

Up to 97 ee

F

FF

NN

NN

ONH2

CF3

MK-0431 (Merck)Sitagliptin (Januvia)

Diabetes 2 ndash DPP IV Inhibitor

P(t-Bu)2

MeFe

P(t-Bu)2Me

Fe P CF32

PPh2

R OMe

NH2 O

R OMe

NH2 ORh Josiphos ligand

R NHPh

NH2 O

R NHPh

NH2 O

H2

Rh Josiphos ligand

H2

30

More Josiphos Applications

Rh-Catalyzed hydrogenation of iminesenamines (Zhong (Merck) 2009)

Ru- and Os-Catalyzed hydrogenation and transfer hydrogenation of aryl methyl ketones (Baratta 2007-2008)

Cu-Catalyzed β-boration of β-unsaturated carbonyl compounds (Yun 2006)

Pd-Catalyzed hydrophosphonation of alkenes (Han 2006)

Cu-Catalyzed Michael addition of Grignard reagents to αβ-unsaturated esters and thioesters (Feringa 2005)

Rh-Catalyzed hydroboration of vinyl arenes (Crudden 2004)

Cu-Catalyzed PMHS reduction of nitroalkenes and acyclic enones (Carreira Lipshutz 2003)

Rh-Catalyzed Michael addition of organotrifluoroborates to enones (Genet 2002)

Rh-Catalyzed ring opening of oxabicyclic substrates (Lautens 2000)

31

Steric vs Electronic Effects1) Structural characteristics and the soft concept of conformational rigidity

Ligands as the carriersof the chiral information

Steric propertieseg bulk conformation

Electronic propertieseg donoracceptor ability

Stereoselectivity(Activity)

Intuitive repulsive ground-state effects(rational design)

Elusivetransition-stateeffects(empiricism )

Steric tuning is achieved by a judicious choice of substituents according to their size and shape ndash Influence on conformation and configuration (diastereomeric intermediates)

Electronic tuning is very often dependent on sterically less relevant peripheral ligand substituents ndash Alteration of donoracceptor properties of coordinating atom

32

Conformation of Pyrazole-Containing Ferrocenyl Ligands

X-ray crystallographic and 2-D NMR studies in solution show comparable conformations in both the free ligands and their complexesIs conformational rigidity a requirement

33

$

amp$

$

$

($

$$ amp$ )$ $ $ $ $ $

$

amp()+-

0)+(1amp2345$4+amp627+898()8424)2amp2342amp+((+amp9(

ampamp2824+

5lt=-amp)gt+gt2)42

The Josiphos Conformational Space as Defined by Two Crucial Torsion AnglesExperimental Values from X-Ray Crystal Structures

M = Cu(I) Ru(II) Pd(0) Pd(II) Pt(II) Rh(I) Ir(I) Ir(III) W(0) Re(I) Re(V)

Sign of torsion angle valid for (R)-(S) absolute configuration

Complexes show a higher conformational degree of freedom of the P1 phosphino group

A proper simplistically understood conformational rigidity of the whole ligand scaffold is not present

34

Orientation of P-M-P Plane Depending on Torsion Angles α1 and α2

α1=-65degα2=-24deg


α1=+9degα2=-21deg

α1=+30degα2=-32deg

α1=-66degα2=+84deg


35

Pd

L1

L2R

R

Pd

L1

L2

R

R

Nu Nu

Pd-Catalyzed Asymmetric Allylic Amination

Stereoselectivity of Pd-catalyzed allylic alkylation and amination depends ultimately on1) ratio of configurational diastereoisomers of π-allyl complexes2) rate of nucleophilic attack on different diastereoisomers3) site of nucleophilic attack (trans to L1 or L2)

36

A Togni U Burckhardt V Gramlich PS Pregosin R Salzmann J Am Chem Soc 1996 118 1031

The Steric Effect of a Crucial Substituent in the Pd-Catalyzed Allylic Amination ndash Shape Rather Than Size

X-rayX-ray

PhPh FeP

NNPd Ph

Ph

71 exo-syn-anti isomer40 ee (S-enantiomer)

+

Ph

FeP

NNPd

Ph

Ph

Ph

100 exo-syn-syn isomergt 99 ee (R-enantiomer)

+

PhPh FeP

NN

Pd Ph

Ph

+

100 exo-syn-anti isomerno reaction

R = Ph 1-Np 2-Np 4-Py Cy 3-NO2-Pht-Bu Adamantyl

Ph Ph

OCOR

NH2

Ph Ph

NHCH2Ph3 mol Pd(dba)2 Ligand

40 degC THF

rac R = Me OEt 85-95 yieldup to gt99 ee

N

Me

N

Fe

PPh2R

37

Nucleophilic Attack trans to Phosphorusis Highly Preferred

P Bloumlchl A Togni Organometallics 1996 15 4125

Ph

FeP

NNPd

Ph

a) R-product

b) S-productgt 200 (gt 99 ee)

Single exo-syn-syn isomer (2D-NMR studies)

NuNu

a)

b)

+

RS

ΔΔGne gt 3 kcalmol-1

Allyl rotation(X-ray studies)

Increased electrophilicity

PN

PdP N

PdP N

+ +

ΔΔGDaggertc = 9 kcalmolΔΔGDagger

tc = 2 kcalmol

(Ab initio studies)

38

NH

NPd

PH3

NH3

trans to P trans to NNH

NPd

PH3

ΔΔGDagger = 8 kJmol42 kJmol

NH

NPd

PH3

NH3

50 kJmol

36 kJmol

NH3+

41 kJmol

NH3+

+

Calculated Energetics (DFT) of Nucleophilic Attackin a Non-Distorted Model Complex


PdP N

PdP N

PdP N

+

+ +

Nucleophilic attack is favored by P trans influenceΔΔGDagger

tc = 8 kJmol

ΔΔGDaggertc = 38 kJmol ΔΔGDagger

ct = 29 kJmol

Enhancedelectrophilicity

for C out of plane

Sterically induced rotation of π-allyl ligand dominates site-selectivityirrespective of cistrans relationship to donor atoms P and N

The Effect of a Sterically Induced Distortion on Frontier Orbitals (LUMO) ndash Computational Studies

40

PhPh Fe

P

NNPd

Ph

Ph

Ph

Ph

FeP

NNPd

Ph

Ph

exo-syn-anti (71)

+

exo-syn-syn (29)

+

S R

Isomer ratio reflects enantioselectivity

9-Anthryl Substituent Induces a Change in the Preferred Configuration at Allyl Ligand

41

PhFe

P

NN

Pd

Enforced anti-arrangement(X-ray and 2D-NMR)

+

Ph

but no reaction with PhCH2NH2

A Triptycyl-Substituted Pyrazole LigandFixation of Pd-Allyl Configuration

in a Rationally Designed Chiral Environment

42

Ph

Ph

PdP N

Ph

Ph

P NPd

Nu

Nu

Pd(II)-(η3-Allyl) Pd(0)-(η2-Olefin)

The Triptycyl Substituted Pd-π-Allyl ComplexWhy Does it Not React With a Nucleophile

Plausible explanation The side-on movement of the allyl fragment that has to take place upon nucleophilic attack in order to form a Pd(0)-olefin complex is hampered by the presence of the triptycyl substituent

43

Both Opposite Ligand Position and Allyl ConfigurationLead to the Same Sense of Induction

The combination of steric configurational and electronic regiochemical control

U Burckhardt D Drommi A Togni Inorg Chim Acta 1999 296 183

PMe

NN

Ph

Ph

PhPh

PdNN

MePd

FeFeP

Ph

Ph

Ph

Ph

Ph Ph

NHCH2Ph

(S)

Ph Ph

OCOOEtNu-Nu-

exo-syn-syn endo-syn-syn

950 ee resp 945 ee

rac

44

Comparing Two Isomeric Ligands

Two different donor combinations P C(carbene) and P sp2-N

The two ligands and their complexes are isoelectronic and essentially isostructural

How do they compare in reactivity and selectivity

For other examples of bidentate ferrocenyl carbene ligands see H Seo H Park BZ Kim SU Son YK Chung Organometallics 2003 22 618

Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

Fe

N CN

PPh2

Me

Fe

N NC

PPh2

MePdR

R+

PdR

R+

X-ray

45

The Nucleophilic Attack by an Amine on Cationic Pd-π-Allyl Complexes

Conditions CHCl3 298 K reactions monitored by UVVIS andor NMRAmines benzylamine piperidine ndash Counterion CF3COOndash

Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

PdR

R+

PdR

R+

Fe

N CN

PPh2

Me Pd

NHR2R

RFe

N CN

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

Fe

N NC

PPh2

Me Pd

NHR2R

RFe

N NC

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

dr 8515exoendo 8218

46

The Kinetics of Nucleophilic Attack by an Amine

Clean second order kinetics for both types of ligands

The nucleophilic attack on the PC complexes is three orders of magnitude slower than on the PN complexes

ndash d[Pd-allyl complex]dt

= k2 sdot [Pd-allyl complex] sdot [Amine]

F Visentin A Togni Organometallics 2007 26 3746

Ligand Allyl subst Amine k2 (molmiddotdmndash3)

PC H Piperidine (226plusmn007)middot10ndash2

PC H Benzylamine (34plusmn01)middot10ndash4

PN H Piperidine 335plusmn009

PN H Benzylamine 0687plusmn0009

PN Ph Piperidine (141plusmn002)middot10ndash2

PC Ph Piperidine ca 5middot10ndash5

47

Pd-Catalyzed Allylic Amination Using the PCarbene LigandldquoNucleophilic Confusionrdquo

Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph

15 mol [Pd(η3-allyl)(PC)]CF3CO2

40 degC THF32 yield after 120 h5 ee S-enantiomer for (R)-(S) ligand

Ph Ph

OCOOEt

Ph Ph

N



NH

Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph

15 mol [Pd(η3-allyl)(PN)]CF3CO2

40 degC THFquant yield after 40 h98 ee S-enantiomer for (R)-(S) ligand

48

N

Me

N

Fe

PPh2

Ph Ph

OCO2Et

Ph Ph

NHCH2Ph

[Pd(dba)2 ]+ Ligand

[Pd(dba)2 ]+ Ligand+ 10 Eq NH4PF6

[Pd(η3-Ph2Allyl)(L)]PF6

[Pd(η3-Ph2Allyl)(L)]PF6+ 2 Eq NBu4F

[Pd(dba)2 ]+ Ligand+ 2 Eq NBu4F

991 (220)

67 (11)

33 (2)

987 (153)

gt995 (gt400)

Catalyst Precursor ee (er)

40 degC THF PhCH2NH2

3 mol Pd-catalyst

PF6- Selectivity

Killer

F- Selectivity Enhancer

U Burckhardt et al Tetrahedron Asymmetry 1997 8 155

A Remarkable Anion Effect in the Pd-CatalyzedAllylic Amination

49

Ph

Ph

P

NPd

+

endo-syn-syn

+

exo-syn-syn

Ph

PhP

NPd

Ph Ph

OCOOEt

Ph Ph

OCOOEtSimilar rates of oxidative addition

(no kinetic resolution)

Slow with PF6-

(tight ion pairs )

Fast with F-

(Coordination)

R-Product S-Product

more stable

F- ensures Curtin-Hammett conditions

S R

A plausible explanation of the anion effect

50

Steric vs Electronic Effects2) The ability of peripheral substituents to influence both activity and selectivity









51

E N Jacobsen et al

Electron-donating groups favor a late transition state and hence a better stereodifferentiation in the oxygen-transfer process as indirectly shown by a more pronounced secondary inverse isotope effect

Electronic Effects in the Asymmetric Mn-Catalyzed Epoxidation of 22-Dimethylchromene

NN

OMn

OCl

X X

HHX = OMe 96 ee

X = NO2 22 ee

52

A L Casalnuovo T V RajanBabu et al J Am Chem Soc 1994 116 9869

An electron-withdrawing group on phosphorus leads to a differential increaseof the rate of product reductive elimination starting from diastereoisomericNiCN(η3-benzyl) complexes

Electronic Effects in the Asymmetric Ni-Catalyzed Hydrocyanation of Vinylarenes

MeO MeO

CN

OOOPh

OPhOPAr2

OAr2P CF3F3C MeMe

HCN [Ni(COD)2] L

Ar =

91 eeL

16 ee

53

See also G Consiglio et al Helv Chim Acta 1995 78 883

Highly Stereoregular Pd-Catalyzed CO Propene Copolymerization Using Ferrocenyl Ligands

13C NMR Spectrum in d2-HFIPMAS 13C NMR Spectrum (RT)

Stereoregularity gt90 and up to gt96 as judged by NMR

OCO O

++

nn2 3

4

1

75 bar COPd-Catalyst50degC 3h

Δ

54

([α]D=-450)

Model PdCl2 complexes displayvery similar conformations of the PAr2 groups in the solid state

A Togni G Consiglio et al Angew Chem Int Ed 2000 39 2486

CatalystProductivity(g(gPd)-1h-1

Polymer)50 220 370 1800

Effect of Ligand Peripheral Substituents on Catalyst Productivity

PCy2Me

Fe P

CF3

CF32

PCy2Me

Fe P

OMe

OMe2

PCy2Me

Fe P

H

H2

PCy2Me

Fe P

CH3

CH32

55

Mesityl substituent decisive for high enantioselectivity of main productMinor electronic and steric effects of R substituents on phenylsFormation of small amounts of achiral product

Markus Baumann

Asymmetric Heck Reaction

NMeN

Fe

Me

Me

Me

P

O+ PhOTf

3 mol [Pd(dba)2]6 mol Ligand

NEt(i-Pr)2 (2 eq)THF 70degC quant

O Ph O Ph O

Ph

+ +

2

Rn

Rn=(m-CF3)2

Rn=(m-SiMe3)2

Rn=(p-OMe)

Rn=(p-CF3)

1 (34ee)

8 (62ee)

1 (46ee)

1 (10ee)

94 (88ee)

90 (95ee)

97 (96ee)

96 (95ee)

5

2

2

3

56

A Schnyder et al Organometallics 1997 16 255

Ligand Electronic Tuning From 5 to 985 ee in the Rh-Catalyzed Hydroboration of Styrene with Catecholborane

NMeN

Fe

PMe Me

F3C

F3CNMeN

Fe

PMe Me

CF3

F3CF3C

F3C

NMeN

Fe

PF3C CF3

MeO

MeO

NMeN

Fe

PMe Me

MeO

MeO

NMeN

Fe

PF3C CF3

NMeN

Fe

PMe Me

NMeN

Fe

PMe Me

Me2N

Me2NNMeN

Fe

PF3C CF3

F3C

F3C

95 ee985 ee

5 ee72 ee

33 ee

98 ee90 ee

40 ee

the worst

and the best

57

Steric and electronic tuning of pyrazole and phosphine ligand fragments

Pioda G Togni A Tetrahedron Asymmetry 1998 9 3903

Up to 85 ee in the hydrosilylation of 13-cyclohexadieneHigh catalytic activity TON up to 104 TOF up to 103 h-1

Pyrazole-Phosphine Ligands in the Pd-Catalyzed Hydrosilylation of Olefins

NMeN

Fe

Me

Me

Me

PPh2

1) HSiCl3 01 mol PdCl2(L)

2) Oxidative Workup

OH

NMeN

Fe PPh2

NMeN

Fe PPh2

Me

39ee 76ee 99ee

Catalytic activity

NMeN

Fe

MeO

OMe

OMe

PPh2

NMeN

Fe

Me

Me

Me

P

CF3

CF3

2

82ee 91ee

58

Correlation of log[(S)(R)] with σp+ indicates the development of a positive chargein the transition state of the enantioselectivity-determining step

X

Fe PPh2

N N

Mes

Me

X

1) cat PdCl2(L)

2) Oxidation

X=Cl 67 ee (S)X=NMe2 64 ee (R)

= L

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=078rsup2=0996

NMe₂

OMe

Me

ClH

Inversion ofenantioselectivity

Fe P X

N N

Mes

Me

1) cat PdCl2(L)

2) Oxidation

X=CF3 68 ee (S)X=NMe2 45 ee (S)

2

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=014rsup2=0986

NMe₂OMe

Me HCl

Linear Free-Energy Relationshipfor the Hydrosilylation of p-Substituted Styrenes

59

Correlation of log[(S)(R)] with σp + indicates the development of a positive chargein the transition state of the enantioselectivity-determining step

Linear Free-Energy Relationship for the Hydrosilylation of Styrene Using p-Substituted Phenylphosphino Ligands

Fe P X

N N

Mes

Me

OH1) cat PdCl2(L)

2) Oxidation


2

60

bull Clean first-order dependence on olefinbull Electron-rich olefins react faster

Overall Rate for the Hydrosilylation of p-Substituted Styrenes Correlates With Hammett Parameter σp

X

Fe PPh2

N N

Mes

Me

X

OH1) cat PdCl2(L)

2) Oxidation

= L

61

Mechanism of the Pd-Catalyzed Hydrosilylation of Styrenes

PdN

P

Cl

Cl

PdN

P H

SiCl3

R

PdN

P

R

SiCl3

N

PdP

HCl3Si

N

Pd

P

Cl3Si

R

R

Olefin insertionbull Enantioselectivity determiningbull HD exchange shows reversibility

Reversible olefin coordinationOpening of chelate ring 1st order in both olefin and Pdfast HSiCl3

oxidative addition0th order in silane

C-Si reductive eliminationbull Rate determining

Unclear formation

σp

σp+

Experiments with perdeutero styrene and HSiCl3 show a nearly statistical hydrogen isotope distribution in the methyl group of the product

62

Result Both a strong trans influence of SiCl3 and a large steric contribution account for bond elongations and distortion

TK Woo

HH P

PdSiCl3SiCl3

NNH H

HH

HH P

PdSiCl3SiCl3

NNH H

FeP

PdSiCl3SiCl3

NN

FeP

PdSiCl3SiCl3

NN

HH P

PdSiCl3SiCl3

NNH H

HH P

PdSiCl3SiCl3

NN

H3CH

HH

H

Model 1

Model 2

Models of Pd(SiCl3)2 Complex for QMMM Computational Studies

63

Olefin insertion onlyslightly exothermic

Stabilization via π-coordinationof benzyl ligand (η3-mode)

High activation barrier forreductive elimination Rate determining

A Magistrato TK Woo A Togni U Roumlthlisberger Organometallics 2004 23 3218

Reaction Profile for the QM Model System

PPd

H

SiCl3NN

HH

PPd

HSiCl3

NN

HH

PPd

HSiCl3

NN

HH

PPd

SiCl3NN

HH PPd

SiCl3NN

HH

1900

22

-02

-83

141

52

PPd

SiCl3NN

HH

PPd

Cl3SiNN

HH

64

Only one configurationalisomer considered

endoendo-syn

PPdH

SiCl3NN

Fe

PPd HSiCl3NN

FeFe P

Pd

SiCl3NN

PPd HSiCl3NN

Fe

Cl3Si

PPd

SiCl3N

Fe

N

PPd

Cl3SiNN

Fe

PPdH

SiCl3NN

Fe

PPd

NN

Fe

Cl3Si

R

-35

09

TS1

TS2

-205

+-103

+styrene

00

42+48

61

Dagger Dagger

Complete Reaction Profile for Styrene QMMM Model 1

65

si-side coordinatedExo +16 kcalmol

Precursor of S-product(observed for styrene)

re-side coordinatedEndo 00

Precursor of R-product(observed for 4-(dimethylamino)styrene)

FeP

PdH

SiCl3NN

PPd

HSiCl3

NN

Fe

Pd(II)-(η2-Styrene) Complexes QMMM Model 1

66

Reaction Pathways for the Formation of Diastereoisomeric η3-Styryl Intermediates ndash QMMM Model

PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPd

H

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPdSiCl3NN

Fe

PPd

SiCl3NN

Fe

48

00

1609

51

-103

-113

Pathway to S-product

Pathway to R-product

endo-syn

exo-synendo

exo

Fast equilibration Curtin-Hammett situation

kcalmol

67



endo-syn

exo-syn

NMe2

PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

NMe2

PPd

SiCl3NN

Fe

NMe2

PPdH

SiCl3NN

Fe

Me2N

PPd

SiCl3NN

Fe

PPdSiCl3

NN

Fe

NMe2

PPd

SiCl3NN

Fe

Me2N

48

00

08

03

16

-172

-155

exo

endo

Reaction Pathways for the Formation of Diastereoisomeric η3-(4-Dimethylamino)styryl Intermediates QMMM Model 1

68

Hydrosilylation of Perdeuterostyrene With Proteosilane

DD

D

D5

HndashSiCl3 [PdL]

DD

D

D5

HO H DD

H

D5

HO H DH

H

D5

HO H DD

D

D5

HO D

oxid workup

+ + +

MeD2 MeD1 MeD0 MeD3MeD0

MeD1

MeD2

13C-1H-HZQCNMR

MeD2

MeD11 equivsilane

5 equivsilane

EI-MS

The deuterium label at the β-carbon of styrene is selectively scrambled by the silane under hydrosilylation conditions

69

Endo RExo SStyrene 4-(Dimethylamino)styrene

e endo-synf endo-antig exo-synh exo-anti

A Magistrato A Togni U Roumlthlisberger Organometallics 2006 25 1151

Comparison of Reaction Profiles for Styrene and 4-(Dimethylamino)styrene

70

styrenestyrenestyrenestyrene 4-dimethylamino)styrene4-dimethylamino)styrene4-dimethylamino)styrene4-dimethylamino)styreneIntermediate Relative

Energy(kcalmol)

(at rt)

ee Intermediate RelativeEnergy

(kcalmol)

(at rt)

ee

endo-syn -103 123

75 (S)[65 (S)]

endo-syn -172 859

81 (R)[64 (R)]

endo-anti -81 03 75 (S)[65 (S)]

endo-anti -156 58 81 (R)[64 (R)]exo-syn -113 204

75 (S)[65 (S)] exo-syn -155 48

81 (R)[64 (R)]

exo-anti -106 669

75 (S)[65 (S)]

exo-anti -153 35

81 (R)[64 (R)]

Prediction of absolute stereoselectivity based upon calculated relative energy of diastereoisomeric η3-benzyl intermediates

71

Conclusions

Many factors contribute in making a ligand to a privileged one modular synthesis being one of the most important initial success is another

A thorough knowledge of structural and mechanistic features is a requirement in order to understand why a privileged ligand is such

However ex-novo design of new privileged ligands is mostly illusory

72




2





3





4




5


SO2

NF

RR

1 (R=H) 2 (R=Cl)

NS

O O

Me

F

O

Ph1) LDA THF

2) 3

OPh

F

79 yield 88 ee

3

SO2

N

O2S

F

4

NO

Me Ph

O

RO

NO

Me Ph

O

RO1) Base

F

80-90 yield 86-99 de

N

N

OHH

ClO

OMe

2)

NN

Cl

F

+

+2 BF4

ndash

5

Bn

OSiMe3

Bn

O

F4 5

MeCN -20degC





6



O

COOtBu

OCOOtBu

F



P

PR2

Pd

HO

OH

PdP

PR2

R2 R2

(BF4)2

R = 35-Me2Ph

O

COOtBu

OCOOtBu

F



N

O

N

O

PhPh CuTfO OTf

P

PPh2

NiCl

Cl

Ph2

N S

OO

Ph N S

OO

Ph

F



26-lutidine


7



Ar=PhenylL2 =DME

Ar=1-NaphthylL=NCMe


OO

Ar

ArOAr

ArO

Ti

Cl


tartaric acid



8




OO 1-Naph

1-NaphO

1-Naph

1-NaphO

Ti

Cl

ClMeCN NCMe

O

O O

90 ee

FO

O O

88 ee

FS

O O

91 ee

F

O

O O

82 ee

F

N

O O

F

84 ee

O

O O

F

86 ee

O

O O

F

dr = 965 35

O

ON

O O

F

59 ee


N N CH2ClF

2 BF4ndash

++

9



RR Cl

Ti

Cl

OO

NCMeMeCN

OO

Np

Np

Np

Np

R OR

O O

Me

Cl

Ti

O

OOO

OR

MeR

MeCN

OO

Np

Np

Np

Np

F

R OR

O O

MeF

N N FCl

S

Cl

Ti

O

OOO

OR

MeR

MeCN

OO

Np

Np

Np

Np

ndash H+


++

+

+

Cl

Ti

O

OOO

OR

MeR

MeCN

OO

Np

Np

Np




10





SS

Cl

Ti

Cl

O O

MeCN NCMe

OO

Np

Np

Np

Np Et OBn

O O

Me

Et OBn

O O

MeF

N N F

Cl

R

O

Ti

O

O O

OBnO

Me Et

O

OONp

Np

Np

Np

OBn

Et

Me++

Nandash

C6H6 rt 80-90


11


OTiO

OOO

O

R

O

O ONp

NpNp

O

R

R

R

OTiO

OOO

R

O

O

O ONp

NpNp

R

OR

R

OTiO

OOO

R

O

O

O ONp

NpNp

O

R

RR

TiOO

O ONp

NpNp

O

OO

R

R

OO

O

R

R

TiOO

O ONp

NpNp

O

OR

OOO

R

O

TiOO

O ONp

NpNp

O

OR

OOO

O

R

R

RR R








12



(Face-on Re)


(Edge-on Re)


(Face-on Si)


(Edge-on Si)

13


Cl

Ti

O

OOO

O

Me

MeCN

OO

Np

Np

Np




14


O

Ti

O

OOO

OBnO

OO

Np

NpNp

BnO




15



Me O

O O

Me HDF

RR Cl

Ti

Cl

OO

THFTHF

OO

Np

Np

Np

Np

R OR

O O

Me

Cl

Ti

O

OOO

OR

MeR

THF

OO

Np

Np

Np

Np

F

R OR

O O

MeF

S

Cl

Ti

O

OOO

OR

MeR

THF

OO

Np

Np

Np

Np

ndash H+


+

+

Cl

Ti

O

OOO

OR

MeR

THF

OO

Np

Np

Np

HD

HD

N FPhSO2

PhSO2




16






17




ClTi

O

OOO

OR

MeR

MeCN

OO

Np

Np

NpNp

NN

F

Cl

N NCl

ClTi

O

OOO

OR

MeR

MeCN

OO

Np

Np

NpNp

ClTi

O

OOO

OR

MeR

MeCN

OO

Np

NpNp

Np

F

N N FCl

++

+

+

SET


+

18


LUMO of [F-TEDA]2+


SOMO of [F-TEDA]+



HOMO

of enolato complex

ndash endash

B3LYP6-31G level

19


SET

R

ORO

O

E ERn

Rm


-

R

ORO

O

ERn

+ RmEndash

O O

MeMe

O N

HMe

Me

ICl

MeS

Me

SMe

N

O

O

Cl

SCl


20




R1 OR3

O O

R2

R1 OR3

O O

R2SPh

R1 OR3

O O

R2F

R1 OR3

O O

R2Cl

R1 OR3

O O

FCl

R1 OR3

O O

R2HO

NCS

Selectfluor


N SO2PhO2N

H

O

RR Cl

Ti

Cl

OO

NCMeMeCN

OO

Np

Np

Np

Np



up to 88 ee




21




22






Step 12 Step 21



23








Josiphos

Pigiphos

Fe

NMe2

MeFe PPh2

NMe2

Me

Fe PPh2

PCy2

Me

PFe PPh2

Fe

Ph2PUgis amine

24




NMe2

MePAr2

R1 R3

OO

R2

H2NNH2

NNH

R3R2

R1

Fe Fe

NMe

NR3

R2

R1

PAr2


AcOH 70-90 degC

80-90 yield

+

25

Ph2PCy2P

Ph2P

PCy2

Ph2PCy2P

Ph2P

Cy2P

PPh2PCy2

Ph2P

PCy2

Si

O

O

HN

O

NH

Si

Si

O

OHN

O

HN

Si

NP N P

NP

NP Si

O

OHN

ONH

Si

Si

OO

HNO NH

Si

Si

O

ONH

O

HN

Si

Si

O

ONH

ONH Si

SiO

ONH

OHN

Si

Si

OO

NH O

HN

Si

PPh2Cy2P

Ph2PCy2P

PPh2

PCy2

PPh2PCy2

Ph2PPCy2

PPh2

Cy2P

PPh2PCy2

PPh2

PCy2

Ph2P

Cy2P

Fe

PPh2Cy2P

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe




26



NH3C

CH3

OCH3

CH3OCl

H

P

MeFe

PPh2


2

Ir

S

NHHN

O

H H

P(t-Bu)2

MeFe

PPh2

COOH

(+)-Biotin(LONZA)

Rh

Sitagliptin(Merck)

Rh

F

FF

NN

NN

ONH2

CF3

PtBu2

MeFe P(4-F3CPh)2

27



H NN

ONHO

O

H NN

ONHO


SC=2000


96 ee

P(t-Bu)2

MeFe PPh2

N NN

OH

O

NH

ONH OH



28




P(t-Bu)2

MeFe PPh2

O

HOOCHN

S

F

O O

O

HOOCHN

S

F

O O

RuCl2(P-P)LnNEt3

H2 EtOH

O

HN

S

F

O O

O

HOHNP-P =

97 ee

29



Up to 97 ee

F

FF

NN

NN

ONH2

CF3



P(t-Bu)2

MeFe

P(t-Bu)2Me

Fe P CF32

PPh2

R OMe

NH2 O

R OMe


R NHPh

NH2 O

R NHPh

NH2 O

H2

Rh Josiphos ligand

H2

30











31










32



33

$

amp$

$

$

($

$$ amp$ )$ $ $ $ $ $

$

amp()+-


ampamp2824+

5lt=-amp)gt+gt2)42






34




α1=+9degα2=-21deg




35

Pd

L1

L2R

R

Pd

L1

L2

R

R

Nu Nu



36



X-rayX-ray

PhPh FeP

NNPd Ph

Ph


+

Ph

FeP

NNPd

Ph

Ph

Ph


+

PhPh FeP

NN

Pd Ph

Ph

+



Ph Ph

OCOR

NH2

Ph Ph


40 degC THF


N

Me

N

Fe

PPh2R

37



Ph

FeP

NNPd

Ph

a) R-product



NuNu

a)

b)

+

RS




PN

PdP N

PdP N

+ +


tc = 2 kcalmol

(Ab initio studies)

38

NH

NPd

PH3

NH3


NPd

PH3


NH

NPd

PH3

NH3

50 kJmol

36 kJmol

NH3+

41 kJmol

NH3+

+



PdP N

PdP N

PdP N

+

+ +


tc = 8 kJmol


ct = 29 kJmol


for C out of plane



40

PhPh Fe

P

NNPd

Ph

Ph

Ph

Ph

FeP

NNPd

Ph

Ph

exo-syn-anti (71)

+

exo-syn-syn (29)

+

S R



41

PhFe

P

NN

Pd


+

Ph




42

Ph

Ph

PdP N

Ph

Ph

P NPd

Nu

Nu




43




PMe

NN

Ph

Ph

PhPh

PdNN

MePd

FeFeP

Ph

Ph

Ph

Ph

Ph Ph

NHCH2Ph

(S)

Ph Ph

OCOOEtNu-Nu-


950 ee resp 945 ee

rac

44






Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

Fe

N CN

PPh2

Me

Fe

N NC

PPh2

MePdR

R+

PdR

R+

X-ray

45



Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

PdR

R+

PdR

R+

Fe

N CN

PPh2

Me Pd

NHR2R

RFe

N CN

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

Fe

N NC

PPh2

Me Pd

NHR2R

RFe

N NC

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

dr 8515exoendo 8218

46














47


Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



Ph Ph

OCOOEt

Ph Ph

N



NH

Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



48

N

Me

N

Fe

PPh2

Ph Ph

OCO2Et

Ph Ph

NHCH2Ph

[Pd(dba)2 ]+ Ligand





991 (220)

67 (11)

33 (2)

987 (153)

gt995 (gt400)



3 mol Pd-catalyst

PF6- Selectivity

Killer




49

Ph

Ph

P

NPd

+

endo-syn-syn

+

exo-syn-syn

Ph

PhP

NPd

Ph Ph

OCOOEt

Ph Ph



Slow with PF6-

(tight ion pairs )

Fast with F-

(Coordination)

R-Product S-Product

more stable


S R


50










51

E N Jacobsen et al



NN

OMn

OCl

X X

HHX = OMe 96 ee

X = NO2 22 ee

52




MeO MeO

CN

OOOPh

OPhOPAr2

OAr2P CF3F3C MeMe

HCN [Ni(COD)2] L

Ar =

91 eeL

16 ee

53





OCO O

++

nn2 3

4

1


Δ

54

([α]D=-450)




Polymer)50 220 370 1800


PCy2Me

Fe P

CF3

CF32

PCy2Me

Fe P

OMe

OMe2

PCy2Me

Fe P

H

H2

PCy2Me

Fe P

CH3

CH32

55


Markus Baumann


NMeN

Fe

Me

Me

Me

P

O+ PhOTf



O Ph O Ph O

Ph

+ +

2

Rn

Rn=(m-CF3)2

Rn=(m-SiMe3)2

Rn=(p-OMe)

Rn=(p-CF3)

1 (34ee)

8 (62ee)

1 (46ee)

1 (10ee)

94 (88ee)

90 (95ee)

97 (96ee)

96 (95ee)

5

2

2

3

56



NMeN

Fe

PMe Me

F3C

F3CNMeN

Fe

PMe Me

CF3

F3CF3C

F3C

NMeN

Fe

PF3C CF3

MeO

MeO

NMeN

Fe

PMe Me

MeO

MeO

NMeN

Fe

PF3C CF3

NMeN

Fe

PMe Me

NMeN

Fe

PMe Me

Me2N

Me2NNMeN

Fe

PF3C CF3

F3C

F3C

95 ee985 ee

5 ee72 ee

33 ee

98 ee90 ee

40 ee

the worst

and the best

57





NMeN

Fe

Me

Me

Me

PPh2


2) Oxidative Workup

OH

NMeN

Fe PPh2

NMeN

Fe PPh2

Me

39ee 76ee 99ee

Catalytic activity

NMeN

Fe

MeO

OMe

OMe

PPh2

NMeN

Fe

Me

Me

Me

P

CF3

CF3

2

82ee 91ee

58


X

Fe PPh2

N N

Mes

Me

X

1) cat PdCl2(L)

2) Oxidation


= L

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=078rsup2=0996

NMe₂

OMe

Me

ClH


Fe P X

N N

Mes

Me

1) cat PdCl2(L)

2) Oxidation


2

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=014rsup2=0986

NMe₂OMe

Me HCl


59



Fe P X

N N

Mes

Me

OH1) cat PdCl2(L)

2) Oxidation


2

60



X

Fe PPh2

N N

Mes

Me

X

OH1) cat PdCl2(L)

2) Oxidation

= L

61


PdN

P

Cl

Cl

PdN

P H

SiCl3

R

PdN

P

R

SiCl3

N

PdP

HCl3Si

N

Pd

P

Cl3Si

R

R





Unclear formation

σp

σp+


62


TK Woo

HH P

PdSiCl3SiCl3

NNH H

HH

HH P

PdSiCl3SiCl3

NNH H

FeP

PdSiCl3SiCl3

NN

FeP

PdSiCl3SiCl3

NN

HH P

PdSiCl3SiCl3

NNH H

HH P

PdSiCl3SiCl3

NN

H3CH

HH

H

Model 1

Model 2


63






PPd

H

SiCl3NN

HH

PPd

HSiCl3

NN

HH

PPd

HSiCl3

NN

HH

PPd

SiCl3NN

HH PPd

SiCl3NN

HH

1900

22

-02

-83

141

52

PPd

SiCl3NN

HH

PPd

Cl3SiNN

HH

64


endoendo-syn

PPdH

SiCl3NN

Fe

PPd HSiCl3NN

FeFe P

Pd

SiCl3NN

PPd HSiCl3NN

Fe

Cl3Si

PPd

SiCl3N

Fe

N

PPd

Cl3SiNN

Fe

PPdH

SiCl3NN

Fe

PPd

NN

Fe

Cl3Si

R

-35

09

TS1

TS2

-205

+-103

+styrene

00

42+48

61

Dagger Dagger


65





FeP

PdH

SiCl3NN

PPd

HSiCl3

NN

Fe


66


PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPd

H

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPdSiCl3NN

Fe

PPd

SiCl3NN

Fe

48

00

1609

51

-103

-113



endo-syn

exo-synendo

exo


kcalmol

67



endo-syn

exo-syn

NMe2

PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

NMe2

PPd

SiCl3NN

Fe

NMe2

PPdH

SiCl3NN

Fe

Me2N

PPd

SiCl3NN

Fe

PPdSiCl3

NN

Fe

NMe2

PPd

SiCl3NN

Fe

Me2N

48

00

08

03

16

-172

-155

exo

endo


68


DD

D

D5

HndashSiCl3 [PdL]

DD

D

D5

HO H DD

H

D5

HO H DH

H

D5

HO H DD

D

D5

HO D

oxid workup

+ + +


MeD1

MeD2

13C-1H-HZQCNMR

MeD2

MeD11 equivsilane

5 equivsilane

EI-MS


69





70


Energy(kcalmol)

(at rt)


(kcalmol)

(at rt)

ee

endo-syn -103 123

75 (S)[65 (S)]

endo-syn -172 859

81 (R)[64 (R)]

endo-anti -81 03 75 (S)[65 (S)]


75 (S)[65 (S)] exo-syn -155 48

81 (R)[64 (R)]

exo-anti -106 669

75 (S)[65 (S)]

exo-anti -153 35

81 (R)[64 (R)]


71

Conclusions




72





3





4




5


SO2

NF

RR

1 (R=H) 2 (R=Cl)

NS

O O

Me

F

O

Ph1) LDA THF

2) 3

OPh

F

79 yield 88 ee

3

SO2

N

O2S

F

4

NO

Me Ph

O

RO

NO

Me Ph

O

RO1) Base

F

80-90 yield 86-99 de

N

N

OHH

ClO

OMe

2)

NN

Cl

F

+

+2 BF4

ndash

5

Bn

OSiMe3

Bn

O

F4 5

MeCN -20degC





6



O

COOtBu

OCOOtBu

F



P

PR2

Pd

HO

OH

PdP

PR2

R2 R2

(BF4)2

R = 35-Me2Ph

O

COOtBu

OCOOtBu

F



N

O

N

O

PhPh CuTfO OTf

P

PPh2

NiCl

Cl

Ph2

N S

OO

Ph N S

OO

Ph

F



26-lutidine


7



Ar=PhenylL2 =DME

Ar=1-NaphthylL=NCMe


OO

Ar

ArOAr

ArO

Ti

Cl


tartaric acid



8




OO 1-Naph

1-NaphO

1-Naph

1-NaphO

Ti

Cl

ClMeCN NCMe

O

O O

90 ee

FO

O O

88 ee

FS

O O

91 ee

F

O

O O

82 ee

F

N

O O

F

84 ee

O

O O

F

86 ee

O

O O

F

dr = 965 35

O

ON

O O

F

59 ee


N N CH2ClF

2 BF4ndash

++

9



RR Cl

Ti

Cl

OO

NCMeMeCN

OO

Np

Np

Np

Np

R OR

O O

Me

Cl

Ti

O

OOO

OR

MeR

MeCN

OO

Np

Np

Np

Np

F

R OR

O O

MeF

N N FCl

S

Cl

Ti

O

OOO

OR

MeR

MeCN

OO

Np

Np

Np

Np

ndash H+


++

+

+

Cl

Ti

O

OOO

OR

MeR

MeCN

OO

Np

Np

Np




10





SS

Cl

Ti

Cl

O O

MeCN NCMe

OO

Np

Np

Np

Np Et OBn

O O

Me

Et OBn

O O

MeF

N N F

Cl

R

O

Ti

O

O O

OBnO

Me Et

O

OONp

Np

Np

Np

OBn

Et

Me++

Nandash

C6H6 rt 80-90


11


OTiO

OOO

O

R

O

O ONp

NpNp

O

R

R

R

OTiO

OOO

R

O

O

O ONp

NpNp

R

OR

R

OTiO

OOO

R

O

O

O ONp

NpNp

O

R

RR

TiOO

O ONp

NpNp

O

OO

R

R

OO

O

R

R

TiOO

O ONp

NpNp

O

OR

OOO

R

O

TiOO

O ONp

NpNp

O

OR

OOO

O

R

R

RR R








12



(Face-on Re)


(Edge-on Re)


(Face-on Si)


(Edge-on Si)

13


Cl

Ti

O

OOO

O

Me

MeCN

OO

Np

Np

Np




14


O

Ti

O

OOO

OBnO

OO

Np

NpNp

BnO




15



Me O

O O

Me HDF

RR Cl

Ti

Cl

OO

THFTHF

OO

Np

Np

Np

Np

R OR

O O

Me

Cl

Ti

O

OOO

OR

MeR

THF

OO

Np

Np

Np

Np

F

R OR

O O

MeF

S

Cl

Ti

O

OOO

OR

MeR

THF

OO

Np

Np

Np

Np

ndash H+


+

+

Cl

Ti

O

OOO

OR

MeR

THF

OO

Np

Np

Np

HD

HD

N FPhSO2

PhSO2




16






17




ClTi

O

OOO

OR

MeR

MeCN

OO

Np

Np

NpNp

NN

F

Cl

N NCl

ClTi

O

OOO

OR

MeR

MeCN

OO

Np

Np

NpNp

ClTi

O

OOO

OR

MeR

MeCN

OO

Np

NpNp

Np

F

N N FCl

++

+

+

SET


+

18


LUMO of [F-TEDA]2+


SOMO of [F-TEDA]+



HOMO

of enolato complex

ndash endash

B3LYP6-31G level

19


SET

R

ORO

O

E ERn

Rm


-

R

ORO

O

ERn

+ RmEndash

O O

MeMe

O N

HMe

Me

ICl

MeS

Me

SMe

N

O

O

Cl

SCl


20




R1 OR3

O O

R2

R1 OR3

O O

R2SPh

R1 OR3

O O

R2F

R1 OR3

O O

R2Cl

R1 OR3

O O

FCl

R1 OR3

O O

R2HO

NCS

Selectfluor


N SO2PhO2N

H

O

RR Cl

Ti

Cl

OO

NCMeMeCN

OO

Np

Np

Np

Np



up to 88 ee




21




22






Step 12 Step 21



23








Josiphos

Pigiphos

Fe

NMe2

MeFe PPh2

NMe2

Me

Fe PPh2

PCy2

Me

PFe PPh2

Fe

Ph2PUgis amine

24




NMe2

MePAr2

R1 R3

OO

R2

H2NNH2

NNH

R3R2

R1

Fe Fe

NMe

NR3

R2

R1

PAr2


AcOH 70-90 degC

80-90 yield

+

25

Ph2PCy2P

Ph2P

PCy2

Ph2PCy2P

Ph2P

Cy2P

PPh2PCy2

Ph2P

PCy2

Si

O

O

HN

O

NH

Si

Si

O

OHN

O

HN

Si

NP N P

NP

NP Si

O

OHN

ONH

Si

Si

OO

HNO NH

Si

Si

O

ONH

O

HN

Si

Si

O

ONH

ONH Si

SiO

ONH

OHN

Si

Si

OO

NH O

HN

Si

PPh2Cy2P

Ph2PCy2P

PPh2

PCy2

PPh2PCy2

Ph2PPCy2

PPh2

Cy2P

PPh2PCy2

PPh2

PCy2

Ph2P

Cy2P

Fe

PPh2Cy2P

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe




26



NH3C

CH3

OCH3

CH3OCl

H

P

MeFe

PPh2


2

Ir

S

NHHN

O

H H

P(t-Bu)2

MeFe

PPh2

COOH

(+)-Biotin(LONZA)

Rh

Sitagliptin(Merck)

Rh

F

FF

NN

NN

ONH2

CF3

PtBu2

MeFe P(4-F3CPh)2

27



H NN

ONHO

O

H NN

ONHO


SC=2000


96 ee

P(t-Bu)2

MeFe PPh2

N NN

OH

O

NH

ONH OH



28




P(t-Bu)2

MeFe PPh2

O

HOOCHN

S

F

O O

O

HOOCHN

S

F

O O

RuCl2(P-P)LnNEt3

H2 EtOH

O

HN

S

F

O O

O

HOHNP-P =

97 ee

29



Up to 97 ee

F

FF

NN

NN

ONH2

CF3



P(t-Bu)2

MeFe

P(t-Bu)2Me

Fe P CF32

PPh2

R OMe

NH2 O

R OMe


R NHPh

NH2 O

R NHPh

NH2 O

H2

Rh Josiphos ligand

H2

30











31










32



33

$

amp$

$

$

($

$$ amp$ )$ $ $ $ $ $

$

amp()+-


ampamp2824+

5lt=-amp)gt+gt2)42






34




α1=+9degα2=-21deg




35

Pd

L1

L2R

R

Pd

L1

L2

R

R

Nu Nu



36



X-rayX-ray

PhPh FeP

NNPd Ph

Ph


+

Ph

FeP

NNPd

Ph

Ph

Ph


+

PhPh FeP

NN

Pd Ph

Ph

+



Ph Ph

OCOR

NH2

Ph Ph


40 degC THF


N

Me

N

Fe

PPh2R

37



Ph

FeP

NNPd

Ph

a) R-product



NuNu

a)

b)

+

RS




PN

PdP N

PdP N

+ +


tc = 2 kcalmol

(Ab initio studies)

38

NH

NPd

PH3

NH3


NPd

PH3


NH

NPd

PH3

NH3

50 kJmol

36 kJmol

NH3+

41 kJmol

NH3+

+



PdP N

PdP N

PdP N

+

+ +


tc = 8 kJmol


ct = 29 kJmol


for C out of plane



40

PhPh Fe

P

NNPd

Ph

Ph

Ph

Ph

FeP

NNPd

Ph

Ph

exo-syn-anti (71)

+

exo-syn-syn (29)

+

S R



41

PhFe

P

NN

Pd


+

Ph




42

Ph

Ph

PdP N

Ph

Ph

P NPd

Nu

Nu




43




PMe

NN

Ph

Ph

PhPh

PdNN

MePd

FeFeP

Ph

Ph

Ph

Ph

Ph Ph

NHCH2Ph

(S)

Ph Ph

OCOOEtNu-Nu-


950 ee resp 945 ee

rac

44






Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

Fe

N CN

PPh2

Me

Fe

N NC

PPh2

MePdR

R+

PdR

R+

X-ray

45



Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

PdR

R+

PdR

R+

Fe

N CN

PPh2

Me Pd

NHR2R

RFe

N CN

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

Fe

N NC

PPh2

Me Pd

NHR2R

RFe

N NC

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

dr 8515exoendo 8218

46














47


Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



Ph Ph

OCOOEt

Ph Ph

N



NH

Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



48

N

Me

N

Fe

PPh2

Ph Ph

OCO2Et

Ph Ph

NHCH2Ph

[Pd(dba)2 ]+ Ligand





991 (220)

67 (11)

33 (2)

987 (153)

gt995 (gt400)



3 mol Pd-catalyst

PF6- Selectivity

Killer




49

Ph

Ph

P

NPd

+

endo-syn-syn

+

exo-syn-syn

Ph

PhP

NPd

Ph Ph

OCOOEt

Ph Ph



Slow with PF6-

(tight ion pairs )

Fast with F-

(Coordination)

R-Product S-Product

more stable


S R


50










51

E N Jacobsen et al



NN

OMn

OCl

X X

HHX = OMe 96 ee

X = NO2 22 ee

52




MeO MeO

CN

OOOPh

OPhOPAr2

OAr2P CF3F3C MeMe

HCN [Ni(COD)2] L

Ar =

91 eeL

16 ee

53





OCO O

++

nn2 3

4

1


Δ

54

([α]D=-450)




Polymer)50 220 370 1800


PCy2Me

Fe P

CF3

CF32

PCy2Me

Fe P

OMe

OMe2

PCy2Me

Fe P

H

H2

PCy2Me

Fe P

CH3

CH32

55


Markus Baumann


NMeN

Fe

Me

Me

Me

P

O+ PhOTf



O Ph O Ph O

Ph

+ +

2

Rn

Rn=(m-CF3)2

Rn=(m-SiMe3)2

Rn=(p-OMe)

Rn=(p-CF3)

1 (34ee)

8 (62ee)

1 (46ee)

1 (10ee)

94 (88ee)

90 (95ee)

97 (96ee)

96 (95ee)

5

2

2

3

56



NMeN

Fe

PMe Me

F3C

F3CNMeN

Fe

PMe Me

CF3

F3CF3C

F3C

NMeN

Fe

PF3C CF3

MeO

MeO

NMeN

Fe

PMe Me

MeO

MeO

NMeN

Fe

PF3C CF3

NMeN

Fe

PMe Me

NMeN

Fe

PMe Me

Me2N

Me2NNMeN

Fe

PF3C CF3

F3C

F3C

95 ee985 ee

5 ee72 ee

33 ee

98 ee90 ee

40 ee

the worst

and the best

57





NMeN

Fe

Me

Me

Me

PPh2


2) Oxidative Workup

OH

NMeN

Fe PPh2

NMeN

Fe PPh2

Me

39ee 76ee 99ee

Catalytic activity

NMeN

Fe

MeO

OMe

OMe

PPh2

NMeN

Fe

Me

Me

Me

P

CF3

CF3

2

82ee 91ee

58


X

Fe PPh2

N N

Mes

Me

X

1) cat PdCl2(L)

2) Oxidation


= L

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=078rsup2=0996

NMe₂

OMe

Me

ClH


Fe P X

N N

Mes

Me

1) cat PdCl2(L)

2) Oxidation


2

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=014rsup2=0986

NMe₂OMe

Me HCl


59



Fe P X

N N

Mes

Me

OH1) cat PdCl2(L)

2) Oxidation


2

60



X

Fe PPh2

N N

Mes

Me

X

OH1) cat PdCl2(L)

2) Oxidation

= L

61


PdN

P

Cl

Cl

PdN

P H

SiCl3

R

PdN

P

R

SiCl3

N

PdP

HCl3Si

N

Pd

P

Cl3Si

R

R





Unclear formation

σp

σp+


62


TK Woo

HH P

PdSiCl3SiCl3

NNH H

HH

HH P

PdSiCl3SiCl3

NNH H

FeP

PdSiCl3SiCl3

NN

FeP

PdSiCl3SiCl3

NN

HH P

PdSiCl3SiCl3

NNH H

HH P

PdSiCl3SiCl3

NN

H3CH

HH

H

Model 1

Model 2


63






PPd

H

SiCl3NN

HH

PPd

HSiCl3

NN

HH

PPd

HSiCl3

NN

HH

PPd

SiCl3NN

HH PPd

SiCl3NN

HH

1900

22

-02

-83

141

52

PPd

SiCl3NN

HH

PPd

Cl3SiNN

HH

64


endoendo-syn

PPdH

SiCl3NN

Fe

PPd HSiCl3NN

FeFe P

Pd

SiCl3NN

PPd HSiCl3NN

Fe

Cl3Si

PPd

SiCl3N

Fe

N

PPd

Cl3SiNN

Fe

PPdH

SiCl3NN

Fe

PPd

NN

Fe

Cl3Si

R

-35

09

TS1

TS2

-205

+-103

+styrene

00

42+48

61

Dagger Dagger


65





FeP

PdH

SiCl3NN

PPd

HSiCl3

NN

Fe


66


PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPd

H

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPdSiCl3NN

Fe

PPd

SiCl3NN

Fe

48

00

1609

51

-103

-113



endo-syn

exo-synendo

exo


kcalmol

67



endo-syn

exo-syn

NMe2

PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

NMe2

PPd

SiCl3NN

Fe

NMe2

PPdH

SiCl3NN

Fe

Me2N

PPd

SiCl3NN

Fe

PPdSiCl3

NN

Fe

NMe2

PPd

SiCl3NN

Fe

Me2N

48

00

08

03

16

-172

-155

exo

endo


68


DD

D

D5

HndashSiCl3 [PdL]

DD

D

D5

HO H DD

H

D5

HO H DH

H

D5

HO H DD

D

D5

HO D

oxid workup

+ + +


MeD1

MeD2

13C-1H-HZQCNMR

MeD2

MeD11 equivsilane

5 equivsilane

EI-MS


69





70


Energy(kcalmol)

(at rt)


(kcalmol)

(at rt)

ee

endo-syn -103 123

75 (S)[65 (S)]

endo-syn -172 859

81 (R)[64 (R)]

endo-anti -81 03 75 (S)[65 (S)]


75 (S)[65 (S)] exo-syn -155 48

81 (R)[64 (R)]

exo-anti -106 669

75 (S)[65 (S)]

exo-anti -153 35

81 (R)[64 (R)]


71

Conclusions




72





4




5


SO2

NF

RR

1 (R=H) 2 (R=Cl)

NS

O O

Me

F

O

Ph1) LDA THF

2) 3

OPh

F

79 yield 88 ee

3

SO2

N

O2S

F

4

NO

Me Ph

O

RO

NO

Me Ph

O

RO1) Base

F

80-90 yield 86-99 de

N

N

OHH

ClO

OMe

2)

NN

Cl

F

+

+2 BF4

ndash

5

Bn

OSiMe3

Bn

O

F4 5

MeCN -20degC





6



O

COOtBu

OCOOtBu

F



P

PR2

Pd

HO

OH

PdP

PR2

R2 R2

(BF4)2

R = 35-Me2Ph

O

COOtBu

OCOOtBu

F



N

O

N

O

PhPh CuTfO OTf

P

PPh2

NiCl

Cl

Ph2

N S

OO

Ph N S

OO

Ph

F



26-lutidine


7



Ar=PhenylL2 =DME

Ar=1-NaphthylL=NCMe


OO

Ar

ArOAr

ArO

Ti

Cl


tartaric acid



8




OO 1-Naph

1-NaphO

1-Naph

1-NaphO

Ti

Cl

ClMeCN NCMe

O

O O

90 ee

FO

O O

88 ee

FS

O O

91 ee

F

O

O O

82 ee

F

N

O O

F

84 ee

O

O O

F

86 ee

O

O O

F

dr = 965 35

O

ON

O O

F

59 ee


N N CH2ClF

2 BF4ndash

++

9



RR Cl

Ti

Cl

OO

NCMeMeCN

OO

Np

Np

Np

Np

R OR

O O

Me

Cl

Ti

O

OOO

OR

MeR

MeCN

OO

Np

Np

Np

Np

F

R OR

O O

MeF

N N FCl

S

Cl

Ti

O

OOO

OR

MeR

MeCN

OO

Np

Np

Np

Np

ndash H+


++

+

+

Cl

Ti

O

OOO

OR

MeR

MeCN

OO

Np

Np

Np




10





SS

Cl

Ti

Cl

O O

MeCN NCMe

OO

Np

Np

Np

Np Et OBn

O O

Me

Et OBn

O O

MeF

N N F

Cl

R

O

Ti

O

O O

OBnO

Me Et

O

OONp

Np

Np

Np

OBn

Et

Me++

Nandash

C6H6 rt 80-90


11


OTiO

OOO

O

R

O

O ONp

NpNp

O

R

R

R

OTiO

OOO

R

O

O

O ONp

NpNp

R

OR

R

OTiO

OOO

R

O

O

O ONp

NpNp

O

R

RR

TiOO

O ONp

NpNp

O

OO

R

R

OO

O

R

R

TiOO

O ONp

NpNp

O

OR

OOO

R

O

TiOO

O ONp

NpNp

O

OR

OOO

O

R

R

RR R








12



(Face-on Re)


(Edge-on Re)


(Face-on Si)


(Edge-on Si)

13


Cl

Ti

O

OOO

O

Me

MeCN

OO

Np

Np

Np




14


O

Ti

O

OOO

OBnO

OO

Np

NpNp

BnO




15



Me O

O O

Me HDF

RR Cl

Ti

Cl

OO

THFTHF

OO

Np

Np

Np

Np

R OR

O O

Me

Cl

Ti

O

OOO

OR

MeR

THF

OO

Np

Np

Np

Np

F

R OR

O O

MeF

S

Cl

Ti

O

OOO

OR

MeR

THF

OO

Np

Np

Np

Np

ndash H+


+

+

Cl

Ti

O

OOO

OR

MeR

THF

OO

Np

Np

Np

HD

HD

N FPhSO2

PhSO2




16






17




ClTi

O

OOO

OR

MeR

MeCN

OO

Np

Np

NpNp

NN

F

Cl

N NCl

ClTi

O

OOO

OR

MeR

MeCN

OO

Np

Np

NpNp

ClTi

O

OOO

OR

MeR

MeCN

OO

Np

NpNp

Np

F

N N FCl

++

+

+

SET


+

18


LUMO of [F-TEDA]2+


SOMO of [F-TEDA]+



HOMO

of enolato complex

ndash endash

B3LYP6-31G level

19


SET

R

ORO

O

E ERn

Rm


-

R

ORO

O

ERn

+ RmEndash

O O

MeMe

O N

HMe

Me

ICl

MeS

Me

SMe

N

O

O

Cl

SCl


20




R1 OR3

O O

R2

R1 OR3

O O

R2SPh

R1 OR3

O O

R2F

R1 OR3

O O

R2Cl

R1 OR3

O O

FCl

R1 OR3

O O

R2HO

NCS

Selectfluor


N SO2PhO2N

H

O

RR Cl

Ti

Cl

OO

NCMeMeCN

OO

Np

Np

Np

Np



up to 88 ee




21




22






Step 12 Step 21



23








Josiphos

Pigiphos

Fe

NMe2

MeFe PPh2

NMe2

Me

Fe PPh2

PCy2

Me

PFe PPh2

Fe

Ph2PUgis amine

24




NMe2

MePAr2

R1 R3

OO

R2

H2NNH2

NNH

R3R2

R1

Fe Fe

NMe

NR3

R2

R1

PAr2


AcOH 70-90 degC

80-90 yield

+

25

Ph2PCy2P

Ph2P

PCy2

Ph2PCy2P

Ph2P

Cy2P

PPh2PCy2

Ph2P

PCy2

Si

O

O

HN

O

NH

Si

Si

O

OHN

O

HN

Si

NP N P

NP

NP Si

O

OHN

ONH

Si

Si

OO

HNO NH

Si

Si

O

ONH

O

HN

Si

Si

O

ONH

ONH Si

SiO

ONH

OHN

Si

Si

OO

NH O

HN

Si

PPh2Cy2P

Ph2PCy2P

PPh2

PCy2

PPh2PCy2

Ph2PPCy2

PPh2

Cy2P

PPh2PCy2

PPh2

PCy2

Ph2P

Cy2P

Fe

PPh2Cy2P

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe




26



NH3C

CH3

OCH3

CH3OCl

H

P

MeFe

PPh2


2

Ir

S

NHHN

O

H H

P(t-Bu)2

MeFe

PPh2

COOH

(+)-Biotin(LONZA)

Rh

Sitagliptin(Merck)

Rh

F

FF

NN

NN

ONH2

CF3

PtBu2

MeFe P(4-F3CPh)2

27



H NN

ONHO

O

H NN

ONHO


SC=2000


96 ee

P(t-Bu)2

MeFe PPh2

N NN

OH

O

NH

ONH OH



28




P(t-Bu)2

MeFe PPh2

O

HOOCHN

S

F

O O

O

HOOCHN

S

F

O O

RuCl2(P-P)LnNEt3

H2 EtOH

O

HN

S

F

O O

O

HOHNP-P =

97 ee

29



Up to 97 ee

F

FF

NN

NN

ONH2

CF3



P(t-Bu)2

MeFe

P(t-Bu)2Me

Fe P CF32

PPh2

R OMe

NH2 O

R OMe


R NHPh

NH2 O

R NHPh

NH2 O

H2

Rh Josiphos ligand

H2

30











31










32



33

$

amp$

$

$

($

$$ amp$ )$ $ $ $ $ $

$

amp()+-


ampamp2824+

5lt=-amp)gt+gt2)42






34




α1=+9degα2=-21deg




35

Pd

L1

L2R

R

Pd

L1

L2

R

R

Nu Nu



36



X-rayX-ray

PhPh FeP

NNPd Ph

Ph


+

Ph

FeP

NNPd

Ph

Ph

Ph


+

PhPh FeP

NN

Pd Ph

Ph

+



Ph Ph

OCOR

NH2

Ph Ph


40 degC THF


N

Me

N

Fe

PPh2R

37



Ph

FeP

NNPd

Ph

a) R-product



NuNu

a)

b)

+

RS




PN

PdP N

PdP N

+ +


tc = 2 kcalmol

(Ab initio studies)

38

NH

NPd

PH3

NH3


NPd

PH3


NH

NPd

PH3

NH3

50 kJmol

36 kJmol

NH3+

41 kJmol

NH3+

+



PdP N

PdP N

PdP N

+

+ +


tc = 8 kJmol


ct = 29 kJmol


for C out of plane



40

PhPh Fe

P

NNPd

Ph

Ph

Ph

Ph

FeP

NNPd

Ph

Ph

exo-syn-anti (71)

+

exo-syn-syn (29)

+

S R



41

PhFe

P

NN

Pd


+

Ph




42

Ph

Ph

PdP N

Ph

Ph

P NPd

Nu

Nu




43




PMe

NN

Ph

Ph

PhPh

PdNN

MePd

FeFeP

Ph

Ph

Ph

Ph

Ph Ph

NHCH2Ph

(S)

Ph Ph

OCOOEtNu-Nu-


950 ee resp 945 ee

rac

44






Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

Fe

N CN

PPh2

Me

Fe

N NC

PPh2

MePdR

R+

PdR

R+

X-ray

45



Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

PdR

R+

PdR

R+

Fe

N CN

PPh2

Me Pd

NHR2R

RFe

N CN

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

Fe

N NC

PPh2

Me Pd

NHR2R

RFe

N NC

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

dr 8515exoendo 8218

46














47


Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



Ph Ph

OCOOEt

Ph Ph

N



NH

Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



48

N

Me

N

Fe

PPh2

Ph Ph

OCO2Et

Ph Ph

NHCH2Ph

[Pd(dba)2 ]+ Ligand





991 (220)

67 (11)

33 (2)

987 (153)

gt995 (gt400)



3 mol Pd-catalyst

PF6- Selectivity

Killer




49

Ph

Ph

P

NPd

+

endo-syn-syn

+

exo-syn-syn

Ph

PhP

NPd

Ph Ph

OCOOEt

Ph Ph



Slow with PF6-

(tight ion pairs )

Fast with F-

(Coordination)

R-Product S-Product

more stable


S R


50










51

E N Jacobsen et al



NN

OMn

OCl

X X

HHX = OMe 96 ee

X = NO2 22 ee

52




MeO MeO

CN

OOOPh

OPhOPAr2

OAr2P CF3F3C MeMe

HCN [Ni(COD)2] L

Ar =

91 eeL

16 ee

53





OCO O

++

nn2 3

4

1


Δ

54

([α]D=-450)




Polymer)50 220 370 1800


PCy2Me

Fe P

CF3

CF32

PCy2Me

Fe P

OMe

OMe2

PCy2Me

Fe P

H

H2

PCy2Me

Fe P

CH3

CH32

55


Markus Baumann


NMeN

Fe

Me

Me

Me

P

O+ PhOTf



O Ph O Ph O

Ph

+ +

2

Rn

Rn=(m-CF3)2

Rn=(m-SiMe3)2

Rn=(p-OMe)

Rn=(p-CF3)

1 (34ee)

8 (62ee)

1 (46ee)

1 (10ee)

94 (88ee)

90 (95ee)

97 (96ee)

96 (95ee)

5

2

2

3

56



NMeN

Fe

PMe Me

F3C

F3CNMeN

Fe

PMe Me

CF3

F3CF3C

F3C

NMeN

Fe

PF3C CF3

MeO

MeO

NMeN

Fe

PMe Me

MeO

MeO

NMeN

Fe

PF3C CF3

NMeN

Fe

PMe Me

NMeN

Fe

PMe Me

Me2N

Me2NNMeN

Fe

PF3C CF3

F3C

F3C

95 ee985 ee

5 ee72 ee

33 ee

98 ee90 ee

40 ee

the worst

and the best

57





NMeN

Fe

Me

Me

Me

PPh2


2) Oxidative Workup

OH

NMeN

Fe PPh2

NMeN

Fe PPh2

Me

39ee 76ee 99ee

Catalytic activity

NMeN

Fe

MeO

OMe

OMe

PPh2

NMeN

Fe

Me

Me

Me

P

CF3

CF3

2

82ee 91ee

58


X

Fe PPh2

N N

Mes

Me

X

1) cat PdCl2(L)

2) Oxidation


= L

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=078rsup2=0996

NMe₂

OMe

Me

ClH


Fe P X

N N

Mes

Me

1) cat PdCl2(L)

2) Oxidation


2

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=014rsup2=0986

NMe₂OMe

Me HCl


59



Fe P X

N N

Mes

Me

OH1) cat PdCl2(L)

2) Oxidation


2

60



X

Fe PPh2

N N

Mes

Me

X

OH1) cat PdCl2(L)

2) Oxidation

= L

61


PdN

P

Cl

Cl

PdN

P H

SiCl3

R

PdN

P

R

SiCl3

N

PdP

HCl3Si

N

Pd

P

Cl3Si

R

R





Unclear formation

σp

σp+


62


TK Woo

HH P

PdSiCl3SiCl3

NNH H

HH

HH P

PdSiCl3SiCl3

NNH H

FeP

PdSiCl3SiCl3

NN

FeP

PdSiCl3SiCl3

NN

HH P

PdSiCl3SiCl3

NNH H

HH P

PdSiCl3SiCl3

NN

H3CH

HH

H

Model 1

Model 2


63






PPd

H

SiCl3NN

HH

PPd

HSiCl3

NN

HH

PPd

HSiCl3

NN

HH

PPd

SiCl3NN

HH PPd

SiCl3NN

HH

1900

22

-02

-83

141

52

PPd

SiCl3NN

HH

PPd

Cl3SiNN

HH

64


endoendo-syn

PPdH

SiCl3NN

Fe

PPd HSiCl3NN

FeFe P

Pd

SiCl3NN

PPd HSiCl3NN

Fe

Cl3Si

PPd

SiCl3N

Fe

N

PPd

Cl3SiNN

Fe

PPdH

SiCl3NN

Fe

PPd

NN

Fe

Cl3Si

R

-35

09

TS1

TS2

-205

+-103

+styrene

00

42+48

61

Dagger Dagger


65





FeP

PdH

SiCl3NN

PPd

HSiCl3

NN

Fe


66


PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPd

H

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPdSiCl3NN

Fe

PPd

SiCl3NN

Fe

48

00

1609

51

-103

-113



endo-syn

exo-synendo

exo


kcalmol

67



endo-syn

exo-syn

NMe2

PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

NMe2

PPd

SiCl3NN

Fe

NMe2

PPdH

SiCl3NN

Fe

Me2N

PPd

SiCl3NN

Fe

PPdSiCl3

NN

Fe

NMe2

PPd

SiCl3NN

Fe

Me2N

48

00

08

03

16

-172

-155

exo

endo


68


DD

D

D5

HndashSiCl3 [PdL]

DD

D

D5

HO H DD

H

D5

HO H DH

H

D5

HO H DD

D

D5

HO D

oxid workup

+ + +


MeD1

MeD2

13C-1H-HZQCNMR

MeD2

MeD11 equivsilane

5 equivsilane

EI-MS


69





70


Energy(kcalmol)

(at rt)


(kcalmol)

(at rt)

ee

endo-syn -103 123

75 (S)[65 (S)]

endo-syn -172 859

81 (R)[64 (R)]

endo-anti -81 03 75 (S)[65 (S)]


75 (S)[65 (S)] exo-syn -155 48

81 (R)[64 (R)]

exo-anti -106 669

75 (S)[65 (S)]

exo-anti -153 35

81 (R)[64 (R)]


71

Conclusions




72




5


SO2

NF

RR

1 (R=H) 2 (R=Cl)

NS

O O

Me

F

O

Ph1) LDA THF

2) 3

OPh

F

79 yield 88 ee

3

SO2

N

O2S

F

4

NO

Me Ph

O

RO

NO

Me Ph

O

RO1) Base

F

80-90 yield 86-99 de

N

N

OHH

ClO

OMe

2)

NN

Cl

F

+

+2 BF4

ndash

5

Bn

OSiMe3

Bn

O

F4 5

MeCN -20degC





6



O

COOtBu

OCOOtBu

F



P

PR2

Pd

HO

OH

PdP

PR2

R2 R2

(BF4)2

R = 35-Me2Ph

O

COOtBu

OCOOtBu

F



N

O

N

O

PhPh CuTfO OTf

P

PPh2

NiCl

Cl

Ph2

N S

OO

Ph N S

OO

Ph

F



26-lutidine


7



Ar=PhenylL2 =DME

Ar=1-NaphthylL=NCMe


OO

Ar

ArOAr

ArO

Ti

Cl


tartaric acid



8




OO 1-Naph

1-NaphO

1-Naph

1-NaphO

Ti

Cl

ClMeCN NCMe

O

O O

90 ee

FO

O O

88 ee

FS

O O

91 ee

F

O

O O

82 ee

F

N

O O

F

84 ee

O

O O

F

86 ee

O

O O

F

dr = 965 35

O

ON

O O

F

59 ee


N N CH2ClF

2 BF4ndash

++

9



RR Cl

Ti

Cl

OO

NCMeMeCN

OO

Np

Np

Np

Np

R OR

O O

Me

Cl

Ti

O

OOO

OR

MeR

MeCN

OO

Np

Np

Np

Np

F

R OR

O O

MeF

N N FCl

S

Cl

Ti

O

OOO

OR

MeR

MeCN

OO

Np

Np

Np

Np

ndash H+


++

+

+

Cl

Ti

O

OOO

OR

MeR

MeCN

OO

Np

Np

Np




10





SS

Cl

Ti

Cl

O O

MeCN NCMe

OO

Np

Np

Np

Np Et OBn

O O

Me

Et OBn

O O

MeF

N N F

Cl

R

O

Ti

O

O O

OBnO

Me Et

O

OONp

Np

Np

Np

OBn

Et

Me++

Nandash

C6H6 rt 80-90


11


OTiO

OOO

O

R

O

O ONp

NpNp

O

R

R

R

OTiO

OOO

R

O

O

O ONp

NpNp

R

OR

R

OTiO

OOO

R

O

O

O ONp

NpNp

O

R

RR

TiOO

O ONp

NpNp

O

OO

R

R

OO

O

R

R

TiOO

O ONp

NpNp

O

OR

OOO

R

O

TiOO

O ONp

NpNp

O

OR

OOO

O

R

R

RR R








12



(Face-on Re)


(Edge-on Re)


(Face-on Si)


(Edge-on Si)

13


Cl

Ti

O

OOO

O

Me

MeCN

OO

Np

Np

Np




14


O

Ti

O

OOO

OBnO

OO

Np

NpNp

BnO




15



Me O

O O

Me HDF

RR Cl

Ti

Cl

OO

THFTHF

OO

Np

Np

Np

Np

R OR

O O

Me

Cl

Ti

O

OOO

OR

MeR

THF

OO

Np

Np

Np

Np

F

R OR

O O

MeF

S

Cl

Ti

O

OOO

OR

MeR

THF

OO

Np

Np

Np

Np

ndash H+


+

+

Cl

Ti

O

OOO

OR

MeR

THF

OO

Np

Np

Np

HD

HD

N FPhSO2

PhSO2




16






17




ClTi

O

OOO

OR

MeR

MeCN

OO

Np

Np

NpNp

NN

F

Cl

N NCl

ClTi

O

OOO

OR

MeR

MeCN

OO

Np

Np

NpNp

ClTi

O

OOO

OR

MeR

MeCN

OO

Np

NpNp

Np

F

N N FCl

++

+

+

SET


+

18


LUMO of [F-TEDA]2+


SOMO of [F-TEDA]+



HOMO

of enolato complex

ndash endash

B3LYP6-31G level

19


SET

R

ORO

O

E ERn

Rm


-

R

ORO

O

ERn

+ RmEndash

O O

MeMe

O N

HMe

Me

ICl

MeS

Me

SMe

N

O

O

Cl

SCl


20




R1 OR3

O O

R2

R1 OR3

O O

R2SPh

R1 OR3

O O

R2F

R1 OR3

O O

R2Cl

R1 OR3

O O

FCl

R1 OR3

O O

R2HO

NCS

Selectfluor


N SO2PhO2N

H

O

RR Cl

Ti

Cl

OO

NCMeMeCN

OO

Np

Np

Np

Np



up to 88 ee




21




22






Step 12 Step 21



23








Josiphos

Pigiphos

Fe

NMe2

MeFe PPh2

NMe2

Me

Fe PPh2

PCy2

Me

PFe PPh2

Fe

Ph2PUgis amine

24




NMe2

MePAr2

R1 R3

OO

R2

H2NNH2

NNH

R3R2

R1

Fe Fe

NMe

NR3

R2

R1

PAr2


AcOH 70-90 degC

80-90 yield

+

25

Ph2PCy2P

Ph2P

PCy2

Ph2PCy2P

Ph2P

Cy2P

PPh2PCy2

Ph2P

PCy2

Si

O

O

HN

O

NH

Si

Si

O

OHN

O

HN

Si

NP N P

NP

NP Si

O

OHN

ONH

Si

Si

OO

HNO NH

Si

Si

O

ONH

O

HN

Si

Si

O

ONH

ONH Si

SiO

ONH

OHN

Si

Si

OO

NH O

HN

Si

PPh2Cy2P

Ph2PCy2P

PPh2

PCy2

PPh2PCy2

Ph2PPCy2

PPh2

Cy2P

PPh2PCy2

PPh2

PCy2

Ph2P

Cy2P

Fe

PPh2Cy2P

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe




26



NH3C

CH3

OCH3

CH3OCl

H

P

MeFe

PPh2


2

Ir

S

NHHN

O

H H

P(t-Bu)2

MeFe

PPh2

COOH

(+)-Biotin(LONZA)

Rh

Sitagliptin(Merck)

Rh

F

FF

NN

NN

ONH2

CF3

PtBu2

MeFe P(4-F3CPh)2

27



H NN

ONHO

O

H NN

ONHO


SC=2000


96 ee

P(t-Bu)2

MeFe PPh2

N NN

OH

O

NH

ONH OH



28




P(t-Bu)2

MeFe PPh2

O

HOOCHN

S

F

O O

O

HOOCHN

S

F

O O

RuCl2(P-P)LnNEt3

H2 EtOH

O

HN

S

F

O O

O

HOHNP-P =

97 ee

29



Up to 97 ee

F

FF

NN

NN

ONH2

CF3



P(t-Bu)2

MeFe

P(t-Bu)2Me

Fe P CF32

PPh2

R OMe

NH2 O

R OMe


R NHPh

NH2 O

R NHPh

NH2 O

H2

Rh Josiphos ligand

H2

30











31










32



33

$

amp$

$

$

($

$$ amp$ )$ $ $ $ $ $

$

amp()+-


ampamp2824+

5lt=-amp)gt+gt2)42






34




α1=+9degα2=-21deg




35

Pd

L1

L2R

R

Pd

L1

L2

R

R

Nu Nu



36



X-rayX-ray

PhPh FeP

NNPd Ph

Ph


+

Ph

FeP

NNPd

Ph

Ph

Ph


+

PhPh FeP

NN

Pd Ph

Ph

+



Ph Ph

OCOR

NH2

Ph Ph


40 degC THF


N

Me

N

Fe

PPh2R

37



Ph

FeP

NNPd

Ph

a) R-product



NuNu

a)

b)

+

RS




PN

PdP N

PdP N

+ +


tc = 2 kcalmol

(Ab initio studies)

38

NH

NPd

PH3

NH3


NPd

PH3


NH

NPd

PH3

NH3

50 kJmol

36 kJmol

NH3+

41 kJmol

NH3+

+



PdP N

PdP N

PdP N

+

+ +


tc = 8 kJmol


ct = 29 kJmol


for C out of plane



40

PhPh Fe

P

NNPd

Ph

Ph

Ph

Ph

FeP

NNPd

Ph

Ph

exo-syn-anti (71)

+

exo-syn-syn (29)

+

S R



41

PhFe

P

NN

Pd


+

Ph




42

Ph

Ph

PdP N

Ph

Ph

P NPd

Nu

Nu




43




PMe

NN

Ph

Ph

PhPh

PdNN

MePd

FeFeP

Ph

Ph

Ph

Ph

Ph Ph

NHCH2Ph

(S)

Ph Ph

OCOOEtNu-Nu-


950 ee resp 945 ee

rac

44






Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

Fe

N CN

PPh2

Me

Fe

N NC

PPh2

MePdR

R+

PdR

R+

X-ray

45



Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

PdR

R+

PdR

R+

Fe

N CN

PPh2

Me Pd

NHR2R

RFe

N CN

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

Fe

N NC

PPh2

Me Pd

NHR2R

RFe

N NC

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

dr 8515exoendo 8218

46














47


Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



Ph Ph

OCOOEt

Ph Ph

N



NH

Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



48

N

Me

N

Fe

PPh2

Ph Ph

OCO2Et

Ph Ph

NHCH2Ph

[Pd(dba)2 ]+ Ligand





991 (220)

67 (11)

33 (2)

987 (153)

gt995 (gt400)



3 mol Pd-catalyst

PF6- Selectivity

Killer




49

Ph

Ph

P

NPd

+

endo-syn-syn

+

exo-syn-syn

Ph

PhP

NPd

Ph Ph

OCOOEt

Ph Ph



Slow with PF6-

(tight ion pairs )

Fast with F-

(Coordination)

R-Product S-Product

more stable


S R


50










51

E N Jacobsen et al



NN

OMn

OCl

X X

HHX = OMe 96 ee

X = NO2 22 ee

52




MeO MeO

CN

OOOPh

OPhOPAr2

OAr2P CF3F3C MeMe

HCN [Ni(COD)2] L

Ar =

91 eeL

16 ee

53





OCO O

++

nn2 3

4

1


Δ

54

([α]D=-450)




Polymer)50 220 370 1800


PCy2Me

Fe P

CF3

CF32

PCy2Me

Fe P

OMe

OMe2

PCy2Me

Fe P

H

H2

PCy2Me

Fe P

CH3

CH32

55


Markus Baumann


NMeN

Fe

Me

Me

Me

P

O+ PhOTf



O Ph O Ph O

Ph

+ +

2

Rn

Rn=(m-CF3)2

Rn=(m-SiMe3)2

Rn=(p-OMe)

Rn=(p-CF3)

1 (34ee)

8 (62ee)

1 (46ee)

1 (10ee)

94 (88ee)

90 (95ee)

97 (96ee)

96 (95ee)

5

2

2

3

56



NMeN

Fe

PMe Me

F3C

F3CNMeN

Fe

PMe Me

CF3

F3CF3C

F3C

NMeN

Fe

PF3C CF3

MeO

MeO

NMeN

Fe

PMe Me

MeO

MeO

NMeN

Fe

PF3C CF3

NMeN

Fe

PMe Me

NMeN

Fe

PMe Me

Me2N

Me2NNMeN

Fe

PF3C CF3

F3C

F3C

95 ee985 ee

5 ee72 ee

33 ee

98 ee90 ee

40 ee

the worst

and the best

57





NMeN

Fe

Me

Me

Me

PPh2


2) Oxidative Workup

OH

NMeN

Fe PPh2

NMeN

Fe PPh2

Me

39ee 76ee 99ee

Catalytic activity

NMeN

Fe

MeO

OMe

OMe

PPh2

NMeN

Fe

Me

Me

Me

P

CF3

CF3

2

82ee 91ee

58


X

Fe PPh2

N N

Mes

Me

X

1) cat PdCl2(L)

2) Oxidation


= L

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=078rsup2=0996

NMe₂

OMe

Me

ClH


Fe P X

N N

Mes

Me

1) cat PdCl2(L)

2) Oxidation


2

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=014rsup2=0986

NMe₂OMe

Me HCl


59



Fe P X

N N

Mes

Me

OH1) cat PdCl2(L)

2) Oxidation


2

60



X

Fe PPh2

N N

Mes

Me

X

OH1) cat PdCl2(L)

2) Oxidation

= L

61


PdN

P

Cl

Cl

PdN

P H

SiCl3

R

PdN

P

R

SiCl3

N

PdP

HCl3Si

N

Pd

P

Cl3Si

R

R





Unclear formation

σp

σp+


62


TK Woo

HH P

PdSiCl3SiCl3

NNH H

HH

HH P

PdSiCl3SiCl3

NNH H

FeP

PdSiCl3SiCl3

NN

FeP

PdSiCl3SiCl3

NN

HH P

PdSiCl3SiCl3

NNH H

HH P

PdSiCl3SiCl3

NN

H3CH

HH

H

Model 1

Model 2


63






PPd

H

SiCl3NN

HH

PPd

HSiCl3

NN

HH

PPd

HSiCl3

NN

HH

PPd

SiCl3NN

HH PPd

SiCl3NN

HH

1900

22

-02

-83

141

52

PPd

SiCl3NN

HH

PPd

Cl3SiNN

HH

64


endoendo-syn

PPdH

SiCl3NN

Fe

PPd HSiCl3NN

FeFe P

Pd

SiCl3NN

PPd HSiCl3NN

Fe

Cl3Si

PPd

SiCl3N

Fe

N

PPd

Cl3SiNN

Fe

PPdH

SiCl3NN

Fe

PPd

NN

Fe

Cl3Si

R

-35

09

TS1

TS2

-205

+-103

+styrene

00

42+48

61

Dagger Dagger


65





FeP

PdH

SiCl3NN

PPd

HSiCl3

NN

Fe


66


PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPd

H

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPdSiCl3NN

Fe

PPd

SiCl3NN

Fe

48

00

1609

51

-103

-113



endo-syn

exo-synendo

exo


kcalmol

67



endo-syn

exo-syn

NMe2

PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

NMe2

PPd

SiCl3NN

Fe

NMe2

PPdH

SiCl3NN

Fe

Me2N

PPd

SiCl3NN

Fe

PPdSiCl3

NN

Fe

NMe2

PPd

SiCl3NN

Fe

Me2N

48

00

08

03

16

-172

-155

exo

endo


68


DD

D

D5

HndashSiCl3 [PdL]

DD

D

D5

HO H DD

H

D5

HO H DH

H

D5

HO H DD

D

D5

HO D

oxid workup

+ + +


MeD1

MeD2

13C-1H-HZQCNMR

MeD2

MeD11 equivsilane

5 equivsilane

EI-MS


69





70


Energy(kcalmol)

(at rt)


(kcalmol)

(at rt)

ee

endo-syn -103 123

75 (S)[65 (S)]

endo-syn -172 859

81 (R)[64 (R)]

endo-anti -81 03 75 (S)[65 (S)]


75 (S)[65 (S)] exo-syn -155 48

81 (R)[64 (R)]

exo-anti -106 669

75 (S)[65 (S)]

exo-anti -153 35

81 (R)[64 (R)]


71

Conclusions




72


SO2

NF

RR

1 (R=H) 2 (R=Cl)

NS

O O

Me

F

O

Ph1) LDA THF

2) 3

OPh

F

79 yield 88 ee

3

SO2

N

O2S

F

4

NO

Me Ph

O

RO

NO

Me Ph

O

RO1) Base

F

80-90 yield 86-99 de

N

N

OHH

ClO

OMe

2)

NN

Cl

F

+

+2 BF4

ndash

5

Bn

OSiMe3

Bn

O

F4 5

MeCN -20degC





6



O

COOtBu

OCOOtBu

F



P

PR2

Pd

HO

OH

PdP

PR2

R2 R2

(BF4)2

R = 35-Me2Ph

O

COOtBu

OCOOtBu

F



N

O

N

O

PhPh CuTfO OTf

P

PPh2

NiCl

Cl

Ph2

N S

OO

Ph N S

OO

Ph

F



26-lutidine


7



Ar=PhenylL2 =DME

Ar=1-NaphthylL=NCMe


OO

Ar

ArOAr

ArO

Ti

Cl


tartaric acid



8




OO 1-Naph

1-NaphO

1-Naph

1-NaphO

Ti

Cl

ClMeCN NCMe

O

O O

90 ee

FO

O O

88 ee

FS

O O

91 ee

F

O

O O

82 ee

F

N

O O

F

84 ee

O

O O

F

86 ee

O

O O

F

dr = 965 35

O

ON

O O

F

59 ee


N N CH2ClF

2 BF4ndash

++

9



RR Cl

Ti

Cl

OO

NCMeMeCN

OO

Np

Np

Np

Np

R OR

O O

Me

Cl

Ti

O

OOO

OR

MeR

MeCN

OO

Np

Np

Np

Np

F

R OR

O O

MeF

N N FCl

S

Cl

Ti

O

OOO

OR

MeR

MeCN

OO

Np

Np

Np

Np

ndash H+


++

+

+

Cl

Ti

O

OOO

OR

MeR

MeCN

OO

Np

Np

Np




10





SS

Cl

Ti

Cl

O O

MeCN NCMe

OO

Np

Np

Np

Np Et OBn

O O

Me

Et OBn

O O

MeF

N N F

Cl

R

O

Ti

O

O O

OBnO

Me Et

O

OONp

Np

Np

Np

OBn

Et

Me++

Nandash

C6H6 rt 80-90


11


OTiO

OOO

O

R

O

O ONp

NpNp

O

R

R

R

OTiO

OOO

R

O

O

O ONp

NpNp

R

OR

R

OTiO

OOO

R

O

O

O ONp

NpNp

O

R

RR

TiOO

O ONp

NpNp

O

OO

R

R

OO

O

R

R

TiOO

O ONp

NpNp

O

OR

OOO

R

O

TiOO

O ONp

NpNp

O

OR

OOO

O

R

R

RR R








12



(Face-on Re)


(Edge-on Re)


(Face-on Si)


(Edge-on Si)

13


Cl

Ti

O

OOO

O

Me

MeCN

OO

Np

Np

Np




14


O

Ti

O

OOO

OBnO

OO

Np

NpNp

BnO




15



Me O

O O

Me HDF

RR Cl

Ti

Cl

OO

THFTHF

OO

Np

Np

Np

Np

R OR

O O

Me

Cl

Ti

O

OOO

OR

MeR

THF

OO

Np

Np

Np

Np

F

R OR

O O

MeF

S

Cl

Ti

O

OOO

OR

MeR

THF

OO

Np

Np

Np

Np

ndash H+


+

+

Cl

Ti

O

OOO

OR

MeR

THF

OO

Np

Np

Np

HD

HD

N FPhSO2

PhSO2




16






17




ClTi

O

OOO

OR

MeR

MeCN

OO

Np

Np

NpNp

NN

F

Cl

N NCl

ClTi

O

OOO

OR

MeR

MeCN

OO

Np

Np

NpNp

ClTi

O

OOO

OR

MeR

MeCN

OO

Np

NpNp

Np

F

N N FCl

++

+

+

SET


+

18


LUMO of [F-TEDA]2+


SOMO of [F-TEDA]+



HOMO

of enolato complex

ndash endash

B3LYP6-31G level

19


SET

R

ORO

O

E ERn

Rm


-

R

ORO

O

ERn

+ RmEndash

O O

MeMe

O N

HMe

Me

ICl

MeS

Me

SMe

N

O

O

Cl

SCl


20




R1 OR3

O O

R2

R1 OR3

O O

R2SPh

R1 OR3

O O

R2F

R1 OR3

O O

R2Cl

R1 OR3

O O

FCl

R1 OR3

O O

R2HO

NCS

Selectfluor


N SO2PhO2N

H

O

RR Cl

Ti

Cl

OO

NCMeMeCN

OO

Np

Np

Np

Np



up to 88 ee




21




22






Step 12 Step 21



23








Josiphos

Pigiphos

Fe

NMe2

MeFe PPh2

NMe2

Me

Fe PPh2

PCy2

Me

PFe PPh2

Fe

Ph2PUgis amine

24




NMe2

MePAr2

R1 R3

OO

R2

H2NNH2

NNH

R3R2

R1

Fe Fe

NMe

NR3

R2

R1

PAr2


AcOH 70-90 degC

80-90 yield

+

25

Ph2PCy2P

Ph2P

PCy2

Ph2PCy2P

Ph2P

Cy2P

PPh2PCy2

Ph2P

PCy2

Si

O

O

HN

O

NH

Si

Si

O

OHN

O

HN

Si

NP N P

NP

NP Si

O

OHN

ONH

Si

Si

OO

HNO NH

Si

Si

O

ONH

O

HN

Si

Si

O

ONH

ONH Si

SiO

ONH

OHN

Si

Si

OO

NH O

HN

Si

PPh2Cy2P

Ph2PCy2P

PPh2

PCy2

PPh2PCy2

Ph2PPCy2

PPh2

Cy2P

PPh2PCy2

PPh2

PCy2

Ph2P

Cy2P

Fe

PPh2Cy2P

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe




26



NH3C

CH3

OCH3

CH3OCl

H

P

MeFe

PPh2


2

Ir

S

NHHN

O

H H

P(t-Bu)2

MeFe

PPh2

COOH

(+)-Biotin(LONZA)

Rh

Sitagliptin(Merck)

Rh

F

FF

NN

NN

ONH2

CF3

PtBu2

MeFe P(4-F3CPh)2

27



H NN

ONHO

O

H NN

ONHO


SC=2000


96 ee

P(t-Bu)2

MeFe PPh2

N NN

OH

O

NH

ONH OH



28




P(t-Bu)2

MeFe PPh2

O

HOOCHN

S

F

O O

O

HOOCHN

S

F

O O

RuCl2(P-P)LnNEt3

H2 EtOH

O

HN

S

F

O O

O

HOHNP-P =

97 ee

29



Up to 97 ee

F

FF

NN

NN

ONH2

CF3



P(t-Bu)2

MeFe

P(t-Bu)2Me

Fe P CF32

PPh2

R OMe

NH2 O

R OMe


R NHPh

NH2 O

R NHPh

NH2 O

H2

Rh Josiphos ligand

H2

30











31










32



33

$

amp$

$

$

($

$$ amp$ )$ $ $ $ $ $

$

amp()+-


ampamp2824+

5lt=-amp)gt+gt2)42






34




α1=+9degα2=-21deg




35

Pd

L1

L2R

R

Pd

L1

L2

R

R

Nu Nu



36



X-rayX-ray

PhPh FeP

NNPd Ph

Ph


+

Ph

FeP

NNPd

Ph

Ph

Ph


+

PhPh FeP

NN

Pd Ph

Ph

+



Ph Ph

OCOR

NH2

Ph Ph


40 degC THF


N

Me

N

Fe

PPh2R

37



Ph

FeP

NNPd

Ph

a) R-product



NuNu

a)

b)

+

RS




PN

PdP N

PdP N

+ +


tc = 2 kcalmol

(Ab initio studies)

38

NH

NPd

PH3

NH3


NPd

PH3


NH

NPd

PH3

NH3

50 kJmol

36 kJmol

NH3+

41 kJmol

NH3+

+



PdP N

PdP N

PdP N

+

+ +


tc = 8 kJmol


ct = 29 kJmol


for C out of plane



40

PhPh Fe

P

NNPd

Ph

Ph

Ph

Ph

FeP

NNPd

Ph

Ph

exo-syn-anti (71)

+

exo-syn-syn (29)

+

S R



41

PhFe

P

NN

Pd


+

Ph




42

Ph

Ph

PdP N

Ph

Ph

P NPd

Nu

Nu




43




PMe

NN

Ph

Ph

PhPh

PdNN

MePd

FeFeP

Ph

Ph

Ph

Ph

Ph Ph

NHCH2Ph

(S)

Ph Ph

OCOOEtNu-Nu-


950 ee resp 945 ee

rac

44






Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

Fe

N CN

PPh2

Me

Fe

N NC

PPh2

MePdR

R+

PdR

R+

X-ray

45



Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

PdR

R+

PdR

R+

Fe

N CN

PPh2

Me Pd

NHR2R

RFe

N CN

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

Fe

N NC

PPh2

Me Pd

NHR2R

RFe

N NC

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

dr 8515exoendo 8218

46














47


Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



Ph Ph

OCOOEt

Ph Ph

N



NH

Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



48

N

Me

N

Fe

PPh2

Ph Ph

OCO2Et

Ph Ph

NHCH2Ph

[Pd(dba)2 ]+ Ligand





991 (220)

67 (11)

33 (2)

987 (153)

gt995 (gt400)



3 mol Pd-catalyst

PF6- Selectivity

Killer




49

Ph

Ph

P

NPd

+

endo-syn-syn

+

exo-syn-syn

Ph

PhP

NPd

Ph Ph

OCOOEt

Ph Ph



Slow with PF6-

(tight ion pairs )

Fast with F-

(Coordination)

R-Product S-Product

more stable


S R


50










51

E N Jacobsen et al



NN

OMn

OCl

X X

HHX = OMe 96 ee

X = NO2 22 ee

52




MeO MeO

CN

OOOPh

OPhOPAr2

OAr2P CF3F3C MeMe

HCN [Ni(COD)2] L

Ar =

91 eeL

16 ee

53





OCO O

++

nn2 3

4

1


Δ

54

([α]D=-450)




Polymer)50 220 370 1800


PCy2Me

Fe P

CF3

CF32

PCy2Me

Fe P

OMe

OMe2

PCy2Me

Fe P

H

H2

PCy2Me

Fe P

CH3

CH32

55


Markus Baumann


NMeN

Fe

Me

Me

Me

P

O+ PhOTf



O Ph O Ph O

Ph

+ +

2

Rn

Rn=(m-CF3)2

Rn=(m-SiMe3)2

Rn=(p-OMe)

Rn=(p-CF3)

1 (34ee)

8 (62ee)

1 (46ee)

1 (10ee)

94 (88ee)

90 (95ee)

97 (96ee)

96 (95ee)

5

2

2

3

56



NMeN

Fe

PMe Me

F3C

F3CNMeN

Fe

PMe Me

CF3

F3CF3C

F3C

NMeN

Fe

PF3C CF3

MeO

MeO

NMeN

Fe

PMe Me

MeO

MeO

NMeN

Fe

PF3C CF3

NMeN

Fe

PMe Me

NMeN

Fe

PMe Me

Me2N

Me2NNMeN

Fe

PF3C CF3

F3C

F3C

95 ee985 ee

5 ee72 ee

33 ee

98 ee90 ee

40 ee

the worst

and the best

57





NMeN

Fe

Me

Me

Me

PPh2


2) Oxidative Workup

OH

NMeN

Fe PPh2

NMeN

Fe PPh2

Me

39ee 76ee 99ee

Catalytic activity

NMeN

Fe

MeO

OMe

OMe

PPh2

NMeN

Fe

Me

Me

Me

P

CF3

CF3

2

82ee 91ee

58


X

Fe PPh2

N N

Mes

Me

X

1) cat PdCl2(L)

2) Oxidation


= L

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=078rsup2=0996

NMe₂

OMe

Me

ClH


Fe P X

N N

Mes

Me

1) cat PdCl2(L)

2) Oxidation


2

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=014rsup2=0986

NMe₂OMe

Me HCl


59



Fe P X

N N

Mes

Me

OH1) cat PdCl2(L)

2) Oxidation


2

60



X

Fe PPh2

N N

Mes

Me

X

OH1) cat PdCl2(L)

2) Oxidation

= L

61


PdN

P

Cl

Cl

PdN

P H

SiCl3

R

PdN

P

R

SiCl3

N

PdP

HCl3Si

N

Pd

P

Cl3Si

R

R





Unclear formation

σp

σp+


62


TK Woo

HH P

PdSiCl3SiCl3

NNH H

HH

HH P

PdSiCl3SiCl3

NNH H

FeP

PdSiCl3SiCl3

NN

FeP

PdSiCl3SiCl3

NN

HH P

PdSiCl3SiCl3

NNH H

HH P

PdSiCl3SiCl3

NN

H3CH

HH

H

Model 1

Model 2


63






PPd

H

SiCl3NN

HH

PPd

HSiCl3

NN

HH

PPd

HSiCl3

NN

HH

PPd

SiCl3NN

HH PPd

SiCl3NN

HH

1900

22

-02

-83

141

52

PPd

SiCl3NN

HH

PPd

Cl3SiNN

HH

64


endoendo-syn

PPdH

SiCl3NN

Fe

PPd HSiCl3NN

FeFe P

Pd

SiCl3NN

PPd HSiCl3NN

Fe

Cl3Si

PPd

SiCl3N

Fe

N

PPd

Cl3SiNN

Fe

PPdH

SiCl3NN

Fe

PPd

NN

Fe

Cl3Si

R

-35

09

TS1

TS2

-205

+-103

+styrene

00

42+48

61

Dagger Dagger


65





FeP

PdH

SiCl3NN

PPd

HSiCl3

NN

Fe


66


PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPd

H

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPdSiCl3NN

Fe

PPd

SiCl3NN

Fe

48

00

1609

51

-103

-113



endo-syn

exo-synendo

exo


kcalmol

67



endo-syn

exo-syn

NMe2

PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

NMe2

PPd

SiCl3NN

Fe

NMe2

PPdH

SiCl3NN

Fe

Me2N

PPd

SiCl3NN

Fe

PPdSiCl3

NN

Fe

NMe2

PPd

SiCl3NN

Fe

Me2N

48

00

08

03

16

-172

-155

exo

endo


68


DD

D

D5

HndashSiCl3 [PdL]

DD

D

D5

HO H DD

H

D5

HO H DH

H

D5

HO H DD

D

D5

HO D

oxid workup

+ + +


MeD1

MeD2

13C-1H-HZQCNMR

MeD2

MeD11 equivsilane

5 equivsilane

EI-MS


69





70


Energy(kcalmol)

(at rt)


(kcalmol)

(at rt)

ee

endo-syn -103 123

75 (S)[65 (S)]

endo-syn -172 859

81 (R)[64 (R)]

endo-anti -81 03 75 (S)[65 (S)]


75 (S)[65 (S)] exo-syn -155 48

81 (R)[64 (R)]

exo-anti -106 669

75 (S)[65 (S)]

exo-anti -153 35

81 (R)[64 (R)]


71

Conclusions




72



O

COOtBu

OCOOtBu

F



P

PR2

Pd

HO

OH

PdP

PR2

R2 R2

(BF4)2

R = 35-Me2Ph

O

COOtBu

OCOOtBu

F



N

O

N

O

PhPh CuTfO OTf

P

PPh2

NiCl

Cl

Ph2

N S

OO

Ph N S

OO

Ph

F



26-lutidine


7



Ar=PhenylL2 =DME

Ar=1-NaphthylL=NCMe


OO

Ar

ArOAr

ArO

Ti

Cl


tartaric acid



8




OO 1-Naph

1-NaphO

1-Naph

1-NaphO

Ti

Cl

ClMeCN NCMe

O

O O

90 ee

FO

O O

88 ee

FS

O O

91 ee

F

O

O O

82 ee

F

N

O O

F

84 ee

O

O O

F

86 ee

O

O O

F

dr = 965 35

O

ON

O O

F

59 ee


N N CH2ClF

2 BF4ndash

++

9



RR Cl

Ti

Cl

OO

NCMeMeCN

OO

Np

Np

Np

Np

R OR

O O

Me

Cl

Ti

O

OOO

OR

MeR

MeCN

OO

Np

Np

Np

Np

F

R OR

O O

MeF

N N FCl

S

Cl

Ti

O

OOO

OR

MeR

MeCN

OO

Np

Np

Np

Np

ndash H+


++

+

+

Cl

Ti

O

OOO

OR

MeR

MeCN

OO

Np

Np

Np




10





SS

Cl

Ti

Cl

O O

MeCN NCMe

OO

Np

Np

Np

Np Et OBn

O O

Me

Et OBn

O O

MeF

N N F

Cl

R

O

Ti

O

O O

OBnO

Me Et

O

OONp

Np

Np

Np

OBn

Et

Me++

Nandash

C6H6 rt 80-90


11


OTiO

OOO

O

R

O

O ONp

NpNp

O

R

R

R

OTiO

OOO

R

O

O

O ONp

NpNp

R

OR

R

OTiO

OOO

R

O

O

O ONp

NpNp

O

R

RR

TiOO

O ONp

NpNp

O

OO

R

R

OO

O

R

R

TiOO

O ONp

NpNp

O

OR

OOO

R

O

TiOO

O ONp

NpNp

O

OR

OOO

O

R

R

RR R








12



(Face-on Re)


(Edge-on Re)


(Face-on Si)


(Edge-on Si)

13


Cl

Ti

O

OOO

O

Me

MeCN

OO

Np

Np

Np




14


O

Ti

O

OOO

OBnO

OO

Np

NpNp

BnO




15



Me O

O O

Me HDF

RR Cl

Ti

Cl

OO

THFTHF

OO

Np

Np

Np

Np

R OR

O O

Me

Cl

Ti

O

OOO

OR

MeR

THF

OO

Np

Np

Np

Np

F

R OR

O O

MeF

S

Cl

Ti

O

OOO

OR

MeR

THF

OO

Np

Np

Np

Np

ndash H+


+

+

Cl

Ti

O

OOO

OR

MeR

THF

OO

Np

Np

Np

HD

HD

N FPhSO2

PhSO2




16






17




ClTi

O

OOO

OR

MeR

MeCN

OO

Np

Np

NpNp

NN

F

Cl

N NCl

ClTi

O

OOO

OR

MeR

MeCN

OO

Np

Np

NpNp

ClTi

O

OOO

OR

MeR

MeCN

OO

Np

NpNp

Np

F

N N FCl

++

+

+

SET


+

18


LUMO of [F-TEDA]2+


SOMO of [F-TEDA]+



HOMO

of enolato complex

ndash endash

B3LYP6-31G level

19


SET

R

ORO

O

E ERn

Rm


-

R

ORO

O

ERn

+ RmEndash

O O

MeMe

O N

HMe

Me

ICl

MeS

Me

SMe

N

O

O

Cl

SCl


20




R1 OR3

O O

R2

R1 OR3

O O

R2SPh

R1 OR3

O O

R2F

R1 OR3

O O

R2Cl

R1 OR3

O O

FCl

R1 OR3

O O

R2HO

NCS

Selectfluor


N SO2PhO2N

H

O

RR Cl

Ti

Cl

OO

NCMeMeCN

OO

Np

Np

Np

Np



up to 88 ee




21




22






Step 12 Step 21



23








Josiphos

Pigiphos

Fe

NMe2

MeFe PPh2

NMe2

Me

Fe PPh2

PCy2

Me

PFe PPh2

Fe

Ph2PUgis amine

24




NMe2

MePAr2

R1 R3

OO

R2

H2NNH2

NNH

R3R2

R1

Fe Fe

NMe

NR3

R2

R1

PAr2


AcOH 70-90 degC

80-90 yield

+

25

Ph2PCy2P

Ph2P

PCy2

Ph2PCy2P

Ph2P

Cy2P

PPh2PCy2

Ph2P

PCy2

Si

O

O

HN

O

NH

Si

Si

O

OHN

O

HN

Si

NP N P

NP

NP Si

O

OHN

ONH

Si

Si

OO

HNO NH

Si

Si

O

ONH

O

HN

Si

Si

O

ONH

ONH Si

SiO

ONH

OHN

Si

Si

OO

NH O

HN

Si

PPh2Cy2P

Ph2PCy2P

PPh2

PCy2

PPh2PCy2

Ph2PPCy2

PPh2

Cy2P

PPh2PCy2

PPh2

PCy2

Ph2P

Cy2P

Fe

PPh2Cy2P

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe




26



NH3C

CH3

OCH3

CH3OCl

H

P

MeFe

PPh2


2

Ir

S

NHHN

O

H H

P(t-Bu)2

MeFe

PPh2

COOH

(+)-Biotin(LONZA)

Rh

Sitagliptin(Merck)

Rh

F

FF

NN

NN

ONH2

CF3

PtBu2

MeFe P(4-F3CPh)2

27



H NN

ONHO

O

H NN

ONHO


SC=2000


96 ee

P(t-Bu)2

MeFe PPh2

N NN

OH

O

NH

ONH OH



28




P(t-Bu)2

MeFe PPh2

O

HOOCHN

S

F

O O

O

HOOCHN

S

F

O O

RuCl2(P-P)LnNEt3

H2 EtOH

O

HN

S

F

O O

O

HOHNP-P =

97 ee

29



Up to 97 ee

F

FF

NN

NN

ONH2

CF3



P(t-Bu)2

MeFe

P(t-Bu)2Me

Fe P CF32

PPh2

R OMe

NH2 O

R OMe


R NHPh

NH2 O

R NHPh

NH2 O

H2

Rh Josiphos ligand

H2

30











31










32



33

$

amp$

$

$

($

$$ amp$ )$ $ $ $ $ $

$

amp()+-


ampamp2824+

5lt=-amp)gt+gt2)42






34




α1=+9degα2=-21deg




35

Pd

L1

L2R

R

Pd

L1

L2

R

R

Nu Nu



36



X-rayX-ray

PhPh FeP

NNPd Ph

Ph


+

Ph

FeP

NNPd

Ph

Ph

Ph


+

PhPh FeP

NN

Pd Ph

Ph

+



Ph Ph

OCOR

NH2

Ph Ph


40 degC THF


N

Me

N

Fe

PPh2R

37



Ph

FeP

NNPd

Ph

a) R-product



NuNu

a)

b)

+

RS




PN

PdP N

PdP N

+ +


tc = 2 kcalmol

(Ab initio studies)

38

NH

NPd

PH3

NH3


NPd

PH3


NH

NPd

PH3

NH3

50 kJmol

36 kJmol

NH3+

41 kJmol

NH3+

+



PdP N

PdP N

PdP N

+

+ +


tc = 8 kJmol


ct = 29 kJmol


for C out of plane



40

PhPh Fe

P

NNPd

Ph

Ph

Ph

Ph

FeP

NNPd

Ph

Ph

exo-syn-anti (71)

+

exo-syn-syn (29)

+

S R



41

PhFe

P

NN

Pd


+

Ph




42

Ph

Ph

PdP N

Ph

Ph

P NPd

Nu

Nu




43




PMe

NN

Ph

Ph

PhPh

PdNN

MePd

FeFeP

Ph

Ph

Ph

Ph

Ph Ph

NHCH2Ph

(S)

Ph Ph

OCOOEtNu-Nu-


950 ee resp 945 ee

rac

44






Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

Fe

N CN

PPh2

Me

Fe

N NC

PPh2

MePdR

R+

PdR

R+

X-ray

45



Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

PdR

R+

PdR

R+

Fe

N CN

PPh2

Me Pd

NHR2R

RFe

N CN

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

Fe

N NC

PPh2

Me Pd

NHR2R

RFe

N NC

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

dr 8515exoendo 8218

46














47


Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



Ph Ph

OCOOEt

Ph Ph

N



NH

Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



48

N

Me

N

Fe

PPh2

Ph Ph

OCO2Et

Ph Ph

NHCH2Ph

[Pd(dba)2 ]+ Ligand





991 (220)

67 (11)

33 (2)

987 (153)

gt995 (gt400)



3 mol Pd-catalyst

PF6- Selectivity

Killer




49

Ph

Ph

P

NPd

+

endo-syn-syn

+

exo-syn-syn

Ph

PhP

NPd

Ph Ph

OCOOEt

Ph Ph



Slow with PF6-

(tight ion pairs )

Fast with F-

(Coordination)

R-Product S-Product

more stable


S R


50










51

E N Jacobsen et al



NN

OMn

OCl

X X

HHX = OMe 96 ee

X = NO2 22 ee

52




MeO MeO

CN

OOOPh

OPhOPAr2

OAr2P CF3F3C MeMe

HCN [Ni(COD)2] L

Ar =

91 eeL

16 ee

53





OCO O

++

nn2 3

4

1


Δ

54

([α]D=-450)




Polymer)50 220 370 1800


PCy2Me

Fe P

CF3

CF32

PCy2Me

Fe P

OMe

OMe2

PCy2Me

Fe P

H

H2

PCy2Me

Fe P

CH3

CH32

55


Markus Baumann


NMeN

Fe

Me

Me

Me

P

O+ PhOTf



O Ph O Ph O

Ph

+ +

2

Rn

Rn=(m-CF3)2

Rn=(m-SiMe3)2

Rn=(p-OMe)

Rn=(p-CF3)

1 (34ee)

8 (62ee)

1 (46ee)

1 (10ee)

94 (88ee)

90 (95ee)

97 (96ee)

96 (95ee)

5

2

2

3

56



NMeN

Fe

PMe Me

F3C

F3CNMeN

Fe

PMe Me

CF3

F3CF3C

F3C

NMeN

Fe

PF3C CF3

MeO

MeO

NMeN

Fe

PMe Me

MeO

MeO

NMeN

Fe

PF3C CF3

NMeN

Fe

PMe Me

NMeN

Fe

PMe Me

Me2N

Me2NNMeN

Fe

PF3C CF3

F3C

F3C

95 ee985 ee

5 ee72 ee

33 ee

98 ee90 ee

40 ee

the worst

and the best

57





NMeN

Fe

Me

Me

Me

PPh2


2) Oxidative Workup

OH

NMeN

Fe PPh2

NMeN

Fe PPh2

Me

39ee 76ee 99ee

Catalytic activity

NMeN

Fe

MeO

OMe

OMe

PPh2

NMeN

Fe

Me

Me

Me

P

CF3

CF3

2

82ee 91ee

58


X

Fe PPh2

N N

Mes

Me

X

1) cat PdCl2(L)

2) Oxidation


= L

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=078rsup2=0996

NMe₂

OMe

Me

ClH


Fe P X

N N

Mes

Me

1) cat PdCl2(L)

2) Oxidation


2

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=014rsup2=0986

NMe₂OMe

Me HCl


59



Fe P X

N N

Mes

Me

OH1) cat PdCl2(L)

2) Oxidation


2

60



X

Fe PPh2

N N

Mes

Me

X

OH1) cat PdCl2(L)

2) Oxidation

= L

61


PdN

P

Cl

Cl

PdN

P H

SiCl3

R

PdN

P

R

SiCl3

N

PdP

HCl3Si

N

Pd

P

Cl3Si

R

R





Unclear formation

σp

σp+


62


TK Woo

HH P

PdSiCl3SiCl3

NNH H

HH

HH P

PdSiCl3SiCl3

NNH H

FeP

PdSiCl3SiCl3

NN

FeP

PdSiCl3SiCl3

NN

HH P

PdSiCl3SiCl3

NNH H

HH P

PdSiCl3SiCl3

NN

H3CH

HH

H

Model 1

Model 2


63






PPd

H

SiCl3NN

HH

PPd

HSiCl3

NN

HH

PPd

HSiCl3

NN

HH

PPd

SiCl3NN

HH PPd

SiCl3NN

HH

1900

22

-02

-83

141

52

PPd

SiCl3NN

HH

PPd

Cl3SiNN

HH

64


endoendo-syn

PPdH

SiCl3NN

Fe

PPd HSiCl3NN

FeFe P

Pd

SiCl3NN

PPd HSiCl3NN

Fe

Cl3Si

PPd

SiCl3N

Fe

N

PPd

Cl3SiNN

Fe

PPdH

SiCl3NN

Fe

PPd

NN

Fe

Cl3Si

R

-35

09

TS1

TS2

-205

+-103

+styrene

00

42+48

61

Dagger Dagger


65





FeP

PdH

SiCl3NN

PPd

HSiCl3

NN

Fe


66


PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPd

H

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPdSiCl3NN

Fe

PPd

SiCl3NN

Fe

48

00

1609

51

-103

-113



endo-syn

exo-synendo

exo


kcalmol

67



endo-syn

exo-syn

NMe2

PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

NMe2

PPd

SiCl3NN

Fe

NMe2

PPdH

SiCl3NN

Fe

Me2N

PPd

SiCl3NN

Fe

PPdSiCl3

NN

Fe

NMe2

PPd

SiCl3NN

Fe

Me2N

48

00

08

03

16

-172

-155

exo

endo


68


DD

D

D5

HndashSiCl3 [PdL]

DD

D

D5

HO H DD

H

D5

HO H DH

H

D5

HO H DD

D

D5

HO D

oxid workup

+ + +


MeD1

MeD2

13C-1H-HZQCNMR

MeD2

MeD11 equivsilane

5 equivsilane

EI-MS


69





70


Energy(kcalmol)

(at rt)


(kcalmol)

(at rt)

ee

endo-syn -103 123

75 (S)[65 (S)]

endo-syn -172 859

81 (R)[64 (R)]

endo-anti -81 03 75 (S)[65 (S)]


75 (S)[65 (S)] exo-syn -155 48

81 (R)[64 (R)]

exo-anti -106 669

75 (S)[65 (S)]

exo-anti -153 35

81 (R)[64 (R)]


71

Conclusions




72



Ar=PhenylL2 =DME

Ar=1-NaphthylL=NCMe


OO

Ar

ArOAr

ArO

Ti

Cl


tartaric acid



8




OO 1-Naph

1-NaphO

1-Naph

1-NaphO

Ti

Cl

ClMeCN NCMe

O

O O

90 ee

FO

O O

88 ee

FS

O O

91 ee

F

O

O O

82 ee

F

N

O O

F

84 ee

O

O O

F

86 ee

O

O O

F

dr = 965 35

O

ON

O O

F

59 ee


N N CH2ClF

2 BF4ndash

++

9



RR Cl

Ti

Cl

OO

NCMeMeCN

OO

Np

Np

Np

Np

R OR

O O

Me

Cl

Ti

O

OOO

OR

MeR

MeCN

OO

Np

Np

Np

Np

F

R OR

O O

MeF

N N FCl

S

Cl

Ti

O

OOO

OR

MeR

MeCN

OO

Np

Np

Np

Np

ndash H+


++

+

+

Cl

Ti

O

OOO

OR

MeR

MeCN

OO

Np

Np

Np




10





SS

Cl

Ti

Cl

O O

MeCN NCMe

OO

Np

Np

Np

Np Et OBn

O O

Me

Et OBn

O O

MeF

N N F

Cl

R

O

Ti

O

O O

OBnO

Me Et

O

OONp

Np

Np

Np

OBn

Et

Me++

Nandash

C6H6 rt 80-90


11


OTiO

OOO

O

R

O

O ONp

NpNp

O

R

R

R

OTiO

OOO

R

O

O

O ONp

NpNp

R

OR

R

OTiO

OOO

R

O

O

O ONp

NpNp

O

R

RR

TiOO

O ONp

NpNp

O

OO

R

R

OO

O

R

R

TiOO

O ONp

NpNp

O

OR

OOO

R

O

TiOO

O ONp

NpNp

O

OR

OOO

O

R

R

RR R








12



(Face-on Re)


(Edge-on Re)


(Face-on Si)


(Edge-on Si)

13


Cl

Ti

O

OOO

O

Me

MeCN

OO

Np

Np

Np




14


O

Ti

O

OOO

OBnO

OO

Np

NpNp

BnO




15



Me O

O O

Me HDF

RR Cl

Ti

Cl

OO

THFTHF

OO

Np

Np

Np

Np

R OR

O O

Me

Cl

Ti

O

OOO

OR

MeR

THF

OO

Np

Np

Np

Np

F

R OR

O O

MeF

S

Cl

Ti

O

OOO

OR

MeR

THF

OO

Np

Np

Np

Np

ndash H+


+

+

Cl

Ti

O

OOO

OR

MeR

THF

OO

Np

Np

Np

HD

HD

N FPhSO2

PhSO2




16






17




ClTi

O

OOO

OR

MeR

MeCN

OO

Np

Np

NpNp

NN

F

Cl

N NCl

ClTi

O

OOO

OR

MeR

MeCN

OO

Np

Np

NpNp

ClTi

O

OOO

OR

MeR

MeCN

OO

Np

NpNp

Np

F

N N FCl

++

+

+

SET


+

18


LUMO of [F-TEDA]2+


SOMO of [F-TEDA]+



HOMO

of enolato complex

ndash endash

B3LYP6-31G level

19


SET

R

ORO

O

E ERn

Rm


-

R

ORO

O

ERn

+ RmEndash

O O

MeMe

O N

HMe

Me

ICl

MeS

Me

SMe

N

O

O

Cl

SCl


20




R1 OR3

O O

R2

R1 OR3

O O

R2SPh

R1 OR3

O O

R2F

R1 OR3

O O

R2Cl

R1 OR3

O O

FCl

R1 OR3

O O

R2HO

NCS

Selectfluor


N SO2PhO2N

H

O

RR Cl

Ti

Cl

OO

NCMeMeCN

OO

Np

Np

Np

Np



up to 88 ee




21




22






Step 12 Step 21



23








Josiphos

Pigiphos

Fe

NMe2

MeFe PPh2

NMe2

Me

Fe PPh2

PCy2

Me

PFe PPh2

Fe

Ph2PUgis amine

24




NMe2

MePAr2

R1 R3

OO

R2

H2NNH2

NNH

R3R2

R1

Fe Fe

NMe

NR3

R2

R1

PAr2


AcOH 70-90 degC

80-90 yield

+

25

Ph2PCy2P

Ph2P

PCy2

Ph2PCy2P

Ph2P

Cy2P

PPh2PCy2

Ph2P

PCy2

Si

O

O

HN

O

NH

Si

Si

O

OHN

O

HN

Si

NP N P

NP

NP Si

O

OHN

ONH

Si

Si

OO

HNO NH

Si

Si

O

ONH

O

HN

Si

Si

O

ONH

ONH Si

SiO

ONH

OHN

Si

Si

OO

NH O

HN

Si

PPh2Cy2P

Ph2PCy2P

PPh2

PCy2

PPh2PCy2

Ph2PPCy2

PPh2

Cy2P

PPh2PCy2

PPh2

PCy2

Ph2P

Cy2P

Fe

PPh2Cy2P

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe




26



NH3C

CH3

OCH3

CH3OCl

H

P

MeFe

PPh2


2

Ir

S

NHHN

O

H H

P(t-Bu)2

MeFe

PPh2

COOH

(+)-Biotin(LONZA)

Rh

Sitagliptin(Merck)

Rh

F

FF

NN

NN

ONH2

CF3

PtBu2

MeFe P(4-F3CPh)2

27



H NN

ONHO

O

H NN

ONHO


SC=2000


96 ee

P(t-Bu)2

MeFe PPh2

N NN

OH

O

NH

ONH OH



28




P(t-Bu)2

MeFe PPh2

O

HOOCHN

S

F

O O

O

HOOCHN

S

F

O O

RuCl2(P-P)LnNEt3

H2 EtOH

O

HN

S

F

O O

O

HOHNP-P =

97 ee

29



Up to 97 ee

F

FF

NN

NN

ONH2

CF3



P(t-Bu)2

MeFe

P(t-Bu)2Me

Fe P CF32

PPh2

R OMe

NH2 O

R OMe


R NHPh

NH2 O

R NHPh

NH2 O

H2

Rh Josiphos ligand

H2

30











31










32



33

$

amp$

$

$

($

$$ amp$ )$ $ $ $ $ $

$

amp()+-


ampamp2824+

5lt=-amp)gt+gt2)42






34




α1=+9degα2=-21deg




35

Pd

L1

L2R

R

Pd

L1

L2

R

R

Nu Nu



36



X-rayX-ray

PhPh FeP

NNPd Ph

Ph


+

Ph

FeP

NNPd

Ph

Ph

Ph


+

PhPh FeP

NN

Pd Ph

Ph

+



Ph Ph

OCOR

NH2

Ph Ph


40 degC THF


N

Me

N

Fe

PPh2R

37



Ph

FeP

NNPd

Ph

a) R-product



NuNu

a)

b)

+

RS




PN

PdP N

PdP N

+ +


tc = 2 kcalmol

(Ab initio studies)

38

NH

NPd

PH3

NH3


NPd

PH3


NH

NPd

PH3

NH3

50 kJmol

36 kJmol

NH3+

41 kJmol

NH3+

+



PdP N

PdP N

PdP N

+

+ +


tc = 8 kJmol


ct = 29 kJmol


for C out of plane



40

PhPh Fe

P

NNPd

Ph

Ph

Ph

Ph

FeP

NNPd

Ph

Ph

exo-syn-anti (71)

+

exo-syn-syn (29)

+

S R



41

PhFe

P

NN

Pd


+

Ph




42

Ph

Ph

PdP N

Ph

Ph

P NPd

Nu

Nu




43




PMe

NN

Ph

Ph

PhPh

PdNN

MePd

FeFeP

Ph

Ph

Ph

Ph

Ph Ph

NHCH2Ph

(S)

Ph Ph

OCOOEtNu-Nu-


950 ee resp 945 ee

rac

44






Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

Fe

N CN

PPh2

Me

Fe

N NC

PPh2

MePdR

R+

PdR

R+

X-ray

45



Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

PdR

R+

PdR

R+

Fe

N CN

PPh2

Me Pd

NHR2R

RFe

N CN

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

Fe

N NC

PPh2

Me Pd

NHR2R

RFe

N NC

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

dr 8515exoendo 8218

46














47


Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



Ph Ph

OCOOEt

Ph Ph

N



NH

Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



48

N

Me

N

Fe

PPh2

Ph Ph

OCO2Et

Ph Ph

NHCH2Ph

[Pd(dba)2 ]+ Ligand





991 (220)

67 (11)

33 (2)

987 (153)

gt995 (gt400)



3 mol Pd-catalyst

PF6- Selectivity

Killer




49

Ph

Ph

P

NPd

+

endo-syn-syn

+

exo-syn-syn

Ph

PhP

NPd

Ph Ph

OCOOEt

Ph Ph



Slow with PF6-

(tight ion pairs )

Fast with F-

(Coordination)

R-Product S-Product

more stable


S R


50










51

E N Jacobsen et al



NN

OMn

OCl

X X

HHX = OMe 96 ee

X = NO2 22 ee

52




MeO MeO

CN

OOOPh

OPhOPAr2

OAr2P CF3F3C MeMe

HCN [Ni(COD)2] L

Ar =

91 eeL

16 ee

53





OCO O

++

nn2 3

4

1


Δ

54

([α]D=-450)




Polymer)50 220 370 1800


PCy2Me

Fe P

CF3

CF32

PCy2Me

Fe P

OMe

OMe2

PCy2Me

Fe P

H

H2

PCy2Me

Fe P

CH3

CH32

55


Markus Baumann


NMeN

Fe

Me

Me

Me

P

O+ PhOTf



O Ph O Ph O

Ph

+ +

2

Rn

Rn=(m-CF3)2

Rn=(m-SiMe3)2

Rn=(p-OMe)

Rn=(p-CF3)

1 (34ee)

8 (62ee)

1 (46ee)

1 (10ee)

94 (88ee)

90 (95ee)

97 (96ee)

96 (95ee)

5

2

2

3

56



NMeN

Fe

PMe Me

F3C

F3CNMeN

Fe

PMe Me

CF3

F3CF3C

F3C

NMeN

Fe

PF3C CF3

MeO

MeO

NMeN

Fe

PMe Me

MeO

MeO

NMeN

Fe

PF3C CF3

NMeN

Fe

PMe Me

NMeN

Fe

PMe Me

Me2N

Me2NNMeN

Fe

PF3C CF3

F3C

F3C

95 ee985 ee

5 ee72 ee

33 ee

98 ee90 ee

40 ee

the worst

and the best

57





NMeN

Fe

Me

Me

Me

PPh2


2) Oxidative Workup

OH

NMeN

Fe PPh2

NMeN

Fe PPh2

Me

39ee 76ee 99ee

Catalytic activity

NMeN

Fe

MeO

OMe

OMe

PPh2

NMeN

Fe

Me

Me

Me

P

CF3

CF3

2

82ee 91ee

58


X

Fe PPh2

N N

Mes

Me

X

1) cat PdCl2(L)

2) Oxidation


= L

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=078rsup2=0996

NMe₂

OMe

Me

ClH


Fe P X

N N

Mes

Me

1) cat PdCl2(L)

2) Oxidation


2

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=014rsup2=0986

NMe₂OMe

Me HCl


59



Fe P X

N N

Mes

Me

OH1) cat PdCl2(L)

2) Oxidation


2

60



X

Fe PPh2

N N

Mes

Me

X

OH1) cat PdCl2(L)

2) Oxidation

= L

61


PdN

P

Cl

Cl

PdN

P H

SiCl3

R

PdN

P

R

SiCl3

N

PdP

HCl3Si

N

Pd

P

Cl3Si

R

R





Unclear formation

σp

σp+


62


TK Woo

HH P

PdSiCl3SiCl3

NNH H

HH

HH P

PdSiCl3SiCl3

NNH H

FeP

PdSiCl3SiCl3

NN

FeP

PdSiCl3SiCl3

NN

HH P

PdSiCl3SiCl3

NNH H

HH P

PdSiCl3SiCl3

NN

H3CH

HH

H

Model 1

Model 2


63






PPd

H

SiCl3NN

HH

PPd

HSiCl3

NN

HH

PPd

HSiCl3

NN

HH

PPd

SiCl3NN

HH PPd

SiCl3NN

HH

1900

22

-02

-83

141

52

PPd

SiCl3NN

HH

PPd

Cl3SiNN

HH

64


endoendo-syn

PPdH

SiCl3NN

Fe

PPd HSiCl3NN

FeFe P

Pd

SiCl3NN

PPd HSiCl3NN

Fe

Cl3Si

PPd

SiCl3N

Fe

N

PPd

Cl3SiNN

Fe

PPdH

SiCl3NN

Fe

PPd

NN

Fe

Cl3Si

R

-35

09

TS1

TS2

-205

+-103

+styrene

00

42+48

61

Dagger Dagger


65





FeP

PdH

SiCl3NN

PPd

HSiCl3

NN

Fe


66


PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPd

H

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPdSiCl3NN

Fe

PPd

SiCl3NN

Fe

48

00

1609

51

-103

-113



endo-syn

exo-synendo

exo


kcalmol

67



endo-syn

exo-syn

NMe2

PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

NMe2

PPd

SiCl3NN

Fe

NMe2

PPdH

SiCl3NN

Fe

Me2N

PPd

SiCl3NN

Fe

PPdSiCl3

NN

Fe

NMe2

PPd

SiCl3NN

Fe

Me2N

48

00

08

03

16

-172

-155

exo

endo


68


DD

D

D5

HndashSiCl3 [PdL]

DD

D

D5

HO H DD

H

D5

HO H DH

H

D5

HO H DD

D

D5

HO D

oxid workup

+ + +


MeD1

MeD2

13C-1H-HZQCNMR

MeD2

MeD11 equivsilane

5 equivsilane

EI-MS


69





70


Energy(kcalmol)

(at rt)


(kcalmol)

(at rt)

ee

endo-syn -103 123

75 (S)[65 (S)]

endo-syn -172 859

81 (R)[64 (R)]

endo-anti -81 03 75 (S)[65 (S)]


75 (S)[65 (S)] exo-syn -155 48

81 (R)[64 (R)]

exo-anti -106 669

75 (S)[65 (S)]

exo-anti -153 35

81 (R)[64 (R)]


71

Conclusions




72




OO 1-Naph

1-NaphO

1-Naph

1-NaphO

Ti

Cl

ClMeCN NCMe

O

O O

90 ee

FO

O O

88 ee

FS

O O

91 ee

F

O

O O

82 ee

F

N

O O

F

84 ee

O

O O

F

86 ee

O

O O

F

dr = 965 35

O

ON

O O

F

59 ee


N N CH2ClF

2 BF4ndash

++

9



RR Cl

Ti

Cl

OO

NCMeMeCN

OO

Np

Np

Np

Np

R OR

O O

Me

Cl

Ti

O

OOO

OR

MeR

MeCN

OO

Np

Np

Np

Np

F

R OR

O O

MeF

N N FCl

S

Cl

Ti

O

OOO

OR

MeR

MeCN

OO

Np

Np

Np

Np

ndash H+


++

+

+

Cl

Ti

O

OOO

OR

MeR

MeCN

OO

Np

Np

Np




10





SS

Cl

Ti

Cl

O O

MeCN NCMe

OO

Np

Np

Np

Np Et OBn

O O

Me

Et OBn

O O

MeF

N N F

Cl

R

O

Ti

O

O O

OBnO

Me Et

O

OONp

Np

Np

Np

OBn

Et

Me++

Nandash

C6H6 rt 80-90


11


OTiO

OOO

O

R

O

O ONp

NpNp

O

R

R

R

OTiO

OOO

R

O

O

O ONp

NpNp

R

OR

R

OTiO

OOO

R

O

O

O ONp

NpNp

O

R

RR

TiOO

O ONp

NpNp

O

OO

R

R

OO

O

R

R

TiOO

O ONp

NpNp

O

OR

OOO

R

O

TiOO

O ONp

NpNp

O

OR

OOO

O

R

R

RR R








12



(Face-on Re)


(Edge-on Re)


(Face-on Si)


(Edge-on Si)

13


Cl

Ti

O

OOO

O

Me

MeCN

OO

Np

Np

Np




14


O

Ti

O

OOO

OBnO

OO

Np

NpNp

BnO




15



Me O

O O

Me HDF

RR Cl

Ti

Cl

OO

THFTHF

OO

Np

Np

Np

Np

R OR

O O

Me

Cl

Ti

O

OOO

OR

MeR

THF

OO

Np

Np

Np

Np

F

R OR

O O

MeF

S

Cl

Ti

O

OOO

OR

MeR

THF

OO

Np

Np

Np

Np

ndash H+


+

+

Cl

Ti

O

OOO

OR

MeR

THF

OO

Np

Np

Np

HD

HD

N FPhSO2

PhSO2




16






17




ClTi

O

OOO

OR

MeR

MeCN

OO

Np

Np

NpNp

NN

F

Cl

N NCl

ClTi

O

OOO

OR

MeR

MeCN

OO

Np

Np

NpNp

ClTi

O

OOO

OR

MeR

MeCN

OO

Np

NpNp

Np

F

N N FCl

++

+

+

SET


+

18


LUMO of [F-TEDA]2+


SOMO of [F-TEDA]+



HOMO

of enolato complex

ndash endash

B3LYP6-31G level

19


SET

R

ORO

O

E ERn

Rm


-

R

ORO

O

ERn

+ RmEndash

O O

MeMe

O N

HMe

Me

ICl

MeS

Me

SMe

N

O

O

Cl

SCl


20




R1 OR3

O O

R2

R1 OR3

O O

R2SPh

R1 OR3

O O

R2F

R1 OR3

O O

R2Cl

R1 OR3

O O

FCl

R1 OR3

O O

R2HO

NCS

Selectfluor


N SO2PhO2N

H

O

RR Cl

Ti

Cl

OO

NCMeMeCN

OO

Np

Np

Np

Np



up to 88 ee




21




22






Step 12 Step 21



23








Josiphos

Pigiphos

Fe

NMe2

MeFe PPh2

NMe2

Me

Fe PPh2

PCy2

Me

PFe PPh2

Fe

Ph2PUgis amine

24




NMe2

MePAr2

R1 R3

OO

R2

H2NNH2

NNH

R3R2

R1

Fe Fe

NMe

NR3

R2

R1

PAr2


AcOH 70-90 degC

80-90 yield

+

25

Ph2PCy2P

Ph2P

PCy2

Ph2PCy2P

Ph2P

Cy2P

PPh2PCy2

Ph2P

PCy2

Si

O

O

HN

O

NH

Si

Si

O

OHN

O

HN

Si

NP N P

NP

NP Si

O

OHN

ONH

Si

Si

OO

HNO NH

Si

Si

O

ONH

O

HN

Si

Si

O

ONH

ONH Si

SiO

ONH

OHN

Si

Si

OO

NH O

HN

Si

PPh2Cy2P

Ph2PCy2P

PPh2

PCy2

PPh2PCy2

Ph2PPCy2

PPh2

Cy2P

PPh2PCy2

PPh2

PCy2

Ph2P

Cy2P

Fe

PPh2Cy2P

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe




26



NH3C

CH3

OCH3

CH3OCl

H

P

MeFe

PPh2


2

Ir

S

NHHN

O

H H

P(t-Bu)2

MeFe

PPh2

COOH

(+)-Biotin(LONZA)

Rh

Sitagliptin(Merck)

Rh

F

FF

NN

NN

ONH2

CF3

PtBu2

MeFe P(4-F3CPh)2

27



H NN

ONHO

O

H NN

ONHO


SC=2000


96 ee

P(t-Bu)2

MeFe PPh2

N NN

OH

O

NH

ONH OH



28




P(t-Bu)2

MeFe PPh2

O

HOOCHN

S

F

O O

O

HOOCHN

S

F

O O

RuCl2(P-P)LnNEt3

H2 EtOH

O

HN

S

F

O O

O

HOHNP-P =

97 ee

29



Up to 97 ee

F

FF

NN

NN

ONH2

CF3



P(t-Bu)2

MeFe

P(t-Bu)2Me

Fe P CF32

PPh2

R OMe

NH2 O

R OMe


R NHPh

NH2 O

R NHPh

NH2 O

H2

Rh Josiphos ligand

H2

30











31










32



33

$

amp$

$

$

($

$$ amp$ )$ $ $ $ $ $

$

amp()+-


ampamp2824+

5lt=-amp)gt+gt2)42






34




α1=+9degα2=-21deg




35

Pd

L1

L2R

R

Pd

L1

L2

R

R

Nu Nu



36



X-rayX-ray

PhPh FeP

NNPd Ph

Ph


+

Ph

FeP

NNPd

Ph

Ph

Ph


+

PhPh FeP

NN

Pd Ph

Ph

+



Ph Ph

OCOR

NH2

Ph Ph


40 degC THF


N

Me

N

Fe

PPh2R

37



Ph

FeP

NNPd

Ph

a) R-product



NuNu

a)

b)

+

RS




PN

PdP N

PdP N

+ +


tc = 2 kcalmol

(Ab initio studies)

38

NH

NPd

PH3

NH3


NPd

PH3


NH

NPd

PH3

NH3

50 kJmol

36 kJmol

NH3+

41 kJmol

NH3+

+



PdP N

PdP N

PdP N

+

+ +


tc = 8 kJmol


ct = 29 kJmol


for C out of plane



40

PhPh Fe

P

NNPd

Ph

Ph

Ph

Ph

FeP

NNPd

Ph

Ph

exo-syn-anti (71)

+

exo-syn-syn (29)

+

S R



41

PhFe

P

NN

Pd


+

Ph




42

Ph

Ph

PdP N

Ph

Ph

P NPd

Nu

Nu




43




PMe

NN

Ph

Ph

PhPh

PdNN

MePd

FeFeP

Ph

Ph

Ph

Ph

Ph Ph

NHCH2Ph

(S)

Ph Ph

OCOOEtNu-Nu-


950 ee resp 945 ee

rac

44






Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

Fe

N CN

PPh2

Me

Fe

N NC

PPh2

MePdR

R+

PdR

R+

X-ray

45



Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

PdR

R+

PdR

R+

Fe

N CN

PPh2

Me Pd

NHR2R

RFe

N CN

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

Fe

N NC

PPh2

Me Pd

NHR2R

RFe

N NC

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

dr 8515exoendo 8218

46














47


Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



Ph Ph

OCOOEt

Ph Ph

N



NH

Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



48

N

Me

N

Fe

PPh2

Ph Ph

OCO2Et

Ph Ph

NHCH2Ph

[Pd(dba)2 ]+ Ligand





991 (220)

67 (11)

33 (2)

987 (153)

gt995 (gt400)



3 mol Pd-catalyst

PF6- Selectivity

Killer




49

Ph

Ph

P

NPd

+

endo-syn-syn

+

exo-syn-syn

Ph

PhP

NPd

Ph Ph

OCOOEt

Ph Ph



Slow with PF6-

(tight ion pairs )

Fast with F-

(Coordination)

R-Product S-Product

more stable


S R


50










51

E N Jacobsen et al



NN

OMn

OCl

X X

HHX = OMe 96 ee

X = NO2 22 ee

52




MeO MeO

CN

OOOPh

OPhOPAr2

OAr2P CF3F3C MeMe

HCN [Ni(COD)2] L

Ar =

91 eeL

16 ee

53





OCO O

++

nn2 3

4

1


Δ

54

([α]D=-450)




Polymer)50 220 370 1800


PCy2Me

Fe P

CF3

CF32

PCy2Me

Fe P

OMe

OMe2

PCy2Me

Fe P

H

H2

PCy2Me

Fe P

CH3

CH32

55


Markus Baumann


NMeN

Fe

Me

Me

Me

P

O+ PhOTf



O Ph O Ph O

Ph

+ +

2

Rn

Rn=(m-CF3)2

Rn=(m-SiMe3)2

Rn=(p-OMe)

Rn=(p-CF3)

1 (34ee)

8 (62ee)

1 (46ee)

1 (10ee)

94 (88ee)

90 (95ee)

97 (96ee)

96 (95ee)

5

2

2

3

56



NMeN

Fe

PMe Me

F3C

F3CNMeN

Fe

PMe Me

CF3

F3CF3C

F3C

NMeN

Fe

PF3C CF3

MeO

MeO

NMeN

Fe

PMe Me

MeO

MeO

NMeN

Fe

PF3C CF3

NMeN

Fe

PMe Me

NMeN

Fe

PMe Me

Me2N

Me2NNMeN

Fe

PF3C CF3

F3C

F3C

95 ee985 ee

5 ee72 ee

33 ee

98 ee90 ee

40 ee

the worst

and the best

57





NMeN

Fe

Me

Me

Me

PPh2


2) Oxidative Workup

OH

NMeN

Fe PPh2

NMeN

Fe PPh2

Me

39ee 76ee 99ee

Catalytic activity

NMeN

Fe

MeO

OMe

OMe

PPh2

NMeN

Fe

Me

Me

Me

P

CF3

CF3

2

82ee 91ee

58


X

Fe PPh2

N N

Mes

Me

X

1) cat PdCl2(L)

2) Oxidation


= L

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=078rsup2=0996

NMe₂

OMe

Me

ClH


Fe P X

N N

Mes

Me

1) cat PdCl2(L)

2) Oxidation


2

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=014rsup2=0986

NMe₂OMe

Me HCl


59



Fe P X

N N

Mes

Me

OH1) cat PdCl2(L)

2) Oxidation


2

60



X

Fe PPh2

N N

Mes

Me

X

OH1) cat PdCl2(L)

2) Oxidation

= L

61


PdN

P

Cl

Cl

PdN

P H

SiCl3

R

PdN

P

R

SiCl3

N

PdP

HCl3Si

N

Pd

P

Cl3Si

R

R





Unclear formation

σp

σp+


62


TK Woo

HH P

PdSiCl3SiCl3

NNH H

HH

HH P

PdSiCl3SiCl3

NNH H

FeP

PdSiCl3SiCl3

NN

FeP

PdSiCl3SiCl3

NN

HH P

PdSiCl3SiCl3

NNH H

HH P

PdSiCl3SiCl3

NN

H3CH

HH

H

Model 1

Model 2


63






PPd

H

SiCl3NN

HH

PPd

HSiCl3

NN

HH

PPd

HSiCl3

NN

HH

PPd

SiCl3NN

HH PPd

SiCl3NN

HH

1900

22

-02

-83

141

52

PPd

SiCl3NN

HH

PPd

Cl3SiNN

HH

64


endoendo-syn

PPdH

SiCl3NN

Fe

PPd HSiCl3NN

FeFe P

Pd

SiCl3NN

PPd HSiCl3NN

Fe

Cl3Si

PPd

SiCl3N

Fe

N

PPd

Cl3SiNN

Fe

PPdH

SiCl3NN

Fe

PPd

NN

Fe

Cl3Si

R

-35

09

TS1

TS2

-205

+-103

+styrene

00

42+48

61

Dagger Dagger


65





FeP

PdH

SiCl3NN

PPd

HSiCl3

NN

Fe


66


PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPd

H

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPdSiCl3NN

Fe

PPd

SiCl3NN

Fe

48

00

1609

51

-103

-113



endo-syn

exo-synendo

exo


kcalmol

67



endo-syn

exo-syn

NMe2

PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

NMe2

PPd

SiCl3NN

Fe

NMe2

PPdH

SiCl3NN

Fe

Me2N

PPd

SiCl3NN

Fe

PPdSiCl3

NN

Fe

NMe2

PPd

SiCl3NN

Fe

Me2N

48

00

08

03

16

-172

-155

exo

endo


68


DD

D

D5

HndashSiCl3 [PdL]

DD

D

D5

HO H DD

H

D5

HO H DH

H

D5

HO H DD

D

D5

HO D

oxid workup

+ + +


MeD1

MeD2

13C-1H-HZQCNMR

MeD2

MeD11 equivsilane

5 equivsilane

EI-MS


69





70


Energy(kcalmol)

(at rt)


(kcalmol)

(at rt)

ee

endo-syn -103 123

75 (S)[65 (S)]

endo-syn -172 859

81 (R)[64 (R)]

endo-anti -81 03 75 (S)[65 (S)]


75 (S)[65 (S)] exo-syn -155 48

81 (R)[64 (R)]

exo-anti -106 669

75 (S)[65 (S)]

exo-anti -153 35

81 (R)[64 (R)]


71

Conclusions




72



RR Cl

Ti

Cl

OO

NCMeMeCN

OO

Np

Np

Np

Np

R OR

O O

Me

Cl

Ti

O

OOO

OR

MeR

MeCN

OO

Np

Np

Np

Np

F

R OR

O O

MeF

N N FCl

S

Cl

Ti

O

OOO

OR

MeR

MeCN

OO

Np

Np

Np

Np

ndash H+


++

+

+

Cl

Ti

O

OOO

OR

MeR

MeCN

OO

Np

Np

Np




10





SS

Cl

Ti

Cl

O O

MeCN NCMe

OO

Np

Np

Np

Np Et OBn

O O

Me

Et OBn

O O

MeF

N N F

Cl

R

O

Ti

O

O O

OBnO

Me Et

O

OONp

Np

Np

Np

OBn

Et

Me++

Nandash

C6H6 rt 80-90


11


OTiO

OOO

O

R

O

O ONp

NpNp

O

R

R

R

OTiO

OOO

R

O

O

O ONp

NpNp

R

OR

R

OTiO

OOO

R

O

O

O ONp

NpNp

O

R

RR

TiOO

O ONp

NpNp

O

OO

R

R

OO

O

R

R

TiOO

O ONp

NpNp

O

OR

OOO

R

O

TiOO

O ONp

NpNp

O

OR

OOO

O

R

R

RR R








12



(Face-on Re)


(Edge-on Re)


(Face-on Si)


(Edge-on Si)

13


Cl

Ti

O

OOO

O

Me

MeCN

OO

Np

Np

Np




14


O

Ti

O

OOO

OBnO

OO

Np

NpNp

BnO




15



Me O

O O

Me HDF

RR Cl

Ti

Cl

OO

THFTHF

OO

Np

Np

Np

Np

R OR

O O

Me

Cl

Ti

O

OOO

OR

MeR

THF

OO

Np

Np

Np

Np

F

R OR

O O

MeF

S

Cl

Ti

O

OOO

OR

MeR

THF

OO

Np

Np

Np

Np

ndash H+


+

+

Cl

Ti

O

OOO

OR

MeR

THF

OO

Np

Np

Np

HD

HD

N FPhSO2

PhSO2




16






17




ClTi

O

OOO

OR

MeR

MeCN

OO

Np

Np

NpNp

NN

F

Cl

N NCl

ClTi

O

OOO

OR

MeR

MeCN

OO

Np

Np

NpNp

ClTi

O

OOO

OR

MeR

MeCN

OO

Np

NpNp

Np

F

N N FCl

++

+

+

SET


+

18


LUMO of [F-TEDA]2+


SOMO of [F-TEDA]+



HOMO

of enolato complex

ndash endash

B3LYP6-31G level

19


SET

R

ORO

O

E ERn

Rm


-

R

ORO

O

ERn

+ RmEndash

O O

MeMe

O N

HMe

Me

ICl

MeS

Me

SMe

N

O

O

Cl

SCl


20




R1 OR3

O O

R2

R1 OR3

O O

R2SPh

R1 OR3

O O

R2F

R1 OR3

O O

R2Cl

R1 OR3

O O

FCl

R1 OR3

O O

R2HO

NCS

Selectfluor


N SO2PhO2N

H

O

RR Cl

Ti

Cl

OO

NCMeMeCN

OO

Np

Np

Np

Np



up to 88 ee




21




22






Step 12 Step 21



23








Josiphos

Pigiphos

Fe

NMe2

MeFe PPh2

NMe2

Me

Fe PPh2

PCy2

Me

PFe PPh2

Fe

Ph2PUgis amine

24




NMe2

MePAr2

R1 R3

OO

R2

H2NNH2

NNH

R3R2

R1

Fe Fe

NMe

NR3

R2

R1

PAr2


AcOH 70-90 degC

80-90 yield

+

25

Ph2PCy2P

Ph2P

PCy2

Ph2PCy2P

Ph2P

Cy2P

PPh2PCy2

Ph2P

PCy2

Si

O

O

HN

O

NH

Si

Si

O

OHN

O

HN

Si

NP N P

NP

NP Si

O

OHN

ONH

Si

Si

OO

HNO NH

Si

Si

O

ONH

O

HN

Si

Si

O

ONH

ONH Si

SiO

ONH

OHN

Si

Si

OO

NH O

HN

Si

PPh2Cy2P

Ph2PCy2P

PPh2

PCy2

PPh2PCy2

Ph2PPCy2

PPh2

Cy2P

PPh2PCy2

PPh2

PCy2

Ph2P

Cy2P

Fe

PPh2Cy2P

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe




26



NH3C

CH3

OCH3

CH3OCl

H

P

MeFe

PPh2


2

Ir

S

NHHN

O

H H

P(t-Bu)2

MeFe

PPh2

COOH

(+)-Biotin(LONZA)

Rh

Sitagliptin(Merck)

Rh

F

FF

NN

NN

ONH2

CF3

PtBu2

MeFe P(4-F3CPh)2

27



H NN

ONHO

O

H NN

ONHO


SC=2000


96 ee

P(t-Bu)2

MeFe PPh2

N NN

OH

O

NH

ONH OH



28




P(t-Bu)2

MeFe PPh2

O

HOOCHN

S

F

O O

O

HOOCHN

S

F

O O

RuCl2(P-P)LnNEt3

H2 EtOH

O

HN

S

F

O O

O

HOHNP-P =

97 ee

29



Up to 97 ee

F

FF

NN

NN

ONH2

CF3



P(t-Bu)2

MeFe

P(t-Bu)2Me

Fe P CF32

PPh2

R OMe

NH2 O

R OMe


R NHPh

NH2 O

R NHPh

NH2 O

H2

Rh Josiphos ligand

H2

30











31










32



33

$

amp$

$

$

($

$$ amp$ )$ $ $ $ $ $

$

amp()+-


ampamp2824+

5lt=-amp)gt+gt2)42






34




α1=+9degα2=-21deg




35

Pd

L1

L2R

R

Pd

L1

L2

R

R

Nu Nu



36



X-rayX-ray

PhPh FeP

NNPd Ph

Ph


+

Ph

FeP

NNPd

Ph

Ph

Ph


+

PhPh FeP

NN

Pd Ph

Ph

+



Ph Ph

OCOR

NH2

Ph Ph


40 degC THF


N

Me

N

Fe

PPh2R

37



Ph

FeP

NNPd

Ph

a) R-product



NuNu

a)

b)

+

RS




PN

PdP N

PdP N

+ +


tc = 2 kcalmol

(Ab initio studies)

38

NH

NPd

PH3

NH3


NPd

PH3


NH

NPd

PH3

NH3

50 kJmol

36 kJmol

NH3+

41 kJmol

NH3+

+



PdP N

PdP N

PdP N

+

+ +


tc = 8 kJmol


ct = 29 kJmol


for C out of plane



40

PhPh Fe

P

NNPd

Ph

Ph

Ph

Ph

FeP

NNPd

Ph

Ph

exo-syn-anti (71)

+

exo-syn-syn (29)

+

S R



41

PhFe

P

NN

Pd


+

Ph




42

Ph

Ph

PdP N

Ph

Ph

P NPd

Nu

Nu




43




PMe

NN

Ph

Ph

PhPh

PdNN

MePd

FeFeP

Ph

Ph

Ph

Ph

Ph Ph

NHCH2Ph

(S)

Ph Ph

OCOOEtNu-Nu-


950 ee resp 945 ee

rac

44






Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

Fe

N CN

PPh2

Me

Fe

N NC

PPh2

MePdR

R+

PdR

R+

X-ray

45



Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

PdR

R+

PdR

R+

Fe

N CN

PPh2

Me Pd

NHR2R

RFe

N CN

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

Fe

N NC

PPh2

Me Pd

NHR2R

RFe

N NC

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

dr 8515exoendo 8218

46














47


Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



Ph Ph

OCOOEt

Ph Ph

N



NH

Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



48

N

Me

N

Fe

PPh2

Ph Ph

OCO2Et

Ph Ph

NHCH2Ph

[Pd(dba)2 ]+ Ligand





991 (220)

67 (11)

33 (2)

987 (153)

gt995 (gt400)



3 mol Pd-catalyst

PF6- Selectivity

Killer




49

Ph

Ph

P

NPd

+

endo-syn-syn

+

exo-syn-syn

Ph

PhP

NPd

Ph Ph

OCOOEt

Ph Ph



Slow with PF6-

(tight ion pairs )

Fast with F-

(Coordination)

R-Product S-Product

more stable


S R


50










51

E N Jacobsen et al



NN

OMn

OCl

X X

HHX = OMe 96 ee

X = NO2 22 ee

52




MeO MeO

CN

OOOPh

OPhOPAr2

OAr2P CF3F3C MeMe

HCN [Ni(COD)2] L

Ar =

91 eeL

16 ee

53





OCO O

++

nn2 3

4

1


Δ

54

([α]D=-450)




Polymer)50 220 370 1800


PCy2Me

Fe P

CF3

CF32

PCy2Me

Fe P

OMe

OMe2

PCy2Me

Fe P

H

H2

PCy2Me

Fe P

CH3

CH32

55


Markus Baumann


NMeN

Fe

Me

Me

Me

P

O+ PhOTf



O Ph O Ph O

Ph

+ +

2

Rn

Rn=(m-CF3)2

Rn=(m-SiMe3)2

Rn=(p-OMe)

Rn=(p-CF3)

1 (34ee)

8 (62ee)

1 (46ee)

1 (10ee)

94 (88ee)

90 (95ee)

97 (96ee)

96 (95ee)

5

2

2

3

56



NMeN

Fe

PMe Me

F3C

F3CNMeN

Fe

PMe Me

CF3

F3CF3C

F3C

NMeN

Fe

PF3C CF3

MeO

MeO

NMeN

Fe

PMe Me

MeO

MeO

NMeN

Fe

PF3C CF3

NMeN

Fe

PMe Me

NMeN

Fe

PMe Me

Me2N

Me2NNMeN

Fe

PF3C CF3

F3C

F3C

95 ee985 ee

5 ee72 ee

33 ee

98 ee90 ee

40 ee

the worst

and the best

57





NMeN

Fe

Me

Me

Me

PPh2


2) Oxidative Workup

OH

NMeN

Fe PPh2

NMeN

Fe PPh2

Me

39ee 76ee 99ee

Catalytic activity

NMeN

Fe

MeO

OMe

OMe

PPh2

NMeN

Fe

Me

Me

Me

P

CF3

CF3

2

82ee 91ee

58


X

Fe PPh2

N N

Mes

Me

X

1) cat PdCl2(L)

2) Oxidation


= L

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=078rsup2=0996

NMe₂

OMe

Me

ClH


Fe P X

N N

Mes

Me

1) cat PdCl2(L)

2) Oxidation


2

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=014rsup2=0986

NMe₂OMe

Me HCl


59



Fe P X

N N

Mes

Me

OH1) cat PdCl2(L)

2) Oxidation


2

60



X

Fe PPh2

N N

Mes

Me

X

OH1) cat PdCl2(L)

2) Oxidation

= L

61


PdN

P

Cl

Cl

PdN

P H

SiCl3

R

PdN

P

R

SiCl3

N

PdP

HCl3Si

N

Pd

P

Cl3Si

R

R





Unclear formation

σp

σp+


62


TK Woo

HH P

PdSiCl3SiCl3

NNH H

HH

HH P

PdSiCl3SiCl3

NNH H

FeP

PdSiCl3SiCl3

NN

FeP

PdSiCl3SiCl3

NN

HH P

PdSiCl3SiCl3

NNH H

HH P

PdSiCl3SiCl3

NN

H3CH

HH

H

Model 1

Model 2


63






PPd

H

SiCl3NN

HH

PPd

HSiCl3

NN

HH

PPd

HSiCl3

NN

HH

PPd

SiCl3NN

HH PPd

SiCl3NN

HH

1900

22

-02

-83

141

52

PPd

SiCl3NN

HH

PPd

Cl3SiNN

HH

64


endoendo-syn

PPdH

SiCl3NN

Fe

PPd HSiCl3NN

FeFe P

Pd

SiCl3NN

PPd HSiCl3NN

Fe

Cl3Si

PPd

SiCl3N

Fe

N

PPd

Cl3SiNN

Fe

PPdH

SiCl3NN

Fe

PPd

NN

Fe

Cl3Si

R

-35

09

TS1

TS2

-205

+-103

+styrene

00

42+48

61

Dagger Dagger


65





FeP

PdH

SiCl3NN

PPd

HSiCl3

NN

Fe


66


PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPd

H

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPdSiCl3NN

Fe

PPd

SiCl3NN

Fe

48

00

1609

51

-103

-113



endo-syn

exo-synendo

exo


kcalmol

67



endo-syn

exo-syn

NMe2

PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

NMe2

PPd

SiCl3NN

Fe

NMe2

PPdH

SiCl3NN

Fe

Me2N

PPd

SiCl3NN

Fe

PPdSiCl3

NN

Fe

NMe2

PPd

SiCl3NN

Fe

Me2N

48

00

08

03

16

-172

-155

exo

endo


68


DD

D

D5

HndashSiCl3 [PdL]

DD

D

D5

HO H DD

H

D5

HO H DH

H

D5

HO H DD

D

D5

HO D

oxid workup

+ + +


MeD1

MeD2

13C-1H-HZQCNMR

MeD2

MeD11 equivsilane

5 equivsilane

EI-MS


69





70


Energy(kcalmol)

(at rt)


(kcalmol)

(at rt)

ee

endo-syn -103 123

75 (S)[65 (S)]

endo-syn -172 859

81 (R)[64 (R)]

endo-anti -81 03 75 (S)[65 (S)]


75 (S)[65 (S)] exo-syn -155 48

81 (R)[64 (R)]

exo-anti -106 669

75 (S)[65 (S)]

exo-anti -153 35

81 (R)[64 (R)]


71

Conclusions




72





SS

Cl

Ti

Cl

O O

MeCN NCMe

OO

Np

Np

Np

Np Et OBn

O O

Me

Et OBn

O O

MeF

N N F

Cl

R

O

Ti

O

O O

OBnO

Me Et

O

OONp

Np

Np

Np

OBn

Et

Me++

Nandash

C6H6 rt 80-90


11


OTiO

OOO

O

R

O

O ONp

NpNp

O

R

R

R

OTiO

OOO

R

O

O

O ONp

NpNp

R

OR

R

OTiO

OOO

R

O

O

O ONp

NpNp

O

R

RR

TiOO

O ONp

NpNp

O

OO

R

R

OO

O

R

R

TiOO

O ONp

NpNp

O

OR

OOO

R

O

TiOO

O ONp

NpNp

O

OR

OOO

O

R

R

RR R








12



(Face-on Re)


(Edge-on Re)


(Face-on Si)


(Edge-on Si)

13


Cl

Ti

O

OOO

O

Me

MeCN

OO

Np

Np

Np




14


O

Ti

O

OOO

OBnO

OO

Np

NpNp

BnO




15



Me O

O O

Me HDF

RR Cl

Ti

Cl

OO

THFTHF

OO

Np

Np

Np

Np

R OR

O O

Me

Cl

Ti

O

OOO

OR

MeR

THF

OO

Np

Np

Np

Np

F

R OR

O O

MeF

S

Cl

Ti

O

OOO

OR

MeR

THF

OO

Np

Np

Np

Np

ndash H+


+

+

Cl

Ti

O

OOO

OR

MeR

THF

OO

Np

Np

Np

HD

HD

N FPhSO2

PhSO2




16






17




ClTi

O

OOO

OR

MeR

MeCN

OO

Np

Np

NpNp

NN

F

Cl

N NCl

ClTi

O

OOO

OR

MeR

MeCN

OO

Np

Np

NpNp

ClTi

O

OOO

OR

MeR

MeCN

OO

Np

NpNp

Np

F

N N FCl

++

+

+

SET


+

18


LUMO of [F-TEDA]2+


SOMO of [F-TEDA]+



HOMO

of enolato complex

ndash endash

B3LYP6-31G level

19


SET

R

ORO

O

E ERn

Rm


-

R

ORO

O

ERn

+ RmEndash

O O

MeMe

O N

HMe

Me

ICl

MeS

Me

SMe

N

O

O

Cl

SCl


20




R1 OR3

O O

R2

R1 OR3

O O

R2SPh

R1 OR3

O O

R2F

R1 OR3

O O

R2Cl

R1 OR3

O O

FCl

R1 OR3

O O

R2HO

NCS

Selectfluor


N SO2PhO2N

H

O

RR Cl

Ti

Cl

OO

NCMeMeCN

OO

Np

Np

Np

Np



up to 88 ee




21




22






Step 12 Step 21



23








Josiphos

Pigiphos

Fe

NMe2

MeFe PPh2

NMe2

Me

Fe PPh2

PCy2

Me

PFe PPh2

Fe

Ph2PUgis amine

24




NMe2

MePAr2

R1 R3

OO

R2

H2NNH2

NNH

R3R2

R1

Fe Fe

NMe

NR3

R2

R1

PAr2


AcOH 70-90 degC

80-90 yield

+

25

Ph2PCy2P

Ph2P

PCy2

Ph2PCy2P

Ph2P

Cy2P

PPh2PCy2

Ph2P

PCy2

Si

O

O

HN

O

NH

Si

Si

O

OHN

O

HN

Si

NP N P

NP

NP Si

O

OHN

ONH

Si

Si

OO

HNO NH

Si

Si

O

ONH

O

HN

Si

Si

O

ONH

ONH Si

SiO

ONH

OHN

Si

Si

OO

NH O

HN

Si

PPh2Cy2P

Ph2PCy2P

PPh2

PCy2

PPh2PCy2

Ph2PPCy2

PPh2

Cy2P

PPh2PCy2

PPh2

PCy2

Ph2P

Cy2P

Fe

PPh2Cy2P

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe




26



NH3C

CH3

OCH3

CH3OCl

H

P

MeFe

PPh2


2

Ir

S

NHHN

O

H H

P(t-Bu)2

MeFe

PPh2

COOH

(+)-Biotin(LONZA)

Rh

Sitagliptin(Merck)

Rh

F

FF

NN

NN

ONH2

CF3

PtBu2

MeFe P(4-F3CPh)2

27



H NN

ONHO

O

H NN

ONHO


SC=2000


96 ee

P(t-Bu)2

MeFe PPh2

N NN

OH

O

NH

ONH OH



28




P(t-Bu)2

MeFe PPh2

O

HOOCHN

S

F

O O

O

HOOCHN

S

F

O O

RuCl2(P-P)LnNEt3

H2 EtOH

O

HN

S

F

O O

O

HOHNP-P =

97 ee

29



Up to 97 ee

F

FF

NN

NN

ONH2

CF3



P(t-Bu)2

MeFe

P(t-Bu)2Me

Fe P CF32

PPh2

R OMe

NH2 O

R OMe


R NHPh

NH2 O

R NHPh

NH2 O

H2

Rh Josiphos ligand

H2

30











31










32



33

$

amp$

$

$

($

$$ amp$ )$ $ $ $ $ $

$

amp()+-


ampamp2824+

5lt=-amp)gt+gt2)42






34




α1=+9degα2=-21deg




35

Pd

L1

L2R

R

Pd

L1

L2

R

R

Nu Nu



36



X-rayX-ray

PhPh FeP

NNPd Ph

Ph


+

Ph

FeP

NNPd

Ph

Ph

Ph


+

PhPh FeP

NN

Pd Ph

Ph

+



Ph Ph

OCOR

NH2

Ph Ph


40 degC THF


N

Me

N

Fe

PPh2R

37



Ph

FeP

NNPd

Ph

a) R-product



NuNu

a)

b)

+

RS




PN

PdP N

PdP N

+ +


tc = 2 kcalmol

(Ab initio studies)

38

NH

NPd

PH3

NH3


NPd

PH3


NH

NPd

PH3

NH3

50 kJmol

36 kJmol

NH3+

41 kJmol

NH3+

+



PdP N

PdP N

PdP N

+

+ +


tc = 8 kJmol


ct = 29 kJmol


for C out of plane



40

PhPh Fe

P

NNPd

Ph

Ph

Ph

Ph

FeP

NNPd

Ph

Ph

exo-syn-anti (71)

+

exo-syn-syn (29)

+

S R



41

PhFe

P

NN

Pd


+

Ph




42

Ph

Ph

PdP N

Ph

Ph

P NPd

Nu

Nu




43




PMe

NN

Ph

Ph

PhPh

PdNN

MePd

FeFeP

Ph

Ph

Ph

Ph

Ph Ph

NHCH2Ph

(S)

Ph Ph

OCOOEtNu-Nu-


950 ee resp 945 ee

rac

44






Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

Fe

N CN

PPh2

Me

Fe

N NC

PPh2

MePdR

R+

PdR

R+

X-ray

45



Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

PdR

R+

PdR

R+

Fe

N CN

PPh2

Me Pd

NHR2R

RFe

N CN

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

Fe

N NC

PPh2

Me Pd

NHR2R

RFe

N NC

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

dr 8515exoendo 8218

46














47


Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



Ph Ph

OCOOEt

Ph Ph

N



NH

Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



48

N

Me

N

Fe

PPh2

Ph Ph

OCO2Et

Ph Ph

NHCH2Ph

[Pd(dba)2 ]+ Ligand





991 (220)

67 (11)

33 (2)

987 (153)

gt995 (gt400)



3 mol Pd-catalyst

PF6- Selectivity

Killer




49

Ph

Ph

P

NPd

+

endo-syn-syn

+

exo-syn-syn

Ph

PhP

NPd

Ph Ph

OCOOEt

Ph Ph



Slow with PF6-

(tight ion pairs )

Fast with F-

(Coordination)

R-Product S-Product

more stable


S R


50










51

E N Jacobsen et al



NN

OMn

OCl

X X

HHX = OMe 96 ee

X = NO2 22 ee

52




MeO MeO

CN

OOOPh

OPhOPAr2

OAr2P CF3F3C MeMe

HCN [Ni(COD)2] L

Ar =

91 eeL

16 ee

53





OCO O

++

nn2 3

4

1


Δ

54

([α]D=-450)




Polymer)50 220 370 1800


PCy2Me

Fe P

CF3

CF32

PCy2Me

Fe P

OMe

OMe2

PCy2Me

Fe P

H

H2

PCy2Me

Fe P

CH3

CH32

55


Markus Baumann


NMeN

Fe

Me

Me

Me

P

O+ PhOTf



O Ph O Ph O

Ph

+ +

2

Rn

Rn=(m-CF3)2

Rn=(m-SiMe3)2

Rn=(p-OMe)

Rn=(p-CF3)

1 (34ee)

8 (62ee)

1 (46ee)

1 (10ee)

94 (88ee)

90 (95ee)

97 (96ee)

96 (95ee)

5

2

2

3

56



NMeN

Fe

PMe Me

F3C

F3CNMeN

Fe

PMe Me

CF3

F3CF3C

F3C

NMeN

Fe

PF3C CF3

MeO

MeO

NMeN

Fe

PMe Me

MeO

MeO

NMeN

Fe

PF3C CF3

NMeN

Fe

PMe Me

NMeN

Fe

PMe Me

Me2N

Me2NNMeN

Fe

PF3C CF3

F3C

F3C

95 ee985 ee

5 ee72 ee

33 ee

98 ee90 ee

40 ee

the worst

and the best

57





NMeN

Fe

Me

Me

Me

PPh2


2) Oxidative Workup

OH

NMeN

Fe PPh2

NMeN

Fe PPh2

Me

39ee 76ee 99ee

Catalytic activity

NMeN

Fe

MeO

OMe

OMe

PPh2

NMeN

Fe

Me

Me

Me

P

CF3

CF3

2

82ee 91ee

58


X

Fe PPh2

N N

Mes

Me

X

1) cat PdCl2(L)

2) Oxidation


= L

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=078rsup2=0996

NMe₂

OMe

Me

ClH


Fe P X

N N

Mes

Me

1) cat PdCl2(L)

2) Oxidation


2

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=014rsup2=0986

NMe₂OMe

Me HCl


59



Fe P X

N N

Mes

Me

OH1) cat PdCl2(L)

2) Oxidation


2

60



X

Fe PPh2

N N

Mes

Me

X

OH1) cat PdCl2(L)

2) Oxidation

= L

61


PdN

P

Cl

Cl

PdN

P H

SiCl3

R

PdN

P

R

SiCl3

N

PdP

HCl3Si

N

Pd

P

Cl3Si

R

R





Unclear formation

σp

σp+


62


TK Woo

HH P

PdSiCl3SiCl3

NNH H

HH

HH P

PdSiCl3SiCl3

NNH H

FeP

PdSiCl3SiCl3

NN

FeP

PdSiCl3SiCl3

NN

HH P

PdSiCl3SiCl3

NNH H

HH P

PdSiCl3SiCl3

NN

H3CH

HH

H

Model 1

Model 2


63






PPd

H

SiCl3NN

HH

PPd

HSiCl3

NN

HH

PPd

HSiCl3

NN

HH

PPd

SiCl3NN

HH PPd

SiCl3NN

HH

1900

22

-02

-83

141

52

PPd

SiCl3NN

HH

PPd

Cl3SiNN

HH

64


endoendo-syn

PPdH

SiCl3NN

Fe

PPd HSiCl3NN

FeFe P

Pd

SiCl3NN

PPd HSiCl3NN

Fe

Cl3Si

PPd

SiCl3N

Fe

N

PPd

Cl3SiNN

Fe

PPdH

SiCl3NN

Fe

PPd

NN

Fe

Cl3Si

R

-35

09

TS1

TS2

-205

+-103

+styrene

00

42+48

61

Dagger Dagger


65





FeP

PdH

SiCl3NN

PPd

HSiCl3

NN

Fe


66


PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPd

H

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPdSiCl3NN

Fe

PPd

SiCl3NN

Fe

48

00

1609

51

-103

-113



endo-syn

exo-synendo

exo


kcalmol

67



endo-syn

exo-syn

NMe2

PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

NMe2

PPd

SiCl3NN

Fe

NMe2

PPdH

SiCl3NN

Fe

Me2N

PPd

SiCl3NN

Fe

PPdSiCl3

NN

Fe

NMe2

PPd

SiCl3NN

Fe

Me2N

48

00

08

03

16

-172

-155

exo

endo


68


DD

D

D5

HndashSiCl3 [PdL]

DD

D

D5

HO H DD

H

D5

HO H DH

H

D5

HO H DD

D

D5

HO D

oxid workup

+ + +


MeD1

MeD2

13C-1H-HZQCNMR

MeD2

MeD11 equivsilane

5 equivsilane

EI-MS


69





70


Energy(kcalmol)

(at rt)


(kcalmol)

(at rt)

ee

endo-syn -103 123

75 (S)[65 (S)]

endo-syn -172 859

81 (R)[64 (R)]

endo-anti -81 03 75 (S)[65 (S)]


75 (S)[65 (S)] exo-syn -155 48

81 (R)[64 (R)]

exo-anti -106 669

75 (S)[65 (S)]

exo-anti -153 35

81 (R)[64 (R)]


71

Conclusions




72


OTiO

OOO

O

R

O

O ONp

NpNp

O

R

R

R

OTiO

OOO

R

O

O

O ONp

NpNp

R

OR

R

OTiO

OOO

R

O

O

O ONp

NpNp

O

R

RR

TiOO

O ONp

NpNp

O

OO

R

R

OO

O

R

R

TiOO

O ONp

NpNp

O

OR

OOO

R

O

TiOO

O ONp

NpNp

O

OR

OOO

O

R

R

RR R








12



(Face-on Re)


(Edge-on Re)


(Face-on Si)


(Edge-on Si)

13


Cl

Ti

O

OOO

O

Me

MeCN

OO

Np

Np

Np




14


O

Ti

O

OOO

OBnO

OO

Np

NpNp

BnO




15



Me O

O O

Me HDF

RR Cl

Ti

Cl

OO

THFTHF

OO

Np

Np

Np

Np

R OR

O O

Me

Cl

Ti

O

OOO

OR

MeR

THF

OO

Np

Np

Np

Np

F

R OR

O O

MeF

S

Cl

Ti

O

OOO

OR

MeR

THF

OO

Np

Np

Np

Np

ndash H+


+

+

Cl

Ti

O

OOO

OR

MeR

THF

OO

Np

Np

Np

HD

HD

N FPhSO2

PhSO2




16






17




ClTi

O

OOO

OR

MeR

MeCN

OO

Np

Np

NpNp

NN

F

Cl

N NCl

ClTi

O

OOO

OR

MeR

MeCN

OO

Np

Np

NpNp

ClTi

O

OOO

OR

MeR

MeCN

OO

Np

NpNp

Np

F

N N FCl

++

+

+

SET


+

18


LUMO of [F-TEDA]2+


SOMO of [F-TEDA]+



HOMO

of enolato complex

ndash endash

B3LYP6-31G level

19


SET

R

ORO

O

E ERn

Rm


-

R

ORO

O

ERn

+ RmEndash

O O

MeMe

O N

HMe

Me

ICl

MeS

Me

SMe

N

O

O

Cl

SCl


20




R1 OR3

O O

R2

R1 OR3

O O

R2SPh

R1 OR3

O O

R2F

R1 OR3

O O

R2Cl

R1 OR3

O O

FCl

R1 OR3

O O

R2HO

NCS

Selectfluor


N SO2PhO2N

H

O

RR Cl

Ti

Cl

OO

NCMeMeCN

OO

Np

Np

Np

Np



up to 88 ee




21




22






Step 12 Step 21



23








Josiphos

Pigiphos

Fe

NMe2

MeFe PPh2

NMe2

Me

Fe PPh2

PCy2

Me

PFe PPh2

Fe

Ph2PUgis amine

24




NMe2

MePAr2

R1 R3

OO

R2

H2NNH2

NNH

R3R2

R1

Fe Fe

NMe

NR3

R2

R1

PAr2


AcOH 70-90 degC

80-90 yield

+

25

Ph2PCy2P

Ph2P

PCy2

Ph2PCy2P

Ph2P

Cy2P

PPh2PCy2

Ph2P

PCy2

Si

O

O

HN

O

NH

Si

Si

O

OHN

O

HN

Si

NP N P

NP

NP Si

O

OHN

ONH

Si

Si

OO

HNO NH

Si

Si

O

ONH

O

HN

Si

Si

O

ONH

ONH Si

SiO

ONH

OHN

Si

Si

OO

NH O

HN

Si

PPh2Cy2P

Ph2PCy2P

PPh2

PCy2

PPh2PCy2

Ph2PPCy2

PPh2

Cy2P

PPh2PCy2

PPh2

PCy2

Ph2P

Cy2P

Fe

PPh2Cy2P

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe




26



NH3C

CH3

OCH3

CH3OCl

H

P

MeFe

PPh2


2

Ir

S

NHHN

O

H H

P(t-Bu)2

MeFe

PPh2

COOH

(+)-Biotin(LONZA)

Rh

Sitagliptin(Merck)

Rh

F

FF

NN

NN

ONH2

CF3

PtBu2

MeFe P(4-F3CPh)2

27



H NN

ONHO

O

H NN

ONHO


SC=2000


96 ee

P(t-Bu)2

MeFe PPh2

N NN

OH

O

NH

ONH OH



28




P(t-Bu)2

MeFe PPh2

O

HOOCHN

S

F

O O

O

HOOCHN

S

F

O O

RuCl2(P-P)LnNEt3

H2 EtOH

O

HN

S

F

O O

O

HOHNP-P =

97 ee

29



Up to 97 ee

F

FF

NN

NN

ONH2

CF3



P(t-Bu)2

MeFe

P(t-Bu)2Me

Fe P CF32

PPh2

R OMe

NH2 O

R OMe


R NHPh

NH2 O

R NHPh

NH2 O

H2

Rh Josiphos ligand

H2

30











31










32



33

$

amp$

$

$

($

$$ amp$ )$ $ $ $ $ $

$

amp()+-


ampamp2824+

5lt=-amp)gt+gt2)42






34




α1=+9degα2=-21deg




35

Pd

L1

L2R

R

Pd

L1

L2

R

R

Nu Nu



36



X-rayX-ray

PhPh FeP

NNPd Ph

Ph


+

Ph

FeP

NNPd

Ph

Ph

Ph


+

PhPh FeP

NN

Pd Ph

Ph

+



Ph Ph

OCOR

NH2

Ph Ph


40 degC THF


N

Me

N

Fe

PPh2R

37



Ph

FeP

NNPd

Ph

a) R-product



NuNu

a)

b)

+

RS




PN

PdP N

PdP N

+ +


tc = 2 kcalmol

(Ab initio studies)

38

NH

NPd

PH3

NH3


NPd

PH3


NH

NPd

PH3

NH3

50 kJmol

36 kJmol

NH3+

41 kJmol

NH3+

+



PdP N

PdP N

PdP N

+

+ +


tc = 8 kJmol


ct = 29 kJmol


for C out of plane



40

PhPh Fe

P

NNPd

Ph

Ph

Ph

Ph

FeP

NNPd

Ph

Ph

exo-syn-anti (71)

+

exo-syn-syn (29)

+

S R



41

PhFe

P

NN

Pd


+

Ph




42

Ph

Ph

PdP N

Ph

Ph

P NPd

Nu

Nu




43




PMe

NN

Ph

Ph

PhPh

PdNN

MePd

FeFeP

Ph

Ph

Ph

Ph

Ph Ph

NHCH2Ph

(S)

Ph Ph

OCOOEtNu-Nu-


950 ee resp 945 ee

rac

44






Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

Fe

N CN

PPh2

Me

Fe

N NC

PPh2

MePdR

R+

PdR

R+

X-ray

45



Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

PdR

R+

PdR

R+

Fe

N CN

PPh2

Me Pd

NHR2R

RFe

N CN

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

Fe

N NC

PPh2

Me Pd

NHR2R

RFe

N NC

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

dr 8515exoendo 8218

46














47


Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



Ph Ph

OCOOEt

Ph Ph

N



NH

Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



48

N

Me

N

Fe

PPh2

Ph Ph

OCO2Et

Ph Ph

NHCH2Ph

[Pd(dba)2 ]+ Ligand





991 (220)

67 (11)

33 (2)

987 (153)

gt995 (gt400)



3 mol Pd-catalyst

PF6- Selectivity

Killer




49

Ph

Ph

P

NPd

+

endo-syn-syn

+

exo-syn-syn

Ph

PhP

NPd

Ph Ph

OCOOEt

Ph Ph



Slow with PF6-

(tight ion pairs )

Fast with F-

(Coordination)

R-Product S-Product

more stable


S R


50










51

E N Jacobsen et al



NN

OMn

OCl

X X

HHX = OMe 96 ee

X = NO2 22 ee

52




MeO MeO

CN

OOOPh

OPhOPAr2

OAr2P CF3F3C MeMe

HCN [Ni(COD)2] L

Ar =

91 eeL

16 ee

53





OCO O

++

nn2 3

4

1


Δ

54

([α]D=-450)




Polymer)50 220 370 1800


PCy2Me

Fe P

CF3

CF32

PCy2Me

Fe P

OMe

OMe2

PCy2Me

Fe P

H

H2

PCy2Me

Fe P

CH3

CH32

55


Markus Baumann


NMeN

Fe

Me

Me

Me

P

O+ PhOTf



O Ph O Ph O

Ph

+ +

2

Rn

Rn=(m-CF3)2

Rn=(m-SiMe3)2

Rn=(p-OMe)

Rn=(p-CF3)

1 (34ee)

8 (62ee)

1 (46ee)

1 (10ee)

94 (88ee)

90 (95ee)

97 (96ee)

96 (95ee)

5

2

2

3

56



NMeN

Fe

PMe Me

F3C

F3CNMeN

Fe

PMe Me

CF3

F3CF3C

F3C

NMeN

Fe

PF3C CF3

MeO

MeO

NMeN

Fe

PMe Me

MeO

MeO

NMeN

Fe

PF3C CF3

NMeN

Fe

PMe Me

NMeN

Fe

PMe Me

Me2N

Me2NNMeN

Fe

PF3C CF3

F3C

F3C

95 ee985 ee

5 ee72 ee

33 ee

98 ee90 ee

40 ee

the worst

and the best

57





NMeN

Fe

Me

Me

Me

PPh2


2) Oxidative Workup

OH

NMeN

Fe PPh2

NMeN

Fe PPh2

Me

39ee 76ee 99ee

Catalytic activity

NMeN

Fe

MeO

OMe

OMe

PPh2

NMeN

Fe

Me

Me

Me

P

CF3

CF3

2

82ee 91ee

58


X

Fe PPh2

N N

Mes

Me

X

1) cat PdCl2(L)

2) Oxidation


= L

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=078rsup2=0996

NMe₂

OMe

Me

ClH


Fe P X

N N

Mes

Me

1) cat PdCl2(L)

2) Oxidation


2

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=014rsup2=0986

NMe₂OMe

Me HCl


59



Fe P X

N N

Mes

Me

OH1) cat PdCl2(L)

2) Oxidation


2

60



X

Fe PPh2

N N

Mes

Me

X

OH1) cat PdCl2(L)

2) Oxidation

= L

61


PdN

P

Cl

Cl

PdN

P H

SiCl3

R

PdN

P

R

SiCl3

N

PdP

HCl3Si

N

Pd

P

Cl3Si

R

R





Unclear formation

σp

σp+


62


TK Woo

HH P

PdSiCl3SiCl3

NNH H

HH

HH P

PdSiCl3SiCl3

NNH H

FeP

PdSiCl3SiCl3

NN

FeP

PdSiCl3SiCl3

NN

HH P

PdSiCl3SiCl3

NNH H

HH P

PdSiCl3SiCl3

NN

H3CH

HH

H

Model 1

Model 2


63






PPd

H

SiCl3NN

HH

PPd

HSiCl3

NN

HH

PPd

HSiCl3

NN

HH

PPd

SiCl3NN

HH PPd

SiCl3NN

HH

1900

22

-02

-83

141

52

PPd

SiCl3NN

HH

PPd

Cl3SiNN

HH

64


endoendo-syn

PPdH

SiCl3NN

Fe

PPd HSiCl3NN

FeFe P

Pd

SiCl3NN

PPd HSiCl3NN

Fe

Cl3Si

PPd

SiCl3N

Fe

N

PPd

Cl3SiNN

Fe

PPdH

SiCl3NN

Fe

PPd

NN

Fe

Cl3Si

R

-35

09

TS1

TS2

-205

+-103

+styrene

00

42+48

61

Dagger Dagger


65





FeP

PdH

SiCl3NN

PPd

HSiCl3

NN

Fe


66


PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPd

H

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPdSiCl3NN

Fe

PPd

SiCl3NN

Fe

48

00

1609

51

-103

-113



endo-syn

exo-synendo

exo


kcalmol

67



endo-syn

exo-syn

NMe2

PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

NMe2

PPd

SiCl3NN

Fe

NMe2

PPdH

SiCl3NN

Fe

Me2N

PPd

SiCl3NN

Fe

PPdSiCl3

NN

Fe

NMe2

PPd

SiCl3NN

Fe

Me2N

48

00

08

03

16

-172

-155

exo

endo


68


DD

D

D5

HndashSiCl3 [PdL]

DD

D

D5

HO H DD

H

D5

HO H DH

H

D5

HO H DD

D

D5

HO D

oxid workup

+ + +


MeD1

MeD2

13C-1H-HZQCNMR

MeD2

MeD11 equivsilane

5 equivsilane

EI-MS


69





70


Energy(kcalmol)

(at rt)


(kcalmol)

(at rt)

ee

endo-syn -103 123

75 (S)[65 (S)]

endo-syn -172 859

81 (R)[64 (R)]

endo-anti -81 03 75 (S)[65 (S)]


75 (S)[65 (S)] exo-syn -155 48

81 (R)[64 (R)]

exo-anti -106 669

75 (S)[65 (S)]

exo-anti -153 35

81 (R)[64 (R)]


71

Conclusions




72



(Face-on Re)


(Edge-on Re)


(Face-on Si)


(Edge-on Si)

13


Cl

Ti

O

OOO

O

Me

MeCN

OO

Np

Np

Np




14


O

Ti

O

OOO

OBnO

OO

Np

NpNp

BnO




15



Me O

O O

Me HDF

RR Cl

Ti

Cl

OO

THFTHF

OO

Np

Np

Np

Np

R OR

O O

Me

Cl

Ti

O

OOO

OR

MeR

THF

OO

Np

Np

Np

Np

F

R OR

O O

MeF

S

Cl

Ti

O

OOO

OR

MeR

THF

OO

Np

Np

Np

Np

ndash H+


+

+

Cl

Ti

O

OOO

OR

MeR

THF

OO

Np

Np

Np

HD

HD

N FPhSO2

PhSO2




16






17




ClTi

O

OOO

OR

MeR

MeCN

OO

Np

Np

NpNp

NN

F

Cl

N NCl

ClTi

O

OOO

OR

MeR

MeCN

OO

Np

Np

NpNp

ClTi

O

OOO

OR

MeR

MeCN

OO

Np

NpNp

Np

F

N N FCl

++

+

+

SET


+

18


LUMO of [F-TEDA]2+


SOMO of [F-TEDA]+



HOMO

of enolato complex

ndash endash

B3LYP6-31G level

19


SET

R

ORO

O

E ERn

Rm


-

R

ORO

O

ERn

+ RmEndash

O O

MeMe

O N

HMe

Me

ICl

MeS

Me

SMe

N

O

O

Cl

SCl


20




R1 OR3

O O

R2

R1 OR3

O O

R2SPh

R1 OR3

O O

R2F

R1 OR3

O O

R2Cl

R1 OR3

O O

FCl

R1 OR3

O O

R2HO

NCS

Selectfluor


N SO2PhO2N

H

O

RR Cl

Ti

Cl

OO

NCMeMeCN

OO

Np

Np

Np

Np



up to 88 ee




21




22






Step 12 Step 21



23








Josiphos

Pigiphos

Fe

NMe2

MeFe PPh2

NMe2

Me

Fe PPh2

PCy2

Me

PFe PPh2

Fe

Ph2PUgis amine

24




NMe2

MePAr2

R1 R3

OO

R2

H2NNH2

NNH

R3R2

R1

Fe Fe

NMe

NR3

R2

R1

PAr2


AcOH 70-90 degC

80-90 yield

+

25

Ph2PCy2P

Ph2P

PCy2

Ph2PCy2P

Ph2P

Cy2P

PPh2PCy2

Ph2P

PCy2

Si

O

O

HN

O

NH

Si

Si

O

OHN

O

HN

Si

NP N P

NP

NP Si

O

OHN

ONH

Si

Si

OO

HNO NH

Si

Si

O

ONH

O

HN

Si

Si

O

ONH

ONH Si

SiO

ONH

OHN

Si

Si

OO

NH O

HN

Si

PPh2Cy2P

Ph2PCy2P

PPh2

PCy2

PPh2PCy2

Ph2PPCy2

PPh2

Cy2P

PPh2PCy2

PPh2

PCy2

Ph2P

Cy2P

Fe

PPh2Cy2P

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe




26



NH3C

CH3

OCH3

CH3OCl

H

P

MeFe

PPh2


2

Ir

S

NHHN

O

H H

P(t-Bu)2

MeFe

PPh2

COOH

(+)-Biotin(LONZA)

Rh

Sitagliptin(Merck)

Rh

F

FF

NN

NN

ONH2

CF3

PtBu2

MeFe P(4-F3CPh)2

27



H NN

ONHO

O

H NN

ONHO


SC=2000


96 ee

P(t-Bu)2

MeFe PPh2

N NN

OH

O

NH

ONH OH



28




P(t-Bu)2

MeFe PPh2

O

HOOCHN

S

F

O O

O

HOOCHN

S

F

O O

RuCl2(P-P)LnNEt3

H2 EtOH

O

HN

S

F

O O

O

HOHNP-P =

97 ee

29



Up to 97 ee

F

FF

NN

NN

ONH2

CF3



P(t-Bu)2

MeFe

P(t-Bu)2Me

Fe P CF32

PPh2

R OMe

NH2 O

R OMe


R NHPh

NH2 O

R NHPh

NH2 O

H2

Rh Josiphos ligand

H2

30











31










32



33

$

amp$

$

$

($

$$ amp$ )$ $ $ $ $ $

$

amp()+-


ampamp2824+

5lt=-amp)gt+gt2)42






34




α1=+9degα2=-21deg




35

Pd

L1

L2R

R

Pd

L1

L2

R

R

Nu Nu



36



X-rayX-ray

PhPh FeP

NNPd Ph

Ph


+

Ph

FeP

NNPd

Ph

Ph

Ph


+

PhPh FeP

NN

Pd Ph

Ph

+



Ph Ph

OCOR

NH2

Ph Ph


40 degC THF


N

Me

N

Fe

PPh2R

37



Ph

FeP

NNPd

Ph

a) R-product



NuNu

a)

b)

+

RS




PN

PdP N

PdP N

+ +


tc = 2 kcalmol

(Ab initio studies)

38

NH

NPd

PH3

NH3


NPd

PH3


NH

NPd

PH3

NH3

50 kJmol

36 kJmol

NH3+

41 kJmol

NH3+

+



PdP N

PdP N

PdP N

+

+ +


tc = 8 kJmol


ct = 29 kJmol


for C out of plane



40

PhPh Fe

P

NNPd

Ph

Ph

Ph

Ph

FeP

NNPd

Ph

Ph

exo-syn-anti (71)

+

exo-syn-syn (29)

+

S R



41

PhFe

P

NN

Pd


+

Ph




42

Ph

Ph

PdP N

Ph

Ph

P NPd

Nu

Nu




43




PMe

NN

Ph

Ph

PhPh

PdNN

MePd

FeFeP

Ph

Ph

Ph

Ph

Ph Ph

NHCH2Ph

(S)

Ph Ph

OCOOEtNu-Nu-


950 ee resp 945 ee

rac

44






Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

Fe

N CN

PPh2

Me

Fe

N NC

PPh2

MePdR

R+

PdR

R+

X-ray

45



Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

PdR

R+

PdR

R+

Fe

N CN

PPh2

Me Pd

NHR2R

RFe

N CN

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

Fe

N NC

PPh2

Me Pd

NHR2R

RFe

N NC

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

dr 8515exoendo 8218

46














47


Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



Ph Ph

OCOOEt

Ph Ph

N



NH

Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



48

N

Me

N

Fe

PPh2

Ph Ph

OCO2Et

Ph Ph

NHCH2Ph

[Pd(dba)2 ]+ Ligand





991 (220)

67 (11)

33 (2)

987 (153)

gt995 (gt400)



3 mol Pd-catalyst

PF6- Selectivity

Killer




49

Ph

Ph

P

NPd

+

endo-syn-syn

+

exo-syn-syn

Ph

PhP

NPd

Ph Ph

OCOOEt

Ph Ph



Slow with PF6-

(tight ion pairs )

Fast with F-

(Coordination)

R-Product S-Product

more stable


S R


50










51

E N Jacobsen et al



NN

OMn

OCl

X X

HHX = OMe 96 ee

X = NO2 22 ee

52




MeO MeO

CN

OOOPh

OPhOPAr2

OAr2P CF3F3C MeMe

HCN [Ni(COD)2] L

Ar =

91 eeL

16 ee

53





OCO O

++

nn2 3

4

1


Δ

54

([α]D=-450)




Polymer)50 220 370 1800


PCy2Me

Fe P

CF3

CF32

PCy2Me

Fe P

OMe

OMe2

PCy2Me

Fe P

H

H2

PCy2Me

Fe P

CH3

CH32

55


Markus Baumann


NMeN

Fe

Me

Me

Me

P

O+ PhOTf



O Ph O Ph O

Ph

+ +

2

Rn

Rn=(m-CF3)2

Rn=(m-SiMe3)2

Rn=(p-OMe)

Rn=(p-CF3)

1 (34ee)

8 (62ee)

1 (46ee)

1 (10ee)

94 (88ee)

90 (95ee)

97 (96ee)

96 (95ee)

5

2

2

3

56



NMeN

Fe

PMe Me

F3C

F3CNMeN

Fe

PMe Me

CF3

F3CF3C

F3C

NMeN

Fe

PF3C CF3

MeO

MeO

NMeN

Fe

PMe Me

MeO

MeO

NMeN

Fe

PF3C CF3

NMeN

Fe

PMe Me

NMeN

Fe

PMe Me

Me2N

Me2NNMeN

Fe

PF3C CF3

F3C

F3C

95 ee985 ee

5 ee72 ee

33 ee

98 ee90 ee

40 ee

the worst

and the best

57





NMeN

Fe

Me

Me

Me

PPh2


2) Oxidative Workup

OH

NMeN

Fe PPh2

NMeN

Fe PPh2

Me

39ee 76ee 99ee

Catalytic activity

NMeN

Fe

MeO

OMe

OMe

PPh2

NMeN

Fe

Me

Me

Me

P

CF3

CF3

2

82ee 91ee

58


X

Fe PPh2

N N

Mes

Me

X

1) cat PdCl2(L)

2) Oxidation


= L

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=078rsup2=0996

NMe₂

OMe

Me

ClH


Fe P X

N N

Mes

Me

1) cat PdCl2(L)

2) Oxidation


2

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=014rsup2=0986

NMe₂OMe

Me HCl


59



Fe P X

N N

Mes

Me

OH1) cat PdCl2(L)

2) Oxidation


2

60



X

Fe PPh2

N N

Mes

Me

X

OH1) cat PdCl2(L)

2) Oxidation

= L

61


PdN

P

Cl

Cl

PdN

P H

SiCl3

R

PdN

P

R

SiCl3

N

PdP

HCl3Si

N

Pd

P

Cl3Si

R

R





Unclear formation

σp

σp+


62


TK Woo

HH P

PdSiCl3SiCl3

NNH H

HH

HH P

PdSiCl3SiCl3

NNH H

FeP

PdSiCl3SiCl3

NN

FeP

PdSiCl3SiCl3

NN

HH P

PdSiCl3SiCl3

NNH H

HH P

PdSiCl3SiCl3

NN

H3CH

HH

H

Model 1

Model 2


63






PPd

H

SiCl3NN

HH

PPd

HSiCl3

NN

HH

PPd

HSiCl3

NN

HH

PPd

SiCl3NN

HH PPd

SiCl3NN

HH

1900

22

-02

-83

141

52

PPd

SiCl3NN

HH

PPd

Cl3SiNN

HH

64


endoendo-syn

PPdH

SiCl3NN

Fe

PPd HSiCl3NN

FeFe P

Pd

SiCl3NN

PPd HSiCl3NN

Fe

Cl3Si

PPd

SiCl3N

Fe

N

PPd

Cl3SiNN

Fe

PPdH

SiCl3NN

Fe

PPd

NN

Fe

Cl3Si

R

-35

09

TS1

TS2

-205

+-103

+styrene

00

42+48

61

Dagger Dagger


65





FeP

PdH

SiCl3NN

PPd

HSiCl3

NN

Fe


66


PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPd

H

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPdSiCl3NN

Fe

PPd

SiCl3NN

Fe

48

00

1609

51

-103

-113



endo-syn

exo-synendo

exo


kcalmol

67



endo-syn

exo-syn

NMe2

PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

NMe2

PPd

SiCl3NN

Fe

NMe2

PPdH

SiCl3NN

Fe

Me2N

PPd

SiCl3NN

Fe

PPdSiCl3

NN

Fe

NMe2

PPd

SiCl3NN

Fe

Me2N

48

00

08

03

16

-172

-155

exo

endo


68


DD

D

D5

HndashSiCl3 [PdL]

DD

D

D5

HO H DD

H

D5

HO H DH

H

D5

HO H DD

D

D5

HO D

oxid workup

+ + +


MeD1

MeD2

13C-1H-HZQCNMR

MeD2

MeD11 equivsilane

5 equivsilane

EI-MS


69





70


Energy(kcalmol)

(at rt)


(kcalmol)

(at rt)

ee

endo-syn -103 123

75 (S)[65 (S)]

endo-syn -172 859

81 (R)[64 (R)]

endo-anti -81 03 75 (S)[65 (S)]


75 (S)[65 (S)] exo-syn -155 48

81 (R)[64 (R)]

exo-anti -106 669

75 (S)[65 (S)]

exo-anti -153 35

81 (R)[64 (R)]


71

Conclusions




72


Cl

Ti

O

OOO

O

Me

MeCN

OO

Np

Np

Np




14


O

Ti

O

OOO

OBnO

OO

Np

NpNp

BnO




15



Me O

O O

Me HDF

RR Cl

Ti

Cl

OO

THFTHF

OO

Np

Np

Np

Np

R OR

O O

Me

Cl

Ti

O

OOO

OR

MeR

THF

OO

Np

Np

Np

Np

F

R OR

O O

MeF

S

Cl

Ti

O

OOO

OR

MeR

THF

OO

Np

Np

Np

Np

ndash H+


+

+

Cl

Ti

O

OOO

OR

MeR

THF

OO

Np

Np

Np

HD

HD

N FPhSO2

PhSO2




16






17




ClTi

O

OOO

OR

MeR

MeCN

OO

Np

Np

NpNp

NN

F

Cl

N NCl

ClTi

O

OOO

OR

MeR

MeCN

OO

Np

Np

NpNp

ClTi

O

OOO

OR

MeR

MeCN

OO

Np

NpNp

Np

F

N N FCl

++

+

+

SET


+

18


LUMO of [F-TEDA]2+


SOMO of [F-TEDA]+



HOMO

of enolato complex

ndash endash

B3LYP6-31G level

19


SET

R

ORO

O

E ERn

Rm


-

R

ORO

O

ERn

+ RmEndash

O O

MeMe

O N

HMe

Me

ICl

MeS

Me

SMe

N

O

O

Cl

SCl


20




R1 OR3

O O

R2

R1 OR3

O O

R2SPh

R1 OR3

O O

R2F

R1 OR3

O O

R2Cl

R1 OR3

O O

FCl

R1 OR3

O O

R2HO

NCS

Selectfluor


N SO2PhO2N

H

O

RR Cl

Ti

Cl

OO

NCMeMeCN

OO

Np

Np

Np

Np



up to 88 ee




21




22






Step 12 Step 21



23








Josiphos

Pigiphos

Fe

NMe2

MeFe PPh2

NMe2

Me

Fe PPh2

PCy2

Me

PFe PPh2

Fe

Ph2PUgis amine

24




NMe2

MePAr2

R1 R3

OO

R2

H2NNH2

NNH

R3R2

R1

Fe Fe

NMe

NR3

R2

R1

PAr2


AcOH 70-90 degC

80-90 yield

+

25

Ph2PCy2P

Ph2P

PCy2

Ph2PCy2P

Ph2P

Cy2P

PPh2PCy2

Ph2P

PCy2

Si

O

O

HN

O

NH

Si

Si

O

OHN

O

HN

Si

NP N P

NP

NP Si

O

OHN

ONH

Si

Si

OO

HNO NH

Si

Si

O

ONH

O

HN

Si

Si

O

ONH

ONH Si

SiO

ONH

OHN

Si

Si

OO

NH O

HN

Si

PPh2Cy2P

Ph2PCy2P

PPh2

PCy2

PPh2PCy2

Ph2PPCy2

PPh2

Cy2P

PPh2PCy2

PPh2

PCy2

Ph2P

Cy2P

Fe

PPh2Cy2P

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe




26



NH3C

CH3

OCH3

CH3OCl

H

P

MeFe

PPh2


2

Ir

S

NHHN

O

H H

P(t-Bu)2

MeFe

PPh2

COOH

(+)-Biotin(LONZA)

Rh

Sitagliptin(Merck)

Rh

F

FF

NN

NN

ONH2

CF3

PtBu2

MeFe P(4-F3CPh)2

27



H NN

ONHO

O

H NN

ONHO


SC=2000


96 ee

P(t-Bu)2

MeFe PPh2

N NN

OH

O

NH

ONH OH



28




P(t-Bu)2

MeFe PPh2

O

HOOCHN

S

F

O O

O

HOOCHN

S

F

O O

RuCl2(P-P)LnNEt3

H2 EtOH

O

HN

S

F

O O

O

HOHNP-P =

97 ee

29



Up to 97 ee

F

FF

NN

NN

ONH2

CF3



P(t-Bu)2

MeFe

P(t-Bu)2Me

Fe P CF32

PPh2

R OMe

NH2 O

R OMe


R NHPh

NH2 O

R NHPh

NH2 O

H2

Rh Josiphos ligand

H2

30











31










32



33

$

amp$

$

$

($

$$ amp$ )$ $ $ $ $ $

$

amp()+-


ampamp2824+

5lt=-amp)gt+gt2)42






34




α1=+9degα2=-21deg




35

Pd

L1

L2R

R

Pd

L1

L2

R

R

Nu Nu



36



X-rayX-ray

PhPh FeP

NNPd Ph

Ph


+

Ph

FeP

NNPd

Ph

Ph

Ph


+

PhPh FeP

NN

Pd Ph

Ph

+



Ph Ph

OCOR

NH2

Ph Ph


40 degC THF


N

Me

N

Fe

PPh2R

37



Ph

FeP

NNPd

Ph

a) R-product



NuNu

a)

b)

+

RS




PN

PdP N

PdP N

+ +


tc = 2 kcalmol

(Ab initio studies)

38

NH

NPd

PH3

NH3


NPd

PH3


NH

NPd

PH3

NH3

50 kJmol

36 kJmol

NH3+

41 kJmol

NH3+

+



PdP N

PdP N

PdP N

+

+ +


tc = 8 kJmol


ct = 29 kJmol


for C out of plane



40

PhPh Fe

P

NNPd

Ph

Ph

Ph

Ph

FeP

NNPd

Ph

Ph

exo-syn-anti (71)

+

exo-syn-syn (29)

+

S R



41

PhFe

P

NN

Pd


+

Ph




42

Ph

Ph

PdP N

Ph

Ph

P NPd

Nu

Nu




43




PMe

NN

Ph

Ph

PhPh

PdNN

MePd

FeFeP

Ph

Ph

Ph

Ph

Ph Ph

NHCH2Ph

(S)

Ph Ph

OCOOEtNu-Nu-


950 ee resp 945 ee

rac

44






Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

Fe

N CN

PPh2

Me

Fe

N NC

PPh2

MePdR

R+

PdR

R+

X-ray

45



Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

PdR

R+

PdR

R+

Fe

N CN

PPh2

Me Pd

NHR2R

RFe

N CN

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

Fe

N NC

PPh2

Me Pd

NHR2R

RFe

N NC

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

dr 8515exoendo 8218

46














47


Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



Ph Ph

OCOOEt

Ph Ph

N



NH

Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



48

N

Me

N

Fe

PPh2

Ph Ph

OCO2Et

Ph Ph

NHCH2Ph

[Pd(dba)2 ]+ Ligand





991 (220)

67 (11)

33 (2)

987 (153)

gt995 (gt400)



3 mol Pd-catalyst

PF6- Selectivity

Killer




49

Ph

Ph

P

NPd

+

endo-syn-syn

+

exo-syn-syn

Ph

PhP

NPd

Ph Ph

OCOOEt

Ph Ph



Slow with PF6-

(tight ion pairs )

Fast with F-

(Coordination)

R-Product S-Product

more stable


S R


50










51

E N Jacobsen et al



NN

OMn

OCl

X X

HHX = OMe 96 ee

X = NO2 22 ee

52




MeO MeO

CN

OOOPh

OPhOPAr2

OAr2P CF3F3C MeMe

HCN [Ni(COD)2] L

Ar =

91 eeL

16 ee

53





OCO O

++

nn2 3

4

1


Δ

54

([α]D=-450)




Polymer)50 220 370 1800


PCy2Me

Fe P

CF3

CF32

PCy2Me

Fe P

OMe

OMe2

PCy2Me

Fe P

H

H2

PCy2Me

Fe P

CH3

CH32

55


Markus Baumann


NMeN

Fe

Me

Me

Me

P

O+ PhOTf



O Ph O Ph O

Ph

+ +

2

Rn

Rn=(m-CF3)2

Rn=(m-SiMe3)2

Rn=(p-OMe)

Rn=(p-CF3)

1 (34ee)

8 (62ee)

1 (46ee)

1 (10ee)

94 (88ee)

90 (95ee)

97 (96ee)

96 (95ee)

5

2

2

3

56



NMeN

Fe

PMe Me

F3C

F3CNMeN

Fe

PMe Me

CF3

F3CF3C

F3C

NMeN

Fe

PF3C CF3

MeO

MeO

NMeN

Fe

PMe Me

MeO

MeO

NMeN

Fe

PF3C CF3

NMeN

Fe

PMe Me

NMeN

Fe

PMe Me

Me2N

Me2NNMeN

Fe

PF3C CF3

F3C

F3C

95 ee985 ee

5 ee72 ee

33 ee

98 ee90 ee

40 ee

the worst

and the best

57





NMeN

Fe

Me

Me

Me

PPh2


2) Oxidative Workup

OH

NMeN

Fe PPh2

NMeN

Fe PPh2

Me

39ee 76ee 99ee

Catalytic activity

NMeN

Fe

MeO

OMe

OMe

PPh2

NMeN

Fe

Me

Me

Me

P

CF3

CF3

2

82ee 91ee

58


X

Fe PPh2

N N

Mes

Me

X

1) cat PdCl2(L)

2) Oxidation


= L

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=078rsup2=0996

NMe₂

OMe

Me

ClH


Fe P X

N N

Mes

Me

1) cat PdCl2(L)

2) Oxidation


2

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=014rsup2=0986

NMe₂OMe

Me HCl


59



Fe P X

N N

Mes

Me

OH1) cat PdCl2(L)

2) Oxidation


2

60



X

Fe PPh2

N N

Mes

Me

X

OH1) cat PdCl2(L)

2) Oxidation

= L

61


PdN

P

Cl

Cl

PdN

P H

SiCl3

R

PdN

P

R

SiCl3

N

PdP

HCl3Si

N

Pd

P

Cl3Si

R

R





Unclear formation

σp

σp+


62


TK Woo

HH P

PdSiCl3SiCl3

NNH H

HH

HH P

PdSiCl3SiCl3

NNH H

FeP

PdSiCl3SiCl3

NN

FeP

PdSiCl3SiCl3

NN

HH P

PdSiCl3SiCl3

NNH H

HH P

PdSiCl3SiCl3

NN

H3CH

HH

H

Model 1

Model 2


63






PPd

H

SiCl3NN

HH

PPd

HSiCl3

NN

HH

PPd

HSiCl3

NN

HH

PPd

SiCl3NN

HH PPd

SiCl3NN

HH

1900

22

-02

-83

141

52

PPd

SiCl3NN

HH

PPd

Cl3SiNN

HH

64


endoendo-syn

PPdH

SiCl3NN

Fe

PPd HSiCl3NN

FeFe P

Pd

SiCl3NN

PPd HSiCl3NN

Fe

Cl3Si

PPd

SiCl3N

Fe

N

PPd

Cl3SiNN

Fe

PPdH

SiCl3NN

Fe

PPd

NN

Fe

Cl3Si

R

-35

09

TS1

TS2

-205

+-103

+styrene

00

42+48

61

Dagger Dagger


65





FeP

PdH

SiCl3NN

PPd

HSiCl3

NN

Fe


66


PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPd

H

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPdSiCl3NN

Fe

PPd

SiCl3NN

Fe

48

00

1609

51

-103

-113



endo-syn

exo-synendo

exo


kcalmol

67



endo-syn

exo-syn

NMe2

PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

NMe2

PPd

SiCl3NN

Fe

NMe2

PPdH

SiCl3NN

Fe

Me2N

PPd

SiCl3NN

Fe

PPdSiCl3

NN

Fe

NMe2

PPd

SiCl3NN

Fe

Me2N

48

00

08

03

16

-172

-155

exo

endo


68


DD

D

D5

HndashSiCl3 [PdL]

DD

D

D5

HO H DD

H

D5

HO H DH

H

D5

HO H DD

D

D5

HO D

oxid workup

+ + +


MeD1

MeD2

13C-1H-HZQCNMR

MeD2

MeD11 equivsilane

5 equivsilane

EI-MS


69





70


Energy(kcalmol)

(at rt)


(kcalmol)

(at rt)

ee

endo-syn -103 123

75 (S)[65 (S)]

endo-syn -172 859

81 (R)[64 (R)]

endo-anti -81 03 75 (S)[65 (S)]


75 (S)[65 (S)] exo-syn -155 48

81 (R)[64 (R)]

exo-anti -106 669

75 (S)[65 (S)]

exo-anti -153 35

81 (R)[64 (R)]


71

Conclusions




72


O

Ti

O

OOO

OBnO

OO

Np

NpNp

BnO




15



Me O

O O

Me HDF

RR Cl

Ti

Cl

OO

THFTHF

OO

Np

Np

Np

Np

R OR

O O

Me

Cl

Ti

O

OOO

OR

MeR

THF

OO

Np

Np

Np

Np

F

R OR

O O

MeF

S

Cl

Ti

O

OOO

OR

MeR

THF

OO

Np

Np

Np

Np

ndash H+


+

+

Cl

Ti

O

OOO

OR

MeR

THF

OO

Np

Np

Np

HD

HD

N FPhSO2

PhSO2




16






17




ClTi

O

OOO

OR

MeR

MeCN

OO

Np

Np

NpNp

NN

F

Cl

N NCl

ClTi

O

OOO

OR

MeR

MeCN

OO

Np

Np

NpNp

ClTi

O

OOO

OR

MeR

MeCN

OO

Np

NpNp

Np

F

N N FCl

++

+

+

SET


+

18


LUMO of [F-TEDA]2+


SOMO of [F-TEDA]+



HOMO

of enolato complex

ndash endash

B3LYP6-31G level

19


SET

R

ORO

O

E ERn

Rm


-

R

ORO

O

ERn

+ RmEndash

O O

MeMe

O N

HMe

Me

ICl

MeS

Me

SMe

N

O

O

Cl

SCl


20




R1 OR3

O O

R2

R1 OR3

O O

R2SPh

R1 OR3

O O

R2F

R1 OR3

O O

R2Cl

R1 OR3

O O

FCl

R1 OR3

O O

R2HO

NCS

Selectfluor


N SO2PhO2N

H

O

RR Cl

Ti

Cl

OO

NCMeMeCN

OO

Np

Np

Np

Np



up to 88 ee




21




22






Step 12 Step 21



23








Josiphos

Pigiphos

Fe

NMe2

MeFe PPh2

NMe2

Me

Fe PPh2

PCy2

Me

PFe PPh2

Fe

Ph2PUgis amine

24




NMe2

MePAr2

R1 R3

OO

R2

H2NNH2

NNH

R3R2

R1

Fe Fe

NMe

NR3

R2

R1

PAr2


AcOH 70-90 degC

80-90 yield

+

25

Ph2PCy2P

Ph2P

PCy2

Ph2PCy2P

Ph2P

Cy2P

PPh2PCy2

Ph2P

PCy2

Si

O

O

HN

O

NH

Si

Si

O

OHN

O

HN

Si

NP N P

NP

NP Si

O

OHN

ONH

Si

Si

OO

HNO NH

Si

Si

O

ONH

O

HN

Si

Si

O

ONH

ONH Si

SiO

ONH

OHN

Si

Si

OO

NH O

HN

Si

PPh2Cy2P

Ph2PCy2P

PPh2

PCy2

PPh2PCy2

Ph2PPCy2

PPh2

Cy2P

PPh2PCy2

PPh2

PCy2

Ph2P

Cy2P

Fe

PPh2Cy2P

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe




26



NH3C

CH3

OCH3

CH3OCl

H

P

MeFe

PPh2


2

Ir

S

NHHN

O

H H

P(t-Bu)2

MeFe

PPh2

COOH

(+)-Biotin(LONZA)

Rh

Sitagliptin(Merck)

Rh

F

FF

NN

NN

ONH2

CF3

PtBu2

MeFe P(4-F3CPh)2

27



H NN

ONHO

O

H NN

ONHO


SC=2000


96 ee

P(t-Bu)2

MeFe PPh2

N NN

OH

O

NH

ONH OH



28




P(t-Bu)2

MeFe PPh2

O

HOOCHN

S

F

O O

O

HOOCHN

S

F

O O

RuCl2(P-P)LnNEt3

H2 EtOH

O

HN

S

F

O O

O

HOHNP-P =

97 ee

29



Up to 97 ee

F

FF

NN

NN

ONH2

CF3



P(t-Bu)2

MeFe

P(t-Bu)2Me

Fe P CF32

PPh2

R OMe

NH2 O

R OMe


R NHPh

NH2 O

R NHPh

NH2 O

H2

Rh Josiphos ligand

H2

30











31










32



33

$

amp$

$

$

($

$$ amp$ )$ $ $ $ $ $

$

amp()+-


ampamp2824+

5lt=-amp)gt+gt2)42






34




α1=+9degα2=-21deg




35

Pd

L1

L2R

R

Pd

L1

L2

R

R

Nu Nu



36



X-rayX-ray

PhPh FeP

NNPd Ph

Ph


+

Ph

FeP

NNPd

Ph

Ph

Ph


+

PhPh FeP

NN

Pd Ph

Ph

+



Ph Ph

OCOR

NH2

Ph Ph


40 degC THF


N

Me

N

Fe

PPh2R

37



Ph

FeP

NNPd

Ph

a) R-product



NuNu

a)

b)

+

RS




PN

PdP N

PdP N

+ +


tc = 2 kcalmol

(Ab initio studies)

38

NH

NPd

PH3

NH3


NPd

PH3


NH

NPd

PH3

NH3

50 kJmol

36 kJmol

NH3+

41 kJmol

NH3+

+



PdP N

PdP N

PdP N

+

+ +


tc = 8 kJmol


ct = 29 kJmol


for C out of plane



40

PhPh Fe

P

NNPd

Ph

Ph

Ph

Ph

FeP

NNPd

Ph

Ph

exo-syn-anti (71)

+

exo-syn-syn (29)

+

S R



41

PhFe

P

NN

Pd


+

Ph




42

Ph

Ph

PdP N

Ph

Ph

P NPd

Nu

Nu




43




PMe

NN

Ph

Ph

PhPh

PdNN

MePd

FeFeP

Ph

Ph

Ph

Ph

Ph Ph

NHCH2Ph

(S)

Ph Ph

OCOOEtNu-Nu-


950 ee resp 945 ee

rac

44






Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

Fe

N CN

PPh2

Me

Fe

N NC

PPh2

MePdR

R+

PdR

R+

X-ray

45



Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

PdR

R+

PdR

R+

Fe

N CN

PPh2

Me Pd

NHR2R

RFe

N CN

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

Fe

N NC

PPh2

Me Pd

NHR2R

RFe

N NC

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

dr 8515exoendo 8218

46














47


Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



Ph Ph

OCOOEt

Ph Ph

N



NH

Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



48

N

Me

N

Fe

PPh2

Ph Ph

OCO2Et

Ph Ph

NHCH2Ph

[Pd(dba)2 ]+ Ligand





991 (220)

67 (11)

33 (2)

987 (153)

gt995 (gt400)



3 mol Pd-catalyst

PF6- Selectivity

Killer




49

Ph

Ph

P

NPd

+

endo-syn-syn

+

exo-syn-syn

Ph

PhP

NPd

Ph Ph

OCOOEt

Ph Ph



Slow with PF6-

(tight ion pairs )

Fast with F-

(Coordination)

R-Product S-Product

more stable


S R


50










51

E N Jacobsen et al



NN

OMn

OCl

X X

HHX = OMe 96 ee

X = NO2 22 ee

52




MeO MeO

CN

OOOPh

OPhOPAr2

OAr2P CF3F3C MeMe

HCN [Ni(COD)2] L

Ar =

91 eeL

16 ee

53





OCO O

++

nn2 3

4

1


Δ

54

([α]D=-450)




Polymer)50 220 370 1800


PCy2Me

Fe P

CF3

CF32

PCy2Me

Fe P

OMe

OMe2

PCy2Me

Fe P

H

H2

PCy2Me

Fe P

CH3

CH32

55


Markus Baumann


NMeN

Fe

Me

Me

Me

P

O+ PhOTf



O Ph O Ph O

Ph

+ +

2

Rn

Rn=(m-CF3)2

Rn=(m-SiMe3)2

Rn=(p-OMe)

Rn=(p-CF3)

1 (34ee)

8 (62ee)

1 (46ee)

1 (10ee)

94 (88ee)

90 (95ee)

97 (96ee)

96 (95ee)

5

2

2

3

56



NMeN

Fe

PMe Me

F3C

F3CNMeN

Fe

PMe Me

CF3

F3CF3C

F3C

NMeN

Fe

PF3C CF3

MeO

MeO

NMeN

Fe

PMe Me

MeO

MeO

NMeN

Fe

PF3C CF3

NMeN

Fe

PMe Me

NMeN

Fe

PMe Me

Me2N

Me2NNMeN

Fe

PF3C CF3

F3C

F3C

95 ee985 ee

5 ee72 ee

33 ee

98 ee90 ee

40 ee

the worst

and the best

57





NMeN

Fe

Me

Me

Me

PPh2


2) Oxidative Workup

OH

NMeN

Fe PPh2

NMeN

Fe PPh2

Me

39ee 76ee 99ee

Catalytic activity

NMeN

Fe

MeO

OMe

OMe

PPh2

NMeN

Fe

Me

Me

Me

P

CF3

CF3

2

82ee 91ee

58


X

Fe PPh2

N N

Mes

Me

X

1) cat PdCl2(L)

2) Oxidation


= L

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=078rsup2=0996

NMe₂

OMe

Me

ClH


Fe P X

N N

Mes

Me

1) cat PdCl2(L)

2) Oxidation


2

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=014rsup2=0986

NMe₂OMe

Me HCl


59



Fe P X

N N

Mes

Me

OH1) cat PdCl2(L)

2) Oxidation


2

60



X

Fe PPh2

N N

Mes

Me

X

OH1) cat PdCl2(L)

2) Oxidation

= L

61


PdN

P

Cl

Cl

PdN

P H

SiCl3

R

PdN

P

R

SiCl3

N

PdP

HCl3Si

N

Pd

P

Cl3Si

R

R





Unclear formation

σp

σp+


62


TK Woo

HH P

PdSiCl3SiCl3

NNH H

HH

HH P

PdSiCl3SiCl3

NNH H

FeP

PdSiCl3SiCl3

NN

FeP

PdSiCl3SiCl3

NN

HH P

PdSiCl3SiCl3

NNH H

HH P

PdSiCl3SiCl3

NN

H3CH

HH

H

Model 1

Model 2


63






PPd

H

SiCl3NN

HH

PPd

HSiCl3

NN

HH

PPd

HSiCl3

NN

HH

PPd

SiCl3NN

HH PPd

SiCl3NN

HH

1900

22

-02

-83

141

52

PPd

SiCl3NN

HH

PPd

Cl3SiNN

HH

64


endoendo-syn

PPdH

SiCl3NN

Fe

PPd HSiCl3NN

FeFe P

Pd

SiCl3NN

PPd HSiCl3NN

Fe

Cl3Si

PPd

SiCl3N

Fe

N

PPd

Cl3SiNN

Fe

PPdH

SiCl3NN

Fe

PPd

NN

Fe

Cl3Si

R

-35

09

TS1

TS2

-205

+-103

+styrene

00

42+48

61

Dagger Dagger


65





FeP

PdH

SiCl3NN

PPd

HSiCl3

NN

Fe


66


PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPd

H

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPdSiCl3NN

Fe

PPd

SiCl3NN

Fe

48

00

1609

51

-103

-113



endo-syn

exo-synendo

exo


kcalmol

67



endo-syn

exo-syn

NMe2

PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

NMe2

PPd

SiCl3NN

Fe

NMe2

PPdH

SiCl3NN

Fe

Me2N

PPd

SiCl3NN

Fe

PPdSiCl3

NN

Fe

NMe2

PPd

SiCl3NN

Fe

Me2N

48

00

08

03

16

-172

-155

exo

endo


68


DD

D

D5

HndashSiCl3 [PdL]

DD

D

D5

HO H DD

H

D5

HO H DH

H

D5

HO H DD

D

D5

HO D

oxid workup

+ + +


MeD1

MeD2

13C-1H-HZQCNMR

MeD2

MeD11 equivsilane

5 equivsilane

EI-MS


69





70


Energy(kcalmol)

(at rt)


(kcalmol)

(at rt)

ee

endo-syn -103 123

75 (S)[65 (S)]

endo-syn -172 859

81 (R)[64 (R)]

endo-anti -81 03 75 (S)[65 (S)]


75 (S)[65 (S)] exo-syn -155 48

81 (R)[64 (R)]

exo-anti -106 669

75 (S)[65 (S)]

exo-anti -153 35

81 (R)[64 (R)]


71

Conclusions




72



Me O

O O

Me HDF

RR Cl

Ti

Cl

OO

THFTHF

OO

Np

Np

Np

Np

R OR

O O

Me

Cl

Ti

O

OOO

OR

MeR

THF

OO

Np

Np

Np

Np

F

R OR

O O

MeF

S

Cl

Ti

O

OOO

OR

MeR

THF

OO

Np

Np

Np

Np

ndash H+


+

+

Cl

Ti

O

OOO

OR

MeR

THF

OO

Np

Np

Np

HD

HD

N FPhSO2

PhSO2




16






17




ClTi

O

OOO

OR

MeR

MeCN

OO

Np

Np

NpNp

NN

F

Cl

N NCl

ClTi

O

OOO

OR

MeR

MeCN

OO

Np

Np

NpNp

ClTi

O

OOO

OR

MeR

MeCN

OO

Np

NpNp

Np

F

N N FCl

++

+

+

SET


+

18


LUMO of [F-TEDA]2+


SOMO of [F-TEDA]+



HOMO

of enolato complex

ndash endash

B3LYP6-31G level

19


SET

R

ORO

O

E ERn

Rm


-

R

ORO

O

ERn

+ RmEndash

O O

MeMe

O N

HMe

Me

ICl

MeS

Me

SMe

N

O

O

Cl

SCl


20




R1 OR3

O O

R2

R1 OR3

O O

R2SPh

R1 OR3

O O

R2F

R1 OR3

O O

R2Cl

R1 OR3

O O

FCl

R1 OR3

O O

R2HO

NCS

Selectfluor


N SO2PhO2N

H

O

RR Cl

Ti

Cl

OO

NCMeMeCN

OO

Np

Np

Np

Np



up to 88 ee




21




22






Step 12 Step 21



23








Josiphos

Pigiphos

Fe

NMe2

MeFe PPh2

NMe2

Me

Fe PPh2

PCy2

Me

PFe PPh2

Fe

Ph2PUgis amine

24




NMe2

MePAr2

R1 R3

OO

R2

H2NNH2

NNH

R3R2

R1

Fe Fe

NMe

NR3

R2

R1

PAr2


AcOH 70-90 degC

80-90 yield

+

25

Ph2PCy2P

Ph2P

PCy2

Ph2PCy2P

Ph2P

Cy2P

PPh2PCy2

Ph2P

PCy2

Si

O

O

HN

O

NH

Si

Si

O

OHN

O

HN

Si

NP N P

NP

NP Si

O

OHN

ONH

Si

Si

OO

HNO NH

Si

Si

O

ONH

O

HN

Si

Si

O

ONH

ONH Si

SiO

ONH

OHN

Si

Si

OO

NH O

HN

Si

PPh2Cy2P

Ph2PCy2P

PPh2

PCy2

PPh2PCy2

Ph2PPCy2

PPh2

Cy2P

PPh2PCy2

PPh2

PCy2

Ph2P

Cy2P

Fe

PPh2Cy2P

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe




26



NH3C

CH3

OCH3

CH3OCl

H

P

MeFe

PPh2


2

Ir

S

NHHN

O

H H

P(t-Bu)2

MeFe

PPh2

COOH

(+)-Biotin(LONZA)

Rh

Sitagliptin(Merck)

Rh

F

FF

NN

NN

ONH2

CF3

PtBu2

MeFe P(4-F3CPh)2

27



H NN

ONHO

O

H NN

ONHO


SC=2000


96 ee

P(t-Bu)2

MeFe PPh2

N NN

OH

O

NH

ONH OH



28




P(t-Bu)2

MeFe PPh2

O

HOOCHN

S

F

O O

O

HOOCHN

S

F

O O

RuCl2(P-P)LnNEt3

H2 EtOH

O

HN

S

F

O O

O

HOHNP-P =

97 ee

29



Up to 97 ee

F

FF

NN

NN

ONH2

CF3



P(t-Bu)2

MeFe

P(t-Bu)2Me

Fe P CF32

PPh2

R OMe

NH2 O

R OMe


R NHPh

NH2 O

R NHPh

NH2 O

H2

Rh Josiphos ligand

H2

30











31










32



33

$

amp$

$

$

($

$$ amp$ )$ $ $ $ $ $

$

amp()+-


ampamp2824+

5lt=-amp)gt+gt2)42






34




α1=+9degα2=-21deg




35

Pd

L1

L2R

R

Pd

L1

L2

R

R

Nu Nu



36



X-rayX-ray

PhPh FeP

NNPd Ph

Ph


+

Ph

FeP

NNPd

Ph

Ph

Ph


+

PhPh FeP

NN

Pd Ph

Ph

+



Ph Ph

OCOR

NH2

Ph Ph


40 degC THF


N

Me

N

Fe

PPh2R

37



Ph

FeP

NNPd

Ph

a) R-product



NuNu

a)

b)

+

RS




PN

PdP N

PdP N

+ +


tc = 2 kcalmol

(Ab initio studies)

38

NH

NPd

PH3

NH3


NPd

PH3


NH

NPd

PH3

NH3

50 kJmol

36 kJmol

NH3+

41 kJmol

NH3+

+



PdP N

PdP N

PdP N

+

+ +


tc = 8 kJmol


ct = 29 kJmol


for C out of plane



40

PhPh Fe

P

NNPd

Ph

Ph

Ph

Ph

FeP

NNPd

Ph

Ph

exo-syn-anti (71)

+

exo-syn-syn (29)

+

S R



41

PhFe

P

NN

Pd


+

Ph




42

Ph

Ph

PdP N

Ph

Ph

P NPd

Nu

Nu




43




PMe

NN

Ph

Ph

PhPh

PdNN

MePd

FeFeP

Ph

Ph

Ph

Ph

Ph Ph

NHCH2Ph

(S)

Ph Ph

OCOOEtNu-Nu-


950 ee resp 945 ee

rac

44






Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

Fe

N CN

PPh2

Me

Fe

N NC

PPh2

MePdR

R+

PdR

R+

X-ray

45



Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

PdR

R+

PdR

R+

Fe

N CN

PPh2

Me Pd

NHR2R

RFe

N CN

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

Fe

N NC

PPh2

Me Pd

NHR2R

RFe

N NC

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

dr 8515exoendo 8218

46














47


Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



Ph Ph

OCOOEt

Ph Ph

N



NH

Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



48

N

Me

N

Fe

PPh2

Ph Ph

OCO2Et

Ph Ph

NHCH2Ph

[Pd(dba)2 ]+ Ligand





991 (220)

67 (11)

33 (2)

987 (153)

gt995 (gt400)



3 mol Pd-catalyst

PF6- Selectivity

Killer




49

Ph

Ph

P

NPd

+

endo-syn-syn

+

exo-syn-syn

Ph

PhP

NPd

Ph Ph

OCOOEt

Ph Ph



Slow with PF6-

(tight ion pairs )

Fast with F-

(Coordination)

R-Product S-Product

more stable


S R


50










51

E N Jacobsen et al



NN

OMn

OCl

X X

HHX = OMe 96 ee

X = NO2 22 ee

52




MeO MeO

CN

OOOPh

OPhOPAr2

OAr2P CF3F3C MeMe

HCN [Ni(COD)2] L

Ar =

91 eeL

16 ee

53





OCO O

++

nn2 3

4

1


Δ

54

([α]D=-450)




Polymer)50 220 370 1800


PCy2Me

Fe P

CF3

CF32

PCy2Me

Fe P

OMe

OMe2

PCy2Me

Fe P

H

H2

PCy2Me

Fe P

CH3

CH32

55


Markus Baumann


NMeN

Fe

Me

Me

Me

P

O+ PhOTf



O Ph O Ph O

Ph

+ +

2

Rn

Rn=(m-CF3)2

Rn=(m-SiMe3)2

Rn=(p-OMe)

Rn=(p-CF3)

1 (34ee)

8 (62ee)

1 (46ee)

1 (10ee)

94 (88ee)

90 (95ee)

97 (96ee)

96 (95ee)

5

2

2

3

56



NMeN

Fe

PMe Me

F3C

F3CNMeN

Fe

PMe Me

CF3

F3CF3C

F3C

NMeN

Fe

PF3C CF3

MeO

MeO

NMeN

Fe

PMe Me

MeO

MeO

NMeN

Fe

PF3C CF3

NMeN

Fe

PMe Me

NMeN

Fe

PMe Me

Me2N

Me2NNMeN

Fe

PF3C CF3

F3C

F3C

95 ee985 ee

5 ee72 ee

33 ee

98 ee90 ee

40 ee

the worst

and the best

57





NMeN

Fe

Me

Me

Me

PPh2


2) Oxidative Workup

OH

NMeN

Fe PPh2

NMeN

Fe PPh2

Me

39ee 76ee 99ee

Catalytic activity

NMeN

Fe

MeO

OMe

OMe

PPh2

NMeN

Fe

Me

Me

Me

P

CF3

CF3

2

82ee 91ee

58


X

Fe PPh2

N N

Mes

Me

X

1) cat PdCl2(L)

2) Oxidation


= L

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=078rsup2=0996

NMe₂

OMe

Me

ClH


Fe P X

N N

Mes

Me

1) cat PdCl2(L)

2) Oxidation


2

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=014rsup2=0986

NMe₂OMe

Me HCl


59



Fe P X

N N

Mes

Me

OH1) cat PdCl2(L)

2) Oxidation


2

60



X

Fe PPh2

N N

Mes

Me

X

OH1) cat PdCl2(L)

2) Oxidation

= L

61


PdN

P

Cl

Cl

PdN

P H

SiCl3

R

PdN

P

R

SiCl3

N

PdP

HCl3Si

N

Pd

P

Cl3Si

R

R





Unclear formation

σp

σp+


62


TK Woo

HH P

PdSiCl3SiCl3

NNH H

HH

HH P

PdSiCl3SiCl3

NNH H

FeP

PdSiCl3SiCl3

NN

FeP

PdSiCl3SiCl3

NN

HH P

PdSiCl3SiCl3

NNH H

HH P

PdSiCl3SiCl3

NN

H3CH

HH

H

Model 1

Model 2


63






PPd

H

SiCl3NN

HH

PPd

HSiCl3

NN

HH

PPd

HSiCl3

NN

HH

PPd

SiCl3NN

HH PPd

SiCl3NN

HH

1900

22

-02

-83

141

52

PPd

SiCl3NN

HH

PPd

Cl3SiNN

HH

64


endoendo-syn

PPdH

SiCl3NN

Fe

PPd HSiCl3NN

FeFe P

Pd

SiCl3NN

PPd HSiCl3NN

Fe

Cl3Si

PPd

SiCl3N

Fe

N

PPd

Cl3SiNN

Fe

PPdH

SiCl3NN

Fe

PPd

NN

Fe

Cl3Si

R

-35

09

TS1

TS2

-205

+-103

+styrene

00

42+48

61

Dagger Dagger


65





FeP

PdH

SiCl3NN

PPd

HSiCl3

NN

Fe


66


PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPd

H

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPdSiCl3NN

Fe

PPd

SiCl3NN

Fe

48

00

1609

51

-103

-113



endo-syn

exo-synendo

exo


kcalmol

67



endo-syn

exo-syn

NMe2

PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

NMe2

PPd

SiCl3NN

Fe

NMe2

PPdH

SiCl3NN

Fe

Me2N

PPd

SiCl3NN

Fe

PPdSiCl3

NN

Fe

NMe2

PPd

SiCl3NN

Fe

Me2N

48

00

08

03

16

-172

-155

exo

endo


68


DD

D

D5

HndashSiCl3 [PdL]

DD

D

D5

HO H DD

H

D5

HO H DH

H

D5

HO H DD

D

D5

HO D

oxid workup

+ + +


MeD1

MeD2

13C-1H-HZQCNMR

MeD2

MeD11 equivsilane

5 equivsilane

EI-MS


69





70


Energy(kcalmol)

(at rt)


(kcalmol)

(at rt)

ee

endo-syn -103 123

75 (S)[65 (S)]

endo-syn -172 859

81 (R)[64 (R)]

endo-anti -81 03 75 (S)[65 (S)]


75 (S)[65 (S)] exo-syn -155 48

81 (R)[64 (R)]

exo-anti -106 669

75 (S)[65 (S)]

exo-anti -153 35

81 (R)[64 (R)]


71

Conclusions




72






17




ClTi

O

OOO

OR

MeR

MeCN

OO

Np

Np

NpNp

NN

F

Cl

N NCl

ClTi

O

OOO

OR

MeR

MeCN

OO

Np

Np

NpNp

ClTi

O

OOO

OR

MeR

MeCN

OO

Np

NpNp

Np

F

N N FCl

++

+

+

SET


+

18


LUMO of [F-TEDA]2+


SOMO of [F-TEDA]+



HOMO

of enolato complex

ndash endash

B3LYP6-31G level

19


SET

R

ORO

O

E ERn

Rm


-

R

ORO

O

ERn

+ RmEndash

O O

MeMe

O N

HMe

Me

ICl

MeS

Me

SMe

N

O

O

Cl

SCl


20




R1 OR3

O O

R2

R1 OR3

O O

R2SPh

R1 OR3

O O

R2F

R1 OR3

O O

R2Cl

R1 OR3

O O

FCl

R1 OR3

O O

R2HO

NCS

Selectfluor


N SO2PhO2N

H

O

RR Cl

Ti

Cl

OO

NCMeMeCN

OO

Np

Np

Np

Np



up to 88 ee




21




22






Step 12 Step 21



23








Josiphos

Pigiphos

Fe

NMe2

MeFe PPh2

NMe2

Me

Fe PPh2

PCy2

Me

PFe PPh2

Fe

Ph2PUgis amine

24




NMe2

MePAr2

R1 R3

OO

R2

H2NNH2

NNH

R3R2

R1

Fe Fe

NMe

NR3

R2

R1

PAr2


AcOH 70-90 degC

80-90 yield

+

25

Ph2PCy2P

Ph2P

PCy2

Ph2PCy2P

Ph2P

Cy2P

PPh2PCy2

Ph2P

PCy2

Si

O

O

HN

O

NH

Si

Si

O

OHN

O

HN

Si

NP N P

NP

NP Si

O

OHN

ONH

Si

Si

OO

HNO NH

Si

Si

O

ONH

O

HN

Si

Si

O

ONH

ONH Si

SiO

ONH

OHN

Si

Si

OO

NH O

HN

Si

PPh2Cy2P

Ph2PCy2P

PPh2

PCy2

PPh2PCy2

Ph2PPCy2

PPh2

Cy2P

PPh2PCy2

PPh2

PCy2

Ph2P

Cy2P

Fe

PPh2Cy2P

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe




26



NH3C

CH3

OCH3

CH3OCl

H

P

MeFe

PPh2


2

Ir

S

NHHN

O

H H

P(t-Bu)2

MeFe

PPh2

COOH

(+)-Biotin(LONZA)

Rh

Sitagliptin(Merck)

Rh

F

FF

NN

NN

ONH2

CF3

PtBu2

MeFe P(4-F3CPh)2

27



H NN

ONHO

O

H NN

ONHO


SC=2000


96 ee

P(t-Bu)2

MeFe PPh2

N NN

OH

O

NH

ONH OH



28




P(t-Bu)2

MeFe PPh2

O

HOOCHN

S

F

O O

O

HOOCHN

S

F

O O

RuCl2(P-P)LnNEt3

H2 EtOH

O

HN

S

F

O O

O

HOHNP-P =

97 ee

29



Up to 97 ee

F

FF

NN

NN

ONH2

CF3



P(t-Bu)2

MeFe

P(t-Bu)2Me

Fe P CF32

PPh2

R OMe

NH2 O

R OMe


R NHPh

NH2 O

R NHPh

NH2 O

H2

Rh Josiphos ligand

H2

30











31










32



33

$

amp$

$

$

($

$$ amp$ )$ $ $ $ $ $

$

amp()+-


ampamp2824+

5lt=-amp)gt+gt2)42






34




α1=+9degα2=-21deg




35

Pd

L1

L2R

R

Pd

L1

L2

R

R

Nu Nu



36



X-rayX-ray

PhPh FeP

NNPd Ph

Ph


+

Ph

FeP

NNPd

Ph

Ph

Ph


+

PhPh FeP

NN

Pd Ph

Ph

+



Ph Ph

OCOR

NH2

Ph Ph


40 degC THF


N

Me

N

Fe

PPh2R

37



Ph

FeP

NNPd

Ph

a) R-product



NuNu

a)

b)

+

RS




PN

PdP N

PdP N

+ +


tc = 2 kcalmol

(Ab initio studies)

38

NH

NPd

PH3

NH3


NPd

PH3


NH

NPd

PH3

NH3

50 kJmol

36 kJmol

NH3+

41 kJmol

NH3+

+



PdP N

PdP N

PdP N

+

+ +


tc = 8 kJmol


ct = 29 kJmol


for C out of plane



40

PhPh Fe

P

NNPd

Ph

Ph

Ph

Ph

FeP

NNPd

Ph

Ph

exo-syn-anti (71)

+

exo-syn-syn (29)

+

S R



41

PhFe

P

NN

Pd


+

Ph




42

Ph

Ph

PdP N

Ph

Ph

P NPd

Nu

Nu




43




PMe

NN

Ph

Ph

PhPh

PdNN

MePd

FeFeP

Ph

Ph

Ph

Ph

Ph Ph

NHCH2Ph

(S)

Ph Ph

OCOOEtNu-Nu-


950 ee resp 945 ee

rac

44






Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

Fe

N CN

PPh2

Me

Fe

N NC

PPh2

MePdR

R+

PdR

R+

X-ray

45



Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

PdR

R+

PdR

R+

Fe

N CN

PPh2

Me Pd

NHR2R

RFe

N CN

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

Fe

N NC

PPh2

Me Pd

NHR2R

RFe

N NC

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

dr 8515exoendo 8218

46














47


Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



Ph Ph

OCOOEt

Ph Ph

N



NH

Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



48

N

Me

N

Fe

PPh2

Ph Ph

OCO2Et

Ph Ph

NHCH2Ph

[Pd(dba)2 ]+ Ligand





991 (220)

67 (11)

33 (2)

987 (153)

gt995 (gt400)



3 mol Pd-catalyst

PF6- Selectivity

Killer




49

Ph

Ph

P

NPd

+

endo-syn-syn

+

exo-syn-syn

Ph

PhP

NPd

Ph Ph

OCOOEt

Ph Ph



Slow with PF6-

(tight ion pairs )

Fast with F-

(Coordination)

R-Product S-Product

more stable


S R


50










51

E N Jacobsen et al



NN

OMn

OCl

X X

HHX = OMe 96 ee

X = NO2 22 ee

52




MeO MeO

CN

OOOPh

OPhOPAr2

OAr2P CF3F3C MeMe

HCN [Ni(COD)2] L

Ar =

91 eeL

16 ee

53





OCO O

++

nn2 3

4

1


Δ

54

([α]D=-450)




Polymer)50 220 370 1800


PCy2Me

Fe P

CF3

CF32

PCy2Me

Fe P

OMe

OMe2

PCy2Me

Fe P

H

H2

PCy2Me

Fe P

CH3

CH32

55


Markus Baumann


NMeN

Fe

Me

Me

Me

P

O+ PhOTf



O Ph O Ph O

Ph

+ +

2

Rn

Rn=(m-CF3)2

Rn=(m-SiMe3)2

Rn=(p-OMe)

Rn=(p-CF3)

1 (34ee)

8 (62ee)

1 (46ee)

1 (10ee)

94 (88ee)

90 (95ee)

97 (96ee)

96 (95ee)

5

2

2

3

56



NMeN

Fe

PMe Me

F3C

F3CNMeN

Fe

PMe Me

CF3

F3CF3C

F3C

NMeN

Fe

PF3C CF3

MeO

MeO

NMeN

Fe

PMe Me

MeO

MeO

NMeN

Fe

PF3C CF3

NMeN

Fe

PMe Me

NMeN

Fe

PMe Me

Me2N

Me2NNMeN

Fe

PF3C CF3

F3C

F3C

95 ee985 ee

5 ee72 ee

33 ee

98 ee90 ee

40 ee

the worst

and the best

57





NMeN

Fe

Me

Me

Me

PPh2


2) Oxidative Workup

OH

NMeN

Fe PPh2

NMeN

Fe PPh2

Me

39ee 76ee 99ee

Catalytic activity

NMeN

Fe

MeO

OMe

OMe

PPh2

NMeN

Fe

Me

Me

Me

P

CF3

CF3

2

82ee 91ee

58


X

Fe PPh2

N N

Mes

Me

X

1) cat PdCl2(L)

2) Oxidation


= L

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=078rsup2=0996

NMe₂

OMe

Me

ClH


Fe P X

N N

Mes

Me

1) cat PdCl2(L)

2) Oxidation


2

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=014rsup2=0986

NMe₂OMe

Me HCl


59



Fe P X

N N

Mes

Me

OH1) cat PdCl2(L)

2) Oxidation


2

60



X

Fe PPh2

N N

Mes

Me

X

OH1) cat PdCl2(L)

2) Oxidation

= L

61


PdN

P

Cl

Cl

PdN

P H

SiCl3

R

PdN

P

R

SiCl3

N

PdP

HCl3Si

N

Pd

P

Cl3Si

R

R





Unclear formation

σp

σp+


62


TK Woo

HH P

PdSiCl3SiCl3

NNH H

HH

HH P

PdSiCl3SiCl3

NNH H

FeP

PdSiCl3SiCl3

NN

FeP

PdSiCl3SiCl3

NN

HH P

PdSiCl3SiCl3

NNH H

HH P

PdSiCl3SiCl3

NN

H3CH

HH

H

Model 1

Model 2


63






PPd

H

SiCl3NN

HH

PPd

HSiCl3

NN

HH

PPd

HSiCl3

NN

HH

PPd

SiCl3NN

HH PPd

SiCl3NN

HH

1900

22

-02

-83

141

52

PPd

SiCl3NN

HH

PPd

Cl3SiNN

HH

64


endoendo-syn

PPdH

SiCl3NN

Fe

PPd HSiCl3NN

FeFe P

Pd

SiCl3NN

PPd HSiCl3NN

Fe

Cl3Si

PPd

SiCl3N

Fe

N

PPd

Cl3SiNN

Fe

PPdH

SiCl3NN

Fe

PPd

NN

Fe

Cl3Si

R

-35

09

TS1

TS2

-205

+-103

+styrene

00

42+48

61

Dagger Dagger


65





FeP

PdH

SiCl3NN

PPd

HSiCl3

NN

Fe


66


PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPd

H

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPdSiCl3NN

Fe

PPd

SiCl3NN

Fe

48

00

1609

51

-103

-113



endo-syn

exo-synendo

exo


kcalmol

67



endo-syn

exo-syn

NMe2

PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

NMe2

PPd

SiCl3NN

Fe

NMe2

PPdH

SiCl3NN

Fe

Me2N

PPd

SiCl3NN

Fe

PPdSiCl3

NN

Fe

NMe2

PPd

SiCl3NN

Fe

Me2N

48

00

08

03

16

-172

-155

exo

endo


68


DD

D

D5

HndashSiCl3 [PdL]

DD

D

D5

HO H DD

H

D5

HO H DH

H

D5

HO H DD

D

D5

HO D

oxid workup

+ + +


MeD1

MeD2

13C-1H-HZQCNMR

MeD2

MeD11 equivsilane

5 equivsilane

EI-MS


69





70


Energy(kcalmol)

(at rt)


(kcalmol)

(at rt)

ee

endo-syn -103 123

75 (S)[65 (S)]

endo-syn -172 859

81 (R)[64 (R)]

endo-anti -81 03 75 (S)[65 (S)]


75 (S)[65 (S)] exo-syn -155 48

81 (R)[64 (R)]

exo-anti -106 669

75 (S)[65 (S)]

exo-anti -153 35

81 (R)[64 (R)]


71

Conclusions




72




ClTi

O

OOO

OR

MeR

MeCN

OO

Np

Np

NpNp

NN

F

Cl

N NCl

ClTi

O

OOO

OR

MeR

MeCN

OO

Np

Np

NpNp

ClTi

O

OOO

OR

MeR

MeCN

OO

Np

NpNp

Np

F

N N FCl

++

+

+

SET


+

18


LUMO of [F-TEDA]2+


SOMO of [F-TEDA]+



HOMO

of enolato complex

ndash endash

B3LYP6-31G level

19


SET

R

ORO

O

E ERn

Rm


-

R

ORO

O

ERn

+ RmEndash

O O

MeMe

O N

HMe

Me

ICl

MeS

Me

SMe

N

O

O

Cl

SCl


20




R1 OR3

O O

R2

R1 OR3

O O

R2SPh

R1 OR3

O O

R2F

R1 OR3

O O

R2Cl

R1 OR3

O O

FCl

R1 OR3

O O

R2HO

NCS

Selectfluor


N SO2PhO2N

H

O

RR Cl

Ti

Cl

OO

NCMeMeCN

OO

Np

Np

Np

Np



up to 88 ee




21




22






Step 12 Step 21



23








Josiphos

Pigiphos

Fe

NMe2

MeFe PPh2

NMe2

Me

Fe PPh2

PCy2

Me

PFe PPh2

Fe

Ph2PUgis amine

24




NMe2

MePAr2

R1 R3

OO

R2

H2NNH2

NNH

R3R2

R1

Fe Fe

NMe

NR3

R2

R1

PAr2


AcOH 70-90 degC

80-90 yield

+

25

Ph2PCy2P

Ph2P

PCy2

Ph2PCy2P

Ph2P

Cy2P

PPh2PCy2

Ph2P

PCy2

Si

O

O

HN

O

NH

Si

Si

O

OHN

O

HN

Si

NP N P

NP

NP Si

O

OHN

ONH

Si

Si

OO

HNO NH

Si

Si

O

ONH

O

HN

Si

Si

O

ONH

ONH Si

SiO

ONH

OHN

Si

Si

OO

NH O

HN

Si

PPh2Cy2P

Ph2PCy2P

PPh2

PCy2

PPh2PCy2

Ph2PPCy2

PPh2

Cy2P

PPh2PCy2

PPh2

PCy2

Ph2P

Cy2P

Fe

PPh2Cy2P

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe




26



NH3C

CH3

OCH3

CH3OCl

H

P

MeFe

PPh2


2

Ir

S

NHHN

O

H H

P(t-Bu)2

MeFe

PPh2

COOH

(+)-Biotin(LONZA)

Rh

Sitagliptin(Merck)

Rh

F

FF

NN

NN

ONH2

CF3

PtBu2

MeFe P(4-F3CPh)2

27



H NN

ONHO

O

H NN

ONHO


SC=2000


96 ee

P(t-Bu)2

MeFe PPh2

N NN

OH

O

NH

ONH OH



28




P(t-Bu)2

MeFe PPh2

O

HOOCHN

S

F

O O

O

HOOCHN

S

F

O O

RuCl2(P-P)LnNEt3

H2 EtOH

O

HN

S

F

O O

O

HOHNP-P =

97 ee

29



Up to 97 ee

F

FF

NN

NN

ONH2

CF3



P(t-Bu)2

MeFe

P(t-Bu)2Me

Fe P CF32

PPh2

R OMe

NH2 O

R OMe


R NHPh

NH2 O

R NHPh

NH2 O

H2

Rh Josiphos ligand

H2

30











31










32



33

$

amp$

$

$

($

$$ amp$ )$ $ $ $ $ $

$

amp()+-


ampamp2824+

5lt=-amp)gt+gt2)42






34




α1=+9degα2=-21deg




35

Pd

L1

L2R

R

Pd

L1

L2

R

R

Nu Nu



36



X-rayX-ray

PhPh FeP

NNPd Ph

Ph


+

Ph

FeP

NNPd

Ph

Ph

Ph


+

PhPh FeP

NN

Pd Ph

Ph

+



Ph Ph

OCOR

NH2

Ph Ph


40 degC THF


N

Me

N

Fe

PPh2R

37



Ph

FeP

NNPd

Ph

a) R-product



NuNu

a)

b)

+

RS




PN

PdP N

PdP N

+ +


tc = 2 kcalmol

(Ab initio studies)

38

NH

NPd

PH3

NH3


NPd

PH3


NH

NPd

PH3

NH3

50 kJmol

36 kJmol

NH3+

41 kJmol

NH3+

+



PdP N

PdP N

PdP N

+

+ +


tc = 8 kJmol


ct = 29 kJmol


for C out of plane



40

PhPh Fe

P

NNPd

Ph

Ph

Ph

Ph

FeP

NNPd

Ph

Ph

exo-syn-anti (71)

+

exo-syn-syn (29)

+

S R



41

PhFe

P

NN

Pd


+

Ph




42

Ph

Ph

PdP N

Ph

Ph

P NPd

Nu

Nu




43




PMe

NN

Ph

Ph

PhPh

PdNN

MePd

FeFeP

Ph

Ph

Ph

Ph

Ph Ph

NHCH2Ph

(S)

Ph Ph

OCOOEtNu-Nu-


950 ee resp 945 ee

rac

44






Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

Fe

N CN

PPh2

Me

Fe

N NC

PPh2

MePdR

R+

PdR

R+

X-ray

45



Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

PdR

R+

PdR

R+

Fe

N CN

PPh2

Me Pd

NHR2R

RFe

N CN

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

Fe

N NC

PPh2

Me Pd

NHR2R

RFe

N NC

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

dr 8515exoendo 8218

46














47


Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



Ph Ph

OCOOEt

Ph Ph

N



NH

Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



48

N

Me

N

Fe

PPh2

Ph Ph

OCO2Et

Ph Ph

NHCH2Ph

[Pd(dba)2 ]+ Ligand





991 (220)

67 (11)

33 (2)

987 (153)

gt995 (gt400)



3 mol Pd-catalyst

PF6- Selectivity

Killer




49

Ph

Ph

P

NPd

+

endo-syn-syn

+

exo-syn-syn

Ph

PhP

NPd

Ph Ph

OCOOEt

Ph Ph



Slow with PF6-

(tight ion pairs )

Fast with F-

(Coordination)

R-Product S-Product

more stable


S R


50










51

E N Jacobsen et al



NN

OMn

OCl

X X

HHX = OMe 96 ee

X = NO2 22 ee

52




MeO MeO

CN

OOOPh

OPhOPAr2

OAr2P CF3F3C MeMe

HCN [Ni(COD)2] L

Ar =

91 eeL

16 ee

53





OCO O

++

nn2 3

4

1


Δ

54

([α]D=-450)




Polymer)50 220 370 1800


PCy2Me

Fe P

CF3

CF32

PCy2Me

Fe P

OMe

OMe2

PCy2Me

Fe P

H

H2

PCy2Me

Fe P

CH3

CH32

55


Markus Baumann


NMeN

Fe

Me

Me

Me

P

O+ PhOTf



O Ph O Ph O

Ph

+ +

2

Rn

Rn=(m-CF3)2

Rn=(m-SiMe3)2

Rn=(p-OMe)

Rn=(p-CF3)

1 (34ee)

8 (62ee)

1 (46ee)

1 (10ee)

94 (88ee)

90 (95ee)

97 (96ee)

96 (95ee)

5

2

2

3

56



NMeN

Fe

PMe Me

F3C

F3CNMeN

Fe

PMe Me

CF3

F3CF3C

F3C

NMeN

Fe

PF3C CF3

MeO

MeO

NMeN

Fe

PMe Me

MeO

MeO

NMeN

Fe

PF3C CF3

NMeN

Fe

PMe Me

NMeN

Fe

PMe Me

Me2N

Me2NNMeN

Fe

PF3C CF3

F3C

F3C

95 ee985 ee

5 ee72 ee

33 ee

98 ee90 ee

40 ee

the worst

and the best

57





NMeN

Fe

Me

Me

Me

PPh2


2) Oxidative Workup

OH

NMeN

Fe PPh2

NMeN

Fe PPh2

Me

39ee 76ee 99ee

Catalytic activity

NMeN

Fe

MeO

OMe

OMe

PPh2

NMeN

Fe

Me

Me

Me

P

CF3

CF3

2

82ee 91ee

58


X

Fe PPh2

N N

Mes

Me

X

1) cat PdCl2(L)

2) Oxidation


= L

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=078rsup2=0996

NMe₂

OMe

Me

ClH


Fe P X

N N

Mes

Me

1) cat PdCl2(L)

2) Oxidation


2

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=014rsup2=0986

NMe₂OMe

Me HCl


59



Fe P X

N N

Mes

Me

OH1) cat PdCl2(L)

2) Oxidation


2

60



X

Fe PPh2

N N

Mes

Me

X

OH1) cat PdCl2(L)

2) Oxidation

= L

61


PdN

P

Cl

Cl

PdN

P H

SiCl3

R

PdN

P

R

SiCl3

N

PdP

HCl3Si

N

Pd

P

Cl3Si

R

R





Unclear formation

σp

σp+


62


TK Woo

HH P

PdSiCl3SiCl3

NNH H

HH

HH P

PdSiCl3SiCl3

NNH H

FeP

PdSiCl3SiCl3

NN

FeP

PdSiCl3SiCl3

NN

HH P

PdSiCl3SiCl3

NNH H

HH P

PdSiCl3SiCl3

NN

H3CH

HH

H

Model 1

Model 2


63






PPd

H

SiCl3NN

HH

PPd

HSiCl3

NN

HH

PPd

HSiCl3

NN

HH

PPd

SiCl3NN

HH PPd

SiCl3NN

HH

1900

22

-02

-83

141

52

PPd

SiCl3NN

HH

PPd

Cl3SiNN

HH

64


endoendo-syn

PPdH

SiCl3NN

Fe

PPd HSiCl3NN

FeFe P

Pd

SiCl3NN

PPd HSiCl3NN

Fe

Cl3Si

PPd

SiCl3N

Fe

N

PPd

Cl3SiNN

Fe

PPdH

SiCl3NN

Fe

PPd

NN

Fe

Cl3Si

R

-35

09

TS1

TS2

-205

+-103

+styrene

00

42+48

61

Dagger Dagger


65





FeP

PdH

SiCl3NN

PPd

HSiCl3

NN

Fe


66


PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPd

H

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPdSiCl3NN

Fe

PPd

SiCl3NN

Fe

48

00

1609

51

-103

-113



endo-syn

exo-synendo

exo


kcalmol

67



endo-syn

exo-syn

NMe2

PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

NMe2

PPd

SiCl3NN

Fe

NMe2

PPdH

SiCl3NN

Fe

Me2N

PPd

SiCl3NN

Fe

PPdSiCl3

NN

Fe

NMe2

PPd

SiCl3NN

Fe

Me2N

48

00

08

03

16

-172

-155

exo

endo


68


DD

D

D5

HndashSiCl3 [PdL]

DD

D

D5

HO H DD

H

D5

HO H DH

H

D5

HO H DD

D

D5

HO D

oxid workup

+ + +


MeD1

MeD2

13C-1H-HZQCNMR

MeD2

MeD11 equivsilane

5 equivsilane

EI-MS


69





70


Energy(kcalmol)

(at rt)


(kcalmol)

(at rt)

ee

endo-syn -103 123

75 (S)[65 (S)]

endo-syn -172 859

81 (R)[64 (R)]

endo-anti -81 03 75 (S)[65 (S)]


75 (S)[65 (S)] exo-syn -155 48

81 (R)[64 (R)]

exo-anti -106 669

75 (S)[65 (S)]

exo-anti -153 35

81 (R)[64 (R)]


71

Conclusions




72


LUMO of [F-TEDA]2+


SOMO of [F-TEDA]+



HOMO

of enolato complex

ndash endash

B3LYP6-31G level

19


SET

R

ORO

O

E ERn

Rm


-

R

ORO

O

ERn

+ RmEndash

O O

MeMe

O N

HMe

Me

ICl

MeS

Me

SMe

N

O

O

Cl

SCl


20




R1 OR3

O O

R2

R1 OR3

O O

R2SPh

R1 OR3

O O

R2F

R1 OR3

O O

R2Cl

R1 OR3

O O

FCl

R1 OR3

O O

R2HO

NCS

Selectfluor


N SO2PhO2N

H

O

RR Cl

Ti

Cl

OO

NCMeMeCN

OO

Np

Np

Np

Np



up to 88 ee




21




22






Step 12 Step 21



23








Josiphos

Pigiphos

Fe

NMe2

MeFe PPh2

NMe2

Me

Fe PPh2

PCy2

Me

PFe PPh2

Fe

Ph2PUgis amine

24




NMe2

MePAr2

R1 R3

OO

R2

H2NNH2

NNH

R3R2

R1

Fe Fe

NMe

NR3

R2

R1

PAr2


AcOH 70-90 degC

80-90 yield

+

25

Ph2PCy2P

Ph2P

PCy2

Ph2PCy2P

Ph2P

Cy2P

PPh2PCy2

Ph2P

PCy2

Si

O

O

HN

O

NH

Si

Si

O

OHN

O

HN

Si

NP N P

NP

NP Si

O

OHN

ONH

Si

Si

OO

HNO NH

Si

Si

O

ONH

O

HN

Si

Si

O

ONH

ONH Si

SiO

ONH

OHN

Si

Si

OO

NH O

HN

Si

PPh2Cy2P

Ph2PCy2P

PPh2

PCy2

PPh2PCy2

Ph2PPCy2

PPh2

Cy2P

PPh2PCy2

PPh2

PCy2

Ph2P

Cy2P

Fe

PPh2Cy2P

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe




26



NH3C

CH3

OCH3

CH3OCl

H

P

MeFe

PPh2


2

Ir

S

NHHN

O

H H

P(t-Bu)2

MeFe

PPh2

COOH

(+)-Biotin(LONZA)

Rh

Sitagliptin(Merck)

Rh

F

FF

NN

NN

ONH2

CF3

PtBu2

MeFe P(4-F3CPh)2

27



H NN

ONHO

O

H NN

ONHO


SC=2000


96 ee

P(t-Bu)2

MeFe PPh2

N NN

OH

O

NH

ONH OH



28




P(t-Bu)2

MeFe PPh2

O

HOOCHN

S

F

O O

O

HOOCHN

S

F

O O

RuCl2(P-P)LnNEt3

H2 EtOH

O

HN

S

F

O O

O

HOHNP-P =

97 ee

29



Up to 97 ee

F

FF

NN

NN

ONH2

CF3



P(t-Bu)2

MeFe

P(t-Bu)2Me

Fe P CF32

PPh2

R OMe

NH2 O

R OMe


R NHPh

NH2 O

R NHPh

NH2 O

H2

Rh Josiphos ligand

H2

30











31










32



33

$

amp$

$

$

($

$$ amp$ )$ $ $ $ $ $

$

amp()+-


ampamp2824+

5lt=-amp)gt+gt2)42






34




α1=+9degα2=-21deg




35

Pd

L1

L2R

R

Pd

L1

L2

R

R

Nu Nu



36



X-rayX-ray

PhPh FeP

NNPd Ph

Ph


+

Ph

FeP

NNPd

Ph

Ph

Ph


+

PhPh FeP

NN

Pd Ph

Ph

+



Ph Ph

OCOR

NH2

Ph Ph


40 degC THF


N

Me

N

Fe

PPh2R

37



Ph

FeP

NNPd

Ph

a) R-product



NuNu

a)

b)

+

RS




PN

PdP N

PdP N

+ +


tc = 2 kcalmol

(Ab initio studies)

38

NH

NPd

PH3

NH3


NPd

PH3


NH

NPd

PH3

NH3

50 kJmol

36 kJmol

NH3+

41 kJmol

NH3+

+



PdP N

PdP N

PdP N

+

+ +


tc = 8 kJmol


ct = 29 kJmol


for C out of plane



40

PhPh Fe

P

NNPd

Ph

Ph

Ph

Ph

FeP

NNPd

Ph

Ph

exo-syn-anti (71)

+

exo-syn-syn (29)

+

S R



41

PhFe

P

NN

Pd


+

Ph




42

Ph

Ph

PdP N

Ph

Ph

P NPd

Nu

Nu




43




PMe

NN

Ph

Ph

PhPh

PdNN

MePd

FeFeP

Ph

Ph

Ph

Ph

Ph Ph

NHCH2Ph

(S)

Ph Ph

OCOOEtNu-Nu-


950 ee resp 945 ee

rac

44






Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

Fe

N CN

PPh2

Me

Fe

N NC

PPh2

MePdR

R+

PdR

R+

X-ray

45



Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

PdR

R+

PdR

R+

Fe

N CN

PPh2

Me Pd

NHR2R

RFe

N CN

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

Fe

N NC

PPh2

Me Pd

NHR2R

RFe

N NC

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

dr 8515exoendo 8218

46














47


Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



Ph Ph

OCOOEt

Ph Ph

N



NH

Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



48

N

Me

N

Fe

PPh2

Ph Ph

OCO2Et

Ph Ph

NHCH2Ph

[Pd(dba)2 ]+ Ligand





991 (220)

67 (11)

33 (2)

987 (153)

gt995 (gt400)



3 mol Pd-catalyst

PF6- Selectivity

Killer




49

Ph

Ph

P

NPd

+

endo-syn-syn

+

exo-syn-syn

Ph

PhP

NPd

Ph Ph

OCOOEt

Ph Ph



Slow with PF6-

(tight ion pairs )

Fast with F-

(Coordination)

R-Product S-Product

more stable


S R


50










51

E N Jacobsen et al



NN

OMn

OCl

X X

HHX = OMe 96 ee

X = NO2 22 ee

52




MeO MeO

CN

OOOPh

OPhOPAr2

OAr2P CF3F3C MeMe

HCN [Ni(COD)2] L

Ar =

91 eeL

16 ee

53





OCO O

++

nn2 3

4

1


Δ

54

([α]D=-450)




Polymer)50 220 370 1800


PCy2Me

Fe P

CF3

CF32

PCy2Me

Fe P

OMe

OMe2

PCy2Me

Fe P

H

H2

PCy2Me

Fe P

CH3

CH32

55


Markus Baumann


NMeN

Fe

Me

Me

Me

P

O+ PhOTf



O Ph O Ph O

Ph

+ +

2

Rn

Rn=(m-CF3)2

Rn=(m-SiMe3)2

Rn=(p-OMe)

Rn=(p-CF3)

1 (34ee)

8 (62ee)

1 (46ee)

1 (10ee)

94 (88ee)

90 (95ee)

97 (96ee)

96 (95ee)

5

2

2

3

56



NMeN

Fe

PMe Me

F3C

F3CNMeN

Fe

PMe Me

CF3

F3CF3C

F3C

NMeN

Fe

PF3C CF3

MeO

MeO

NMeN

Fe

PMe Me

MeO

MeO

NMeN

Fe

PF3C CF3

NMeN

Fe

PMe Me

NMeN

Fe

PMe Me

Me2N

Me2NNMeN

Fe

PF3C CF3

F3C

F3C

95 ee985 ee

5 ee72 ee

33 ee

98 ee90 ee

40 ee

the worst

and the best

57





NMeN

Fe

Me

Me

Me

PPh2


2) Oxidative Workup

OH

NMeN

Fe PPh2

NMeN

Fe PPh2

Me

39ee 76ee 99ee

Catalytic activity

NMeN

Fe

MeO

OMe

OMe

PPh2

NMeN

Fe

Me

Me

Me

P

CF3

CF3

2

82ee 91ee

58


X

Fe PPh2

N N

Mes

Me

X

1) cat PdCl2(L)

2) Oxidation


= L

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=078rsup2=0996

NMe₂

OMe

Me

ClH


Fe P X

N N

Mes

Me

1) cat PdCl2(L)

2) Oxidation


2

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=014rsup2=0986

NMe₂OMe

Me HCl


59



Fe P X

N N

Mes

Me

OH1) cat PdCl2(L)

2) Oxidation


2

60



X

Fe PPh2

N N

Mes

Me

X

OH1) cat PdCl2(L)

2) Oxidation

= L

61


PdN

P

Cl

Cl

PdN

P H

SiCl3

R

PdN

P

R

SiCl3

N

PdP

HCl3Si

N

Pd

P

Cl3Si

R

R





Unclear formation

σp

σp+


62


TK Woo

HH P

PdSiCl3SiCl3

NNH H

HH

HH P

PdSiCl3SiCl3

NNH H

FeP

PdSiCl3SiCl3

NN

FeP

PdSiCl3SiCl3

NN

HH P

PdSiCl3SiCl3

NNH H

HH P

PdSiCl3SiCl3

NN

H3CH

HH

H

Model 1

Model 2


63






PPd

H

SiCl3NN

HH

PPd

HSiCl3

NN

HH

PPd

HSiCl3

NN

HH

PPd

SiCl3NN

HH PPd

SiCl3NN

HH

1900

22

-02

-83

141

52

PPd

SiCl3NN

HH

PPd

Cl3SiNN

HH

64


endoendo-syn

PPdH

SiCl3NN

Fe

PPd HSiCl3NN

FeFe P

Pd

SiCl3NN

PPd HSiCl3NN

Fe

Cl3Si

PPd

SiCl3N

Fe

N

PPd

Cl3SiNN

Fe

PPdH

SiCl3NN

Fe

PPd

NN

Fe

Cl3Si

R

-35

09

TS1

TS2

-205

+-103

+styrene

00

42+48

61

Dagger Dagger


65





FeP

PdH

SiCl3NN

PPd

HSiCl3

NN

Fe


66


PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPd

H

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPdSiCl3NN

Fe

PPd

SiCl3NN

Fe

48

00

1609

51

-103

-113



endo-syn

exo-synendo

exo


kcalmol

67



endo-syn

exo-syn

NMe2

PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

NMe2

PPd

SiCl3NN

Fe

NMe2

PPdH

SiCl3NN

Fe

Me2N

PPd

SiCl3NN

Fe

PPdSiCl3

NN

Fe

NMe2

PPd

SiCl3NN

Fe

Me2N

48

00

08

03

16

-172

-155

exo

endo


68


DD

D

D5

HndashSiCl3 [PdL]

DD

D

D5

HO H DD

H

D5

HO H DH

H

D5

HO H DD

D

D5

HO D

oxid workup

+ + +


MeD1

MeD2

13C-1H-HZQCNMR

MeD2

MeD11 equivsilane

5 equivsilane

EI-MS


69





70


Energy(kcalmol)

(at rt)


(kcalmol)

(at rt)

ee

endo-syn -103 123

75 (S)[65 (S)]

endo-syn -172 859

81 (R)[64 (R)]

endo-anti -81 03 75 (S)[65 (S)]


75 (S)[65 (S)] exo-syn -155 48

81 (R)[64 (R)]

exo-anti -106 669

75 (S)[65 (S)]

exo-anti -153 35

81 (R)[64 (R)]


71

Conclusions




72


SET

R

ORO

O

E ERn

Rm


-

R

ORO

O

ERn

+ RmEndash

O O

MeMe

O N

HMe

Me

ICl

MeS

Me

SMe

N

O

O

Cl

SCl


20




R1 OR3

O O

R2

R1 OR3

O O

R2SPh

R1 OR3

O O

R2F

R1 OR3

O O

R2Cl

R1 OR3

O O

FCl

R1 OR3

O O

R2HO

NCS

Selectfluor


N SO2PhO2N

H

O

RR Cl

Ti

Cl

OO

NCMeMeCN

OO

Np

Np

Np

Np



up to 88 ee




21




22






Step 12 Step 21



23








Josiphos

Pigiphos

Fe

NMe2

MeFe PPh2

NMe2

Me

Fe PPh2

PCy2

Me

PFe PPh2

Fe

Ph2PUgis amine

24




NMe2

MePAr2

R1 R3

OO

R2

H2NNH2

NNH

R3R2

R1

Fe Fe

NMe

NR3

R2

R1

PAr2


AcOH 70-90 degC

80-90 yield

+

25

Ph2PCy2P

Ph2P

PCy2

Ph2PCy2P

Ph2P

Cy2P

PPh2PCy2

Ph2P

PCy2

Si

O

O

HN

O

NH

Si

Si

O

OHN

O

HN

Si

NP N P

NP

NP Si

O

OHN

ONH

Si

Si

OO

HNO NH

Si

Si

O

ONH

O

HN

Si

Si

O

ONH

ONH Si

SiO

ONH

OHN

Si

Si

OO

NH O

HN

Si

PPh2Cy2P

Ph2PCy2P

PPh2

PCy2

PPh2PCy2

Ph2PPCy2

PPh2

Cy2P

PPh2PCy2

PPh2

PCy2

Ph2P

Cy2P

Fe

PPh2Cy2P

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe




26



NH3C

CH3

OCH3

CH3OCl

H

P

MeFe

PPh2


2

Ir

S

NHHN

O

H H

P(t-Bu)2

MeFe

PPh2

COOH

(+)-Biotin(LONZA)

Rh

Sitagliptin(Merck)

Rh

F

FF

NN

NN

ONH2

CF3

PtBu2

MeFe P(4-F3CPh)2

27



H NN

ONHO

O

H NN

ONHO


SC=2000


96 ee

P(t-Bu)2

MeFe PPh2

N NN

OH

O

NH

ONH OH



28




P(t-Bu)2

MeFe PPh2

O

HOOCHN

S

F

O O

O

HOOCHN

S

F

O O

RuCl2(P-P)LnNEt3

H2 EtOH

O

HN

S

F

O O

O

HOHNP-P =

97 ee

29



Up to 97 ee

F

FF

NN

NN

ONH2

CF3



P(t-Bu)2

MeFe

P(t-Bu)2Me

Fe P CF32

PPh2

R OMe

NH2 O

R OMe


R NHPh

NH2 O

R NHPh

NH2 O

H2

Rh Josiphos ligand

H2

30











31










32



33

$

amp$

$

$

($

$$ amp$ )$ $ $ $ $ $

$

amp()+-


ampamp2824+

5lt=-amp)gt+gt2)42






34




α1=+9degα2=-21deg




35

Pd

L1

L2R

R

Pd

L1

L2

R

R

Nu Nu



36



X-rayX-ray

PhPh FeP

NNPd Ph

Ph


+

Ph

FeP

NNPd

Ph

Ph

Ph


+

PhPh FeP

NN

Pd Ph

Ph

+



Ph Ph

OCOR

NH2

Ph Ph


40 degC THF


N

Me

N

Fe

PPh2R

37



Ph

FeP

NNPd

Ph

a) R-product



NuNu

a)

b)

+

RS




PN

PdP N

PdP N

+ +


tc = 2 kcalmol

(Ab initio studies)

38

NH

NPd

PH3

NH3


NPd

PH3


NH

NPd

PH3

NH3

50 kJmol

36 kJmol

NH3+

41 kJmol

NH3+

+



PdP N

PdP N

PdP N

+

+ +


tc = 8 kJmol


ct = 29 kJmol


for C out of plane



40

PhPh Fe

P

NNPd

Ph

Ph

Ph

Ph

FeP

NNPd

Ph

Ph

exo-syn-anti (71)

+

exo-syn-syn (29)

+

S R



41

PhFe

P

NN

Pd


+

Ph




42

Ph

Ph

PdP N

Ph

Ph

P NPd

Nu

Nu




43




PMe

NN

Ph

Ph

PhPh

PdNN

MePd

FeFeP

Ph

Ph

Ph

Ph

Ph Ph

NHCH2Ph

(S)

Ph Ph

OCOOEtNu-Nu-


950 ee resp 945 ee

rac

44






Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

Fe

N CN

PPh2

Me

Fe

N NC

PPh2

MePdR

R+

PdR

R+

X-ray

45



Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

PdR

R+

PdR

R+

Fe

N CN

PPh2

Me Pd

NHR2R

RFe

N CN

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

Fe

N NC

PPh2

Me Pd

NHR2R

RFe

N NC

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

dr 8515exoendo 8218

46














47


Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



Ph Ph

OCOOEt

Ph Ph

N



NH

Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



48

N

Me

N

Fe

PPh2

Ph Ph

OCO2Et

Ph Ph

NHCH2Ph

[Pd(dba)2 ]+ Ligand





991 (220)

67 (11)

33 (2)

987 (153)

gt995 (gt400)



3 mol Pd-catalyst

PF6- Selectivity

Killer




49

Ph

Ph

P

NPd

+

endo-syn-syn

+

exo-syn-syn

Ph

PhP

NPd

Ph Ph

OCOOEt

Ph Ph



Slow with PF6-

(tight ion pairs )

Fast with F-

(Coordination)

R-Product S-Product

more stable


S R


50










51

E N Jacobsen et al



NN

OMn

OCl

X X

HHX = OMe 96 ee

X = NO2 22 ee

52




MeO MeO

CN

OOOPh

OPhOPAr2

OAr2P CF3F3C MeMe

HCN [Ni(COD)2] L

Ar =

91 eeL

16 ee

53





OCO O

++

nn2 3

4

1


Δ

54

([α]D=-450)




Polymer)50 220 370 1800


PCy2Me

Fe P

CF3

CF32

PCy2Me

Fe P

OMe

OMe2

PCy2Me

Fe P

H

H2

PCy2Me

Fe P

CH3

CH32

55


Markus Baumann


NMeN

Fe

Me

Me

Me

P

O+ PhOTf



O Ph O Ph O

Ph

+ +

2

Rn

Rn=(m-CF3)2

Rn=(m-SiMe3)2

Rn=(p-OMe)

Rn=(p-CF3)

1 (34ee)

8 (62ee)

1 (46ee)

1 (10ee)

94 (88ee)

90 (95ee)

97 (96ee)

96 (95ee)

5

2

2

3

56



NMeN

Fe

PMe Me

F3C

F3CNMeN

Fe

PMe Me

CF3

F3CF3C

F3C

NMeN

Fe

PF3C CF3

MeO

MeO

NMeN

Fe

PMe Me

MeO

MeO

NMeN

Fe

PF3C CF3

NMeN

Fe

PMe Me

NMeN

Fe

PMe Me

Me2N

Me2NNMeN

Fe

PF3C CF3

F3C

F3C

95 ee985 ee

5 ee72 ee

33 ee

98 ee90 ee

40 ee

the worst

and the best

57





NMeN

Fe

Me

Me

Me

PPh2


2) Oxidative Workup

OH

NMeN

Fe PPh2

NMeN

Fe PPh2

Me

39ee 76ee 99ee

Catalytic activity

NMeN

Fe

MeO

OMe

OMe

PPh2

NMeN

Fe

Me

Me

Me

P

CF3

CF3

2

82ee 91ee

58


X

Fe PPh2

N N

Mes

Me

X

1) cat PdCl2(L)

2) Oxidation


= L

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=078rsup2=0996

NMe₂

OMe

Me

ClH


Fe P X

N N

Mes

Me

1) cat PdCl2(L)

2) Oxidation


2

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=014rsup2=0986

NMe₂OMe

Me HCl


59



Fe P X

N N

Mes

Me

OH1) cat PdCl2(L)

2) Oxidation


2

60



X

Fe PPh2

N N

Mes

Me

X

OH1) cat PdCl2(L)

2) Oxidation

= L

61


PdN

P

Cl

Cl

PdN

P H

SiCl3

R

PdN

P

R

SiCl3

N

PdP

HCl3Si

N

Pd

P

Cl3Si

R

R





Unclear formation

σp

σp+


62


TK Woo

HH P

PdSiCl3SiCl3

NNH H

HH

HH P

PdSiCl3SiCl3

NNH H

FeP

PdSiCl3SiCl3

NN

FeP

PdSiCl3SiCl3

NN

HH P

PdSiCl3SiCl3

NNH H

HH P

PdSiCl3SiCl3

NN

H3CH

HH

H

Model 1

Model 2


63






PPd

H

SiCl3NN

HH

PPd

HSiCl3

NN

HH

PPd

HSiCl3

NN

HH

PPd

SiCl3NN

HH PPd

SiCl3NN

HH

1900

22

-02

-83

141

52

PPd

SiCl3NN

HH

PPd

Cl3SiNN

HH

64


endoendo-syn

PPdH

SiCl3NN

Fe

PPd HSiCl3NN

FeFe P

Pd

SiCl3NN

PPd HSiCl3NN

Fe

Cl3Si

PPd

SiCl3N

Fe

N

PPd

Cl3SiNN

Fe

PPdH

SiCl3NN

Fe

PPd

NN

Fe

Cl3Si

R

-35

09

TS1

TS2

-205

+-103

+styrene

00

42+48

61

Dagger Dagger


65





FeP

PdH

SiCl3NN

PPd

HSiCl3

NN

Fe


66


PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPd

H

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPdSiCl3NN

Fe

PPd

SiCl3NN

Fe

48

00

1609

51

-103

-113



endo-syn

exo-synendo

exo


kcalmol

67



endo-syn

exo-syn

NMe2

PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

NMe2

PPd

SiCl3NN

Fe

NMe2

PPdH

SiCl3NN

Fe

Me2N

PPd

SiCl3NN

Fe

PPdSiCl3

NN

Fe

NMe2

PPd

SiCl3NN

Fe

Me2N

48

00

08

03

16

-172

-155

exo

endo


68


DD

D

D5

HndashSiCl3 [PdL]

DD

D

D5

HO H DD

H

D5

HO H DH

H

D5

HO H DD

D

D5

HO D

oxid workup

+ + +


MeD1

MeD2

13C-1H-HZQCNMR

MeD2

MeD11 equivsilane

5 equivsilane

EI-MS


69





70


Energy(kcalmol)

(at rt)


(kcalmol)

(at rt)

ee

endo-syn -103 123

75 (S)[65 (S)]

endo-syn -172 859

81 (R)[64 (R)]

endo-anti -81 03 75 (S)[65 (S)]


75 (S)[65 (S)] exo-syn -155 48

81 (R)[64 (R)]

exo-anti -106 669

75 (S)[65 (S)]

exo-anti -153 35

81 (R)[64 (R)]


71

Conclusions




72




R1 OR3

O O

R2

R1 OR3

O O

R2SPh

R1 OR3

O O

R2F

R1 OR3

O O

R2Cl

R1 OR3

O O

FCl

R1 OR3

O O

R2HO

NCS

Selectfluor


N SO2PhO2N

H

O

RR Cl

Ti

Cl

OO

NCMeMeCN

OO

Np

Np

Np

Np



up to 88 ee




21




22






Step 12 Step 21



23








Josiphos

Pigiphos

Fe

NMe2

MeFe PPh2

NMe2

Me

Fe PPh2

PCy2

Me

PFe PPh2

Fe

Ph2PUgis amine

24




NMe2

MePAr2

R1 R3

OO

R2

H2NNH2

NNH

R3R2

R1

Fe Fe

NMe

NR3

R2

R1

PAr2


AcOH 70-90 degC

80-90 yield

+

25

Ph2PCy2P

Ph2P

PCy2

Ph2PCy2P

Ph2P

Cy2P

PPh2PCy2

Ph2P

PCy2

Si

O

O

HN

O

NH

Si

Si

O

OHN

O

HN

Si

NP N P

NP

NP Si

O

OHN

ONH

Si

Si

OO

HNO NH

Si

Si

O

ONH

O

HN

Si

Si

O

ONH

ONH Si

SiO

ONH

OHN

Si

Si

OO

NH O

HN

Si

PPh2Cy2P

Ph2PCy2P

PPh2

PCy2

PPh2PCy2

Ph2PPCy2

PPh2

Cy2P

PPh2PCy2

PPh2

PCy2

Ph2P

Cy2P

Fe

PPh2Cy2P

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe




26



NH3C

CH3

OCH3

CH3OCl

H

P

MeFe

PPh2


2

Ir

S

NHHN

O

H H

P(t-Bu)2

MeFe

PPh2

COOH

(+)-Biotin(LONZA)

Rh

Sitagliptin(Merck)

Rh

F

FF

NN

NN

ONH2

CF3

PtBu2

MeFe P(4-F3CPh)2

27



H NN

ONHO

O

H NN

ONHO


SC=2000


96 ee

P(t-Bu)2

MeFe PPh2

N NN

OH

O

NH

ONH OH



28




P(t-Bu)2

MeFe PPh2

O

HOOCHN

S

F

O O

O

HOOCHN

S

F

O O

RuCl2(P-P)LnNEt3

H2 EtOH

O

HN

S

F

O O

O

HOHNP-P =

97 ee

29



Up to 97 ee

F

FF

NN

NN

ONH2

CF3



P(t-Bu)2

MeFe

P(t-Bu)2Me

Fe P CF32

PPh2

R OMe

NH2 O

R OMe


R NHPh

NH2 O

R NHPh

NH2 O

H2

Rh Josiphos ligand

H2

30











31










32



33

$

amp$

$

$

($

$$ amp$ )$ $ $ $ $ $

$

amp()+-


ampamp2824+

5lt=-amp)gt+gt2)42






34




α1=+9degα2=-21deg




35

Pd

L1

L2R

R

Pd

L1

L2

R

R

Nu Nu



36



X-rayX-ray

PhPh FeP

NNPd Ph

Ph


+

Ph

FeP

NNPd

Ph

Ph

Ph


+

PhPh FeP

NN

Pd Ph

Ph

+



Ph Ph

OCOR

NH2

Ph Ph


40 degC THF


N

Me

N

Fe

PPh2R

37



Ph

FeP

NNPd

Ph

a) R-product



NuNu

a)

b)

+

RS




PN

PdP N

PdP N

+ +


tc = 2 kcalmol

(Ab initio studies)

38

NH

NPd

PH3

NH3


NPd

PH3


NH

NPd

PH3

NH3

50 kJmol

36 kJmol

NH3+

41 kJmol

NH3+

+



PdP N

PdP N

PdP N

+

+ +


tc = 8 kJmol


ct = 29 kJmol


for C out of plane



40

PhPh Fe

P

NNPd

Ph

Ph

Ph

Ph

FeP

NNPd

Ph

Ph

exo-syn-anti (71)

+

exo-syn-syn (29)

+

S R



41

PhFe

P

NN

Pd


+

Ph




42

Ph

Ph

PdP N

Ph

Ph

P NPd

Nu

Nu




43




PMe

NN

Ph

Ph

PhPh

PdNN

MePd

FeFeP

Ph

Ph

Ph

Ph

Ph Ph

NHCH2Ph

(S)

Ph Ph

OCOOEtNu-Nu-


950 ee resp 945 ee

rac

44






Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

Fe

N CN

PPh2

Me

Fe

N NC

PPh2

MePdR

R+

PdR

R+

X-ray

45



Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

PdR

R+

PdR

R+

Fe

N CN

PPh2

Me Pd

NHR2R

RFe

N CN

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

Fe

N NC

PPh2

Me Pd

NHR2R

RFe

N NC

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

dr 8515exoendo 8218

46














47


Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



Ph Ph

OCOOEt

Ph Ph

N



NH

Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



48

N

Me

N

Fe

PPh2

Ph Ph

OCO2Et

Ph Ph

NHCH2Ph

[Pd(dba)2 ]+ Ligand





991 (220)

67 (11)

33 (2)

987 (153)

gt995 (gt400)



3 mol Pd-catalyst

PF6- Selectivity

Killer




49

Ph

Ph

P

NPd

+

endo-syn-syn

+

exo-syn-syn

Ph

PhP

NPd

Ph Ph

OCOOEt

Ph Ph



Slow with PF6-

(tight ion pairs )

Fast with F-

(Coordination)

R-Product S-Product

more stable


S R


50










51

E N Jacobsen et al



NN

OMn

OCl

X X

HHX = OMe 96 ee

X = NO2 22 ee

52




MeO MeO

CN

OOOPh

OPhOPAr2

OAr2P CF3F3C MeMe

HCN [Ni(COD)2] L

Ar =

91 eeL

16 ee

53





OCO O

++

nn2 3

4

1


Δ

54

([α]D=-450)




Polymer)50 220 370 1800


PCy2Me

Fe P

CF3

CF32

PCy2Me

Fe P

OMe

OMe2

PCy2Me

Fe P

H

H2

PCy2Me

Fe P

CH3

CH32

55


Markus Baumann


NMeN

Fe

Me

Me

Me

P

O+ PhOTf



O Ph O Ph O

Ph

+ +

2

Rn

Rn=(m-CF3)2

Rn=(m-SiMe3)2

Rn=(p-OMe)

Rn=(p-CF3)

1 (34ee)

8 (62ee)

1 (46ee)

1 (10ee)

94 (88ee)

90 (95ee)

97 (96ee)

96 (95ee)

5

2

2

3

56



NMeN

Fe

PMe Me

F3C

F3CNMeN

Fe

PMe Me

CF3

F3CF3C

F3C

NMeN

Fe

PF3C CF3

MeO

MeO

NMeN

Fe

PMe Me

MeO

MeO

NMeN

Fe

PF3C CF3

NMeN

Fe

PMe Me

NMeN

Fe

PMe Me

Me2N

Me2NNMeN

Fe

PF3C CF3

F3C

F3C

95 ee985 ee

5 ee72 ee

33 ee

98 ee90 ee

40 ee

the worst

and the best

57





NMeN

Fe

Me

Me

Me

PPh2


2) Oxidative Workup

OH

NMeN

Fe PPh2

NMeN

Fe PPh2

Me

39ee 76ee 99ee

Catalytic activity

NMeN

Fe

MeO

OMe

OMe

PPh2

NMeN

Fe

Me

Me

Me

P

CF3

CF3

2

82ee 91ee

58


X

Fe PPh2

N N

Mes

Me

X

1) cat PdCl2(L)

2) Oxidation


= L

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=078rsup2=0996

NMe₂

OMe

Me

ClH


Fe P X

N N

Mes

Me

1) cat PdCl2(L)

2) Oxidation


2

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=014rsup2=0986

NMe₂OMe

Me HCl


59



Fe P X

N N

Mes

Me

OH1) cat PdCl2(L)

2) Oxidation


2

60



X

Fe PPh2

N N

Mes

Me

X

OH1) cat PdCl2(L)

2) Oxidation

= L

61


PdN

P

Cl

Cl

PdN

P H

SiCl3

R

PdN

P

R

SiCl3

N

PdP

HCl3Si

N

Pd

P

Cl3Si

R

R





Unclear formation

σp

σp+


62


TK Woo

HH P

PdSiCl3SiCl3

NNH H

HH

HH P

PdSiCl3SiCl3

NNH H

FeP

PdSiCl3SiCl3

NN

FeP

PdSiCl3SiCl3

NN

HH P

PdSiCl3SiCl3

NNH H

HH P

PdSiCl3SiCl3

NN

H3CH

HH

H

Model 1

Model 2


63






PPd

H

SiCl3NN

HH

PPd

HSiCl3

NN

HH

PPd

HSiCl3

NN

HH

PPd

SiCl3NN

HH PPd

SiCl3NN

HH

1900

22

-02

-83

141

52

PPd

SiCl3NN

HH

PPd

Cl3SiNN

HH

64


endoendo-syn

PPdH

SiCl3NN

Fe

PPd HSiCl3NN

FeFe P

Pd

SiCl3NN

PPd HSiCl3NN

Fe

Cl3Si

PPd

SiCl3N

Fe

N

PPd

Cl3SiNN

Fe

PPdH

SiCl3NN

Fe

PPd

NN

Fe

Cl3Si

R

-35

09

TS1

TS2

-205

+-103

+styrene

00

42+48

61

Dagger Dagger


65





FeP

PdH

SiCl3NN

PPd

HSiCl3

NN

Fe


66


PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPd

H

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPdSiCl3NN

Fe

PPd

SiCl3NN

Fe

48

00

1609

51

-103

-113



endo-syn

exo-synendo

exo


kcalmol

67



endo-syn

exo-syn

NMe2

PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

NMe2

PPd

SiCl3NN

Fe

NMe2

PPdH

SiCl3NN

Fe

Me2N

PPd

SiCl3NN

Fe

PPdSiCl3

NN

Fe

NMe2

PPd

SiCl3NN

Fe

Me2N

48

00

08

03

16

-172

-155

exo

endo


68


DD

D

D5

HndashSiCl3 [PdL]

DD

D

D5

HO H DD

H

D5

HO H DH

H

D5

HO H DD

D

D5

HO D

oxid workup

+ + +


MeD1

MeD2

13C-1H-HZQCNMR

MeD2

MeD11 equivsilane

5 equivsilane

EI-MS


69





70


Energy(kcalmol)

(at rt)


(kcalmol)

(at rt)

ee

endo-syn -103 123

75 (S)[65 (S)]

endo-syn -172 859

81 (R)[64 (R)]

endo-anti -81 03 75 (S)[65 (S)]


75 (S)[65 (S)] exo-syn -155 48

81 (R)[64 (R)]

exo-anti -106 669

75 (S)[65 (S)]

exo-anti -153 35

81 (R)[64 (R)]


71

Conclusions




72




22






Step 12 Step 21



23








Josiphos

Pigiphos

Fe

NMe2

MeFe PPh2

NMe2

Me

Fe PPh2

PCy2

Me

PFe PPh2

Fe

Ph2PUgis amine

24




NMe2

MePAr2

R1 R3

OO

R2

H2NNH2

NNH

R3R2

R1

Fe Fe

NMe

NR3

R2

R1

PAr2


AcOH 70-90 degC

80-90 yield

+

25

Ph2PCy2P

Ph2P

PCy2

Ph2PCy2P

Ph2P

Cy2P

PPh2PCy2

Ph2P

PCy2

Si

O

O

HN

O

NH

Si

Si

O

OHN

O

HN

Si

NP N P

NP

NP Si

O

OHN

ONH

Si

Si

OO

HNO NH

Si

Si

O

ONH

O

HN

Si

Si

O

ONH

ONH Si

SiO

ONH

OHN

Si

Si

OO

NH O

HN

Si

PPh2Cy2P

Ph2PCy2P

PPh2

PCy2

PPh2PCy2

Ph2PPCy2

PPh2

Cy2P

PPh2PCy2

PPh2

PCy2

Ph2P

Cy2P

Fe

PPh2Cy2P

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe




26



NH3C

CH3

OCH3

CH3OCl

H

P

MeFe

PPh2


2

Ir

S

NHHN

O

H H

P(t-Bu)2

MeFe

PPh2

COOH

(+)-Biotin(LONZA)

Rh

Sitagliptin(Merck)

Rh

F

FF

NN

NN

ONH2

CF3

PtBu2

MeFe P(4-F3CPh)2

27



H NN

ONHO

O

H NN

ONHO


SC=2000


96 ee

P(t-Bu)2

MeFe PPh2

N NN

OH

O

NH

ONH OH



28




P(t-Bu)2

MeFe PPh2

O

HOOCHN

S

F

O O

O

HOOCHN

S

F

O O

RuCl2(P-P)LnNEt3

H2 EtOH

O

HN

S

F

O O

O

HOHNP-P =

97 ee

29



Up to 97 ee

F

FF

NN

NN

ONH2

CF3



P(t-Bu)2

MeFe

P(t-Bu)2Me

Fe P CF32

PPh2

R OMe

NH2 O

R OMe


R NHPh

NH2 O

R NHPh

NH2 O

H2

Rh Josiphos ligand

H2

30











31










32



33

$

amp$

$

$

($

$$ amp$ )$ $ $ $ $ $

$

amp()+-


ampamp2824+

5lt=-amp)gt+gt2)42






34




α1=+9degα2=-21deg




35

Pd

L1

L2R

R

Pd

L1

L2

R

R

Nu Nu



36



X-rayX-ray

PhPh FeP

NNPd Ph

Ph


+

Ph

FeP

NNPd

Ph

Ph

Ph


+

PhPh FeP

NN

Pd Ph

Ph

+



Ph Ph

OCOR

NH2

Ph Ph


40 degC THF


N

Me

N

Fe

PPh2R

37



Ph

FeP

NNPd

Ph

a) R-product



NuNu

a)

b)

+

RS




PN

PdP N

PdP N

+ +


tc = 2 kcalmol

(Ab initio studies)

38

NH

NPd

PH3

NH3


NPd

PH3


NH

NPd

PH3

NH3

50 kJmol

36 kJmol

NH3+

41 kJmol

NH3+

+



PdP N

PdP N

PdP N

+

+ +


tc = 8 kJmol


ct = 29 kJmol


for C out of plane



40

PhPh Fe

P

NNPd

Ph

Ph

Ph

Ph

FeP

NNPd

Ph

Ph

exo-syn-anti (71)

+

exo-syn-syn (29)

+

S R



41

PhFe

P

NN

Pd


+

Ph




42

Ph

Ph

PdP N

Ph

Ph

P NPd

Nu

Nu




43




PMe

NN

Ph

Ph

PhPh

PdNN

MePd

FeFeP

Ph

Ph

Ph

Ph

Ph Ph

NHCH2Ph

(S)

Ph Ph

OCOOEtNu-Nu-


950 ee resp 945 ee

rac

44






Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

Fe

N CN

PPh2

Me

Fe

N NC

PPh2

MePdR

R+

PdR

R+

X-ray

45



Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

PdR

R+

PdR

R+

Fe

N CN

PPh2

Me Pd

NHR2R

RFe

N CN

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

Fe

N NC

PPh2

Me Pd

NHR2R

RFe

N NC

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

dr 8515exoendo 8218

46














47


Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



Ph Ph

OCOOEt

Ph Ph

N



NH

Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



48

N

Me

N

Fe

PPh2

Ph Ph

OCO2Et

Ph Ph

NHCH2Ph

[Pd(dba)2 ]+ Ligand





991 (220)

67 (11)

33 (2)

987 (153)

gt995 (gt400)



3 mol Pd-catalyst

PF6- Selectivity

Killer




49

Ph

Ph

P

NPd

+

endo-syn-syn

+

exo-syn-syn

Ph

PhP

NPd

Ph Ph

OCOOEt

Ph Ph



Slow with PF6-

(tight ion pairs )

Fast with F-

(Coordination)

R-Product S-Product

more stable


S R


50










51

E N Jacobsen et al



NN

OMn

OCl

X X

HHX = OMe 96 ee

X = NO2 22 ee

52




MeO MeO

CN

OOOPh

OPhOPAr2

OAr2P CF3F3C MeMe

HCN [Ni(COD)2] L

Ar =

91 eeL

16 ee

53





OCO O

++

nn2 3

4

1


Δ

54

([α]D=-450)




Polymer)50 220 370 1800


PCy2Me

Fe P

CF3

CF32

PCy2Me

Fe P

OMe

OMe2

PCy2Me

Fe P

H

H2

PCy2Me

Fe P

CH3

CH32

55


Markus Baumann


NMeN

Fe

Me

Me

Me

P

O+ PhOTf



O Ph O Ph O

Ph

+ +

2

Rn

Rn=(m-CF3)2

Rn=(m-SiMe3)2

Rn=(p-OMe)

Rn=(p-CF3)

1 (34ee)

8 (62ee)

1 (46ee)

1 (10ee)

94 (88ee)

90 (95ee)

97 (96ee)

96 (95ee)

5

2

2

3

56



NMeN

Fe

PMe Me

F3C

F3CNMeN

Fe

PMe Me

CF3

F3CF3C

F3C

NMeN

Fe

PF3C CF3

MeO

MeO

NMeN

Fe

PMe Me

MeO

MeO

NMeN

Fe

PF3C CF3

NMeN

Fe

PMe Me

NMeN

Fe

PMe Me

Me2N

Me2NNMeN

Fe

PF3C CF3

F3C

F3C

95 ee985 ee

5 ee72 ee

33 ee

98 ee90 ee

40 ee

the worst

and the best

57





NMeN

Fe

Me

Me

Me

PPh2


2) Oxidative Workup

OH

NMeN

Fe PPh2

NMeN

Fe PPh2

Me

39ee 76ee 99ee

Catalytic activity

NMeN

Fe

MeO

OMe

OMe

PPh2

NMeN

Fe

Me

Me

Me

P

CF3

CF3

2

82ee 91ee

58


X

Fe PPh2

N N

Mes

Me

X

1) cat PdCl2(L)

2) Oxidation


= L

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=078rsup2=0996

NMe₂

OMe

Me

ClH


Fe P X

N N

Mes

Me

1) cat PdCl2(L)

2) Oxidation


2

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=014rsup2=0986

NMe₂OMe

Me HCl


59



Fe P X

N N

Mes

Me

OH1) cat PdCl2(L)

2) Oxidation


2

60



X

Fe PPh2

N N

Mes

Me

X

OH1) cat PdCl2(L)

2) Oxidation

= L

61


PdN

P

Cl

Cl

PdN

P H

SiCl3

R

PdN

P

R

SiCl3

N

PdP

HCl3Si

N

Pd

P

Cl3Si

R

R





Unclear formation

σp

σp+


62


TK Woo

HH P

PdSiCl3SiCl3

NNH H

HH

HH P

PdSiCl3SiCl3

NNH H

FeP

PdSiCl3SiCl3

NN

FeP

PdSiCl3SiCl3

NN

HH P

PdSiCl3SiCl3

NNH H

HH P

PdSiCl3SiCl3

NN

H3CH

HH

H

Model 1

Model 2


63






PPd

H

SiCl3NN

HH

PPd

HSiCl3

NN

HH

PPd

HSiCl3

NN

HH

PPd

SiCl3NN

HH PPd

SiCl3NN

HH

1900

22

-02

-83

141

52

PPd

SiCl3NN

HH

PPd

Cl3SiNN

HH

64


endoendo-syn

PPdH

SiCl3NN

Fe

PPd HSiCl3NN

FeFe P

Pd

SiCl3NN

PPd HSiCl3NN

Fe

Cl3Si

PPd

SiCl3N

Fe

N

PPd

Cl3SiNN

Fe

PPdH

SiCl3NN

Fe

PPd

NN

Fe

Cl3Si

R

-35

09

TS1

TS2

-205

+-103

+styrene

00

42+48

61

Dagger Dagger


65





FeP

PdH

SiCl3NN

PPd

HSiCl3

NN

Fe


66


PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPd

H

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPdSiCl3NN

Fe

PPd

SiCl3NN

Fe

48

00

1609

51

-103

-113



endo-syn

exo-synendo

exo


kcalmol

67



endo-syn

exo-syn

NMe2

PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

NMe2

PPd

SiCl3NN

Fe

NMe2

PPdH

SiCl3NN

Fe

Me2N

PPd

SiCl3NN

Fe

PPdSiCl3

NN

Fe

NMe2

PPd

SiCl3NN

Fe

Me2N

48

00

08

03

16

-172

-155

exo

endo


68


DD

D

D5

HndashSiCl3 [PdL]

DD

D

D5

HO H DD

H

D5

HO H DH

H

D5

HO H DD

D

D5

HO D

oxid workup

+ + +


MeD1

MeD2

13C-1H-HZQCNMR

MeD2

MeD11 equivsilane

5 equivsilane

EI-MS


69





70


Energy(kcalmol)

(at rt)


(kcalmol)

(at rt)

ee

endo-syn -103 123

75 (S)[65 (S)]

endo-syn -172 859

81 (R)[64 (R)]

endo-anti -81 03 75 (S)[65 (S)]


75 (S)[65 (S)] exo-syn -155 48

81 (R)[64 (R)]

exo-anti -106 669

75 (S)[65 (S)]

exo-anti -153 35

81 (R)[64 (R)]


71

Conclusions




72






Step 12 Step 21



23








Josiphos

Pigiphos

Fe

NMe2

MeFe PPh2

NMe2

Me

Fe PPh2

PCy2

Me

PFe PPh2

Fe

Ph2PUgis amine

24




NMe2

MePAr2

R1 R3

OO

R2

H2NNH2

NNH

R3R2

R1

Fe Fe

NMe

NR3

R2

R1

PAr2


AcOH 70-90 degC

80-90 yield

+

25

Ph2PCy2P

Ph2P

PCy2

Ph2PCy2P

Ph2P

Cy2P

PPh2PCy2

Ph2P

PCy2

Si

O

O

HN

O

NH

Si

Si

O

OHN

O

HN

Si

NP N P

NP

NP Si

O

OHN

ONH

Si

Si

OO

HNO NH

Si

Si

O

ONH

O

HN

Si

Si

O

ONH

ONH Si

SiO

ONH

OHN

Si

Si

OO

NH O

HN

Si

PPh2Cy2P

Ph2PCy2P

PPh2

PCy2

PPh2PCy2

Ph2PPCy2

PPh2

Cy2P

PPh2PCy2

PPh2

PCy2

Ph2P

Cy2P

Fe

PPh2Cy2P

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe




26



NH3C

CH3

OCH3

CH3OCl

H

P

MeFe

PPh2


2

Ir

S

NHHN

O

H H

P(t-Bu)2

MeFe

PPh2

COOH

(+)-Biotin(LONZA)

Rh

Sitagliptin(Merck)

Rh

F

FF

NN

NN

ONH2

CF3

PtBu2

MeFe P(4-F3CPh)2

27



H NN

ONHO

O

H NN

ONHO


SC=2000


96 ee

P(t-Bu)2

MeFe PPh2

N NN

OH

O

NH

ONH OH



28




P(t-Bu)2

MeFe PPh2

O

HOOCHN

S

F

O O

O

HOOCHN

S

F

O O

RuCl2(P-P)LnNEt3

H2 EtOH

O

HN

S

F

O O

O

HOHNP-P =

97 ee

29



Up to 97 ee

F

FF

NN

NN

ONH2

CF3



P(t-Bu)2

MeFe

P(t-Bu)2Me

Fe P CF32

PPh2

R OMe

NH2 O

R OMe


R NHPh

NH2 O

R NHPh

NH2 O

H2

Rh Josiphos ligand

H2

30











31










32



33

$

amp$

$

$

($

$$ amp$ )$ $ $ $ $ $

$

amp()+-


ampamp2824+

5lt=-amp)gt+gt2)42






34




α1=+9degα2=-21deg




35

Pd

L1

L2R

R

Pd

L1

L2

R

R

Nu Nu



36



X-rayX-ray

PhPh FeP

NNPd Ph

Ph


+

Ph

FeP

NNPd

Ph

Ph

Ph


+

PhPh FeP

NN

Pd Ph

Ph

+



Ph Ph

OCOR

NH2

Ph Ph


40 degC THF


N

Me

N

Fe

PPh2R

37



Ph

FeP

NNPd

Ph

a) R-product



NuNu

a)

b)

+

RS




PN

PdP N

PdP N

+ +


tc = 2 kcalmol

(Ab initio studies)

38

NH

NPd

PH3

NH3


NPd

PH3


NH

NPd

PH3

NH3

50 kJmol

36 kJmol

NH3+

41 kJmol

NH3+

+



PdP N

PdP N

PdP N

+

+ +


tc = 8 kJmol


ct = 29 kJmol


for C out of plane



40

PhPh Fe

P

NNPd

Ph

Ph

Ph

Ph

FeP

NNPd

Ph

Ph

exo-syn-anti (71)

+

exo-syn-syn (29)

+

S R



41

PhFe

P

NN

Pd


+

Ph




42

Ph

Ph

PdP N

Ph

Ph

P NPd

Nu

Nu




43




PMe

NN

Ph

Ph

PhPh

PdNN

MePd

FeFeP

Ph

Ph

Ph

Ph

Ph Ph

NHCH2Ph

(S)

Ph Ph

OCOOEtNu-Nu-


950 ee resp 945 ee

rac

44






Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

Fe

N CN

PPh2

Me

Fe

N NC

PPh2

MePdR

R+

PdR

R+

X-ray

45



Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

PdR

R+

PdR

R+

Fe

N CN

PPh2

Me Pd

NHR2R

RFe

N CN

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

Fe

N NC

PPh2

Me Pd

NHR2R

RFe

N NC

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

dr 8515exoendo 8218

46














47


Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



Ph Ph

OCOOEt

Ph Ph

N



NH

Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



48

N

Me

N

Fe

PPh2

Ph Ph

OCO2Et

Ph Ph

NHCH2Ph

[Pd(dba)2 ]+ Ligand





991 (220)

67 (11)

33 (2)

987 (153)

gt995 (gt400)



3 mol Pd-catalyst

PF6- Selectivity

Killer




49

Ph

Ph

P

NPd

+

endo-syn-syn

+

exo-syn-syn

Ph

PhP

NPd

Ph Ph

OCOOEt

Ph Ph



Slow with PF6-

(tight ion pairs )

Fast with F-

(Coordination)

R-Product S-Product

more stable


S R


50










51

E N Jacobsen et al



NN

OMn

OCl

X X

HHX = OMe 96 ee

X = NO2 22 ee

52




MeO MeO

CN

OOOPh

OPhOPAr2

OAr2P CF3F3C MeMe

HCN [Ni(COD)2] L

Ar =

91 eeL

16 ee

53





OCO O

++

nn2 3

4

1


Δ

54

([α]D=-450)




Polymer)50 220 370 1800


PCy2Me

Fe P

CF3

CF32

PCy2Me

Fe P

OMe

OMe2

PCy2Me

Fe P

H

H2

PCy2Me

Fe P

CH3

CH32

55


Markus Baumann


NMeN

Fe

Me

Me

Me

P

O+ PhOTf



O Ph O Ph O

Ph

+ +

2

Rn

Rn=(m-CF3)2

Rn=(m-SiMe3)2

Rn=(p-OMe)

Rn=(p-CF3)

1 (34ee)

8 (62ee)

1 (46ee)

1 (10ee)

94 (88ee)

90 (95ee)

97 (96ee)

96 (95ee)

5

2

2

3

56



NMeN

Fe

PMe Me

F3C

F3CNMeN

Fe

PMe Me

CF3

F3CF3C

F3C

NMeN

Fe

PF3C CF3

MeO

MeO

NMeN

Fe

PMe Me

MeO

MeO

NMeN

Fe

PF3C CF3

NMeN

Fe

PMe Me

NMeN

Fe

PMe Me

Me2N

Me2NNMeN

Fe

PF3C CF3

F3C

F3C

95 ee985 ee

5 ee72 ee

33 ee

98 ee90 ee

40 ee

the worst

and the best

57





NMeN

Fe

Me

Me

Me

PPh2


2) Oxidative Workup

OH

NMeN

Fe PPh2

NMeN

Fe PPh2

Me

39ee 76ee 99ee

Catalytic activity

NMeN

Fe

MeO

OMe

OMe

PPh2

NMeN

Fe

Me

Me

Me

P

CF3

CF3

2

82ee 91ee

58


X

Fe PPh2

N N

Mes

Me

X

1) cat PdCl2(L)

2) Oxidation


= L

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=078rsup2=0996

NMe₂

OMe

Me

ClH


Fe P X

N N

Mes

Me

1) cat PdCl2(L)

2) Oxidation


2

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=014rsup2=0986

NMe₂OMe

Me HCl


59



Fe P X

N N

Mes

Me

OH1) cat PdCl2(L)

2) Oxidation


2

60



X

Fe PPh2

N N

Mes

Me

X

OH1) cat PdCl2(L)

2) Oxidation

= L

61


PdN

P

Cl

Cl

PdN

P H

SiCl3

R

PdN

P

R

SiCl3

N

PdP

HCl3Si

N

Pd

P

Cl3Si

R

R





Unclear formation

σp

σp+


62


TK Woo

HH P

PdSiCl3SiCl3

NNH H

HH

HH P

PdSiCl3SiCl3

NNH H

FeP

PdSiCl3SiCl3

NN

FeP

PdSiCl3SiCl3

NN

HH P

PdSiCl3SiCl3

NNH H

HH P

PdSiCl3SiCl3

NN

H3CH

HH

H

Model 1

Model 2


63






PPd

H

SiCl3NN

HH

PPd

HSiCl3

NN

HH

PPd

HSiCl3

NN

HH

PPd

SiCl3NN

HH PPd

SiCl3NN

HH

1900

22

-02

-83

141

52

PPd

SiCl3NN

HH

PPd

Cl3SiNN

HH

64


endoendo-syn

PPdH

SiCl3NN

Fe

PPd HSiCl3NN

FeFe P

Pd

SiCl3NN

PPd HSiCl3NN

Fe

Cl3Si

PPd

SiCl3N

Fe

N

PPd

Cl3SiNN

Fe

PPdH

SiCl3NN

Fe

PPd

NN

Fe

Cl3Si

R

-35

09

TS1

TS2

-205

+-103

+styrene

00

42+48

61

Dagger Dagger


65





FeP

PdH

SiCl3NN

PPd

HSiCl3

NN

Fe


66


PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPd

H

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPdSiCl3NN

Fe

PPd

SiCl3NN

Fe

48

00

1609

51

-103

-113



endo-syn

exo-synendo

exo


kcalmol

67



endo-syn

exo-syn

NMe2

PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

NMe2

PPd

SiCl3NN

Fe

NMe2

PPdH

SiCl3NN

Fe

Me2N

PPd

SiCl3NN

Fe

PPdSiCl3

NN

Fe

NMe2

PPd

SiCl3NN

Fe

Me2N

48

00

08

03

16

-172

-155

exo

endo


68


DD

D

D5

HndashSiCl3 [PdL]

DD

D

D5

HO H DD

H

D5

HO H DH

H

D5

HO H DD

D

D5

HO D

oxid workup

+ + +


MeD1

MeD2

13C-1H-HZQCNMR

MeD2

MeD11 equivsilane

5 equivsilane

EI-MS


69





70


Energy(kcalmol)

(at rt)


(kcalmol)

(at rt)

ee

endo-syn -103 123

75 (S)[65 (S)]

endo-syn -172 859

81 (R)[64 (R)]

endo-anti -81 03 75 (S)[65 (S)]


75 (S)[65 (S)] exo-syn -155 48

81 (R)[64 (R)]

exo-anti -106 669

75 (S)[65 (S)]

exo-anti -153 35

81 (R)[64 (R)]


71

Conclusions




72








Josiphos

Pigiphos

Fe

NMe2

MeFe PPh2

NMe2

Me

Fe PPh2

PCy2

Me

PFe PPh2

Fe

Ph2PUgis amine

24




NMe2

MePAr2

R1 R3

OO

R2

H2NNH2

NNH

R3R2

R1

Fe Fe

NMe

NR3

R2

R1

PAr2


AcOH 70-90 degC

80-90 yield

+

25

Ph2PCy2P

Ph2P

PCy2

Ph2PCy2P

Ph2P

Cy2P

PPh2PCy2

Ph2P

PCy2

Si

O

O

HN

O

NH

Si

Si

O

OHN

O

HN

Si

NP N P

NP

NP Si

O

OHN

ONH

Si

Si

OO

HNO NH

Si

Si

O

ONH

O

HN

Si

Si

O

ONH

ONH Si

SiO

ONH

OHN

Si

Si

OO

NH O

HN

Si

PPh2Cy2P

Ph2PCy2P

PPh2

PCy2

PPh2PCy2

Ph2PPCy2

PPh2

Cy2P

PPh2PCy2

PPh2

PCy2

Ph2P

Cy2P

Fe

PPh2Cy2P

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe




26



NH3C

CH3

OCH3

CH3OCl

H

P

MeFe

PPh2


2

Ir

S

NHHN

O

H H

P(t-Bu)2

MeFe

PPh2

COOH

(+)-Biotin(LONZA)

Rh

Sitagliptin(Merck)

Rh

F

FF

NN

NN

ONH2

CF3

PtBu2

MeFe P(4-F3CPh)2

27



H NN

ONHO

O

H NN

ONHO


SC=2000


96 ee

P(t-Bu)2

MeFe PPh2

N NN

OH

O

NH

ONH OH



28




P(t-Bu)2

MeFe PPh2

O

HOOCHN

S

F

O O

O

HOOCHN

S

F

O O

RuCl2(P-P)LnNEt3

H2 EtOH

O

HN

S

F

O O

O

HOHNP-P =

97 ee

29



Up to 97 ee

F

FF

NN

NN

ONH2

CF3



P(t-Bu)2

MeFe

P(t-Bu)2Me

Fe P CF32

PPh2

R OMe

NH2 O

R OMe


R NHPh

NH2 O

R NHPh

NH2 O

H2

Rh Josiphos ligand

H2

30











31










32



33

$

amp$

$

$

($

$$ amp$ )$ $ $ $ $ $

$

amp()+-


ampamp2824+

5lt=-amp)gt+gt2)42






34




α1=+9degα2=-21deg




35

Pd

L1

L2R

R

Pd

L1

L2

R

R

Nu Nu



36



X-rayX-ray

PhPh FeP

NNPd Ph

Ph


+

Ph

FeP

NNPd

Ph

Ph

Ph


+

PhPh FeP

NN

Pd Ph

Ph

+



Ph Ph

OCOR

NH2

Ph Ph


40 degC THF


N

Me

N

Fe

PPh2R

37



Ph

FeP

NNPd

Ph

a) R-product



NuNu

a)

b)

+

RS




PN

PdP N

PdP N

+ +


tc = 2 kcalmol

(Ab initio studies)

38

NH

NPd

PH3

NH3


NPd

PH3


NH

NPd

PH3

NH3

50 kJmol

36 kJmol

NH3+

41 kJmol

NH3+

+



PdP N

PdP N

PdP N

+

+ +


tc = 8 kJmol


ct = 29 kJmol


for C out of plane



40

PhPh Fe

P

NNPd

Ph

Ph

Ph

Ph

FeP

NNPd

Ph

Ph

exo-syn-anti (71)

+

exo-syn-syn (29)

+

S R



41

PhFe

P

NN

Pd


+

Ph




42

Ph

Ph

PdP N

Ph

Ph

P NPd

Nu

Nu




43




PMe

NN

Ph

Ph

PhPh

PdNN

MePd

FeFeP

Ph

Ph

Ph

Ph

Ph Ph

NHCH2Ph

(S)

Ph Ph

OCOOEtNu-Nu-


950 ee resp 945 ee

rac

44






Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

Fe

N CN

PPh2

Me

Fe

N NC

PPh2

MePdR

R+

PdR

R+

X-ray

45



Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

PdR

R+

PdR

R+

Fe

N CN

PPh2

Me Pd

NHR2R

RFe

N CN

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

Fe

N NC

PPh2

Me Pd

NHR2R

RFe

N NC

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

dr 8515exoendo 8218

46














47


Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



Ph Ph

OCOOEt

Ph Ph

N



NH

Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



48

N

Me

N

Fe

PPh2

Ph Ph

OCO2Et

Ph Ph

NHCH2Ph

[Pd(dba)2 ]+ Ligand





991 (220)

67 (11)

33 (2)

987 (153)

gt995 (gt400)



3 mol Pd-catalyst

PF6- Selectivity

Killer




49

Ph

Ph

P

NPd

+

endo-syn-syn

+

exo-syn-syn

Ph

PhP

NPd

Ph Ph

OCOOEt

Ph Ph



Slow with PF6-

(tight ion pairs )

Fast with F-

(Coordination)

R-Product S-Product

more stable


S R


50










51

E N Jacobsen et al



NN

OMn

OCl

X X

HHX = OMe 96 ee

X = NO2 22 ee

52




MeO MeO

CN

OOOPh

OPhOPAr2

OAr2P CF3F3C MeMe

HCN [Ni(COD)2] L

Ar =

91 eeL

16 ee

53





OCO O

++

nn2 3

4

1


Δ

54

([α]D=-450)




Polymer)50 220 370 1800


PCy2Me

Fe P

CF3

CF32

PCy2Me

Fe P

OMe

OMe2

PCy2Me

Fe P

H

H2

PCy2Me

Fe P

CH3

CH32

55


Markus Baumann


NMeN

Fe

Me

Me

Me

P

O+ PhOTf



O Ph O Ph O

Ph

+ +

2

Rn

Rn=(m-CF3)2

Rn=(m-SiMe3)2

Rn=(p-OMe)

Rn=(p-CF3)

1 (34ee)

8 (62ee)

1 (46ee)

1 (10ee)

94 (88ee)

90 (95ee)

97 (96ee)

96 (95ee)

5

2

2

3

56



NMeN

Fe

PMe Me

F3C

F3CNMeN

Fe

PMe Me

CF3

F3CF3C

F3C

NMeN

Fe

PF3C CF3

MeO

MeO

NMeN

Fe

PMe Me

MeO

MeO

NMeN

Fe

PF3C CF3

NMeN

Fe

PMe Me

NMeN

Fe

PMe Me

Me2N

Me2NNMeN

Fe

PF3C CF3

F3C

F3C

95 ee985 ee

5 ee72 ee

33 ee

98 ee90 ee

40 ee

the worst

and the best

57





NMeN

Fe

Me

Me

Me

PPh2


2) Oxidative Workup

OH

NMeN

Fe PPh2

NMeN

Fe PPh2

Me

39ee 76ee 99ee

Catalytic activity

NMeN

Fe

MeO

OMe

OMe

PPh2

NMeN

Fe

Me

Me

Me

P

CF3

CF3

2

82ee 91ee

58


X

Fe PPh2

N N

Mes

Me

X

1) cat PdCl2(L)

2) Oxidation


= L

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=078rsup2=0996

NMe₂

OMe

Me

ClH


Fe P X

N N

Mes

Me

1) cat PdCl2(L)

2) Oxidation


2

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=014rsup2=0986

NMe₂OMe

Me HCl


59



Fe P X

N N

Mes

Me

OH1) cat PdCl2(L)

2) Oxidation


2

60



X

Fe PPh2

N N

Mes

Me

X

OH1) cat PdCl2(L)

2) Oxidation

= L

61


PdN

P

Cl

Cl

PdN

P H

SiCl3

R

PdN

P

R

SiCl3

N

PdP

HCl3Si

N

Pd

P

Cl3Si

R

R





Unclear formation

σp

σp+


62


TK Woo

HH P

PdSiCl3SiCl3

NNH H

HH

HH P

PdSiCl3SiCl3

NNH H

FeP

PdSiCl3SiCl3

NN

FeP

PdSiCl3SiCl3

NN

HH P

PdSiCl3SiCl3

NNH H

HH P

PdSiCl3SiCl3

NN

H3CH

HH

H

Model 1

Model 2


63






PPd

H

SiCl3NN

HH

PPd

HSiCl3

NN

HH

PPd

HSiCl3

NN

HH

PPd

SiCl3NN

HH PPd

SiCl3NN

HH

1900

22

-02

-83

141

52

PPd

SiCl3NN

HH

PPd

Cl3SiNN

HH

64


endoendo-syn

PPdH

SiCl3NN

Fe

PPd HSiCl3NN

FeFe P

Pd

SiCl3NN

PPd HSiCl3NN

Fe

Cl3Si

PPd

SiCl3N

Fe

N

PPd

Cl3SiNN

Fe

PPdH

SiCl3NN

Fe

PPd

NN

Fe

Cl3Si

R

-35

09

TS1

TS2

-205

+-103

+styrene

00

42+48

61

Dagger Dagger


65





FeP

PdH

SiCl3NN

PPd

HSiCl3

NN

Fe


66


PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPd

H

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPdSiCl3NN

Fe

PPd

SiCl3NN

Fe

48

00

1609

51

-103

-113



endo-syn

exo-synendo

exo


kcalmol

67



endo-syn

exo-syn

NMe2

PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

NMe2

PPd

SiCl3NN

Fe

NMe2

PPdH

SiCl3NN

Fe

Me2N

PPd

SiCl3NN

Fe

PPdSiCl3

NN

Fe

NMe2

PPd

SiCl3NN

Fe

Me2N

48

00

08

03

16

-172

-155

exo

endo


68


DD

D

D5

HndashSiCl3 [PdL]

DD

D

D5

HO H DD

H

D5

HO H DH

H

D5

HO H DD

D

D5

HO D

oxid workup

+ + +


MeD1

MeD2

13C-1H-HZQCNMR

MeD2

MeD11 equivsilane

5 equivsilane

EI-MS


69





70


Energy(kcalmol)

(at rt)


(kcalmol)

(at rt)

ee

endo-syn -103 123

75 (S)[65 (S)]

endo-syn -172 859

81 (R)[64 (R)]

endo-anti -81 03 75 (S)[65 (S)]


75 (S)[65 (S)] exo-syn -155 48

81 (R)[64 (R)]

exo-anti -106 669

75 (S)[65 (S)]

exo-anti -153 35

81 (R)[64 (R)]


71

Conclusions




72




NMe2

MePAr2

R1 R3

OO

R2

H2NNH2

NNH

R3R2

R1

Fe Fe

NMe

NR3

R2

R1

PAr2


AcOH 70-90 degC

80-90 yield

+

25

Ph2PCy2P

Ph2P

PCy2

Ph2PCy2P

Ph2P

Cy2P

PPh2PCy2

Ph2P

PCy2

Si

O

O

HN

O

NH

Si

Si

O

OHN

O

HN

Si

NP N P

NP

NP Si

O

OHN

ONH

Si

Si

OO

HNO NH

Si

Si

O

ONH

O

HN

Si

Si

O

ONH

ONH Si

SiO

ONH

OHN

Si

Si

OO

NH O

HN

Si

PPh2Cy2P

Ph2PCy2P

PPh2

PCy2

PPh2PCy2

Ph2PPCy2

PPh2

Cy2P

PPh2PCy2

PPh2

PCy2

Ph2P

Cy2P

Fe

PPh2Cy2P

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe




26



NH3C

CH3

OCH3

CH3OCl

H

P

MeFe

PPh2


2

Ir

S

NHHN

O

H H

P(t-Bu)2

MeFe

PPh2

COOH

(+)-Biotin(LONZA)

Rh

Sitagliptin(Merck)

Rh

F

FF

NN

NN

ONH2

CF3

PtBu2

MeFe P(4-F3CPh)2

27



H NN

ONHO

O

H NN

ONHO


SC=2000


96 ee

P(t-Bu)2

MeFe PPh2

N NN

OH

O

NH

ONH OH



28




P(t-Bu)2

MeFe PPh2

O

HOOCHN

S

F

O O

O

HOOCHN

S

F

O O

RuCl2(P-P)LnNEt3

H2 EtOH

O

HN

S

F

O O

O

HOHNP-P =

97 ee

29



Up to 97 ee

F

FF

NN

NN

ONH2

CF3



P(t-Bu)2

MeFe

P(t-Bu)2Me

Fe P CF32

PPh2

R OMe

NH2 O

R OMe


R NHPh

NH2 O

R NHPh

NH2 O

H2

Rh Josiphos ligand

H2

30











31










32



33

$

amp$

$

$

($

$$ amp$ )$ $ $ $ $ $

$

amp()+-


ampamp2824+

5lt=-amp)gt+gt2)42






34




α1=+9degα2=-21deg




35

Pd

L1

L2R

R

Pd

L1

L2

R

R

Nu Nu



36



X-rayX-ray

PhPh FeP

NNPd Ph

Ph


+

Ph

FeP

NNPd

Ph

Ph

Ph


+

PhPh FeP

NN

Pd Ph

Ph

+



Ph Ph

OCOR

NH2

Ph Ph


40 degC THF


N

Me

N

Fe

PPh2R

37



Ph

FeP

NNPd

Ph

a) R-product



NuNu

a)

b)

+

RS




PN

PdP N

PdP N

+ +


tc = 2 kcalmol

(Ab initio studies)

38

NH

NPd

PH3

NH3


NPd

PH3


NH

NPd

PH3

NH3

50 kJmol

36 kJmol

NH3+

41 kJmol

NH3+

+



PdP N

PdP N

PdP N

+

+ +


tc = 8 kJmol


ct = 29 kJmol


for C out of plane



40

PhPh Fe

P

NNPd

Ph

Ph

Ph

Ph

FeP

NNPd

Ph

Ph

exo-syn-anti (71)

+

exo-syn-syn (29)

+

S R



41

PhFe

P

NN

Pd


+

Ph




42

Ph

Ph

PdP N

Ph

Ph

P NPd

Nu

Nu




43




PMe

NN

Ph

Ph

PhPh

PdNN

MePd

FeFeP

Ph

Ph

Ph

Ph

Ph Ph

NHCH2Ph

(S)

Ph Ph

OCOOEtNu-Nu-


950 ee resp 945 ee

rac

44






Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

Fe

N CN

PPh2

Me

Fe

N NC

PPh2

MePdR

R+

PdR

R+

X-ray

45



Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

PdR

R+

PdR

R+

Fe

N CN

PPh2

Me Pd

NHR2R

RFe

N CN

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

Fe

N NC

PPh2

Me Pd

NHR2R

RFe

N NC

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

dr 8515exoendo 8218

46














47


Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



Ph Ph

OCOOEt

Ph Ph

N



NH

Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



48

N

Me

N

Fe

PPh2

Ph Ph

OCO2Et

Ph Ph

NHCH2Ph

[Pd(dba)2 ]+ Ligand





991 (220)

67 (11)

33 (2)

987 (153)

gt995 (gt400)



3 mol Pd-catalyst

PF6- Selectivity

Killer




49

Ph

Ph

P

NPd

+

endo-syn-syn

+

exo-syn-syn

Ph

PhP

NPd

Ph Ph

OCOOEt

Ph Ph



Slow with PF6-

(tight ion pairs )

Fast with F-

(Coordination)

R-Product S-Product

more stable


S R


50










51

E N Jacobsen et al



NN

OMn

OCl

X X

HHX = OMe 96 ee

X = NO2 22 ee

52




MeO MeO

CN

OOOPh

OPhOPAr2

OAr2P CF3F3C MeMe

HCN [Ni(COD)2] L

Ar =

91 eeL

16 ee

53





OCO O

++

nn2 3

4

1


Δ

54

([α]D=-450)




Polymer)50 220 370 1800


PCy2Me

Fe P

CF3

CF32

PCy2Me

Fe P

OMe

OMe2

PCy2Me

Fe P

H

H2

PCy2Me

Fe P

CH3

CH32

55


Markus Baumann


NMeN

Fe

Me

Me

Me

P

O+ PhOTf



O Ph O Ph O

Ph

+ +

2

Rn

Rn=(m-CF3)2

Rn=(m-SiMe3)2

Rn=(p-OMe)

Rn=(p-CF3)

1 (34ee)

8 (62ee)

1 (46ee)

1 (10ee)

94 (88ee)

90 (95ee)

97 (96ee)

96 (95ee)

5

2

2

3

56



NMeN

Fe

PMe Me

F3C

F3CNMeN

Fe

PMe Me

CF3

F3CF3C

F3C

NMeN

Fe

PF3C CF3

MeO

MeO

NMeN

Fe

PMe Me

MeO

MeO

NMeN

Fe

PF3C CF3

NMeN

Fe

PMe Me

NMeN

Fe

PMe Me

Me2N

Me2NNMeN

Fe

PF3C CF3

F3C

F3C

95 ee985 ee

5 ee72 ee

33 ee

98 ee90 ee

40 ee

the worst

and the best

57





NMeN

Fe

Me

Me

Me

PPh2


2) Oxidative Workup

OH

NMeN

Fe PPh2

NMeN

Fe PPh2

Me

39ee 76ee 99ee

Catalytic activity

NMeN

Fe

MeO

OMe

OMe

PPh2

NMeN

Fe

Me

Me

Me

P

CF3

CF3

2

82ee 91ee

58


X

Fe PPh2

N N

Mes

Me

X

1) cat PdCl2(L)

2) Oxidation


= L

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=078rsup2=0996

NMe₂

OMe

Me

ClH


Fe P X

N N

Mes

Me

1) cat PdCl2(L)

2) Oxidation


2

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=014rsup2=0986

NMe₂OMe

Me HCl


59



Fe P X

N N

Mes

Me

OH1) cat PdCl2(L)

2) Oxidation


2

60



X

Fe PPh2

N N

Mes

Me

X

OH1) cat PdCl2(L)

2) Oxidation

= L

61


PdN

P

Cl

Cl

PdN

P H

SiCl3

R

PdN

P

R

SiCl3

N

PdP

HCl3Si

N

Pd

P

Cl3Si

R

R





Unclear formation

σp

σp+


62


TK Woo

HH P

PdSiCl3SiCl3

NNH H

HH

HH P

PdSiCl3SiCl3

NNH H

FeP

PdSiCl3SiCl3

NN

FeP

PdSiCl3SiCl3

NN

HH P

PdSiCl3SiCl3

NNH H

HH P

PdSiCl3SiCl3

NN

H3CH

HH

H

Model 1

Model 2


63






PPd

H

SiCl3NN

HH

PPd

HSiCl3

NN

HH

PPd

HSiCl3

NN

HH

PPd

SiCl3NN

HH PPd

SiCl3NN

HH

1900

22

-02

-83

141

52

PPd

SiCl3NN

HH

PPd

Cl3SiNN

HH

64


endoendo-syn

PPdH

SiCl3NN

Fe

PPd HSiCl3NN

FeFe P

Pd

SiCl3NN

PPd HSiCl3NN

Fe

Cl3Si

PPd

SiCl3N

Fe

N

PPd

Cl3SiNN

Fe

PPdH

SiCl3NN

Fe

PPd

NN

Fe

Cl3Si

R

-35

09

TS1

TS2

-205

+-103

+styrene

00

42+48

61

Dagger Dagger


65





FeP

PdH

SiCl3NN

PPd

HSiCl3

NN

Fe


66


PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPd

H

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPdSiCl3NN

Fe

PPd

SiCl3NN

Fe

48

00

1609

51

-103

-113



endo-syn

exo-synendo

exo


kcalmol

67



endo-syn

exo-syn

NMe2

PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

NMe2

PPd

SiCl3NN

Fe

NMe2

PPdH

SiCl3NN

Fe

Me2N

PPd

SiCl3NN

Fe

PPdSiCl3

NN

Fe

NMe2

PPd

SiCl3NN

Fe

Me2N

48

00

08

03

16

-172

-155

exo

endo


68


DD

D

D5

HndashSiCl3 [PdL]

DD

D

D5

HO H DD

H

D5

HO H DH

H

D5

HO H DD

D

D5

HO D

oxid workup

+ + +


MeD1

MeD2

13C-1H-HZQCNMR

MeD2

MeD11 equivsilane

5 equivsilane

EI-MS


69





70


Energy(kcalmol)

(at rt)


(kcalmol)

(at rt)

ee

endo-syn -103 123

75 (S)[65 (S)]

endo-syn -172 859

81 (R)[64 (R)]

endo-anti -81 03 75 (S)[65 (S)]


75 (S)[65 (S)] exo-syn -155 48

81 (R)[64 (R)]

exo-anti -106 669

75 (S)[65 (S)]

exo-anti -153 35

81 (R)[64 (R)]


71

Conclusions




72

Ph2PCy2P

Ph2P

PCy2

Ph2PCy2P

Ph2P

Cy2P

PPh2PCy2

Ph2P

PCy2

Si

O

O

HN

O

NH

Si

Si

O

OHN

O

HN

Si

NP N P

NP

NP Si

O

OHN

ONH

Si

Si

OO

HNO NH

Si

Si

O

ONH

O

HN

Si

Si

O

ONH

ONH Si

SiO

ONH

OHN

Si

Si

OO

NH O

HN

Si

PPh2Cy2P

Ph2PCy2P

PPh2

PCy2

PPh2PCy2

Ph2PPCy2

PPh2

Cy2P

PPh2PCy2

PPh2

PCy2

Ph2P

Cy2P

Fe

PPh2Cy2P

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe




26



NH3C

CH3

OCH3

CH3OCl

H

P

MeFe

PPh2


2

Ir

S

NHHN

O

H H

P(t-Bu)2

MeFe

PPh2

COOH

(+)-Biotin(LONZA)

Rh

Sitagliptin(Merck)

Rh

F

FF

NN

NN

ONH2

CF3

PtBu2

MeFe P(4-F3CPh)2

27



H NN

ONHO

O

H NN

ONHO


SC=2000


96 ee

P(t-Bu)2

MeFe PPh2

N NN

OH

O

NH

ONH OH



28




P(t-Bu)2

MeFe PPh2

O

HOOCHN

S

F

O O

O

HOOCHN

S

F

O O

RuCl2(P-P)LnNEt3

H2 EtOH

O

HN

S

F

O O

O

HOHNP-P =

97 ee

29



Up to 97 ee

F

FF

NN

NN

ONH2

CF3



P(t-Bu)2

MeFe

P(t-Bu)2Me

Fe P CF32

PPh2

R OMe

NH2 O

R OMe


R NHPh

NH2 O

R NHPh

NH2 O

H2

Rh Josiphos ligand

H2

30











31










32



33

$

amp$

$

$

($

$$ amp$ )$ $ $ $ $ $

$

amp()+-


ampamp2824+

5lt=-amp)gt+gt2)42






34




α1=+9degα2=-21deg




35

Pd

L1

L2R

R

Pd

L1

L2

R

R

Nu Nu



36



X-rayX-ray

PhPh FeP

NNPd Ph

Ph


+

Ph

FeP

NNPd

Ph

Ph

Ph


+

PhPh FeP

NN

Pd Ph

Ph

+



Ph Ph

OCOR

NH2

Ph Ph


40 degC THF


N

Me

N

Fe

PPh2R

37



Ph

FeP

NNPd

Ph

a) R-product



NuNu

a)

b)

+

RS




PN

PdP N

PdP N

+ +


tc = 2 kcalmol

(Ab initio studies)

38

NH

NPd

PH3

NH3


NPd

PH3


NH

NPd

PH3

NH3

50 kJmol

36 kJmol

NH3+

41 kJmol

NH3+

+



PdP N

PdP N

PdP N

+

+ +


tc = 8 kJmol


ct = 29 kJmol


for C out of plane



40

PhPh Fe

P

NNPd

Ph

Ph

Ph

Ph

FeP

NNPd

Ph

Ph

exo-syn-anti (71)

+

exo-syn-syn (29)

+

S R



41

PhFe

P

NN

Pd


+

Ph




42

Ph

Ph

PdP N

Ph

Ph

P NPd

Nu

Nu




43




PMe

NN

Ph

Ph

PhPh

PdNN

MePd

FeFeP

Ph

Ph

Ph

Ph

Ph Ph

NHCH2Ph

(S)

Ph Ph

OCOOEtNu-Nu-


950 ee resp 945 ee

rac

44






Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

Fe

N CN

PPh2

Me

Fe

N NC

PPh2

MePdR

R+

PdR

R+

X-ray

45



Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

PdR

R+

PdR

R+

Fe

N CN

PPh2

Me Pd

NHR2R

RFe

N CN

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

Fe

N NC

PPh2

Me Pd

NHR2R

RFe

N NC

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

dr 8515exoendo 8218

46














47


Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



Ph Ph

OCOOEt

Ph Ph

N



NH

Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



48

N

Me

N

Fe

PPh2

Ph Ph

OCO2Et

Ph Ph

NHCH2Ph

[Pd(dba)2 ]+ Ligand





991 (220)

67 (11)

33 (2)

987 (153)

gt995 (gt400)



3 mol Pd-catalyst

PF6- Selectivity

Killer




49

Ph

Ph

P

NPd

+

endo-syn-syn

+

exo-syn-syn

Ph

PhP

NPd

Ph Ph

OCOOEt

Ph Ph



Slow with PF6-

(tight ion pairs )

Fast with F-

(Coordination)

R-Product S-Product

more stable


S R


50










51

E N Jacobsen et al



NN

OMn

OCl

X X

HHX = OMe 96 ee

X = NO2 22 ee

52




MeO MeO

CN

OOOPh

OPhOPAr2

OAr2P CF3F3C MeMe

HCN [Ni(COD)2] L

Ar =

91 eeL

16 ee

53





OCO O

++

nn2 3

4

1


Δ

54

([α]D=-450)




Polymer)50 220 370 1800


PCy2Me

Fe P

CF3

CF32

PCy2Me

Fe P

OMe

OMe2

PCy2Me

Fe P

H

H2

PCy2Me

Fe P

CH3

CH32

55


Markus Baumann


NMeN

Fe

Me

Me

Me

P

O+ PhOTf



O Ph O Ph O

Ph

+ +

2

Rn

Rn=(m-CF3)2

Rn=(m-SiMe3)2

Rn=(p-OMe)

Rn=(p-CF3)

1 (34ee)

8 (62ee)

1 (46ee)

1 (10ee)

94 (88ee)

90 (95ee)

97 (96ee)

96 (95ee)

5

2

2

3

56



NMeN

Fe

PMe Me

F3C

F3CNMeN

Fe

PMe Me

CF3

F3CF3C

F3C

NMeN

Fe

PF3C CF3

MeO

MeO

NMeN

Fe

PMe Me

MeO

MeO

NMeN

Fe

PF3C CF3

NMeN

Fe

PMe Me

NMeN

Fe

PMe Me

Me2N

Me2NNMeN

Fe

PF3C CF3

F3C

F3C

95 ee985 ee

5 ee72 ee

33 ee

98 ee90 ee

40 ee

the worst

and the best

57





NMeN

Fe

Me

Me

Me

PPh2


2) Oxidative Workup

OH

NMeN

Fe PPh2

NMeN

Fe PPh2

Me

39ee 76ee 99ee

Catalytic activity

NMeN

Fe

MeO

OMe

OMe

PPh2

NMeN

Fe

Me

Me

Me

P

CF3

CF3

2

82ee 91ee

58


X

Fe PPh2

N N

Mes

Me

X

1) cat PdCl2(L)

2) Oxidation


= L

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=078rsup2=0996

NMe₂

OMe

Me

ClH


Fe P X

N N

Mes

Me

1) cat PdCl2(L)

2) Oxidation


2

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=014rsup2=0986

NMe₂OMe

Me HCl


59



Fe P X

N N

Mes

Me

OH1) cat PdCl2(L)

2) Oxidation


2

60



X

Fe PPh2

N N

Mes

Me

X

OH1) cat PdCl2(L)

2) Oxidation

= L

61


PdN

P

Cl

Cl

PdN

P H

SiCl3

R

PdN

P

R

SiCl3

N

PdP

HCl3Si

N

Pd

P

Cl3Si

R

R





Unclear formation

σp

σp+


62


TK Woo

HH P

PdSiCl3SiCl3

NNH H

HH

HH P

PdSiCl3SiCl3

NNH H

FeP

PdSiCl3SiCl3

NN

FeP

PdSiCl3SiCl3

NN

HH P

PdSiCl3SiCl3

NNH H

HH P

PdSiCl3SiCl3

NN

H3CH

HH

H

Model 1

Model 2


63






PPd

H

SiCl3NN

HH

PPd

HSiCl3

NN

HH

PPd

HSiCl3

NN

HH

PPd

SiCl3NN

HH PPd

SiCl3NN

HH

1900

22

-02

-83

141

52

PPd

SiCl3NN

HH

PPd

Cl3SiNN

HH

64


endoendo-syn

PPdH

SiCl3NN

Fe

PPd HSiCl3NN

FeFe P

Pd

SiCl3NN

PPd HSiCl3NN

Fe

Cl3Si

PPd

SiCl3N

Fe

N

PPd

Cl3SiNN

Fe

PPdH

SiCl3NN

Fe

PPd

NN

Fe

Cl3Si

R

-35

09

TS1

TS2

-205

+-103

+styrene

00

42+48

61

Dagger Dagger


65





FeP

PdH

SiCl3NN

PPd

HSiCl3

NN

Fe


66


PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPd

H

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPdSiCl3NN

Fe

PPd

SiCl3NN

Fe

48

00

1609

51

-103

-113



endo-syn

exo-synendo

exo


kcalmol

67



endo-syn

exo-syn

NMe2

PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

NMe2

PPd

SiCl3NN

Fe

NMe2

PPdH

SiCl3NN

Fe

Me2N

PPd

SiCl3NN

Fe

PPdSiCl3

NN

Fe

NMe2

PPd

SiCl3NN

Fe

Me2N

48

00

08

03

16

-172

-155

exo

endo


68


DD

D

D5

HndashSiCl3 [PdL]

DD

D

D5

HO H DD

H

D5

HO H DH

H

D5

HO H DD

D

D5

HO D

oxid workup

+ + +


MeD1

MeD2

13C-1H-HZQCNMR

MeD2

MeD11 equivsilane

5 equivsilane

EI-MS


69





70


Energy(kcalmol)

(at rt)


(kcalmol)

(at rt)

ee

endo-syn -103 123

75 (S)[65 (S)]

endo-syn -172 859

81 (R)[64 (R)]

endo-anti -81 03 75 (S)[65 (S)]


75 (S)[65 (S)] exo-syn -155 48

81 (R)[64 (R)]

exo-anti -106 669

75 (S)[65 (S)]

exo-anti -153 35

81 (R)[64 (R)]


71

Conclusions




72



NH3C

CH3

OCH3

CH3OCl

H

P

MeFe

PPh2


2

Ir

S

NHHN

O

H H

P(t-Bu)2

MeFe

PPh2

COOH

(+)-Biotin(LONZA)

Rh

Sitagliptin(Merck)

Rh

F

FF

NN

NN

ONH2

CF3

PtBu2

MeFe P(4-F3CPh)2

27



H NN

ONHO

O

H NN

ONHO


SC=2000


96 ee

P(t-Bu)2

MeFe PPh2

N NN

OH

O

NH

ONH OH



28




P(t-Bu)2

MeFe PPh2

O

HOOCHN

S

F

O O

O

HOOCHN

S

F

O O

RuCl2(P-P)LnNEt3

H2 EtOH

O

HN

S

F

O O

O

HOHNP-P =

97 ee

29



Up to 97 ee

F

FF

NN

NN

ONH2

CF3



P(t-Bu)2

MeFe

P(t-Bu)2Me

Fe P CF32

PPh2

R OMe

NH2 O

R OMe


R NHPh

NH2 O

R NHPh

NH2 O

H2

Rh Josiphos ligand

H2

30











31










32



33

$

amp$

$

$

($

$$ amp$ )$ $ $ $ $ $

$

amp()+-


ampamp2824+

5lt=-amp)gt+gt2)42






34




α1=+9degα2=-21deg




35

Pd

L1

L2R

R

Pd

L1

L2

R

R

Nu Nu



36



X-rayX-ray

PhPh FeP

NNPd Ph

Ph


+

Ph

FeP

NNPd

Ph

Ph

Ph


+

PhPh FeP

NN

Pd Ph

Ph

+



Ph Ph

OCOR

NH2

Ph Ph


40 degC THF


N

Me

N

Fe

PPh2R

37



Ph

FeP

NNPd

Ph

a) R-product



NuNu

a)

b)

+

RS




PN

PdP N

PdP N

+ +


tc = 2 kcalmol

(Ab initio studies)

38

NH

NPd

PH3

NH3


NPd

PH3


NH

NPd

PH3

NH3

50 kJmol

36 kJmol

NH3+

41 kJmol

NH3+

+



PdP N

PdP N

PdP N

+

+ +


tc = 8 kJmol


ct = 29 kJmol


for C out of plane



40

PhPh Fe

P

NNPd

Ph

Ph

Ph

Ph

FeP

NNPd

Ph

Ph

exo-syn-anti (71)

+

exo-syn-syn (29)

+

S R



41

PhFe

P

NN

Pd


+

Ph




42

Ph

Ph

PdP N

Ph

Ph

P NPd

Nu

Nu




43




PMe

NN

Ph

Ph

PhPh

PdNN

MePd

FeFeP

Ph

Ph

Ph

Ph

Ph Ph

NHCH2Ph

(S)

Ph Ph

OCOOEtNu-Nu-


950 ee resp 945 ee

rac

44






Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

Fe

N CN

PPh2

Me

Fe

N NC

PPh2

MePdR

R+

PdR

R+

X-ray

45



Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

PdR

R+

PdR

R+

Fe

N CN

PPh2

Me Pd

NHR2R

RFe

N CN

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

Fe

N NC

PPh2

Me Pd

NHR2R

RFe

N NC

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

dr 8515exoendo 8218

46














47


Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



Ph Ph

OCOOEt

Ph Ph

N



NH

Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



48

N

Me

N

Fe

PPh2

Ph Ph

OCO2Et

Ph Ph

NHCH2Ph

[Pd(dba)2 ]+ Ligand





991 (220)

67 (11)

33 (2)

987 (153)

gt995 (gt400)



3 mol Pd-catalyst

PF6- Selectivity

Killer




49

Ph

Ph

P

NPd

+

endo-syn-syn

+

exo-syn-syn

Ph

PhP

NPd

Ph Ph

OCOOEt

Ph Ph



Slow with PF6-

(tight ion pairs )

Fast with F-

(Coordination)

R-Product S-Product

more stable


S R


50










51

E N Jacobsen et al



NN

OMn

OCl

X X

HHX = OMe 96 ee

X = NO2 22 ee

52




MeO MeO

CN

OOOPh

OPhOPAr2

OAr2P CF3F3C MeMe

HCN [Ni(COD)2] L

Ar =

91 eeL

16 ee

53





OCO O

++

nn2 3

4

1


Δ

54

([α]D=-450)




Polymer)50 220 370 1800


PCy2Me

Fe P

CF3

CF32

PCy2Me

Fe P

OMe

OMe2

PCy2Me

Fe P

H

H2

PCy2Me

Fe P

CH3

CH32

55


Markus Baumann


NMeN

Fe

Me

Me

Me

P

O+ PhOTf



O Ph O Ph O

Ph

+ +

2

Rn

Rn=(m-CF3)2

Rn=(m-SiMe3)2

Rn=(p-OMe)

Rn=(p-CF3)

1 (34ee)

8 (62ee)

1 (46ee)

1 (10ee)

94 (88ee)

90 (95ee)

97 (96ee)

96 (95ee)

5

2

2

3

56



NMeN

Fe

PMe Me

F3C

F3CNMeN

Fe

PMe Me

CF3

F3CF3C

F3C

NMeN

Fe

PF3C CF3

MeO

MeO

NMeN

Fe

PMe Me

MeO

MeO

NMeN

Fe

PF3C CF3

NMeN

Fe

PMe Me

NMeN

Fe

PMe Me

Me2N

Me2NNMeN

Fe

PF3C CF3

F3C

F3C

95 ee985 ee

5 ee72 ee

33 ee

98 ee90 ee

40 ee

the worst

and the best

57





NMeN

Fe

Me

Me

Me

PPh2


2) Oxidative Workup

OH

NMeN

Fe PPh2

NMeN

Fe PPh2

Me

39ee 76ee 99ee

Catalytic activity

NMeN

Fe

MeO

OMe

OMe

PPh2

NMeN

Fe

Me

Me

Me

P

CF3

CF3

2

82ee 91ee

58


X

Fe PPh2

N N

Mes

Me

X

1) cat PdCl2(L)

2) Oxidation


= L

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=078rsup2=0996

NMe₂

OMe

Me

ClH


Fe P X

N N

Mes

Me

1) cat PdCl2(L)

2) Oxidation


2

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=014rsup2=0986

NMe₂OMe

Me HCl


59



Fe P X

N N

Mes

Me

OH1) cat PdCl2(L)

2) Oxidation


2

60



X

Fe PPh2

N N

Mes

Me

X

OH1) cat PdCl2(L)

2) Oxidation

= L

61


PdN

P

Cl

Cl

PdN

P H

SiCl3

R

PdN

P

R

SiCl3

N

PdP

HCl3Si

N

Pd

P

Cl3Si

R

R





Unclear formation

σp

σp+


62


TK Woo

HH P

PdSiCl3SiCl3

NNH H

HH

HH P

PdSiCl3SiCl3

NNH H

FeP

PdSiCl3SiCl3

NN

FeP

PdSiCl3SiCl3

NN

HH P

PdSiCl3SiCl3

NNH H

HH P

PdSiCl3SiCl3

NN

H3CH

HH

H

Model 1

Model 2


63






PPd

H

SiCl3NN

HH

PPd

HSiCl3

NN

HH

PPd

HSiCl3

NN

HH

PPd

SiCl3NN

HH PPd

SiCl3NN

HH

1900

22

-02

-83

141

52

PPd

SiCl3NN

HH

PPd

Cl3SiNN

HH

64


endoendo-syn

PPdH

SiCl3NN

Fe

PPd HSiCl3NN

FeFe P

Pd

SiCl3NN

PPd HSiCl3NN

Fe

Cl3Si

PPd

SiCl3N

Fe

N

PPd

Cl3SiNN

Fe

PPdH

SiCl3NN

Fe

PPd

NN

Fe

Cl3Si

R

-35

09

TS1

TS2

-205

+-103

+styrene

00

42+48

61

Dagger Dagger


65





FeP

PdH

SiCl3NN

PPd

HSiCl3

NN

Fe


66


PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPd

H

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPdSiCl3NN

Fe

PPd

SiCl3NN

Fe

48

00

1609

51

-103

-113



endo-syn

exo-synendo

exo


kcalmol

67



endo-syn

exo-syn

NMe2

PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

NMe2

PPd

SiCl3NN

Fe

NMe2

PPdH

SiCl3NN

Fe

Me2N

PPd

SiCl3NN

Fe

PPdSiCl3

NN

Fe

NMe2

PPd

SiCl3NN

Fe

Me2N

48

00

08

03

16

-172

-155

exo

endo


68


DD

D

D5

HndashSiCl3 [PdL]

DD

D

D5

HO H DD

H

D5

HO H DH

H

D5

HO H DD

D

D5

HO D

oxid workup

+ + +


MeD1

MeD2

13C-1H-HZQCNMR

MeD2

MeD11 equivsilane

5 equivsilane

EI-MS


69





70


Energy(kcalmol)

(at rt)


(kcalmol)

(at rt)

ee

endo-syn -103 123

75 (S)[65 (S)]

endo-syn -172 859

81 (R)[64 (R)]

endo-anti -81 03 75 (S)[65 (S)]


75 (S)[65 (S)] exo-syn -155 48

81 (R)[64 (R)]

exo-anti -106 669

75 (S)[65 (S)]

exo-anti -153 35

81 (R)[64 (R)]


71

Conclusions




72



H NN

ONHO

O

H NN

ONHO


SC=2000


96 ee

P(t-Bu)2

MeFe PPh2

N NN

OH

O

NH

ONH OH



28




P(t-Bu)2

MeFe PPh2

O

HOOCHN

S

F

O O

O

HOOCHN

S

F

O O

RuCl2(P-P)LnNEt3

H2 EtOH

O

HN

S

F

O O

O

HOHNP-P =

97 ee

29



Up to 97 ee

F

FF

NN

NN

ONH2

CF3



P(t-Bu)2

MeFe

P(t-Bu)2Me

Fe P CF32

PPh2

R OMe

NH2 O

R OMe


R NHPh

NH2 O

R NHPh

NH2 O

H2

Rh Josiphos ligand

H2

30











31










32



33

$

amp$

$

$

($

$$ amp$ )$ $ $ $ $ $

$

amp()+-


ampamp2824+

5lt=-amp)gt+gt2)42






34




α1=+9degα2=-21deg




35

Pd

L1

L2R

R

Pd

L1

L2

R

R

Nu Nu



36



X-rayX-ray

PhPh FeP

NNPd Ph

Ph


+

Ph

FeP

NNPd

Ph

Ph

Ph


+

PhPh FeP

NN

Pd Ph

Ph

+



Ph Ph

OCOR

NH2

Ph Ph


40 degC THF


N

Me

N

Fe

PPh2R

37



Ph

FeP

NNPd

Ph

a) R-product



NuNu

a)

b)

+

RS




PN

PdP N

PdP N

+ +


tc = 2 kcalmol

(Ab initio studies)

38

NH

NPd

PH3

NH3


NPd

PH3


NH

NPd

PH3

NH3

50 kJmol

36 kJmol

NH3+

41 kJmol

NH3+

+



PdP N

PdP N

PdP N

+

+ +


tc = 8 kJmol


ct = 29 kJmol


for C out of plane



40

PhPh Fe

P

NNPd

Ph

Ph

Ph

Ph

FeP

NNPd

Ph

Ph

exo-syn-anti (71)

+

exo-syn-syn (29)

+

S R



41

PhFe

P

NN

Pd


+

Ph




42

Ph

Ph

PdP N

Ph

Ph

P NPd

Nu

Nu




43




PMe

NN

Ph

Ph

PhPh

PdNN

MePd

FeFeP

Ph

Ph

Ph

Ph

Ph Ph

NHCH2Ph

(S)

Ph Ph

OCOOEtNu-Nu-


950 ee resp 945 ee

rac

44






Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

Fe

N CN

PPh2

Me

Fe

N NC

PPh2

MePdR

R+

PdR

R+

X-ray

45



Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

PdR

R+

PdR

R+

Fe

N CN

PPh2

Me Pd

NHR2R

RFe

N CN

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

Fe

N NC

PPh2

Me Pd

NHR2R

RFe

N NC

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

dr 8515exoendo 8218

46














47


Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



Ph Ph

OCOOEt

Ph Ph

N



NH

Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



48

N

Me

N

Fe

PPh2

Ph Ph

OCO2Et

Ph Ph

NHCH2Ph

[Pd(dba)2 ]+ Ligand





991 (220)

67 (11)

33 (2)

987 (153)

gt995 (gt400)



3 mol Pd-catalyst

PF6- Selectivity

Killer




49

Ph

Ph

P

NPd

+

endo-syn-syn

+

exo-syn-syn

Ph

PhP

NPd

Ph Ph

OCOOEt

Ph Ph



Slow with PF6-

(tight ion pairs )

Fast with F-

(Coordination)

R-Product S-Product

more stable


S R


50










51

E N Jacobsen et al



NN

OMn

OCl

X X

HHX = OMe 96 ee

X = NO2 22 ee

52




MeO MeO

CN

OOOPh

OPhOPAr2

OAr2P CF3F3C MeMe

HCN [Ni(COD)2] L

Ar =

91 eeL

16 ee

53





OCO O

++

nn2 3

4

1


Δ

54

([α]D=-450)




Polymer)50 220 370 1800


PCy2Me

Fe P

CF3

CF32

PCy2Me

Fe P

OMe

OMe2

PCy2Me

Fe P

H

H2

PCy2Me

Fe P

CH3

CH32

55


Markus Baumann


NMeN

Fe

Me

Me

Me

P

O+ PhOTf



O Ph O Ph O

Ph

+ +

2

Rn

Rn=(m-CF3)2

Rn=(m-SiMe3)2

Rn=(p-OMe)

Rn=(p-CF3)

1 (34ee)

8 (62ee)

1 (46ee)

1 (10ee)

94 (88ee)

90 (95ee)

97 (96ee)

96 (95ee)

5

2

2

3

56



NMeN

Fe

PMe Me

F3C

F3CNMeN

Fe

PMe Me

CF3

F3CF3C

F3C

NMeN

Fe

PF3C CF3

MeO

MeO

NMeN

Fe

PMe Me

MeO

MeO

NMeN

Fe

PF3C CF3

NMeN

Fe

PMe Me

NMeN

Fe

PMe Me

Me2N

Me2NNMeN

Fe

PF3C CF3

F3C

F3C

95 ee985 ee

5 ee72 ee

33 ee

98 ee90 ee

40 ee

the worst

and the best

57





NMeN

Fe

Me

Me

Me

PPh2


2) Oxidative Workup

OH

NMeN

Fe PPh2

NMeN

Fe PPh2

Me

39ee 76ee 99ee

Catalytic activity

NMeN

Fe

MeO

OMe

OMe

PPh2

NMeN

Fe

Me

Me

Me

P

CF3

CF3

2

82ee 91ee

58


X

Fe PPh2

N N

Mes

Me

X

1) cat PdCl2(L)

2) Oxidation


= L

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=078rsup2=0996

NMe₂

OMe

Me

ClH


Fe P X

N N

Mes

Me

1) cat PdCl2(L)

2) Oxidation


2

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=014rsup2=0986

NMe₂OMe

Me HCl


59



Fe P X

N N

Mes

Me

OH1) cat PdCl2(L)

2) Oxidation


2

60



X

Fe PPh2

N N

Mes

Me

X

OH1) cat PdCl2(L)

2) Oxidation

= L

61


PdN

P

Cl

Cl

PdN

P H

SiCl3

R

PdN

P

R

SiCl3

N

PdP

HCl3Si

N

Pd

P

Cl3Si

R

R





Unclear formation

σp

σp+


62


TK Woo

HH P

PdSiCl3SiCl3

NNH H

HH

HH P

PdSiCl3SiCl3

NNH H

FeP

PdSiCl3SiCl3

NN

FeP

PdSiCl3SiCl3

NN

HH P

PdSiCl3SiCl3

NNH H

HH P

PdSiCl3SiCl3

NN

H3CH

HH

H

Model 1

Model 2


63






PPd

H

SiCl3NN

HH

PPd

HSiCl3

NN

HH

PPd

HSiCl3

NN

HH

PPd

SiCl3NN

HH PPd

SiCl3NN

HH

1900

22

-02

-83

141

52

PPd

SiCl3NN

HH

PPd

Cl3SiNN

HH

64


endoendo-syn

PPdH

SiCl3NN

Fe

PPd HSiCl3NN

FeFe P

Pd

SiCl3NN

PPd HSiCl3NN

Fe

Cl3Si

PPd

SiCl3N

Fe

N

PPd

Cl3SiNN

Fe

PPdH

SiCl3NN

Fe

PPd

NN

Fe

Cl3Si

R

-35

09

TS1

TS2

-205

+-103

+styrene

00

42+48

61

Dagger Dagger


65





FeP

PdH

SiCl3NN

PPd

HSiCl3

NN

Fe


66


PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPd

H

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPdSiCl3NN

Fe

PPd

SiCl3NN

Fe

48

00

1609

51

-103

-113



endo-syn

exo-synendo

exo


kcalmol

67



endo-syn

exo-syn

NMe2

PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

NMe2

PPd

SiCl3NN

Fe

NMe2

PPdH

SiCl3NN

Fe

Me2N

PPd

SiCl3NN

Fe

PPdSiCl3

NN

Fe

NMe2

PPd

SiCl3NN

Fe

Me2N

48

00

08

03

16

-172

-155

exo

endo


68


DD

D

D5

HndashSiCl3 [PdL]

DD

D

D5

HO H DD

H

D5

HO H DH

H

D5

HO H DD

D

D5

HO D

oxid workup

+ + +


MeD1

MeD2

13C-1H-HZQCNMR

MeD2

MeD11 equivsilane

5 equivsilane

EI-MS


69





70


Energy(kcalmol)

(at rt)


(kcalmol)

(at rt)

ee

endo-syn -103 123

75 (S)[65 (S)]

endo-syn -172 859

81 (R)[64 (R)]

endo-anti -81 03 75 (S)[65 (S)]


75 (S)[65 (S)] exo-syn -155 48

81 (R)[64 (R)]

exo-anti -106 669

75 (S)[65 (S)]

exo-anti -153 35

81 (R)[64 (R)]


71

Conclusions




72




P(t-Bu)2

MeFe PPh2

O

HOOCHN

S

F

O O

O

HOOCHN

S

F

O O

RuCl2(P-P)LnNEt3

H2 EtOH

O

HN

S

F

O O

O

HOHNP-P =

97 ee

29



Up to 97 ee

F

FF

NN

NN

ONH2

CF3



P(t-Bu)2

MeFe

P(t-Bu)2Me

Fe P CF32

PPh2

R OMe

NH2 O

R OMe


R NHPh

NH2 O

R NHPh

NH2 O

H2

Rh Josiphos ligand

H2

30











31










32



33

$

amp$

$

$

($

$$ amp$ )$ $ $ $ $ $

$

amp()+-


ampamp2824+

5lt=-amp)gt+gt2)42






34




α1=+9degα2=-21deg




35

Pd

L1

L2R

R

Pd

L1

L2

R

R

Nu Nu



36



X-rayX-ray

PhPh FeP

NNPd Ph

Ph


+

Ph

FeP

NNPd

Ph

Ph

Ph


+

PhPh FeP

NN

Pd Ph

Ph

+



Ph Ph

OCOR

NH2

Ph Ph


40 degC THF


N

Me

N

Fe

PPh2R

37



Ph

FeP

NNPd

Ph

a) R-product



NuNu

a)

b)

+

RS




PN

PdP N

PdP N

+ +


tc = 2 kcalmol

(Ab initio studies)

38

NH

NPd

PH3

NH3


NPd

PH3


NH

NPd

PH3

NH3

50 kJmol

36 kJmol

NH3+

41 kJmol

NH3+

+



PdP N

PdP N

PdP N

+

+ +


tc = 8 kJmol


ct = 29 kJmol


for C out of plane



40

PhPh Fe

P

NNPd

Ph

Ph

Ph

Ph

FeP

NNPd

Ph

Ph

exo-syn-anti (71)

+

exo-syn-syn (29)

+

S R



41

PhFe

P

NN

Pd


+

Ph




42

Ph

Ph

PdP N

Ph

Ph

P NPd

Nu

Nu




43




PMe

NN

Ph

Ph

PhPh

PdNN

MePd

FeFeP

Ph

Ph

Ph

Ph

Ph Ph

NHCH2Ph

(S)

Ph Ph

OCOOEtNu-Nu-


950 ee resp 945 ee

rac

44






Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

Fe

N CN

PPh2

Me

Fe

N NC

PPh2

MePdR

R+

PdR

R+

X-ray

45



Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

PdR

R+

PdR

R+

Fe

N CN

PPh2

Me Pd

NHR2R

RFe

N CN

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

Fe

N NC

PPh2

Me Pd

NHR2R

RFe

N NC

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

dr 8515exoendo 8218

46














47


Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



Ph Ph

OCOOEt

Ph Ph

N



NH

Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



48

N

Me

N

Fe

PPh2

Ph Ph

OCO2Et

Ph Ph

NHCH2Ph

[Pd(dba)2 ]+ Ligand





991 (220)

67 (11)

33 (2)

987 (153)

gt995 (gt400)



3 mol Pd-catalyst

PF6- Selectivity

Killer




49

Ph

Ph

P

NPd

+

endo-syn-syn

+

exo-syn-syn

Ph

PhP

NPd

Ph Ph

OCOOEt

Ph Ph



Slow with PF6-

(tight ion pairs )

Fast with F-

(Coordination)

R-Product S-Product

more stable


S R


50










51

E N Jacobsen et al



NN

OMn

OCl

X X

HHX = OMe 96 ee

X = NO2 22 ee

52




MeO MeO

CN

OOOPh

OPhOPAr2

OAr2P CF3F3C MeMe

HCN [Ni(COD)2] L

Ar =

91 eeL

16 ee

53





OCO O

++

nn2 3

4

1


Δ

54

([α]D=-450)




Polymer)50 220 370 1800


PCy2Me

Fe P

CF3

CF32

PCy2Me

Fe P

OMe

OMe2

PCy2Me

Fe P

H

H2

PCy2Me

Fe P

CH3

CH32

55


Markus Baumann


NMeN

Fe

Me

Me

Me

P

O+ PhOTf



O Ph O Ph O

Ph

+ +

2

Rn

Rn=(m-CF3)2

Rn=(m-SiMe3)2

Rn=(p-OMe)

Rn=(p-CF3)

1 (34ee)

8 (62ee)

1 (46ee)

1 (10ee)

94 (88ee)

90 (95ee)

97 (96ee)

96 (95ee)

5

2

2

3

56



NMeN

Fe

PMe Me

F3C

F3CNMeN

Fe

PMe Me

CF3

F3CF3C

F3C

NMeN

Fe

PF3C CF3

MeO

MeO

NMeN

Fe

PMe Me

MeO

MeO

NMeN

Fe

PF3C CF3

NMeN

Fe

PMe Me

NMeN

Fe

PMe Me

Me2N

Me2NNMeN

Fe

PF3C CF3

F3C

F3C

95 ee985 ee

5 ee72 ee

33 ee

98 ee90 ee

40 ee

the worst

and the best

57





NMeN

Fe

Me

Me

Me

PPh2


2) Oxidative Workup

OH

NMeN

Fe PPh2

NMeN

Fe PPh2

Me

39ee 76ee 99ee

Catalytic activity

NMeN

Fe

MeO

OMe

OMe

PPh2

NMeN

Fe

Me

Me

Me

P

CF3

CF3

2

82ee 91ee

58


X

Fe PPh2

N N

Mes

Me

X

1) cat PdCl2(L)

2) Oxidation


= L

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=078rsup2=0996

NMe₂

OMe

Me

ClH


Fe P X

N N

Mes

Me

1) cat PdCl2(L)

2) Oxidation


2

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=014rsup2=0986

NMe₂OMe

Me HCl


59



Fe P X

N N

Mes

Me

OH1) cat PdCl2(L)

2) Oxidation


2

60



X

Fe PPh2

N N

Mes

Me

X

OH1) cat PdCl2(L)

2) Oxidation

= L

61


PdN

P

Cl

Cl

PdN

P H

SiCl3

R

PdN

P

R

SiCl3

N

PdP

HCl3Si

N

Pd

P

Cl3Si

R

R





Unclear formation

σp

σp+


62


TK Woo

HH P

PdSiCl3SiCl3

NNH H

HH

HH P

PdSiCl3SiCl3

NNH H

FeP

PdSiCl3SiCl3

NN

FeP

PdSiCl3SiCl3

NN

HH P

PdSiCl3SiCl3

NNH H

HH P

PdSiCl3SiCl3

NN

H3CH

HH

H

Model 1

Model 2


63






PPd

H

SiCl3NN

HH

PPd

HSiCl3

NN

HH

PPd

HSiCl3

NN

HH

PPd

SiCl3NN

HH PPd

SiCl3NN

HH

1900

22

-02

-83

141

52

PPd

SiCl3NN

HH

PPd

Cl3SiNN

HH

64


endoendo-syn

PPdH

SiCl3NN

Fe

PPd HSiCl3NN

FeFe P

Pd

SiCl3NN

PPd HSiCl3NN

Fe

Cl3Si

PPd

SiCl3N

Fe

N

PPd

Cl3SiNN

Fe

PPdH

SiCl3NN

Fe

PPd

NN

Fe

Cl3Si

R

-35

09

TS1

TS2

-205

+-103

+styrene

00

42+48

61

Dagger Dagger


65





FeP

PdH

SiCl3NN

PPd

HSiCl3

NN

Fe


66


PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPd

H

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPdSiCl3NN

Fe

PPd

SiCl3NN

Fe

48

00

1609

51

-103

-113



endo-syn

exo-synendo

exo


kcalmol

67



endo-syn

exo-syn

NMe2

PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

NMe2

PPd

SiCl3NN

Fe

NMe2

PPdH

SiCl3NN

Fe

Me2N

PPd

SiCl3NN

Fe

PPdSiCl3

NN

Fe

NMe2

PPd

SiCl3NN

Fe

Me2N

48

00

08

03

16

-172

-155

exo

endo


68


DD

D

D5

HndashSiCl3 [PdL]

DD

D

D5

HO H DD

H

D5

HO H DH

H

D5

HO H DD

D

D5

HO D

oxid workup

+ + +


MeD1

MeD2

13C-1H-HZQCNMR

MeD2

MeD11 equivsilane

5 equivsilane

EI-MS


69





70


Energy(kcalmol)

(at rt)


(kcalmol)

(at rt)

ee

endo-syn -103 123

75 (S)[65 (S)]

endo-syn -172 859

81 (R)[64 (R)]

endo-anti -81 03 75 (S)[65 (S)]


75 (S)[65 (S)] exo-syn -155 48

81 (R)[64 (R)]

exo-anti -106 669

75 (S)[65 (S)]

exo-anti -153 35

81 (R)[64 (R)]


71

Conclusions




72



Up to 97 ee

F

FF

NN

NN

ONH2

CF3



P(t-Bu)2

MeFe

P(t-Bu)2Me

Fe P CF32

PPh2

R OMe

NH2 O

R OMe


R NHPh

NH2 O

R NHPh

NH2 O

H2

Rh Josiphos ligand

H2

30











31










32



33

$

amp$

$

$

($

$$ amp$ )$ $ $ $ $ $

$

amp()+-


ampamp2824+

5lt=-amp)gt+gt2)42






34




α1=+9degα2=-21deg




35

Pd

L1

L2R

R

Pd

L1

L2

R

R

Nu Nu



36



X-rayX-ray

PhPh FeP

NNPd Ph

Ph


+

Ph

FeP

NNPd

Ph

Ph

Ph


+

PhPh FeP

NN

Pd Ph

Ph

+



Ph Ph

OCOR

NH2

Ph Ph


40 degC THF


N

Me

N

Fe

PPh2R

37



Ph

FeP

NNPd

Ph

a) R-product



NuNu

a)

b)

+

RS




PN

PdP N

PdP N

+ +


tc = 2 kcalmol

(Ab initio studies)

38

NH

NPd

PH3

NH3


NPd

PH3


NH

NPd

PH3

NH3

50 kJmol

36 kJmol

NH3+

41 kJmol

NH3+

+



PdP N

PdP N

PdP N

+

+ +


tc = 8 kJmol


ct = 29 kJmol


for C out of plane



40

PhPh Fe

P

NNPd

Ph

Ph

Ph

Ph

FeP

NNPd

Ph

Ph

exo-syn-anti (71)

+

exo-syn-syn (29)

+

S R



41

PhFe

P

NN

Pd


+

Ph




42

Ph

Ph

PdP N

Ph

Ph

P NPd

Nu

Nu




43




PMe

NN

Ph

Ph

PhPh

PdNN

MePd

FeFeP

Ph

Ph

Ph

Ph

Ph Ph

NHCH2Ph

(S)

Ph Ph

OCOOEtNu-Nu-


950 ee resp 945 ee

rac

44






Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

Fe

N CN

PPh2

Me

Fe

N NC

PPh2

MePdR

R+

PdR

R+

X-ray

45



Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

PdR

R+

PdR

R+

Fe

N CN

PPh2

Me Pd

NHR2R

RFe

N CN

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

Fe

N NC

PPh2

Me Pd

NHR2R

RFe

N NC

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

dr 8515exoendo 8218

46














47


Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



Ph Ph

OCOOEt

Ph Ph

N



NH

Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



48

N

Me

N

Fe

PPh2

Ph Ph

OCO2Et

Ph Ph

NHCH2Ph

[Pd(dba)2 ]+ Ligand





991 (220)

67 (11)

33 (2)

987 (153)

gt995 (gt400)



3 mol Pd-catalyst

PF6- Selectivity

Killer




49

Ph

Ph

P

NPd

+

endo-syn-syn

+

exo-syn-syn

Ph

PhP

NPd

Ph Ph

OCOOEt

Ph Ph



Slow with PF6-

(tight ion pairs )

Fast with F-

(Coordination)

R-Product S-Product

more stable


S R


50










51

E N Jacobsen et al



NN

OMn

OCl

X X

HHX = OMe 96 ee

X = NO2 22 ee

52




MeO MeO

CN

OOOPh

OPhOPAr2

OAr2P CF3F3C MeMe

HCN [Ni(COD)2] L

Ar =

91 eeL

16 ee

53





OCO O

++

nn2 3

4

1


Δ

54

([α]D=-450)




Polymer)50 220 370 1800


PCy2Me

Fe P

CF3

CF32

PCy2Me

Fe P

OMe

OMe2

PCy2Me

Fe P

H

H2

PCy2Me

Fe P

CH3

CH32

55


Markus Baumann


NMeN

Fe

Me

Me

Me

P

O+ PhOTf



O Ph O Ph O

Ph

+ +

2

Rn

Rn=(m-CF3)2

Rn=(m-SiMe3)2

Rn=(p-OMe)

Rn=(p-CF3)

1 (34ee)

8 (62ee)

1 (46ee)

1 (10ee)

94 (88ee)

90 (95ee)

97 (96ee)

96 (95ee)

5

2

2

3

56



NMeN

Fe

PMe Me

F3C

F3CNMeN

Fe

PMe Me

CF3

F3CF3C

F3C

NMeN

Fe

PF3C CF3

MeO

MeO

NMeN

Fe

PMe Me

MeO

MeO

NMeN

Fe

PF3C CF3

NMeN

Fe

PMe Me

NMeN

Fe

PMe Me

Me2N

Me2NNMeN

Fe

PF3C CF3

F3C

F3C

95 ee985 ee

5 ee72 ee

33 ee

98 ee90 ee

40 ee

the worst

and the best

57





NMeN

Fe

Me

Me

Me

PPh2


2) Oxidative Workup

OH

NMeN

Fe PPh2

NMeN

Fe PPh2

Me

39ee 76ee 99ee

Catalytic activity

NMeN

Fe

MeO

OMe

OMe

PPh2

NMeN

Fe

Me

Me

Me

P

CF3

CF3

2

82ee 91ee

58


X

Fe PPh2

N N

Mes

Me

X

1) cat PdCl2(L)

2) Oxidation


= L

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=078rsup2=0996

NMe₂

OMe

Me

ClH


Fe P X

N N

Mes

Me

1) cat PdCl2(L)

2) Oxidation


2

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=014rsup2=0986

NMe₂OMe

Me HCl


59



Fe P X

N N

Mes

Me

OH1) cat PdCl2(L)

2) Oxidation


2

60



X

Fe PPh2

N N

Mes

Me

X

OH1) cat PdCl2(L)

2) Oxidation

= L

61


PdN

P

Cl

Cl

PdN

P H

SiCl3

R

PdN

P

R

SiCl3

N

PdP

HCl3Si

N

Pd

P

Cl3Si

R

R





Unclear formation

σp

σp+


62


TK Woo

HH P

PdSiCl3SiCl3

NNH H

HH

HH P

PdSiCl3SiCl3

NNH H

FeP

PdSiCl3SiCl3

NN

FeP

PdSiCl3SiCl3

NN

HH P

PdSiCl3SiCl3

NNH H

HH P

PdSiCl3SiCl3

NN

H3CH

HH

H

Model 1

Model 2


63






PPd

H

SiCl3NN

HH

PPd

HSiCl3

NN

HH

PPd

HSiCl3

NN

HH

PPd

SiCl3NN

HH PPd

SiCl3NN

HH

1900

22

-02

-83

141

52

PPd

SiCl3NN

HH

PPd

Cl3SiNN

HH

64


endoendo-syn

PPdH

SiCl3NN

Fe

PPd HSiCl3NN

FeFe P

Pd

SiCl3NN

PPd HSiCl3NN

Fe

Cl3Si

PPd

SiCl3N

Fe

N

PPd

Cl3SiNN

Fe

PPdH

SiCl3NN

Fe

PPd

NN

Fe

Cl3Si

R

-35

09

TS1

TS2

-205

+-103

+styrene

00

42+48

61

Dagger Dagger


65





FeP

PdH

SiCl3NN

PPd

HSiCl3

NN

Fe


66


PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPd

H

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPdSiCl3NN

Fe

PPd

SiCl3NN

Fe

48

00

1609

51

-103

-113



endo-syn

exo-synendo

exo


kcalmol

67



endo-syn

exo-syn

NMe2

PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

NMe2

PPd

SiCl3NN

Fe

NMe2

PPdH

SiCl3NN

Fe

Me2N

PPd

SiCl3NN

Fe

PPdSiCl3

NN

Fe

NMe2

PPd

SiCl3NN

Fe

Me2N

48

00

08

03

16

-172

-155

exo

endo


68


DD

D

D5

HndashSiCl3 [PdL]

DD

D

D5

HO H DD

H

D5

HO H DH

H

D5

HO H DD

D

D5

HO D

oxid workup

+ + +


MeD1

MeD2

13C-1H-HZQCNMR

MeD2

MeD11 equivsilane

5 equivsilane

EI-MS


69





70


Energy(kcalmol)

(at rt)


(kcalmol)

(at rt)

ee

endo-syn -103 123

75 (S)[65 (S)]

endo-syn -172 859

81 (R)[64 (R)]

endo-anti -81 03 75 (S)[65 (S)]


75 (S)[65 (S)] exo-syn -155 48

81 (R)[64 (R)]

exo-anti -106 669

75 (S)[65 (S)]

exo-anti -153 35

81 (R)[64 (R)]


71

Conclusions




72











31










32



33

$

amp$

$

$

($

$$ amp$ )$ $ $ $ $ $

$

amp()+-


ampamp2824+

5lt=-amp)gt+gt2)42






34




α1=+9degα2=-21deg




35

Pd

L1

L2R

R

Pd

L1

L2

R

R

Nu Nu



36



X-rayX-ray

PhPh FeP

NNPd Ph

Ph


+

Ph

FeP

NNPd

Ph

Ph

Ph


+

PhPh FeP

NN

Pd Ph

Ph

+



Ph Ph

OCOR

NH2

Ph Ph


40 degC THF


N

Me

N

Fe

PPh2R

37



Ph

FeP

NNPd

Ph

a) R-product



NuNu

a)

b)

+

RS




PN

PdP N

PdP N

+ +


tc = 2 kcalmol

(Ab initio studies)

38

NH

NPd

PH3

NH3


NPd

PH3


NH

NPd

PH3

NH3

50 kJmol

36 kJmol

NH3+

41 kJmol

NH3+

+



PdP N

PdP N

PdP N

+

+ +


tc = 8 kJmol


ct = 29 kJmol


for C out of plane



40

PhPh Fe

P

NNPd

Ph

Ph

Ph

Ph

FeP

NNPd

Ph

Ph

exo-syn-anti (71)

+

exo-syn-syn (29)

+

S R



41

PhFe

P

NN

Pd


+

Ph




42

Ph

Ph

PdP N

Ph

Ph

P NPd

Nu

Nu




43




PMe

NN

Ph

Ph

PhPh

PdNN

MePd

FeFeP

Ph

Ph

Ph

Ph

Ph Ph

NHCH2Ph

(S)

Ph Ph

OCOOEtNu-Nu-


950 ee resp 945 ee

rac

44






Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

Fe

N CN

PPh2

Me

Fe

N NC

PPh2

MePdR

R+

PdR

R+

X-ray

45



Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

PdR

R+

PdR

R+

Fe

N CN

PPh2

Me Pd

NHR2R

RFe

N CN

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

Fe

N NC

PPh2

Me Pd

NHR2R

RFe

N NC

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

dr 8515exoendo 8218

46














47


Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



Ph Ph

OCOOEt

Ph Ph

N



NH

Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



48

N

Me

N

Fe

PPh2

Ph Ph

OCO2Et

Ph Ph

NHCH2Ph

[Pd(dba)2 ]+ Ligand





991 (220)

67 (11)

33 (2)

987 (153)

gt995 (gt400)



3 mol Pd-catalyst

PF6- Selectivity

Killer




49

Ph

Ph

P

NPd

+

endo-syn-syn

+

exo-syn-syn

Ph

PhP

NPd

Ph Ph

OCOOEt

Ph Ph



Slow with PF6-

(tight ion pairs )

Fast with F-

(Coordination)

R-Product S-Product

more stable


S R


50










51

E N Jacobsen et al



NN

OMn

OCl

X X

HHX = OMe 96 ee

X = NO2 22 ee

52




MeO MeO

CN

OOOPh

OPhOPAr2

OAr2P CF3F3C MeMe

HCN [Ni(COD)2] L

Ar =

91 eeL

16 ee

53





OCO O

++

nn2 3

4

1


Δ

54

([α]D=-450)




Polymer)50 220 370 1800


PCy2Me

Fe P

CF3

CF32

PCy2Me

Fe P

OMe

OMe2

PCy2Me

Fe P

H

H2

PCy2Me

Fe P

CH3

CH32

55


Markus Baumann


NMeN

Fe

Me

Me

Me

P

O+ PhOTf



O Ph O Ph O

Ph

+ +

2

Rn

Rn=(m-CF3)2

Rn=(m-SiMe3)2

Rn=(p-OMe)

Rn=(p-CF3)

1 (34ee)

8 (62ee)

1 (46ee)

1 (10ee)

94 (88ee)

90 (95ee)

97 (96ee)

96 (95ee)

5

2

2

3

56



NMeN

Fe

PMe Me

F3C

F3CNMeN

Fe

PMe Me

CF3

F3CF3C

F3C

NMeN

Fe

PF3C CF3

MeO

MeO

NMeN

Fe

PMe Me

MeO

MeO

NMeN

Fe

PF3C CF3

NMeN

Fe

PMe Me

NMeN

Fe

PMe Me

Me2N

Me2NNMeN

Fe

PF3C CF3

F3C

F3C

95 ee985 ee

5 ee72 ee

33 ee

98 ee90 ee

40 ee

the worst

and the best

57





NMeN

Fe

Me

Me

Me

PPh2


2) Oxidative Workup

OH

NMeN

Fe PPh2

NMeN

Fe PPh2

Me

39ee 76ee 99ee

Catalytic activity

NMeN

Fe

MeO

OMe

OMe

PPh2

NMeN

Fe

Me

Me

Me

P

CF3

CF3

2

82ee 91ee

58


X

Fe PPh2

N N

Mes

Me

X

1) cat PdCl2(L)

2) Oxidation


= L

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=078rsup2=0996

NMe₂

OMe

Me

ClH


Fe P X

N N

Mes

Me

1) cat PdCl2(L)

2) Oxidation


2

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=014rsup2=0986

NMe₂OMe

Me HCl


59



Fe P X

N N

Mes

Me

OH1) cat PdCl2(L)

2) Oxidation


2

60



X

Fe PPh2

N N

Mes

Me

X

OH1) cat PdCl2(L)

2) Oxidation

= L

61


PdN

P

Cl

Cl

PdN

P H

SiCl3

R

PdN

P

R

SiCl3

N

PdP

HCl3Si

N

Pd

P

Cl3Si

R

R





Unclear formation

σp

σp+


62


TK Woo

HH P

PdSiCl3SiCl3

NNH H

HH

HH P

PdSiCl3SiCl3

NNH H

FeP

PdSiCl3SiCl3

NN

FeP

PdSiCl3SiCl3

NN

HH P

PdSiCl3SiCl3

NNH H

HH P

PdSiCl3SiCl3

NN

H3CH

HH

H

Model 1

Model 2


63






PPd

H

SiCl3NN

HH

PPd

HSiCl3

NN

HH

PPd

HSiCl3

NN

HH

PPd

SiCl3NN

HH PPd

SiCl3NN

HH

1900

22

-02

-83

141

52

PPd

SiCl3NN

HH

PPd

Cl3SiNN

HH

64


endoendo-syn

PPdH

SiCl3NN

Fe

PPd HSiCl3NN

FeFe P

Pd

SiCl3NN

PPd HSiCl3NN

Fe

Cl3Si

PPd

SiCl3N

Fe

N

PPd

Cl3SiNN

Fe

PPdH

SiCl3NN

Fe

PPd

NN

Fe

Cl3Si

R

-35

09

TS1

TS2

-205

+-103

+styrene

00

42+48

61

Dagger Dagger


65





FeP

PdH

SiCl3NN

PPd

HSiCl3

NN

Fe


66


PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPd

H

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPdSiCl3NN

Fe

PPd

SiCl3NN

Fe

48

00

1609

51

-103

-113



endo-syn

exo-synendo

exo


kcalmol

67



endo-syn

exo-syn

NMe2

PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

NMe2

PPd

SiCl3NN

Fe

NMe2

PPdH

SiCl3NN

Fe

Me2N

PPd

SiCl3NN

Fe

PPdSiCl3

NN

Fe

NMe2

PPd

SiCl3NN

Fe

Me2N

48

00

08

03

16

-172

-155

exo

endo


68


DD

D

D5

HndashSiCl3 [PdL]

DD

D

D5

HO H DD

H

D5

HO H DH

H

D5

HO H DD

D

D5

HO D

oxid workup

+ + +


MeD1

MeD2

13C-1H-HZQCNMR

MeD2

MeD11 equivsilane

5 equivsilane

EI-MS


69





70


Energy(kcalmol)

(at rt)


(kcalmol)

(at rt)

ee

endo-syn -103 123

75 (S)[65 (S)]

endo-syn -172 859

81 (R)[64 (R)]

endo-anti -81 03 75 (S)[65 (S)]


75 (S)[65 (S)] exo-syn -155 48

81 (R)[64 (R)]

exo-anti -106 669

75 (S)[65 (S)]

exo-anti -153 35

81 (R)[64 (R)]


71

Conclusions




72










32



33

$

amp$

$

$

($

$$ amp$ )$ $ $ $ $ $

$

amp()+-


ampamp2824+

5lt=-amp)gt+gt2)42






34




α1=+9degα2=-21deg




35

Pd

L1

L2R

R

Pd

L1

L2

R

R

Nu Nu



36



X-rayX-ray

PhPh FeP

NNPd Ph

Ph


+

Ph

FeP

NNPd

Ph

Ph

Ph


+

PhPh FeP

NN

Pd Ph

Ph

+



Ph Ph

OCOR

NH2

Ph Ph


40 degC THF


N

Me

N

Fe

PPh2R

37



Ph

FeP

NNPd

Ph

a) R-product



NuNu

a)

b)

+

RS




PN

PdP N

PdP N

+ +


tc = 2 kcalmol

(Ab initio studies)

38

NH

NPd

PH3

NH3


NPd

PH3


NH

NPd

PH3

NH3

50 kJmol

36 kJmol

NH3+

41 kJmol

NH3+

+



PdP N

PdP N

PdP N

+

+ +


tc = 8 kJmol


ct = 29 kJmol


for C out of plane



40

PhPh Fe

P

NNPd

Ph

Ph

Ph

Ph

FeP

NNPd

Ph

Ph

exo-syn-anti (71)

+

exo-syn-syn (29)

+

S R



41

PhFe

P

NN

Pd


+

Ph




42

Ph

Ph

PdP N

Ph

Ph

P NPd

Nu

Nu




43




PMe

NN

Ph

Ph

PhPh

PdNN

MePd

FeFeP

Ph

Ph

Ph

Ph

Ph Ph

NHCH2Ph

(S)

Ph Ph

OCOOEtNu-Nu-


950 ee resp 945 ee

rac

44






Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

Fe

N CN

PPh2

Me

Fe

N NC

PPh2

MePdR

R+

PdR

R+

X-ray

45



Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

PdR

R+

PdR

R+

Fe

N CN

PPh2

Me Pd

NHR2R

RFe

N CN

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

Fe

N NC

PPh2

Me Pd

NHR2R

RFe

N NC

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

dr 8515exoendo 8218

46














47


Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



Ph Ph

OCOOEt

Ph Ph

N



NH

Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



48

N

Me

N

Fe

PPh2

Ph Ph

OCO2Et

Ph Ph

NHCH2Ph

[Pd(dba)2 ]+ Ligand





991 (220)

67 (11)

33 (2)

987 (153)

gt995 (gt400)



3 mol Pd-catalyst

PF6- Selectivity

Killer




49

Ph

Ph

P

NPd

+

endo-syn-syn

+

exo-syn-syn

Ph

PhP

NPd

Ph Ph

OCOOEt

Ph Ph



Slow with PF6-

(tight ion pairs )

Fast with F-

(Coordination)

R-Product S-Product

more stable


S R


50










51

E N Jacobsen et al



NN

OMn

OCl

X X

HHX = OMe 96 ee

X = NO2 22 ee

52




MeO MeO

CN

OOOPh

OPhOPAr2

OAr2P CF3F3C MeMe

HCN [Ni(COD)2] L

Ar =

91 eeL

16 ee

53





OCO O

++

nn2 3

4

1


Δ

54

([α]D=-450)




Polymer)50 220 370 1800


PCy2Me

Fe P

CF3

CF32

PCy2Me

Fe P

OMe

OMe2

PCy2Me

Fe P

H

H2

PCy2Me

Fe P

CH3

CH32

55


Markus Baumann


NMeN

Fe

Me

Me

Me

P

O+ PhOTf



O Ph O Ph O

Ph

+ +

2

Rn

Rn=(m-CF3)2

Rn=(m-SiMe3)2

Rn=(p-OMe)

Rn=(p-CF3)

1 (34ee)

8 (62ee)

1 (46ee)

1 (10ee)

94 (88ee)

90 (95ee)

97 (96ee)

96 (95ee)

5

2

2

3

56



NMeN

Fe

PMe Me

F3C

F3CNMeN

Fe

PMe Me

CF3

F3CF3C

F3C

NMeN

Fe

PF3C CF3

MeO

MeO

NMeN

Fe

PMe Me

MeO

MeO

NMeN

Fe

PF3C CF3

NMeN

Fe

PMe Me

NMeN

Fe

PMe Me

Me2N

Me2NNMeN

Fe

PF3C CF3

F3C

F3C

95 ee985 ee

5 ee72 ee

33 ee

98 ee90 ee

40 ee

the worst

and the best

57





NMeN

Fe

Me

Me

Me

PPh2


2) Oxidative Workup

OH

NMeN

Fe PPh2

NMeN

Fe PPh2

Me

39ee 76ee 99ee

Catalytic activity

NMeN

Fe

MeO

OMe

OMe

PPh2

NMeN

Fe

Me

Me

Me

P

CF3

CF3

2

82ee 91ee

58


X

Fe PPh2

N N

Mes

Me

X

1) cat PdCl2(L)

2) Oxidation


= L

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=078rsup2=0996

NMe₂

OMe

Me

ClH


Fe P X

N N

Mes

Me

1) cat PdCl2(L)

2) Oxidation


2

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=014rsup2=0986

NMe₂OMe

Me HCl


59



Fe P X

N N

Mes

Me

OH1) cat PdCl2(L)

2) Oxidation


2

60



X

Fe PPh2

N N

Mes

Me

X

OH1) cat PdCl2(L)

2) Oxidation

= L

61


PdN

P

Cl

Cl

PdN

P H

SiCl3

R

PdN

P

R

SiCl3

N

PdP

HCl3Si

N

Pd

P

Cl3Si

R

R





Unclear formation

σp

σp+


62


TK Woo

HH P

PdSiCl3SiCl3

NNH H

HH

HH P

PdSiCl3SiCl3

NNH H

FeP

PdSiCl3SiCl3

NN

FeP

PdSiCl3SiCl3

NN

HH P

PdSiCl3SiCl3

NNH H

HH P

PdSiCl3SiCl3

NN

H3CH

HH

H

Model 1

Model 2


63






PPd

H

SiCl3NN

HH

PPd

HSiCl3

NN

HH

PPd

HSiCl3

NN

HH

PPd

SiCl3NN

HH PPd

SiCl3NN

HH

1900

22

-02

-83

141

52

PPd

SiCl3NN

HH

PPd

Cl3SiNN

HH

64


endoendo-syn

PPdH

SiCl3NN

Fe

PPd HSiCl3NN

FeFe P

Pd

SiCl3NN

PPd HSiCl3NN

Fe

Cl3Si

PPd

SiCl3N

Fe

N

PPd

Cl3SiNN

Fe

PPdH

SiCl3NN

Fe

PPd

NN

Fe

Cl3Si

R

-35

09

TS1

TS2

-205

+-103

+styrene

00

42+48

61

Dagger Dagger


65





FeP

PdH

SiCl3NN

PPd

HSiCl3

NN

Fe


66


PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPd

H

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPdSiCl3NN

Fe

PPd

SiCl3NN

Fe

48

00

1609

51

-103

-113



endo-syn

exo-synendo

exo


kcalmol

67



endo-syn

exo-syn

NMe2

PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

NMe2

PPd

SiCl3NN

Fe

NMe2

PPdH

SiCl3NN

Fe

Me2N

PPd

SiCl3NN

Fe

PPdSiCl3

NN

Fe

NMe2

PPd

SiCl3NN

Fe

Me2N

48

00

08

03

16

-172

-155

exo

endo


68


DD

D

D5

HndashSiCl3 [PdL]

DD

D

D5

HO H DD

H

D5

HO H DH

H

D5

HO H DD

D

D5

HO D

oxid workup

+ + +


MeD1

MeD2

13C-1H-HZQCNMR

MeD2

MeD11 equivsilane

5 equivsilane

EI-MS


69





70


Energy(kcalmol)

(at rt)


(kcalmol)

(at rt)

ee

endo-syn -103 123

75 (S)[65 (S)]

endo-syn -172 859

81 (R)[64 (R)]

endo-anti -81 03 75 (S)[65 (S)]


75 (S)[65 (S)] exo-syn -155 48

81 (R)[64 (R)]

exo-anti -106 669

75 (S)[65 (S)]

exo-anti -153 35

81 (R)[64 (R)]


71

Conclusions




72



33

$

amp$

$

$

($

$$ amp$ )$ $ $ $ $ $

$

amp()+-


ampamp2824+

5lt=-amp)gt+gt2)42






34




α1=+9degα2=-21deg




35

Pd

L1

L2R

R

Pd

L1

L2

R

R

Nu Nu



36



X-rayX-ray

PhPh FeP

NNPd Ph

Ph


+

Ph

FeP

NNPd

Ph

Ph

Ph


+

PhPh FeP

NN

Pd Ph

Ph

+



Ph Ph

OCOR

NH2

Ph Ph


40 degC THF


N

Me

N

Fe

PPh2R

37



Ph

FeP

NNPd

Ph

a) R-product



NuNu

a)

b)

+

RS




PN

PdP N

PdP N

+ +


tc = 2 kcalmol

(Ab initio studies)

38

NH

NPd

PH3

NH3


NPd

PH3


NH

NPd

PH3

NH3

50 kJmol

36 kJmol

NH3+

41 kJmol

NH3+

+



PdP N

PdP N

PdP N

+

+ +


tc = 8 kJmol


ct = 29 kJmol


for C out of plane



40

PhPh Fe

P

NNPd

Ph

Ph

Ph

Ph

FeP

NNPd

Ph

Ph

exo-syn-anti (71)

+

exo-syn-syn (29)

+

S R



41

PhFe

P

NN

Pd


+

Ph




42

Ph

Ph

PdP N

Ph

Ph

P NPd

Nu

Nu




43




PMe

NN

Ph

Ph

PhPh

PdNN

MePd

FeFeP

Ph

Ph

Ph

Ph

Ph Ph

NHCH2Ph

(S)

Ph Ph

OCOOEtNu-Nu-


950 ee resp 945 ee

rac

44






Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

Fe

N CN

PPh2

Me

Fe

N NC

PPh2

MePdR

R+

PdR

R+

X-ray

45



Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

PdR

R+

PdR

R+

Fe

N CN

PPh2

Me Pd

NHR2R

RFe

N CN

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

Fe

N NC

PPh2

Me Pd

NHR2R

RFe

N NC

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

dr 8515exoendo 8218

46














47


Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



Ph Ph

OCOOEt

Ph Ph

N



NH

Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



48

N

Me

N

Fe

PPh2

Ph Ph

OCO2Et

Ph Ph

NHCH2Ph

[Pd(dba)2 ]+ Ligand





991 (220)

67 (11)

33 (2)

987 (153)

gt995 (gt400)



3 mol Pd-catalyst

PF6- Selectivity

Killer




49

Ph

Ph

P

NPd

+

endo-syn-syn

+

exo-syn-syn

Ph

PhP

NPd

Ph Ph

OCOOEt

Ph Ph



Slow with PF6-

(tight ion pairs )

Fast with F-

(Coordination)

R-Product S-Product

more stable


S R


50










51

E N Jacobsen et al



NN

OMn

OCl

X X

HHX = OMe 96 ee

X = NO2 22 ee

52




MeO MeO

CN

OOOPh

OPhOPAr2

OAr2P CF3F3C MeMe

HCN [Ni(COD)2] L

Ar =

91 eeL

16 ee

53





OCO O

++

nn2 3

4

1


Δ

54

([α]D=-450)




Polymer)50 220 370 1800


PCy2Me

Fe P

CF3

CF32

PCy2Me

Fe P

OMe

OMe2

PCy2Me

Fe P

H

H2

PCy2Me

Fe P

CH3

CH32

55


Markus Baumann


NMeN

Fe

Me

Me

Me

P

O+ PhOTf



O Ph O Ph O

Ph

+ +

2

Rn

Rn=(m-CF3)2

Rn=(m-SiMe3)2

Rn=(p-OMe)

Rn=(p-CF3)

1 (34ee)

8 (62ee)

1 (46ee)

1 (10ee)

94 (88ee)

90 (95ee)

97 (96ee)

96 (95ee)

5

2

2

3

56



NMeN

Fe

PMe Me

F3C

F3CNMeN

Fe

PMe Me

CF3

F3CF3C

F3C

NMeN

Fe

PF3C CF3

MeO

MeO

NMeN

Fe

PMe Me

MeO

MeO

NMeN

Fe

PF3C CF3

NMeN

Fe

PMe Me

NMeN

Fe

PMe Me

Me2N

Me2NNMeN

Fe

PF3C CF3

F3C

F3C

95 ee985 ee

5 ee72 ee

33 ee

98 ee90 ee

40 ee

the worst

and the best

57





NMeN

Fe

Me

Me

Me

PPh2


2) Oxidative Workup

OH

NMeN

Fe PPh2

NMeN

Fe PPh2

Me

39ee 76ee 99ee

Catalytic activity

NMeN

Fe

MeO

OMe

OMe

PPh2

NMeN

Fe

Me

Me

Me

P

CF3

CF3

2

82ee 91ee

58


X

Fe PPh2

N N

Mes

Me

X

1) cat PdCl2(L)

2) Oxidation


= L

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=078rsup2=0996

NMe₂

OMe

Me

ClH


Fe P X

N N

Mes

Me

1) cat PdCl2(L)

2) Oxidation


2

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=014rsup2=0986

NMe₂OMe

Me HCl


59



Fe P X

N N

Mes

Me

OH1) cat PdCl2(L)

2) Oxidation


2

60



X

Fe PPh2

N N

Mes

Me

X

OH1) cat PdCl2(L)

2) Oxidation

= L

61


PdN

P

Cl

Cl

PdN

P H

SiCl3

R

PdN

P

R

SiCl3

N

PdP

HCl3Si

N

Pd

P

Cl3Si

R

R





Unclear formation

σp

σp+


62


TK Woo

HH P

PdSiCl3SiCl3

NNH H

HH

HH P

PdSiCl3SiCl3

NNH H

FeP

PdSiCl3SiCl3

NN

FeP

PdSiCl3SiCl3

NN

HH P

PdSiCl3SiCl3

NNH H

HH P

PdSiCl3SiCl3

NN

H3CH

HH

H

Model 1

Model 2


63






PPd

H

SiCl3NN

HH

PPd

HSiCl3

NN

HH

PPd

HSiCl3

NN

HH

PPd

SiCl3NN

HH PPd

SiCl3NN

HH

1900

22

-02

-83

141

52

PPd

SiCl3NN

HH

PPd

Cl3SiNN

HH

64


endoendo-syn

PPdH

SiCl3NN

Fe

PPd HSiCl3NN

FeFe P

Pd

SiCl3NN

PPd HSiCl3NN

Fe

Cl3Si

PPd

SiCl3N

Fe

N

PPd

Cl3SiNN

Fe

PPdH

SiCl3NN

Fe

PPd

NN

Fe

Cl3Si

R

-35

09

TS1

TS2

-205

+-103

+styrene

00

42+48

61

Dagger Dagger


65





FeP

PdH

SiCl3NN

PPd

HSiCl3

NN

Fe


66


PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPd

H

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPdSiCl3NN

Fe

PPd

SiCl3NN

Fe

48

00

1609

51

-103

-113



endo-syn

exo-synendo

exo


kcalmol

67



endo-syn

exo-syn

NMe2

PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

NMe2

PPd

SiCl3NN

Fe

NMe2

PPdH

SiCl3NN

Fe

Me2N

PPd

SiCl3NN

Fe

PPdSiCl3

NN

Fe

NMe2

PPd

SiCl3NN

Fe

Me2N

48

00

08

03

16

-172

-155

exo

endo


68


DD

D

D5

HndashSiCl3 [PdL]

DD

D

D5

HO H DD

H

D5

HO H DH

H

D5

HO H DD

D

D5

HO D

oxid workup

+ + +


MeD1

MeD2

13C-1H-HZQCNMR

MeD2

MeD11 equivsilane

5 equivsilane

EI-MS


69





70


Energy(kcalmol)

(at rt)


(kcalmol)

(at rt)

ee

endo-syn -103 123

75 (S)[65 (S)]

endo-syn -172 859

81 (R)[64 (R)]

endo-anti -81 03 75 (S)[65 (S)]


75 (S)[65 (S)] exo-syn -155 48

81 (R)[64 (R)]

exo-anti -106 669

75 (S)[65 (S)]

exo-anti -153 35

81 (R)[64 (R)]


71

Conclusions




72

$

amp$

$

$

($

$$ amp$ )$ $ $ $ $ $

$

amp()+-


ampamp2824+

5lt=-amp)gt+gt2)42






34




α1=+9degα2=-21deg




35

Pd

L1

L2R

R

Pd

L1

L2

R

R

Nu Nu



36



X-rayX-ray

PhPh FeP

NNPd Ph

Ph


+

Ph

FeP

NNPd

Ph

Ph

Ph


+

PhPh FeP

NN

Pd Ph

Ph

+



Ph Ph

OCOR

NH2

Ph Ph


40 degC THF


N

Me

N

Fe

PPh2R

37



Ph

FeP

NNPd

Ph

a) R-product



NuNu

a)

b)

+

RS




PN

PdP N

PdP N

+ +


tc = 2 kcalmol

(Ab initio studies)

38

NH

NPd

PH3

NH3


NPd

PH3


NH

NPd

PH3

NH3

50 kJmol

36 kJmol

NH3+

41 kJmol

NH3+

+



PdP N

PdP N

PdP N

+

+ +


tc = 8 kJmol


ct = 29 kJmol


for C out of plane



40

PhPh Fe

P

NNPd

Ph

Ph

Ph

Ph

FeP

NNPd

Ph

Ph

exo-syn-anti (71)

+

exo-syn-syn (29)

+

S R



41

PhFe

P

NN

Pd


+

Ph




42

Ph

Ph

PdP N

Ph

Ph

P NPd

Nu

Nu




43




PMe

NN

Ph

Ph

PhPh

PdNN

MePd

FeFeP

Ph

Ph

Ph

Ph

Ph Ph

NHCH2Ph

(S)

Ph Ph

OCOOEtNu-Nu-


950 ee resp 945 ee

rac

44






Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

Fe

N CN

PPh2

Me

Fe

N NC

PPh2

MePdR

R+

PdR

R+

X-ray

45



Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

PdR

R+

PdR

R+

Fe

N CN

PPh2

Me Pd

NHR2R

RFe

N CN

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

Fe

N NC

PPh2

Me Pd

NHR2R

RFe

N NC

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

dr 8515exoendo 8218

46














47


Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



Ph Ph

OCOOEt

Ph Ph

N



NH

Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



48

N

Me

N

Fe

PPh2

Ph Ph

OCO2Et

Ph Ph

NHCH2Ph

[Pd(dba)2 ]+ Ligand





991 (220)

67 (11)

33 (2)

987 (153)

gt995 (gt400)



3 mol Pd-catalyst

PF6- Selectivity

Killer




49

Ph

Ph

P

NPd

+

endo-syn-syn

+

exo-syn-syn

Ph

PhP

NPd

Ph Ph

OCOOEt

Ph Ph



Slow with PF6-

(tight ion pairs )

Fast with F-

(Coordination)

R-Product S-Product

more stable


S R


50










51

E N Jacobsen et al



NN

OMn

OCl

X X

HHX = OMe 96 ee

X = NO2 22 ee

52




MeO MeO

CN

OOOPh

OPhOPAr2

OAr2P CF3F3C MeMe

HCN [Ni(COD)2] L

Ar =

91 eeL

16 ee

53





OCO O

++

nn2 3

4

1


Δ

54

([α]D=-450)




Polymer)50 220 370 1800


PCy2Me

Fe P

CF3

CF32

PCy2Me

Fe P

OMe

OMe2

PCy2Me

Fe P

H

H2

PCy2Me

Fe P

CH3

CH32

55


Markus Baumann


NMeN

Fe

Me

Me

Me

P

O+ PhOTf



O Ph O Ph O

Ph

+ +

2

Rn

Rn=(m-CF3)2

Rn=(m-SiMe3)2

Rn=(p-OMe)

Rn=(p-CF3)

1 (34ee)

8 (62ee)

1 (46ee)

1 (10ee)

94 (88ee)

90 (95ee)

97 (96ee)

96 (95ee)

5

2

2

3

56



NMeN

Fe

PMe Me

F3C

F3CNMeN

Fe

PMe Me

CF3

F3CF3C

F3C

NMeN

Fe

PF3C CF3

MeO

MeO

NMeN

Fe

PMe Me

MeO

MeO

NMeN

Fe

PF3C CF3

NMeN

Fe

PMe Me

NMeN

Fe

PMe Me

Me2N

Me2NNMeN

Fe

PF3C CF3

F3C

F3C

95 ee985 ee

5 ee72 ee

33 ee

98 ee90 ee

40 ee

the worst

and the best

57





NMeN

Fe

Me

Me

Me

PPh2


2) Oxidative Workup

OH

NMeN

Fe PPh2

NMeN

Fe PPh2

Me

39ee 76ee 99ee

Catalytic activity

NMeN

Fe

MeO

OMe

OMe

PPh2

NMeN

Fe

Me

Me

Me

P

CF3

CF3

2

82ee 91ee

58


X

Fe PPh2

N N

Mes

Me

X

1) cat PdCl2(L)

2) Oxidation


= L

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=078rsup2=0996

NMe₂

OMe

Me

ClH


Fe P X

N N

Mes

Me

1) cat PdCl2(L)

2) Oxidation


2

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=014rsup2=0986

NMe₂OMe

Me HCl


59



Fe P X

N N

Mes

Me

OH1) cat PdCl2(L)

2) Oxidation


2

60



X

Fe PPh2

N N

Mes

Me

X

OH1) cat PdCl2(L)

2) Oxidation

= L

61


PdN

P

Cl

Cl

PdN

P H

SiCl3

R

PdN

P

R

SiCl3

N

PdP

HCl3Si

N

Pd

P

Cl3Si

R

R





Unclear formation

σp

σp+


62


TK Woo

HH P

PdSiCl3SiCl3

NNH H

HH

HH P

PdSiCl3SiCl3

NNH H

FeP

PdSiCl3SiCl3

NN

FeP

PdSiCl3SiCl3

NN

HH P

PdSiCl3SiCl3

NNH H

HH P

PdSiCl3SiCl3

NN

H3CH

HH

H

Model 1

Model 2


63






PPd

H

SiCl3NN

HH

PPd

HSiCl3

NN

HH

PPd

HSiCl3

NN

HH

PPd

SiCl3NN

HH PPd

SiCl3NN

HH

1900

22

-02

-83

141

52

PPd

SiCl3NN

HH

PPd

Cl3SiNN

HH

64


endoendo-syn

PPdH

SiCl3NN

Fe

PPd HSiCl3NN

FeFe P

Pd

SiCl3NN

PPd HSiCl3NN

Fe

Cl3Si

PPd

SiCl3N

Fe

N

PPd

Cl3SiNN

Fe

PPdH

SiCl3NN

Fe

PPd

NN

Fe

Cl3Si

R

-35

09

TS1

TS2

-205

+-103

+styrene

00

42+48

61

Dagger Dagger


65





FeP

PdH

SiCl3NN

PPd

HSiCl3

NN

Fe


66


PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPd

H

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPdSiCl3NN

Fe

PPd

SiCl3NN

Fe

48

00

1609

51

-103

-113



endo-syn

exo-synendo

exo


kcalmol

67



endo-syn

exo-syn

NMe2

PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

NMe2

PPd

SiCl3NN

Fe

NMe2

PPdH

SiCl3NN

Fe

Me2N

PPd

SiCl3NN

Fe

PPdSiCl3

NN

Fe

NMe2

PPd

SiCl3NN

Fe

Me2N

48

00

08

03

16

-172

-155

exo

endo


68


DD

D

D5

HndashSiCl3 [PdL]

DD

D

D5

HO H DD

H

D5

HO H DH

H

D5

HO H DD

D

D5

HO D

oxid workup

+ + +


MeD1

MeD2

13C-1H-HZQCNMR

MeD2

MeD11 equivsilane

5 equivsilane

EI-MS


69





70


Energy(kcalmol)

(at rt)


(kcalmol)

(at rt)

ee

endo-syn -103 123

75 (S)[65 (S)]

endo-syn -172 859

81 (R)[64 (R)]

endo-anti -81 03 75 (S)[65 (S)]


75 (S)[65 (S)] exo-syn -155 48

81 (R)[64 (R)]

exo-anti -106 669

75 (S)[65 (S)]

exo-anti -153 35

81 (R)[64 (R)]


71

Conclusions




72




α1=+9degα2=-21deg




35

Pd

L1

L2R

R

Pd

L1

L2

R

R

Nu Nu



36



X-rayX-ray

PhPh FeP

NNPd Ph

Ph


+

Ph

FeP

NNPd

Ph

Ph

Ph


+

PhPh FeP

NN

Pd Ph

Ph

+



Ph Ph

OCOR

NH2

Ph Ph


40 degC THF


N

Me

N

Fe

PPh2R

37



Ph

FeP

NNPd

Ph

a) R-product



NuNu

a)

b)

+

RS




PN

PdP N

PdP N

+ +


tc = 2 kcalmol

(Ab initio studies)

38

NH

NPd

PH3

NH3


NPd

PH3


NH

NPd

PH3

NH3

50 kJmol

36 kJmol

NH3+

41 kJmol

NH3+

+



PdP N

PdP N

PdP N

+

+ +


tc = 8 kJmol


ct = 29 kJmol


for C out of plane



40

PhPh Fe

P

NNPd

Ph

Ph

Ph

Ph

FeP

NNPd

Ph

Ph

exo-syn-anti (71)

+

exo-syn-syn (29)

+

S R



41

PhFe

P

NN

Pd


+

Ph




42

Ph

Ph

PdP N

Ph

Ph

P NPd

Nu

Nu




43




PMe

NN

Ph

Ph

PhPh

PdNN

MePd

FeFeP

Ph

Ph

Ph

Ph

Ph Ph

NHCH2Ph

(S)

Ph Ph

OCOOEtNu-Nu-


950 ee resp 945 ee

rac

44






Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

Fe

N CN

PPh2

Me

Fe

N NC

PPh2

MePdR

R+

PdR

R+

X-ray

45



Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

PdR

R+

PdR

R+

Fe

N CN

PPh2

Me Pd

NHR2R

RFe

N CN

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

Fe

N NC

PPh2

Me Pd

NHR2R

RFe

N NC

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

dr 8515exoendo 8218

46














47


Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



Ph Ph

OCOOEt

Ph Ph

N



NH

Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



48

N

Me

N

Fe

PPh2

Ph Ph

OCO2Et

Ph Ph

NHCH2Ph

[Pd(dba)2 ]+ Ligand





991 (220)

67 (11)

33 (2)

987 (153)

gt995 (gt400)



3 mol Pd-catalyst

PF6- Selectivity

Killer




49

Ph

Ph

P

NPd

+

endo-syn-syn

+

exo-syn-syn

Ph

PhP

NPd

Ph Ph

OCOOEt

Ph Ph



Slow with PF6-

(tight ion pairs )

Fast with F-

(Coordination)

R-Product S-Product

more stable


S R


50










51

E N Jacobsen et al



NN

OMn

OCl

X X

HHX = OMe 96 ee

X = NO2 22 ee

52




MeO MeO

CN

OOOPh

OPhOPAr2

OAr2P CF3F3C MeMe

HCN [Ni(COD)2] L

Ar =

91 eeL

16 ee

53





OCO O

++

nn2 3

4

1


Δ

54

([α]D=-450)




Polymer)50 220 370 1800


PCy2Me

Fe P

CF3

CF32

PCy2Me

Fe P

OMe

OMe2

PCy2Me

Fe P

H

H2

PCy2Me

Fe P

CH3

CH32

55


Markus Baumann


NMeN

Fe

Me

Me

Me

P

O+ PhOTf



O Ph O Ph O

Ph

+ +

2

Rn

Rn=(m-CF3)2

Rn=(m-SiMe3)2

Rn=(p-OMe)

Rn=(p-CF3)

1 (34ee)

8 (62ee)

1 (46ee)

1 (10ee)

94 (88ee)

90 (95ee)

97 (96ee)

96 (95ee)

5

2

2

3

56



NMeN

Fe

PMe Me

F3C

F3CNMeN

Fe

PMe Me

CF3

F3CF3C

F3C

NMeN

Fe

PF3C CF3

MeO

MeO

NMeN

Fe

PMe Me

MeO

MeO

NMeN

Fe

PF3C CF3

NMeN

Fe

PMe Me

NMeN

Fe

PMe Me

Me2N

Me2NNMeN

Fe

PF3C CF3

F3C

F3C

95 ee985 ee

5 ee72 ee

33 ee

98 ee90 ee

40 ee

the worst

and the best

57





NMeN

Fe

Me

Me

Me

PPh2


2) Oxidative Workup

OH

NMeN

Fe PPh2

NMeN

Fe PPh2

Me

39ee 76ee 99ee

Catalytic activity

NMeN

Fe

MeO

OMe

OMe

PPh2

NMeN

Fe

Me

Me

Me

P

CF3

CF3

2

82ee 91ee

58


X

Fe PPh2

N N

Mes

Me

X

1) cat PdCl2(L)

2) Oxidation


= L

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=078rsup2=0996

NMe₂

OMe

Me

ClH


Fe P X

N N

Mes

Me

1) cat PdCl2(L)

2) Oxidation


2

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=014rsup2=0986

NMe₂OMe

Me HCl


59



Fe P X

N N

Mes

Me

OH1) cat PdCl2(L)

2) Oxidation


2

60



X

Fe PPh2

N N

Mes

Me

X

OH1) cat PdCl2(L)

2) Oxidation

= L

61


PdN

P

Cl

Cl

PdN

P H

SiCl3

R

PdN

P

R

SiCl3

N

PdP

HCl3Si

N

Pd

P

Cl3Si

R

R





Unclear formation

σp

σp+


62


TK Woo

HH P

PdSiCl3SiCl3

NNH H

HH

HH P

PdSiCl3SiCl3

NNH H

FeP

PdSiCl3SiCl3

NN

FeP

PdSiCl3SiCl3

NN

HH P

PdSiCl3SiCl3

NNH H

HH P

PdSiCl3SiCl3

NN

H3CH

HH

H

Model 1

Model 2


63






PPd

H

SiCl3NN

HH

PPd

HSiCl3

NN

HH

PPd

HSiCl3

NN

HH

PPd

SiCl3NN

HH PPd

SiCl3NN

HH

1900

22

-02

-83

141

52

PPd

SiCl3NN

HH

PPd

Cl3SiNN

HH

64


endoendo-syn

PPdH

SiCl3NN

Fe

PPd HSiCl3NN

FeFe P

Pd

SiCl3NN

PPd HSiCl3NN

Fe

Cl3Si

PPd

SiCl3N

Fe

N

PPd

Cl3SiNN

Fe

PPdH

SiCl3NN

Fe

PPd

NN

Fe

Cl3Si

R

-35

09

TS1

TS2

-205

+-103

+styrene

00

42+48

61

Dagger Dagger


65





FeP

PdH

SiCl3NN

PPd

HSiCl3

NN

Fe


66


PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPd

H

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPdSiCl3NN

Fe

PPd

SiCl3NN

Fe

48

00

1609

51

-103

-113



endo-syn

exo-synendo

exo


kcalmol

67



endo-syn

exo-syn

NMe2

PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

NMe2

PPd

SiCl3NN

Fe

NMe2

PPdH

SiCl3NN

Fe

Me2N

PPd

SiCl3NN

Fe

PPdSiCl3

NN

Fe

NMe2

PPd

SiCl3NN

Fe

Me2N

48

00

08

03

16

-172

-155

exo

endo


68


DD

D

D5

HndashSiCl3 [PdL]

DD

D

D5

HO H DD

H

D5

HO H DH

H

D5

HO H DD

D

D5

HO D

oxid workup

+ + +


MeD1

MeD2

13C-1H-HZQCNMR

MeD2

MeD11 equivsilane

5 equivsilane

EI-MS


69





70


Energy(kcalmol)

(at rt)


(kcalmol)

(at rt)

ee

endo-syn -103 123

75 (S)[65 (S)]

endo-syn -172 859

81 (R)[64 (R)]

endo-anti -81 03 75 (S)[65 (S)]


75 (S)[65 (S)] exo-syn -155 48

81 (R)[64 (R)]

exo-anti -106 669

75 (S)[65 (S)]

exo-anti -153 35

81 (R)[64 (R)]


71

Conclusions




72

Pd

L1

L2R

R

Pd

L1

L2

R

R

Nu Nu



36



X-rayX-ray

PhPh FeP

NNPd Ph

Ph


+

Ph

FeP

NNPd

Ph

Ph

Ph


+

PhPh FeP

NN

Pd Ph

Ph

+



Ph Ph

OCOR

NH2

Ph Ph


40 degC THF


N

Me

N

Fe

PPh2R

37



Ph

FeP

NNPd

Ph

a) R-product



NuNu

a)

b)

+

RS




PN

PdP N

PdP N

+ +


tc = 2 kcalmol

(Ab initio studies)

38

NH

NPd

PH3

NH3


NPd

PH3


NH

NPd

PH3

NH3

50 kJmol

36 kJmol

NH3+

41 kJmol

NH3+

+



PdP N

PdP N

PdP N

+

+ +


tc = 8 kJmol


ct = 29 kJmol


for C out of plane



40

PhPh Fe

P

NNPd

Ph

Ph

Ph

Ph

FeP

NNPd

Ph

Ph

exo-syn-anti (71)

+

exo-syn-syn (29)

+

S R



41

PhFe

P

NN

Pd


+

Ph




42

Ph

Ph

PdP N

Ph

Ph

P NPd

Nu

Nu




43




PMe

NN

Ph

Ph

PhPh

PdNN

MePd

FeFeP

Ph

Ph

Ph

Ph

Ph Ph

NHCH2Ph

(S)

Ph Ph

OCOOEtNu-Nu-


950 ee resp 945 ee

rac

44






Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

Fe

N CN

PPh2

Me

Fe

N NC

PPh2

MePdR

R+

PdR

R+

X-ray

45



Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

PdR

R+

PdR

R+

Fe

N CN

PPh2

Me Pd

NHR2R

RFe

N CN

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

Fe

N NC

PPh2

Me Pd

NHR2R

RFe

N NC

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

dr 8515exoendo 8218

46














47


Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



Ph Ph

OCOOEt

Ph Ph

N



NH

Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



48

N

Me

N

Fe

PPh2

Ph Ph

OCO2Et

Ph Ph

NHCH2Ph

[Pd(dba)2 ]+ Ligand





991 (220)

67 (11)

33 (2)

987 (153)

gt995 (gt400)



3 mol Pd-catalyst

PF6- Selectivity

Killer




49

Ph

Ph

P

NPd

+

endo-syn-syn

+

exo-syn-syn

Ph

PhP

NPd

Ph Ph

OCOOEt

Ph Ph



Slow with PF6-

(tight ion pairs )

Fast with F-

(Coordination)

R-Product S-Product

more stable


S R


50










51

E N Jacobsen et al



NN

OMn

OCl

X X

HHX = OMe 96 ee

X = NO2 22 ee

52




MeO MeO

CN

OOOPh

OPhOPAr2

OAr2P CF3F3C MeMe

HCN [Ni(COD)2] L

Ar =

91 eeL

16 ee

53





OCO O

++

nn2 3

4

1


Δ

54

([α]D=-450)




Polymer)50 220 370 1800


PCy2Me

Fe P

CF3

CF32

PCy2Me

Fe P

OMe

OMe2

PCy2Me

Fe P

H

H2

PCy2Me

Fe P

CH3

CH32

55


Markus Baumann


NMeN

Fe

Me

Me

Me

P

O+ PhOTf



O Ph O Ph O

Ph

+ +

2

Rn

Rn=(m-CF3)2

Rn=(m-SiMe3)2

Rn=(p-OMe)

Rn=(p-CF3)

1 (34ee)

8 (62ee)

1 (46ee)

1 (10ee)

94 (88ee)

90 (95ee)

97 (96ee)

96 (95ee)

5

2

2

3

56



NMeN

Fe

PMe Me

F3C

F3CNMeN

Fe

PMe Me

CF3

F3CF3C

F3C

NMeN

Fe

PF3C CF3

MeO

MeO

NMeN

Fe

PMe Me

MeO

MeO

NMeN

Fe

PF3C CF3

NMeN

Fe

PMe Me

NMeN

Fe

PMe Me

Me2N

Me2NNMeN

Fe

PF3C CF3

F3C

F3C

95 ee985 ee

5 ee72 ee

33 ee

98 ee90 ee

40 ee

the worst

and the best

57





NMeN

Fe

Me

Me

Me

PPh2


2) Oxidative Workup

OH

NMeN

Fe PPh2

NMeN

Fe PPh2

Me

39ee 76ee 99ee

Catalytic activity

NMeN

Fe

MeO

OMe

OMe

PPh2

NMeN

Fe

Me

Me

Me

P

CF3

CF3

2

82ee 91ee

58


X

Fe PPh2

N N

Mes

Me

X

1) cat PdCl2(L)

2) Oxidation


= L

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=078rsup2=0996

NMe₂

OMe

Me

ClH


Fe P X

N N

Mes

Me

1) cat PdCl2(L)

2) Oxidation


2

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=014rsup2=0986

NMe₂OMe

Me HCl


59



Fe P X

N N

Mes

Me

OH1) cat PdCl2(L)

2) Oxidation


2

60



X

Fe PPh2

N N

Mes

Me

X

OH1) cat PdCl2(L)

2) Oxidation

= L

61


PdN

P

Cl

Cl

PdN

P H

SiCl3

R

PdN

P

R

SiCl3

N

PdP

HCl3Si

N

Pd

P

Cl3Si

R

R





Unclear formation

σp

σp+


62


TK Woo

HH P

PdSiCl3SiCl3

NNH H

HH

HH P

PdSiCl3SiCl3

NNH H

FeP

PdSiCl3SiCl3

NN

FeP

PdSiCl3SiCl3

NN

HH P

PdSiCl3SiCl3

NNH H

HH P

PdSiCl3SiCl3

NN

H3CH

HH

H

Model 1

Model 2


63






PPd

H

SiCl3NN

HH

PPd

HSiCl3

NN

HH

PPd

HSiCl3

NN

HH

PPd

SiCl3NN

HH PPd

SiCl3NN

HH

1900

22

-02

-83

141

52

PPd

SiCl3NN

HH

PPd

Cl3SiNN

HH

64


endoendo-syn

PPdH

SiCl3NN

Fe

PPd HSiCl3NN

FeFe P

Pd

SiCl3NN

PPd HSiCl3NN

Fe

Cl3Si

PPd

SiCl3N

Fe

N

PPd

Cl3SiNN

Fe

PPdH

SiCl3NN

Fe

PPd

NN

Fe

Cl3Si

R

-35

09

TS1

TS2

-205

+-103

+styrene

00

42+48

61

Dagger Dagger


65





FeP

PdH

SiCl3NN

PPd

HSiCl3

NN

Fe


66


PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPd

H

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPdSiCl3NN

Fe

PPd

SiCl3NN

Fe

48

00

1609

51

-103

-113



endo-syn

exo-synendo

exo


kcalmol

67



endo-syn

exo-syn

NMe2

PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

NMe2

PPd

SiCl3NN

Fe

NMe2

PPdH

SiCl3NN

Fe

Me2N

PPd

SiCl3NN

Fe

PPdSiCl3

NN

Fe

NMe2

PPd

SiCl3NN

Fe

Me2N

48

00

08

03

16

-172

-155

exo

endo


68


DD

D

D5

HndashSiCl3 [PdL]

DD

D

D5

HO H DD

H

D5

HO H DH

H

D5

HO H DD

D

D5

HO D

oxid workup

+ + +


MeD1

MeD2

13C-1H-HZQCNMR

MeD2

MeD11 equivsilane

5 equivsilane

EI-MS


69





70


Energy(kcalmol)

(at rt)


(kcalmol)

(at rt)

ee

endo-syn -103 123

75 (S)[65 (S)]

endo-syn -172 859

81 (R)[64 (R)]

endo-anti -81 03 75 (S)[65 (S)]


75 (S)[65 (S)] exo-syn -155 48

81 (R)[64 (R)]

exo-anti -106 669

75 (S)[65 (S)]

exo-anti -153 35

81 (R)[64 (R)]


71

Conclusions




72



X-rayX-ray

PhPh FeP

NNPd Ph

Ph


+

Ph

FeP

NNPd

Ph

Ph

Ph


+

PhPh FeP

NN

Pd Ph

Ph

+



Ph Ph

OCOR

NH2

Ph Ph


40 degC THF


N

Me

N

Fe

PPh2R

37



Ph

FeP

NNPd

Ph

a) R-product



NuNu

a)

b)

+

RS




PN

PdP N

PdP N

+ +


tc = 2 kcalmol

(Ab initio studies)

38

NH

NPd

PH3

NH3


NPd

PH3


NH

NPd

PH3

NH3

50 kJmol

36 kJmol

NH3+

41 kJmol

NH3+

+



PdP N

PdP N

PdP N

+

+ +


tc = 8 kJmol


ct = 29 kJmol


for C out of plane



40

PhPh Fe

P

NNPd

Ph

Ph

Ph

Ph

FeP

NNPd

Ph

Ph

exo-syn-anti (71)

+

exo-syn-syn (29)

+

S R



41

PhFe

P

NN

Pd


+

Ph




42

Ph

Ph

PdP N

Ph

Ph

P NPd

Nu

Nu




43




PMe

NN

Ph

Ph

PhPh

PdNN

MePd

FeFeP

Ph

Ph

Ph

Ph

Ph Ph

NHCH2Ph

(S)

Ph Ph

OCOOEtNu-Nu-


950 ee resp 945 ee

rac

44






Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

Fe

N CN

PPh2

Me

Fe

N NC

PPh2

MePdR

R+

PdR

R+

X-ray

45



Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

PdR

R+

PdR

R+

Fe

N CN

PPh2

Me Pd

NHR2R

RFe

N CN

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

Fe

N NC

PPh2

Me Pd

NHR2R

RFe

N NC

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

dr 8515exoendo 8218

46














47


Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



Ph Ph

OCOOEt

Ph Ph

N



NH

Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



48

N

Me

N

Fe

PPh2

Ph Ph

OCO2Et

Ph Ph

NHCH2Ph

[Pd(dba)2 ]+ Ligand





991 (220)

67 (11)

33 (2)

987 (153)

gt995 (gt400)



3 mol Pd-catalyst

PF6- Selectivity

Killer




49

Ph

Ph

P

NPd

+

endo-syn-syn

+

exo-syn-syn

Ph

PhP

NPd

Ph Ph

OCOOEt

Ph Ph



Slow with PF6-

(tight ion pairs )

Fast with F-

(Coordination)

R-Product S-Product

more stable


S R


50










51

E N Jacobsen et al



NN

OMn

OCl

X X

HHX = OMe 96 ee

X = NO2 22 ee

52




MeO MeO

CN

OOOPh

OPhOPAr2

OAr2P CF3F3C MeMe

HCN [Ni(COD)2] L

Ar =

91 eeL

16 ee

53





OCO O

++

nn2 3

4

1


Δ

54

([α]D=-450)




Polymer)50 220 370 1800


PCy2Me

Fe P

CF3

CF32

PCy2Me

Fe P

OMe

OMe2

PCy2Me

Fe P

H

H2

PCy2Me

Fe P

CH3

CH32

55


Markus Baumann


NMeN

Fe

Me

Me

Me

P

O+ PhOTf



O Ph O Ph O

Ph

+ +

2

Rn

Rn=(m-CF3)2

Rn=(m-SiMe3)2

Rn=(p-OMe)

Rn=(p-CF3)

1 (34ee)

8 (62ee)

1 (46ee)

1 (10ee)

94 (88ee)

90 (95ee)

97 (96ee)

96 (95ee)

5

2

2

3

56



NMeN

Fe

PMe Me

F3C

F3CNMeN

Fe

PMe Me

CF3

F3CF3C

F3C

NMeN

Fe

PF3C CF3

MeO

MeO

NMeN

Fe

PMe Me

MeO

MeO

NMeN

Fe

PF3C CF3

NMeN

Fe

PMe Me

NMeN

Fe

PMe Me

Me2N

Me2NNMeN

Fe

PF3C CF3

F3C

F3C

95 ee985 ee

5 ee72 ee

33 ee

98 ee90 ee

40 ee

the worst

and the best

57





NMeN

Fe

Me

Me

Me

PPh2


2) Oxidative Workup

OH

NMeN

Fe PPh2

NMeN

Fe PPh2

Me

39ee 76ee 99ee

Catalytic activity

NMeN

Fe

MeO

OMe

OMe

PPh2

NMeN

Fe

Me

Me

Me

P

CF3

CF3

2

82ee 91ee

58


X

Fe PPh2

N N

Mes

Me

X

1) cat PdCl2(L)

2) Oxidation


= L

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=078rsup2=0996

NMe₂

OMe

Me

ClH


Fe P X

N N

Mes

Me

1) cat PdCl2(L)

2) Oxidation


2

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=014rsup2=0986

NMe₂OMe

Me HCl


59



Fe P X

N N

Mes

Me

OH1) cat PdCl2(L)

2) Oxidation


2

60



X

Fe PPh2

N N

Mes

Me

X

OH1) cat PdCl2(L)

2) Oxidation

= L

61


PdN

P

Cl

Cl

PdN

P H

SiCl3

R

PdN

P

R

SiCl3

N

PdP

HCl3Si

N

Pd

P

Cl3Si

R

R





Unclear formation

σp

σp+


62


TK Woo

HH P

PdSiCl3SiCl3

NNH H

HH

HH P

PdSiCl3SiCl3

NNH H

FeP

PdSiCl3SiCl3

NN

FeP

PdSiCl3SiCl3

NN

HH P

PdSiCl3SiCl3

NNH H

HH P

PdSiCl3SiCl3

NN

H3CH

HH

H

Model 1

Model 2


63






PPd

H

SiCl3NN

HH

PPd

HSiCl3

NN

HH

PPd

HSiCl3

NN

HH

PPd

SiCl3NN

HH PPd

SiCl3NN

HH

1900

22

-02

-83

141

52

PPd

SiCl3NN

HH

PPd

Cl3SiNN

HH

64


endoendo-syn

PPdH

SiCl3NN

Fe

PPd HSiCl3NN

FeFe P

Pd

SiCl3NN

PPd HSiCl3NN

Fe

Cl3Si

PPd

SiCl3N

Fe

N

PPd

Cl3SiNN

Fe

PPdH

SiCl3NN

Fe

PPd

NN

Fe

Cl3Si

R

-35

09

TS1

TS2

-205

+-103

+styrene

00

42+48

61

Dagger Dagger


65





FeP

PdH

SiCl3NN

PPd

HSiCl3

NN

Fe


66


PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPd

H

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPdSiCl3NN

Fe

PPd

SiCl3NN

Fe

48

00

1609

51

-103

-113



endo-syn

exo-synendo

exo


kcalmol

67



endo-syn

exo-syn

NMe2

PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

NMe2

PPd

SiCl3NN

Fe

NMe2

PPdH

SiCl3NN

Fe

Me2N

PPd

SiCl3NN

Fe

PPdSiCl3

NN

Fe

NMe2

PPd

SiCl3NN

Fe

Me2N

48

00

08

03

16

-172

-155

exo

endo


68


DD

D

D5

HndashSiCl3 [PdL]

DD

D

D5

HO H DD

H

D5

HO H DH

H

D5

HO H DD

D

D5

HO D

oxid workup

+ + +


MeD1

MeD2

13C-1H-HZQCNMR

MeD2

MeD11 equivsilane

5 equivsilane

EI-MS


69





70


Energy(kcalmol)

(at rt)


(kcalmol)

(at rt)

ee

endo-syn -103 123

75 (S)[65 (S)]

endo-syn -172 859

81 (R)[64 (R)]

endo-anti -81 03 75 (S)[65 (S)]


75 (S)[65 (S)] exo-syn -155 48

81 (R)[64 (R)]

exo-anti -106 669

75 (S)[65 (S)]

exo-anti -153 35

81 (R)[64 (R)]


71

Conclusions




72



Ph

FeP

NNPd

Ph

a) R-product



NuNu

a)

b)

+

RS




PN

PdP N

PdP N

+ +


tc = 2 kcalmol

(Ab initio studies)

38

NH

NPd

PH3

NH3


NPd

PH3


NH

NPd

PH3

NH3

50 kJmol

36 kJmol

NH3+

41 kJmol

NH3+

+



PdP N

PdP N

PdP N

+

+ +


tc = 8 kJmol


ct = 29 kJmol


for C out of plane



40

PhPh Fe

P

NNPd

Ph

Ph

Ph

Ph

FeP

NNPd

Ph

Ph

exo-syn-anti (71)

+

exo-syn-syn (29)

+

S R



41

PhFe

P

NN

Pd


+

Ph




42

Ph

Ph

PdP N

Ph

Ph

P NPd

Nu

Nu




43




PMe

NN

Ph

Ph

PhPh

PdNN

MePd

FeFeP

Ph

Ph

Ph

Ph

Ph Ph

NHCH2Ph

(S)

Ph Ph

OCOOEtNu-Nu-


950 ee resp 945 ee

rac

44






Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

Fe

N CN

PPh2

Me

Fe

N NC

PPh2

MePdR

R+

PdR

R+

X-ray

45



Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

PdR

R+

PdR

R+

Fe

N CN

PPh2

Me Pd

NHR2R

RFe

N CN

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

Fe

N NC

PPh2

Me Pd

NHR2R

RFe

N NC

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

dr 8515exoendo 8218

46














47


Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



Ph Ph

OCOOEt

Ph Ph

N



NH

Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



48

N

Me

N

Fe

PPh2

Ph Ph

OCO2Et

Ph Ph

NHCH2Ph

[Pd(dba)2 ]+ Ligand





991 (220)

67 (11)

33 (2)

987 (153)

gt995 (gt400)



3 mol Pd-catalyst

PF6- Selectivity

Killer




49

Ph

Ph

P

NPd

+

endo-syn-syn

+

exo-syn-syn

Ph

PhP

NPd

Ph Ph

OCOOEt

Ph Ph



Slow with PF6-

(tight ion pairs )

Fast with F-

(Coordination)

R-Product S-Product

more stable


S R


50










51

E N Jacobsen et al



NN

OMn

OCl

X X

HHX = OMe 96 ee

X = NO2 22 ee

52




MeO MeO

CN

OOOPh

OPhOPAr2

OAr2P CF3F3C MeMe

HCN [Ni(COD)2] L

Ar =

91 eeL

16 ee

53





OCO O

++

nn2 3

4

1


Δ

54

([α]D=-450)




Polymer)50 220 370 1800


PCy2Me

Fe P

CF3

CF32

PCy2Me

Fe P

OMe

OMe2

PCy2Me

Fe P

H

H2

PCy2Me

Fe P

CH3

CH32

55


Markus Baumann


NMeN

Fe

Me

Me

Me

P

O+ PhOTf



O Ph O Ph O

Ph

+ +

2

Rn

Rn=(m-CF3)2

Rn=(m-SiMe3)2

Rn=(p-OMe)

Rn=(p-CF3)

1 (34ee)

8 (62ee)

1 (46ee)

1 (10ee)

94 (88ee)

90 (95ee)

97 (96ee)

96 (95ee)

5

2

2

3

56



NMeN

Fe

PMe Me

F3C

F3CNMeN

Fe

PMe Me

CF3

F3CF3C

F3C

NMeN

Fe

PF3C CF3

MeO

MeO

NMeN

Fe

PMe Me

MeO

MeO

NMeN

Fe

PF3C CF3

NMeN

Fe

PMe Me

NMeN

Fe

PMe Me

Me2N

Me2NNMeN

Fe

PF3C CF3

F3C

F3C

95 ee985 ee

5 ee72 ee

33 ee

98 ee90 ee

40 ee

the worst

and the best

57





NMeN

Fe

Me

Me

Me

PPh2


2) Oxidative Workup

OH

NMeN

Fe PPh2

NMeN

Fe PPh2

Me

39ee 76ee 99ee

Catalytic activity

NMeN

Fe

MeO

OMe

OMe

PPh2

NMeN

Fe

Me

Me

Me

P

CF3

CF3

2

82ee 91ee

58


X

Fe PPh2

N N

Mes

Me

X

1) cat PdCl2(L)

2) Oxidation


= L

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=078rsup2=0996

NMe₂

OMe

Me

ClH


Fe P X

N N

Mes

Me

1) cat PdCl2(L)

2) Oxidation


2

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=014rsup2=0986

NMe₂OMe

Me HCl


59



Fe P X

N N

Mes

Me

OH1) cat PdCl2(L)

2) Oxidation


2

60



X

Fe PPh2

N N

Mes

Me

X

OH1) cat PdCl2(L)

2) Oxidation

= L

61


PdN

P

Cl

Cl

PdN

P H

SiCl3

R

PdN

P

R

SiCl3

N

PdP

HCl3Si

N

Pd

P

Cl3Si

R

R





Unclear formation

σp

σp+


62


TK Woo

HH P

PdSiCl3SiCl3

NNH H

HH

HH P

PdSiCl3SiCl3

NNH H

FeP

PdSiCl3SiCl3

NN

FeP

PdSiCl3SiCl3

NN

HH P

PdSiCl3SiCl3

NNH H

HH P

PdSiCl3SiCl3

NN

H3CH

HH

H

Model 1

Model 2


63






PPd

H

SiCl3NN

HH

PPd

HSiCl3

NN

HH

PPd

HSiCl3

NN

HH

PPd

SiCl3NN

HH PPd

SiCl3NN

HH

1900

22

-02

-83

141

52

PPd

SiCl3NN

HH

PPd

Cl3SiNN

HH

64


endoendo-syn

PPdH

SiCl3NN

Fe

PPd HSiCl3NN

FeFe P

Pd

SiCl3NN

PPd HSiCl3NN

Fe

Cl3Si

PPd

SiCl3N

Fe

N

PPd

Cl3SiNN

Fe

PPdH

SiCl3NN

Fe

PPd

NN

Fe

Cl3Si

R

-35

09

TS1

TS2

-205

+-103

+styrene

00

42+48

61

Dagger Dagger


65





FeP

PdH

SiCl3NN

PPd

HSiCl3

NN

Fe


66


PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPd

H

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPdSiCl3NN

Fe

PPd

SiCl3NN

Fe

48

00

1609

51

-103

-113



endo-syn

exo-synendo

exo


kcalmol

67



endo-syn

exo-syn

NMe2

PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

NMe2

PPd

SiCl3NN

Fe

NMe2

PPdH

SiCl3NN

Fe

Me2N

PPd

SiCl3NN

Fe

PPdSiCl3

NN

Fe

NMe2

PPd

SiCl3NN

Fe

Me2N

48

00

08

03

16

-172

-155

exo

endo


68


DD

D

D5

HndashSiCl3 [PdL]

DD

D

D5

HO H DD

H

D5

HO H DH

H

D5

HO H DD

D

D5

HO D

oxid workup

+ + +


MeD1

MeD2

13C-1H-HZQCNMR

MeD2

MeD11 equivsilane

5 equivsilane

EI-MS


69





70


Energy(kcalmol)

(at rt)


(kcalmol)

(at rt)

ee

endo-syn -103 123

75 (S)[65 (S)]

endo-syn -172 859

81 (R)[64 (R)]

endo-anti -81 03 75 (S)[65 (S)]


75 (S)[65 (S)] exo-syn -155 48

81 (R)[64 (R)]

exo-anti -106 669

75 (S)[65 (S)]

exo-anti -153 35

81 (R)[64 (R)]


71

Conclusions




72

NH

NPd

PH3

NH3


NPd

PH3


NH

NPd

PH3

NH3

50 kJmol

36 kJmol

NH3+

41 kJmol

NH3+

+



PdP N

PdP N

PdP N

+

+ +


tc = 8 kJmol


ct = 29 kJmol


for C out of plane



40

PhPh Fe

P

NNPd

Ph

Ph

Ph

Ph

FeP

NNPd

Ph

Ph

exo-syn-anti (71)

+

exo-syn-syn (29)

+

S R



41

PhFe

P

NN

Pd


+

Ph




42

Ph

Ph

PdP N

Ph

Ph

P NPd

Nu

Nu




43




PMe

NN

Ph

Ph

PhPh

PdNN

MePd

FeFeP

Ph

Ph

Ph

Ph

Ph Ph

NHCH2Ph

(S)

Ph Ph

OCOOEtNu-Nu-


950 ee resp 945 ee

rac

44






Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

Fe

N CN

PPh2

Me

Fe

N NC

PPh2

MePdR

R+

PdR

R+

X-ray

45



Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

PdR

R+

PdR

R+

Fe

N CN

PPh2

Me Pd

NHR2R

RFe

N CN

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

Fe

N NC

PPh2

Me Pd

NHR2R

RFe

N NC

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

dr 8515exoendo 8218

46














47


Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



Ph Ph

OCOOEt

Ph Ph

N



NH

Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



48

N

Me

N

Fe

PPh2

Ph Ph

OCO2Et

Ph Ph

NHCH2Ph

[Pd(dba)2 ]+ Ligand





991 (220)

67 (11)

33 (2)

987 (153)

gt995 (gt400)



3 mol Pd-catalyst

PF6- Selectivity

Killer




49

Ph

Ph

P

NPd

+

endo-syn-syn

+

exo-syn-syn

Ph

PhP

NPd

Ph Ph

OCOOEt

Ph Ph



Slow with PF6-

(tight ion pairs )

Fast with F-

(Coordination)

R-Product S-Product

more stable


S R


50










51

E N Jacobsen et al



NN

OMn

OCl

X X

HHX = OMe 96 ee

X = NO2 22 ee

52




MeO MeO

CN

OOOPh

OPhOPAr2

OAr2P CF3F3C MeMe

HCN [Ni(COD)2] L

Ar =

91 eeL

16 ee

53





OCO O

++

nn2 3

4

1


Δ

54

([α]D=-450)




Polymer)50 220 370 1800


PCy2Me

Fe P

CF3

CF32

PCy2Me

Fe P

OMe

OMe2

PCy2Me

Fe P

H

H2

PCy2Me

Fe P

CH3

CH32

55


Markus Baumann


NMeN

Fe

Me

Me

Me

P

O+ PhOTf



O Ph O Ph O

Ph

+ +

2

Rn

Rn=(m-CF3)2

Rn=(m-SiMe3)2

Rn=(p-OMe)

Rn=(p-CF3)

1 (34ee)

8 (62ee)

1 (46ee)

1 (10ee)

94 (88ee)

90 (95ee)

97 (96ee)

96 (95ee)

5

2

2

3

56



NMeN

Fe

PMe Me

F3C

F3CNMeN

Fe

PMe Me

CF3

F3CF3C

F3C

NMeN

Fe

PF3C CF3

MeO

MeO

NMeN

Fe

PMe Me

MeO

MeO

NMeN

Fe

PF3C CF3

NMeN

Fe

PMe Me

NMeN

Fe

PMe Me

Me2N

Me2NNMeN

Fe

PF3C CF3

F3C

F3C

95 ee985 ee

5 ee72 ee

33 ee

98 ee90 ee

40 ee

the worst

and the best

57





NMeN

Fe

Me

Me

Me

PPh2


2) Oxidative Workup

OH

NMeN

Fe PPh2

NMeN

Fe PPh2

Me

39ee 76ee 99ee

Catalytic activity

NMeN

Fe

MeO

OMe

OMe

PPh2

NMeN

Fe

Me

Me

Me

P

CF3

CF3

2

82ee 91ee

58


X

Fe PPh2

N N

Mes

Me

X

1) cat PdCl2(L)

2) Oxidation


= L

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=078rsup2=0996

NMe₂

OMe

Me

ClH


Fe P X

N N

Mes

Me

1) cat PdCl2(L)

2) Oxidation


2

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=014rsup2=0986

NMe₂OMe

Me HCl


59



Fe P X

N N

Mes

Me

OH1) cat PdCl2(L)

2) Oxidation


2

60



X

Fe PPh2

N N

Mes

Me

X

OH1) cat PdCl2(L)

2) Oxidation

= L

61


PdN

P

Cl

Cl

PdN

P H

SiCl3

R

PdN

P

R

SiCl3

N

PdP

HCl3Si

N

Pd

P

Cl3Si

R

R





Unclear formation

σp

σp+


62


TK Woo

HH P

PdSiCl3SiCl3

NNH H

HH

HH P

PdSiCl3SiCl3

NNH H

FeP

PdSiCl3SiCl3

NN

FeP

PdSiCl3SiCl3

NN

HH P

PdSiCl3SiCl3

NNH H

HH P

PdSiCl3SiCl3

NN

H3CH

HH

H

Model 1

Model 2


63






PPd

H

SiCl3NN

HH

PPd

HSiCl3

NN

HH

PPd

HSiCl3

NN

HH

PPd

SiCl3NN

HH PPd

SiCl3NN

HH

1900

22

-02

-83

141

52

PPd

SiCl3NN

HH

PPd

Cl3SiNN

HH

64


endoendo-syn

PPdH

SiCl3NN

Fe

PPd HSiCl3NN

FeFe P

Pd

SiCl3NN

PPd HSiCl3NN

Fe

Cl3Si

PPd

SiCl3N

Fe

N

PPd

Cl3SiNN

Fe

PPdH

SiCl3NN

Fe

PPd

NN

Fe

Cl3Si

R

-35

09

TS1

TS2

-205

+-103

+styrene

00

42+48

61

Dagger Dagger


65





FeP

PdH

SiCl3NN

PPd

HSiCl3

NN

Fe


66


PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPd

H

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPdSiCl3NN

Fe

PPd

SiCl3NN

Fe

48

00

1609

51

-103

-113



endo-syn

exo-synendo

exo


kcalmol

67



endo-syn

exo-syn

NMe2

PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

NMe2

PPd

SiCl3NN

Fe

NMe2

PPdH

SiCl3NN

Fe

Me2N

PPd

SiCl3NN

Fe

PPdSiCl3

NN

Fe

NMe2

PPd

SiCl3NN

Fe

Me2N

48

00

08

03

16

-172

-155

exo

endo


68


DD

D

D5

HndashSiCl3 [PdL]

DD

D

D5

HO H DD

H

D5

HO H DH

H

D5

HO H DD

D

D5

HO D

oxid workup

+ + +


MeD1

MeD2

13C-1H-HZQCNMR

MeD2

MeD11 equivsilane

5 equivsilane

EI-MS


69





70


Energy(kcalmol)

(at rt)


(kcalmol)

(at rt)

ee

endo-syn -103 123

75 (S)[65 (S)]

endo-syn -172 859

81 (R)[64 (R)]

endo-anti -81 03 75 (S)[65 (S)]


75 (S)[65 (S)] exo-syn -155 48

81 (R)[64 (R)]

exo-anti -106 669

75 (S)[65 (S)]

exo-anti -153 35

81 (R)[64 (R)]


71

Conclusions




72

PdP N

PdP N

PdP N

+

+ +


tc = 8 kJmol


ct = 29 kJmol


for C out of plane



40

PhPh Fe

P

NNPd

Ph

Ph

Ph

Ph

FeP

NNPd

Ph

Ph

exo-syn-anti (71)

+

exo-syn-syn (29)

+

S R



41

PhFe

P

NN

Pd


+

Ph




42

Ph

Ph

PdP N

Ph

Ph

P NPd

Nu

Nu




43




PMe

NN

Ph

Ph

PhPh

PdNN

MePd

FeFeP

Ph

Ph

Ph

Ph

Ph Ph

NHCH2Ph

(S)

Ph Ph

OCOOEtNu-Nu-


950 ee resp 945 ee

rac

44






Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

Fe

N CN

PPh2

Me

Fe

N NC

PPh2

MePdR

R+

PdR

R+

X-ray

45



Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

PdR

R+

PdR

R+

Fe

N CN

PPh2

Me Pd

NHR2R

RFe

N CN

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

Fe

N NC

PPh2

Me Pd

NHR2R

RFe

N NC

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

dr 8515exoendo 8218

46














47


Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



Ph Ph

OCOOEt

Ph Ph

N



NH

Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



48

N

Me

N

Fe

PPh2

Ph Ph

OCO2Et

Ph Ph

NHCH2Ph

[Pd(dba)2 ]+ Ligand





991 (220)

67 (11)

33 (2)

987 (153)

gt995 (gt400)



3 mol Pd-catalyst

PF6- Selectivity

Killer




49

Ph

Ph

P

NPd

+

endo-syn-syn

+

exo-syn-syn

Ph

PhP

NPd

Ph Ph

OCOOEt

Ph Ph



Slow with PF6-

(tight ion pairs )

Fast with F-

(Coordination)

R-Product S-Product

more stable


S R


50










51

E N Jacobsen et al



NN

OMn

OCl

X X

HHX = OMe 96 ee

X = NO2 22 ee

52




MeO MeO

CN

OOOPh

OPhOPAr2

OAr2P CF3F3C MeMe

HCN [Ni(COD)2] L

Ar =

91 eeL

16 ee

53





OCO O

++

nn2 3

4

1


Δ

54

([α]D=-450)




Polymer)50 220 370 1800


PCy2Me

Fe P

CF3

CF32

PCy2Me

Fe P

OMe

OMe2

PCy2Me

Fe P

H

H2

PCy2Me

Fe P

CH3

CH32

55


Markus Baumann


NMeN

Fe

Me

Me

Me

P

O+ PhOTf



O Ph O Ph O

Ph

+ +

2

Rn

Rn=(m-CF3)2

Rn=(m-SiMe3)2

Rn=(p-OMe)

Rn=(p-CF3)

1 (34ee)

8 (62ee)

1 (46ee)

1 (10ee)

94 (88ee)

90 (95ee)

97 (96ee)

96 (95ee)

5

2

2

3

56



NMeN

Fe

PMe Me

F3C

F3CNMeN

Fe

PMe Me

CF3

F3CF3C

F3C

NMeN

Fe

PF3C CF3

MeO

MeO

NMeN

Fe

PMe Me

MeO

MeO

NMeN

Fe

PF3C CF3

NMeN

Fe

PMe Me

NMeN

Fe

PMe Me

Me2N

Me2NNMeN

Fe

PF3C CF3

F3C

F3C

95 ee985 ee

5 ee72 ee

33 ee

98 ee90 ee

40 ee

the worst

and the best

57





NMeN

Fe

Me

Me

Me

PPh2


2) Oxidative Workup

OH

NMeN

Fe PPh2

NMeN

Fe PPh2

Me

39ee 76ee 99ee

Catalytic activity

NMeN

Fe

MeO

OMe

OMe

PPh2

NMeN

Fe

Me

Me

Me

P

CF3

CF3

2

82ee 91ee

58


X

Fe PPh2

N N

Mes

Me

X

1) cat PdCl2(L)

2) Oxidation


= L

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=078rsup2=0996

NMe₂

OMe

Me

ClH


Fe P X

N N

Mes

Me

1) cat PdCl2(L)

2) Oxidation


2

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=014rsup2=0986

NMe₂OMe

Me HCl


59



Fe P X

N N

Mes

Me

OH1) cat PdCl2(L)

2) Oxidation


2

60



X

Fe PPh2

N N

Mes

Me

X

OH1) cat PdCl2(L)

2) Oxidation

= L

61


PdN

P

Cl

Cl

PdN

P H

SiCl3

R

PdN

P

R

SiCl3

N

PdP

HCl3Si

N

Pd

P

Cl3Si

R

R





Unclear formation

σp

σp+


62


TK Woo

HH P

PdSiCl3SiCl3

NNH H

HH

HH P

PdSiCl3SiCl3

NNH H

FeP

PdSiCl3SiCl3

NN

FeP

PdSiCl3SiCl3

NN

HH P

PdSiCl3SiCl3

NNH H

HH P

PdSiCl3SiCl3

NN

H3CH

HH

H

Model 1

Model 2


63






PPd

H

SiCl3NN

HH

PPd

HSiCl3

NN

HH

PPd

HSiCl3

NN

HH

PPd

SiCl3NN

HH PPd

SiCl3NN

HH

1900

22

-02

-83

141

52

PPd

SiCl3NN

HH

PPd

Cl3SiNN

HH

64


endoendo-syn

PPdH

SiCl3NN

Fe

PPd HSiCl3NN

FeFe P

Pd

SiCl3NN

PPd HSiCl3NN

Fe

Cl3Si

PPd

SiCl3N

Fe

N

PPd

Cl3SiNN

Fe

PPdH

SiCl3NN

Fe

PPd

NN

Fe

Cl3Si

R

-35

09

TS1

TS2

-205

+-103

+styrene

00

42+48

61

Dagger Dagger


65





FeP

PdH

SiCl3NN

PPd

HSiCl3

NN

Fe


66


PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPd

H

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPdSiCl3NN

Fe

PPd

SiCl3NN

Fe

48

00

1609

51

-103

-113



endo-syn

exo-synendo

exo


kcalmol

67



endo-syn

exo-syn

NMe2

PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

NMe2

PPd

SiCl3NN

Fe

NMe2

PPdH

SiCl3NN

Fe

Me2N

PPd

SiCl3NN

Fe

PPdSiCl3

NN

Fe

NMe2

PPd

SiCl3NN

Fe

Me2N

48

00

08

03

16

-172

-155

exo

endo


68


DD

D

D5

HndashSiCl3 [PdL]

DD

D

D5

HO H DD

H

D5

HO H DH

H

D5

HO H DD

D

D5

HO D

oxid workup

+ + +


MeD1

MeD2

13C-1H-HZQCNMR

MeD2

MeD11 equivsilane

5 equivsilane

EI-MS


69





70


Energy(kcalmol)

(at rt)


(kcalmol)

(at rt)

ee

endo-syn -103 123

75 (S)[65 (S)]

endo-syn -172 859

81 (R)[64 (R)]

endo-anti -81 03 75 (S)[65 (S)]


75 (S)[65 (S)] exo-syn -155 48

81 (R)[64 (R)]

exo-anti -106 669

75 (S)[65 (S)]

exo-anti -153 35

81 (R)[64 (R)]


71

Conclusions




72

PhPh Fe

P

NNPd

Ph

Ph

Ph

Ph

FeP

NNPd

Ph

Ph

exo-syn-anti (71)

+

exo-syn-syn (29)

+

S R



41

PhFe

P

NN

Pd


+

Ph




42

Ph

Ph

PdP N

Ph

Ph

P NPd

Nu

Nu




43




PMe

NN

Ph

Ph

PhPh

PdNN

MePd

FeFeP

Ph

Ph

Ph

Ph

Ph Ph

NHCH2Ph

(S)

Ph Ph

OCOOEtNu-Nu-


950 ee resp 945 ee

rac

44






Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

Fe

N CN

PPh2

Me

Fe

N NC

PPh2

MePdR

R+

PdR

R+

X-ray

45



Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

PdR

R+

PdR

R+

Fe

N CN

PPh2

Me Pd

NHR2R

RFe

N CN

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

Fe

N NC

PPh2

Me Pd

NHR2R

RFe

N NC

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

dr 8515exoendo 8218

46














47


Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



Ph Ph

OCOOEt

Ph Ph

N



NH

Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



48

N

Me

N

Fe

PPh2

Ph Ph

OCO2Et

Ph Ph

NHCH2Ph

[Pd(dba)2 ]+ Ligand





991 (220)

67 (11)

33 (2)

987 (153)

gt995 (gt400)



3 mol Pd-catalyst

PF6- Selectivity

Killer




49

Ph

Ph

P

NPd

+

endo-syn-syn

+

exo-syn-syn

Ph

PhP

NPd

Ph Ph

OCOOEt

Ph Ph



Slow with PF6-

(tight ion pairs )

Fast with F-

(Coordination)

R-Product S-Product

more stable


S R


50










51

E N Jacobsen et al



NN

OMn

OCl

X X

HHX = OMe 96 ee

X = NO2 22 ee

52




MeO MeO

CN

OOOPh

OPhOPAr2

OAr2P CF3F3C MeMe

HCN [Ni(COD)2] L

Ar =

91 eeL

16 ee

53





OCO O

++

nn2 3

4

1


Δ

54

([α]D=-450)




Polymer)50 220 370 1800


PCy2Me

Fe P

CF3

CF32

PCy2Me

Fe P

OMe

OMe2

PCy2Me

Fe P

H

H2

PCy2Me

Fe P

CH3

CH32

55


Markus Baumann


NMeN

Fe

Me

Me

Me

P

O+ PhOTf



O Ph O Ph O

Ph

+ +

2

Rn

Rn=(m-CF3)2

Rn=(m-SiMe3)2

Rn=(p-OMe)

Rn=(p-CF3)

1 (34ee)

8 (62ee)

1 (46ee)

1 (10ee)

94 (88ee)

90 (95ee)

97 (96ee)

96 (95ee)

5

2

2

3

56



NMeN

Fe

PMe Me

F3C

F3CNMeN

Fe

PMe Me

CF3

F3CF3C

F3C

NMeN

Fe

PF3C CF3

MeO

MeO

NMeN

Fe

PMe Me

MeO

MeO

NMeN

Fe

PF3C CF3

NMeN

Fe

PMe Me

NMeN

Fe

PMe Me

Me2N

Me2NNMeN

Fe

PF3C CF3

F3C

F3C

95 ee985 ee

5 ee72 ee

33 ee

98 ee90 ee

40 ee

the worst

and the best

57





NMeN

Fe

Me

Me

Me

PPh2


2) Oxidative Workup

OH

NMeN

Fe PPh2

NMeN

Fe PPh2

Me

39ee 76ee 99ee

Catalytic activity

NMeN

Fe

MeO

OMe

OMe

PPh2

NMeN

Fe

Me

Me

Me

P

CF3

CF3

2

82ee 91ee

58


X

Fe PPh2

N N

Mes

Me

X

1) cat PdCl2(L)

2) Oxidation


= L

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=078rsup2=0996

NMe₂

OMe

Me

ClH


Fe P X

N N

Mes

Me

1) cat PdCl2(L)

2) Oxidation


2

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=014rsup2=0986

NMe₂OMe

Me HCl


59



Fe P X

N N

Mes

Me

OH1) cat PdCl2(L)

2) Oxidation


2

60



X

Fe PPh2

N N

Mes

Me

X

OH1) cat PdCl2(L)

2) Oxidation

= L

61


PdN

P

Cl

Cl

PdN

P H

SiCl3

R

PdN

P

R

SiCl3

N

PdP

HCl3Si

N

Pd

P

Cl3Si

R

R





Unclear formation

σp

σp+


62


TK Woo

HH P

PdSiCl3SiCl3

NNH H

HH

HH P

PdSiCl3SiCl3

NNH H

FeP

PdSiCl3SiCl3

NN

FeP

PdSiCl3SiCl3

NN

HH P

PdSiCl3SiCl3

NNH H

HH P

PdSiCl3SiCl3

NN

H3CH

HH

H

Model 1

Model 2


63






PPd

H

SiCl3NN

HH

PPd

HSiCl3

NN

HH

PPd

HSiCl3

NN

HH

PPd

SiCl3NN

HH PPd

SiCl3NN

HH

1900

22

-02

-83

141

52

PPd

SiCl3NN

HH

PPd

Cl3SiNN

HH

64


endoendo-syn

PPdH

SiCl3NN

Fe

PPd HSiCl3NN

FeFe P

Pd

SiCl3NN

PPd HSiCl3NN

Fe

Cl3Si

PPd

SiCl3N

Fe

N

PPd

Cl3SiNN

Fe

PPdH

SiCl3NN

Fe

PPd

NN

Fe

Cl3Si

R

-35

09

TS1

TS2

-205

+-103

+styrene

00

42+48

61

Dagger Dagger


65





FeP

PdH

SiCl3NN

PPd

HSiCl3

NN

Fe


66


PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPd

H

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPdSiCl3NN

Fe

PPd

SiCl3NN

Fe

48

00

1609

51

-103

-113



endo-syn

exo-synendo

exo


kcalmol

67



endo-syn

exo-syn

NMe2

PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

NMe2

PPd

SiCl3NN

Fe

NMe2

PPdH

SiCl3NN

Fe

Me2N

PPd

SiCl3NN

Fe

PPdSiCl3

NN

Fe

NMe2

PPd

SiCl3NN

Fe

Me2N

48

00

08

03

16

-172

-155

exo

endo


68


DD

D

D5

HndashSiCl3 [PdL]

DD

D

D5

HO H DD

H

D5

HO H DH

H

D5

HO H DD

D

D5

HO D

oxid workup

+ + +


MeD1

MeD2

13C-1H-HZQCNMR

MeD2

MeD11 equivsilane

5 equivsilane

EI-MS


69





70


Energy(kcalmol)

(at rt)


(kcalmol)

(at rt)

ee

endo-syn -103 123

75 (S)[65 (S)]

endo-syn -172 859

81 (R)[64 (R)]

endo-anti -81 03 75 (S)[65 (S)]


75 (S)[65 (S)] exo-syn -155 48

81 (R)[64 (R)]

exo-anti -106 669

75 (S)[65 (S)]

exo-anti -153 35

81 (R)[64 (R)]


71

Conclusions




72

PhFe

P

NN

Pd


+

Ph




42

Ph

Ph

PdP N

Ph

Ph

P NPd

Nu

Nu




43




PMe

NN

Ph

Ph

PhPh

PdNN

MePd

FeFeP

Ph

Ph

Ph

Ph

Ph Ph

NHCH2Ph

(S)

Ph Ph

OCOOEtNu-Nu-


950 ee resp 945 ee

rac

44






Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

Fe

N CN

PPh2

Me

Fe

N NC

PPh2

MePdR

R+

PdR

R+

X-ray

45



Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

PdR

R+

PdR

R+

Fe

N CN

PPh2

Me Pd

NHR2R

RFe

N CN

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

Fe

N NC

PPh2

Me Pd

NHR2R

RFe

N NC

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

dr 8515exoendo 8218

46














47


Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



Ph Ph

OCOOEt

Ph Ph

N



NH

Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



48

N

Me

N

Fe

PPh2

Ph Ph

OCO2Et

Ph Ph

NHCH2Ph

[Pd(dba)2 ]+ Ligand





991 (220)

67 (11)

33 (2)

987 (153)

gt995 (gt400)



3 mol Pd-catalyst

PF6- Selectivity

Killer




49

Ph

Ph

P

NPd

+

endo-syn-syn

+

exo-syn-syn

Ph

PhP

NPd

Ph Ph

OCOOEt

Ph Ph



Slow with PF6-

(tight ion pairs )

Fast with F-

(Coordination)

R-Product S-Product

more stable


S R


50










51

E N Jacobsen et al



NN

OMn

OCl

X X

HHX = OMe 96 ee

X = NO2 22 ee

52




MeO MeO

CN

OOOPh

OPhOPAr2

OAr2P CF3F3C MeMe

HCN [Ni(COD)2] L

Ar =

91 eeL

16 ee

53





OCO O

++

nn2 3

4

1


Δ

54

([α]D=-450)




Polymer)50 220 370 1800


PCy2Me

Fe P

CF3

CF32

PCy2Me

Fe P

OMe

OMe2

PCy2Me

Fe P

H

H2

PCy2Me

Fe P

CH3

CH32

55


Markus Baumann


NMeN

Fe

Me

Me

Me

P

O+ PhOTf



O Ph O Ph O

Ph

+ +

2

Rn

Rn=(m-CF3)2

Rn=(m-SiMe3)2

Rn=(p-OMe)

Rn=(p-CF3)

1 (34ee)

8 (62ee)

1 (46ee)

1 (10ee)

94 (88ee)

90 (95ee)

97 (96ee)

96 (95ee)

5

2

2

3

56



NMeN

Fe

PMe Me

F3C

F3CNMeN

Fe

PMe Me

CF3

F3CF3C

F3C

NMeN

Fe

PF3C CF3

MeO

MeO

NMeN

Fe

PMe Me

MeO

MeO

NMeN

Fe

PF3C CF3

NMeN

Fe

PMe Me

NMeN

Fe

PMe Me

Me2N

Me2NNMeN

Fe

PF3C CF3

F3C

F3C

95 ee985 ee

5 ee72 ee

33 ee

98 ee90 ee

40 ee

the worst

and the best

57





NMeN

Fe

Me

Me

Me

PPh2


2) Oxidative Workup

OH

NMeN

Fe PPh2

NMeN

Fe PPh2

Me

39ee 76ee 99ee

Catalytic activity

NMeN

Fe

MeO

OMe

OMe

PPh2

NMeN

Fe

Me

Me

Me

P

CF3

CF3

2

82ee 91ee

58


X

Fe PPh2

N N

Mes

Me

X

1) cat PdCl2(L)

2) Oxidation


= L

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=078rsup2=0996

NMe₂

OMe

Me

ClH


Fe P X

N N

Mes

Me

1) cat PdCl2(L)

2) Oxidation


2

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=014rsup2=0986

NMe₂OMe

Me HCl


59



Fe P X

N N

Mes

Me

OH1) cat PdCl2(L)

2) Oxidation


2

60



X

Fe PPh2

N N

Mes

Me

X

OH1) cat PdCl2(L)

2) Oxidation

= L

61


PdN

P

Cl

Cl

PdN

P H

SiCl3

R

PdN

P

R

SiCl3

N

PdP

HCl3Si

N

Pd

P

Cl3Si

R

R





Unclear formation

σp

σp+


62


TK Woo

HH P

PdSiCl3SiCl3

NNH H

HH

HH P

PdSiCl3SiCl3

NNH H

FeP

PdSiCl3SiCl3

NN

FeP

PdSiCl3SiCl3

NN

HH P

PdSiCl3SiCl3

NNH H

HH P

PdSiCl3SiCl3

NN

H3CH

HH

H

Model 1

Model 2


63






PPd

H

SiCl3NN

HH

PPd

HSiCl3

NN

HH

PPd

HSiCl3

NN

HH

PPd

SiCl3NN

HH PPd

SiCl3NN

HH

1900

22

-02

-83

141

52

PPd

SiCl3NN

HH

PPd

Cl3SiNN

HH

64


endoendo-syn

PPdH

SiCl3NN

Fe

PPd HSiCl3NN

FeFe P

Pd

SiCl3NN

PPd HSiCl3NN

Fe

Cl3Si

PPd

SiCl3N

Fe

N

PPd

Cl3SiNN

Fe

PPdH

SiCl3NN

Fe

PPd

NN

Fe

Cl3Si

R

-35

09

TS1

TS2

-205

+-103

+styrene

00

42+48

61

Dagger Dagger


65





FeP

PdH

SiCl3NN

PPd

HSiCl3

NN

Fe


66


PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPd

H

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPdSiCl3NN

Fe

PPd

SiCl3NN

Fe

48

00

1609

51

-103

-113



endo-syn

exo-synendo

exo


kcalmol

67



endo-syn

exo-syn

NMe2

PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

NMe2

PPd

SiCl3NN

Fe

NMe2

PPdH

SiCl3NN

Fe

Me2N

PPd

SiCl3NN

Fe

PPdSiCl3

NN

Fe

NMe2

PPd

SiCl3NN

Fe

Me2N

48

00

08

03

16

-172

-155

exo

endo


68


DD

D

D5

HndashSiCl3 [PdL]

DD

D

D5

HO H DD

H

D5

HO H DH

H

D5

HO H DD

D

D5

HO D

oxid workup

+ + +


MeD1

MeD2

13C-1H-HZQCNMR

MeD2

MeD11 equivsilane

5 equivsilane

EI-MS


69





70


Energy(kcalmol)

(at rt)


(kcalmol)

(at rt)

ee

endo-syn -103 123

75 (S)[65 (S)]

endo-syn -172 859

81 (R)[64 (R)]

endo-anti -81 03 75 (S)[65 (S)]


75 (S)[65 (S)] exo-syn -155 48

81 (R)[64 (R)]

exo-anti -106 669

75 (S)[65 (S)]

exo-anti -153 35

81 (R)[64 (R)]


71

Conclusions




72

Ph

Ph

PdP N

Ph

Ph

P NPd

Nu

Nu




43




PMe

NN

Ph

Ph

PhPh

PdNN

MePd

FeFeP

Ph

Ph

Ph

Ph

Ph Ph

NHCH2Ph

(S)

Ph Ph

OCOOEtNu-Nu-


950 ee resp 945 ee

rac

44






Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

Fe

N CN

PPh2

Me

Fe

N NC

PPh2

MePdR

R+

PdR

R+

X-ray

45



Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

PdR

R+

PdR

R+

Fe

N CN

PPh2

Me Pd

NHR2R

RFe

N CN

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

Fe

N NC

PPh2

Me Pd

NHR2R

RFe

N NC

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

dr 8515exoendo 8218

46














47


Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



Ph Ph

OCOOEt

Ph Ph

N



NH

Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



48

N

Me

N

Fe

PPh2

Ph Ph

OCO2Et

Ph Ph

NHCH2Ph

[Pd(dba)2 ]+ Ligand





991 (220)

67 (11)

33 (2)

987 (153)

gt995 (gt400)



3 mol Pd-catalyst

PF6- Selectivity

Killer




49

Ph

Ph

P

NPd

+

endo-syn-syn

+

exo-syn-syn

Ph

PhP

NPd

Ph Ph

OCOOEt

Ph Ph



Slow with PF6-

(tight ion pairs )

Fast with F-

(Coordination)

R-Product S-Product

more stable


S R


50










51

E N Jacobsen et al



NN

OMn

OCl

X X

HHX = OMe 96 ee

X = NO2 22 ee

52




MeO MeO

CN

OOOPh

OPhOPAr2

OAr2P CF3F3C MeMe

HCN [Ni(COD)2] L

Ar =

91 eeL

16 ee

53





OCO O

++

nn2 3

4

1


Δ

54

([α]D=-450)




Polymer)50 220 370 1800


PCy2Me

Fe P

CF3

CF32

PCy2Me

Fe P

OMe

OMe2

PCy2Me

Fe P

H

H2

PCy2Me

Fe P

CH3

CH32

55


Markus Baumann


NMeN

Fe

Me

Me

Me

P

O+ PhOTf



O Ph O Ph O

Ph

+ +

2

Rn

Rn=(m-CF3)2

Rn=(m-SiMe3)2

Rn=(p-OMe)

Rn=(p-CF3)

1 (34ee)

8 (62ee)

1 (46ee)

1 (10ee)

94 (88ee)

90 (95ee)

97 (96ee)

96 (95ee)

5

2

2

3

56



NMeN

Fe

PMe Me

F3C

F3CNMeN

Fe

PMe Me

CF3

F3CF3C

F3C

NMeN

Fe

PF3C CF3

MeO

MeO

NMeN

Fe

PMe Me

MeO

MeO

NMeN

Fe

PF3C CF3

NMeN

Fe

PMe Me

NMeN

Fe

PMe Me

Me2N

Me2NNMeN

Fe

PF3C CF3

F3C

F3C

95 ee985 ee

5 ee72 ee

33 ee

98 ee90 ee

40 ee

the worst

and the best

57





NMeN

Fe

Me

Me

Me

PPh2


2) Oxidative Workup

OH

NMeN

Fe PPh2

NMeN

Fe PPh2

Me

39ee 76ee 99ee

Catalytic activity

NMeN

Fe

MeO

OMe

OMe

PPh2

NMeN

Fe

Me

Me

Me

P

CF3

CF3

2

82ee 91ee

58


X

Fe PPh2

N N

Mes

Me

X

1) cat PdCl2(L)

2) Oxidation


= L

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=078rsup2=0996

NMe₂

OMe

Me

ClH


Fe P X

N N

Mes

Me

1) cat PdCl2(L)

2) Oxidation


2

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=014rsup2=0986

NMe₂OMe

Me HCl


59



Fe P X

N N

Mes

Me

OH1) cat PdCl2(L)

2) Oxidation


2

60



X

Fe PPh2

N N

Mes

Me

X

OH1) cat PdCl2(L)

2) Oxidation

= L

61


PdN

P

Cl

Cl

PdN

P H

SiCl3

R

PdN

P

R

SiCl3

N

PdP

HCl3Si

N

Pd

P

Cl3Si

R

R





Unclear formation

σp

σp+


62


TK Woo

HH P

PdSiCl3SiCl3

NNH H

HH

HH P

PdSiCl3SiCl3

NNH H

FeP

PdSiCl3SiCl3

NN

FeP

PdSiCl3SiCl3

NN

HH P

PdSiCl3SiCl3

NNH H

HH P

PdSiCl3SiCl3

NN

H3CH

HH

H

Model 1

Model 2


63






PPd

H

SiCl3NN

HH

PPd

HSiCl3

NN

HH

PPd

HSiCl3

NN

HH

PPd

SiCl3NN

HH PPd

SiCl3NN

HH

1900

22

-02

-83

141

52

PPd

SiCl3NN

HH

PPd

Cl3SiNN

HH

64


endoendo-syn

PPdH

SiCl3NN

Fe

PPd HSiCl3NN

FeFe P

Pd

SiCl3NN

PPd HSiCl3NN

Fe

Cl3Si

PPd

SiCl3N

Fe

N

PPd

Cl3SiNN

Fe

PPdH

SiCl3NN

Fe

PPd

NN

Fe

Cl3Si

R

-35

09

TS1

TS2

-205

+-103

+styrene

00

42+48

61

Dagger Dagger


65





FeP

PdH

SiCl3NN

PPd

HSiCl3

NN

Fe


66


PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPd

H

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPdSiCl3NN

Fe

PPd

SiCl3NN

Fe

48

00

1609

51

-103

-113



endo-syn

exo-synendo

exo


kcalmol

67



endo-syn

exo-syn

NMe2

PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

NMe2

PPd

SiCl3NN

Fe

NMe2

PPdH

SiCl3NN

Fe

Me2N

PPd

SiCl3NN

Fe

PPdSiCl3

NN

Fe

NMe2

PPd

SiCl3NN

Fe

Me2N

48

00

08

03

16

-172

-155

exo

endo


68


DD

D

D5

HndashSiCl3 [PdL]

DD

D

D5

HO H DD

H

D5

HO H DH

H

D5

HO H DD

D

D5

HO D

oxid workup

+ + +


MeD1

MeD2

13C-1H-HZQCNMR

MeD2

MeD11 equivsilane

5 equivsilane

EI-MS


69





70


Energy(kcalmol)

(at rt)


(kcalmol)

(at rt)

ee

endo-syn -103 123

75 (S)[65 (S)]

endo-syn -172 859

81 (R)[64 (R)]

endo-anti -81 03 75 (S)[65 (S)]


75 (S)[65 (S)] exo-syn -155 48

81 (R)[64 (R)]

exo-anti -106 669

75 (S)[65 (S)]

exo-anti -153 35

81 (R)[64 (R)]


71

Conclusions




72




PMe

NN

Ph

Ph

PhPh

PdNN

MePd

FeFeP

Ph

Ph

Ph

Ph

Ph Ph

NHCH2Ph

(S)

Ph Ph

OCOOEtNu-Nu-


950 ee resp 945 ee

rac

44






Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

Fe

N CN

PPh2

Me

Fe

N NC

PPh2

MePdR

R+

PdR

R+

X-ray

45



Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

PdR

R+

PdR

R+

Fe

N CN

PPh2

Me Pd

NHR2R

RFe

N CN

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

Fe

N NC

PPh2

Me Pd

NHR2R

RFe

N NC

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

dr 8515exoendo 8218

46














47


Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



Ph Ph

OCOOEt

Ph Ph

N



NH

Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



48

N

Me

N

Fe

PPh2

Ph Ph

OCO2Et

Ph Ph

NHCH2Ph

[Pd(dba)2 ]+ Ligand





991 (220)

67 (11)

33 (2)

987 (153)

gt995 (gt400)



3 mol Pd-catalyst

PF6- Selectivity

Killer




49

Ph

Ph

P

NPd

+

endo-syn-syn

+

exo-syn-syn

Ph

PhP

NPd

Ph Ph

OCOOEt

Ph Ph



Slow with PF6-

(tight ion pairs )

Fast with F-

(Coordination)

R-Product S-Product

more stable


S R


50










51

E N Jacobsen et al



NN

OMn

OCl

X X

HHX = OMe 96 ee

X = NO2 22 ee

52




MeO MeO

CN

OOOPh

OPhOPAr2

OAr2P CF3F3C MeMe

HCN [Ni(COD)2] L

Ar =

91 eeL

16 ee

53





OCO O

++

nn2 3

4

1


Δ

54

([α]D=-450)




Polymer)50 220 370 1800


PCy2Me

Fe P

CF3

CF32

PCy2Me

Fe P

OMe

OMe2

PCy2Me

Fe P

H

H2

PCy2Me

Fe P

CH3

CH32

55


Markus Baumann


NMeN

Fe

Me

Me

Me

P

O+ PhOTf



O Ph O Ph O

Ph

+ +

2

Rn

Rn=(m-CF3)2

Rn=(m-SiMe3)2

Rn=(p-OMe)

Rn=(p-CF3)

1 (34ee)

8 (62ee)

1 (46ee)

1 (10ee)

94 (88ee)

90 (95ee)

97 (96ee)

96 (95ee)

5

2

2

3

56



NMeN

Fe

PMe Me

F3C

F3CNMeN

Fe

PMe Me

CF3

F3CF3C

F3C

NMeN

Fe

PF3C CF3

MeO

MeO

NMeN

Fe

PMe Me

MeO

MeO

NMeN

Fe

PF3C CF3

NMeN

Fe

PMe Me

NMeN

Fe

PMe Me

Me2N

Me2NNMeN

Fe

PF3C CF3

F3C

F3C

95 ee985 ee

5 ee72 ee

33 ee

98 ee90 ee

40 ee

the worst

and the best

57





NMeN

Fe

Me

Me

Me

PPh2


2) Oxidative Workup

OH

NMeN

Fe PPh2

NMeN

Fe PPh2

Me

39ee 76ee 99ee

Catalytic activity

NMeN

Fe

MeO

OMe

OMe

PPh2

NMeN

Fe

Me

Me

Me

P

CF3

CF3

2

82ee 91ee

58


X

Fe PPh2

N N

Mes

Me

X

1) cat PdCl2(L)

2) Oxidation


= L

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=078rsup2=0996

NMe₂

OMe

Me

ClH


Fe P X

N N

Mes

Me

1) cat PdCl2(L)

2) Oxidation


2

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=014rsup2=0986

NMe₂OMe

Me HCl


59



Fe P X

N N

Mes

Me

OH1) cat PdCl2(L)

2) Oxidation


2

60



X

Fe PPh2

N N

Mes

Me

X

OH1) cat PdCl2(L)

2) Oxidation

= L

61


PdN

P

Cl

Cl

PdN

P H

SiCl3

R

PdN

P

R

SiCl3

N

PdP

HCl3Si

N

Pd

P

Cl3Si

R

R





Unclear formation

σp

σp+


62


TK Woo

HH P

PdSiCl3SiCl3

NNH H

HH

HH P

PdSiCl3SiCl3

NNH H

FeP

PdSiCl3SiCl3

NN

FeP

PdSiCl3SiCl3

NN

HH P

PdSiCl3SiCl3

NNH H

HH P

PdSiCl3SiCl3

NN

H3CH

HH

H

Model 1

Model 2


63






PPd

H

SiCl3NN

HH

PPd

HSiCl3

NN

HH

PPd

HSiCl3

NN

HH

PPd

SiCl3NN

HH PPd

SiCl3NN

HH

1900

22

-02

-83

141

52

PPd

SiCl3NN

HH

PPd

Cl3SiNN

HH

64


endoendo-syn

PPdH

SiCl3NN

Fe

PPd HSiCl3NN

FeFe P

Pd

SiCl3NN

PPd HSiCl3NN

Fe

Cl3Si

PPd

SiCl3N

Fe

N

PPd

Cl3SiNN

Fe

PPdH

SiCl3NN

Fe

PPd

NN

Fe

Cl3Si

R

-35

09

TS1

TS2

-205

+-103

+styrene

00

42+48

61

Dagger Dagger


65





FeP

PdH

SiCl3NN

PPd

HSiCl3

NN

Fe


66


PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPd

H

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPdSiCl3NN

Fe

PPd

SiCl3NN

Fe

48

00

1609

51

-103

-113



endo-syn

exo-synendo

exo


kcalmol

67



endo-syn

exo-syn

NMe2

PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

NMe2

PPd

SiCl3NN

Fe

NMe2

PPdH

SiCl3NN

Fe

Me2N

PPd

SiCl3NN

Fe

PPdSiCl3

NN

Fe

NMe2

PPd

SiCl3NN

Fe

Me2N

48

00

08

03

16

-172

-155

exo

endo


68


DD

D

D5

HndashSiCl3 [PdL]

DD

D

D5

HO H DD

H

D5

HO H DH

H

D5

HO H DD

D

D5

HO D

oxid workup

+ + +


MeD1

MeD2

13C-1H-HZQCNMR

MeD2

MeD11 equivsilane

5 equivsilane

EI-MS


69





70


Energy(kcalmol)

(at rt)


(kcalmol)

(at rt)

ee

endo-syn -103 123

75 (S)[65 (S)]

endo-syn -172 859

81 (R)[64 (R)]

endo-anti -81 03 75 (S)[65 (S)]


75 (S)[65 (S)] exo-syn -155 48

81 (R)[64 (R)]

exo-anti -106 669

75 (S)[65 (S)]

exo-anti -153 35

81 (R)[64 (R)]


71

Conclusions




72






Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

Fe

N CN

PPh2

Me

Fe

N NC

PPh2

MePdR

R+

PdR

R+

X-ray

45



Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

PdR

R+

PdR

R+

Fe

N CN

PPh2

Me Pd

NHR2R

RFe

N CN

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

Fe

N NC

PPh2

Me Pd

NHR2R

RFe

N NC

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

dr 8515exoendo 8218

46














47


Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



Ph Ph

OCOOEt

Ph Ph

N



NH

Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



48

N

Me

N

Fe

PPh2

Ph Ph

OCO2Et

Ph Ph

NHCH2Ph

[Pd(dba)2 ]+ Ligand





991 (220)

67 (11)

33 (2)

987 (153)

gt995 (gt400)



3 mol Pd-catalyst

PF6- Selectivity

Killer




49

Ph

Ph

P

NPd

+

endo-syn-syn

+

exo-syn-syn

Ph

PhP

NPd

Ph Ph

OCOOEt

Ph Ph



Slow with PF6-

(tight ion pairs )

Fast with F-

(Coordination)

R-Product S-Product

more stable


S R


50










51

E N Jacobsen et al



NN

OMn

OCl

X X

HHX = OMe 96 ee

X = NO2 22 ee

52




MeO MeO

CN

OOOPh

OPhOPAr2

OAr2P CF3F3C MeMe

HCN [Ni(COD)2] L

Ar =

91 eeL

16 ee

53





OCO O

++

nn2 3

4

1


Δ

54

([α]D=-450)




Polymer)50 220 370 1800


PCy2Me

Fe P

CF3

CF32

PCy2Me

Fe P

OMe

OMe2

PCy2Me

Fe P

H

H2

PCy2Me

Fe P

CH3

CH32

55


Markus Baumann


NMeN

Fe

Me

Me

Me

P

O+ PhOTf



O Ph O Ph O

Ph

+ +

2

Rn

Rn=(m-CF3)2

Rn=(m-SiMe3)2

Rn=(p-OMe)

Rn=(p-CF3)

1 (34ee)

8 (62ee)

1 (46ee)

1 (10ee)

94 (88ee)

90 (95ee)

97 (96ee)

96 (95ee)

5

2

2

3

56



NMeN

Fe

PMe Me

F3C

F3CNMeN

Fe

PMe Me

CF3

F3CF3C

F3C

NMeN

Fe

PF3C CF3

MeO

MeO

NMeN

Fe

PMe Me

MeO

MeO

NMeN

Fe

PF3C CF3

NMeN

Fe

PMe Me

NMeN

Fe

PMe Me

Me2N

Me2NNMeN

Fe

PF3C CF3

F3C

F3C

95 ee985 ee

5 ee72 ee

33 ee

98 ee90 ee

40 ee

the worst

and the best

57





NMeN

Fe

Me

Me

Me

PPh2


2) Oxidative Workup

OH

NMeN

Fe PPh2

NMeN

Fe PPh2

Me

39ee 76ee 99ee

Catalytic activity

NMeN

Fe

MeO

OMe

OMe

PPh2

NMeN

Fe

Me

Me

Me

P

CF3

CF3

2

82ee 91ee

58


X

Fe PPh2

N N

Mes

Me

X

1) cat PdCl2(L)

2) Oxidation


= L

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=078rsup2=0996

NMe₂

OMe

Me

ClH


Fe P X

N N

Mes

Me

1) cat PdCl2(L)

2) Oxidation


2

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=014rsup2=0986

NMe₂OMe

Me HCl


59



Fe P X

N N

Mes

Me

OH1) cat PdCl2(L)

2) Oxidation


2

60



X

Fe PPh2

N N

Mes

Me

X

OH1) cat PdCl2(L)

2) Oxidation

= L

61


PdN

P

Cl

Cl

PdN

P H

SiCl3

R

PdN

P

R

SiCl3

N

PdP

HCl3Si

N

Pd

P

Cl3Si

R

R





Unclear formation

σp

σp+


62


TK Woo

HH P

PdSiCl3SiCl3

NNH H

HH

HH P

PdSiCl3SiCl3

NNH H

FeP

PdSiCl3SiCl3

NN

FeP

PdSiCl3SiCl3

NN

HH P

PdSiCl3SiCl3

NNH H

HH P

PdSiCl3SiCl3

NN

H3CH

HH

H

Model 1

Model 2


63






PPd

H

SiCl3NN

HH

PPd

HSiCl3

NN

HH

PPd

HSiCl3

NN

HH

PPd

SiCl3NN

HH PPd

SiCl3NN

HH

1900

22

-02

-83

141

52

PPd

SiCl3NN

HH

PPd

Cl3SiNN

HH

64


endoendo-syn

PPdH

SiCl3NN

Fe

PPd HSiCl3NN

FeFe P

Pd

SiCl3NN

PPd HSiCl3NN

Fe

Cl3Si

PPd

SiCl3N

Fe

N

PPd

Cl3SiNN

Fe

PPdH

SiCl3NN

Fe

PPd

NN

Fe

Cl3Si

R

-35

09

TS1

TS2

-205

+-103

+styrene

00

42+48

61

Dagger Dagger


65





FeP

PdH

SiCl3NN

PPd

HSiCl3

NN

Fe


66


PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPd

H

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPdSiCl3NN

Fe

PPd

SiCl3NN

Fe

48

00

1609

51

-103

-113



endo-syn

exo-synendo

exo


kcalmol

67



endo-syn

exo-syn

NMe2

PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

NMe2

PPd

SiCl3NN

Fe

NMe2

PPdH

SiCl3NN

Fe

Me2N

PPd

SiCl3NN

Fe

PPdSiCl3

NN

Fe

NMe2

PPd

SiCl3NN

Fe

Me2N

48

00

08

03

16

-172

-155

exo

endo


68


DD

D

D5

HndashSiCl3 [PdL]

DD

D

D5

HO H DD

H

D5

HO H DH

H

D5

HO H DD

D

D5

HO D

oxid workup

+ + +


MeD1

MeD2

13C-1H-HZQCNMR

MeD2

MeD11 equivsilane

5 equivsilane

EI-MS


69





70


Energy(kcalmol)

(at rt)


(kcalmol)

(at rt)

ee

endo-syn -103 123

75 (S)[65 (S)]

endo-syn -172 859

81 (R)[64 (R)]

endo-anti -81 03 75 (S)[65 (S)]


75 (S)[65 (S)] exo-syn -155 48

81 (R)[64 (R)]

exo-anti -106 669

75 (S)[65 (S)]

exo-anti -153 35

81 (R)[64 (R)]


71

Conclusions




72



Fe

N CN

PPh2

Me

Fe

N NC

PPh2

Me

PdR

R+

PdR

R+

Fe

N CN

PPh2

Me Pd

NHR2R

RFe

N CN

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

Fe

N NC

PPh2

Me Pd

NHR2R

RFe

N NC

PPh2

Me Pd

COOMe

MeOOC

NHR2

slow

k2

DMFU

fast

dr 8515exoendo 8218

46














47


Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



Ph Ph

OCOOEt

Ph Ph

N



NH

Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



48

N

Me

N

Fe

PPh2

Ph Ph

OCO2Et

Ph Ph

NHCH2Ph

[Pd(dba)2 ]+ Ligand





991 (220)

67 (11)

33 (2)

987 (153)

gt995 (gt400)



3 mol Pd-catalyst

PF6- Selectivity

Killer




49

Ph

Ph

P

NPd

+

endo-syn-syn

+

exo-syn-syn

Ph

PhP

NPd

Ph Ph

OCOOEt

Ph Ph



Slow with PF6-

(tight ion pairs )

Fast with F-

(Coordination)

R-Product S-Product

more stable


S R


50










51

E N Jacobsen et al



NN

OMn

OCl

X X

HHX = OMe 96 ee

X = NO2 22 ee

52




MeO MeO

CN

OOOPh

OPhOPAr2

OAr2P CF3F3C MeMe

HCN [Ni(COD)2] L

Ar =

91 eeL

16 ee

53





OCO O

++

nn2 3

4

1


Δ

54

([α]D=-450)




Polymer)50 220 370 1800


PCy2Me

Fe P

CF3

CF32

PCy2Me

Fe P

OMe

OMe2

PCy2Me

Fe P

H

H2

PCy2Me

Fe P

CH3

CH32

55


Markus Baumann


NMeN

Fe

Me

Me

Me

P

O+ PhOTf



O Ph O Ph O

Ph

+ +

2

Rn

Rn=(m-CF3)2

Rn=(m-SiMe3)2

Rn=(p-OMe)

Rn=(p-CF3)

1 (34ee)

8 (62ee)

1 (46ee)

1 (10ee)

94 (88ee)

90 (95ee)

97 (96ee)

96 (95ee)

5

2

2

3

56



NMeN

Fe

PMe Me

F3C

F3CNMeN

Fe

PMe Me

CF3

F3CF3C

F3C

NMeN

Fe

PF3C CF3

MeO

MeO

NMeN

Fe

PMe Me

MeO

MeO

NMeN

Fe

PF3C CF3

NMeN

Fe

PMe Me

NMeN

Fe

PMe Me

Me2N

Me2NNMeN

Fe

PF3C CF3

F3C

F3C

95 ee985 ee

5 ee72 ee

33 ee

98 ee90 ee

40 ee

the worst

and the best

57





NMeN

Fe

Me

Me

Me

PPh2


2) Oxidative Workup

OH

NMeN

Fe PPh2

NMeN

Fe PPh2

Me

39ee 76ee 99ee

Catalytic activity

NMeN

Fe

MeO

OMe

OMe

PPh2

NMeN

Fe

Me

Me

Me

P

CF3

CF3

2

82ee 91ee

58


X

Fe PPh2

N N

Mes

Me

X

1) cat PdCl2(L)

2) Oxidation


= L

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=078rsup2=0996

NMe₂

OMe

Me

ClH


Fe P X

N N

Mes

Me

1) cat PdCl2(L)

2) Oxidation


2

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=014rsup2=0986

NMe₂OMe

Me HCl


59



Fe P X

N N

Mes

Me

OH1) cat PdCl2(L)

2) Oxidation


2

60



X

Fe PPh2

N N

Mes

Me

X

OH1) cat PdCl2(L)

2) Oxidation

= L

61


PdN

P

Cl

Cl

PdN

P H

SiCl3

R

PdN

P

R

SiCl3

N

PdP

HCl3Si

N

Pd

P

Cl3Si

R

R





Unclear formation

σp

σp+


62


TK Woo

HH P

PdSiCl3SiCl3

NNH H

HH

HH P

PdSiCl3SiCl3

NNH H

FeP

PdSiCl3SiCl3

NN

FeP

PdSiCl3SiCl3

NN

HH P

PdSiCl3SiCl3

NNH H

HH P

PdSiCl3SiCl3

NN

H3CH

HH

H

Model 1

Model 2


63






PPd

H

SiCl3NN

HH

PPd

HSiCl3

NN

HH

PPd

HSiCl3

NN

HH

PPd

SiCl3NN

HH PPd

SiCl3NN

HH

1900

22

-02

-83

141

52

PPd

SiCl3NN

HH

PPd

Cl3SiNN

HH

64


endoendo-syn

PPdH

SiCl3NN

Fe

PPd HSiCl3NN

FeFe P

Pd

SiCl3NN

PPd HSiCl3NN

Fe

Cl3Si

PPd

SiCl3N

Fe

N

PPd

Cl3SiNN

Fe

PPdH

SiCl3NN

Fe

PPd

NN

Fe

Cl3Si

R

-35

09

TS1

TS2

-205

+-103

+styrene

00

42+48

61

Dagger Dagger


65





FeP

PdH

SiCl3NN

PPd

HSiCl3

NN

Fe


66


PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPd

H

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPdSiCl3NN

Fe

PPd

SiCl3NN

Fe

48

00

1609

51

-103

-113



endo-syn

exo-synendo

exo


kcalmol

67



endo-syn

exo-syn

NMe2

PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

NMe2

PPd

SiCl3NN

Fe

NMe2

PPdH

SiCl3NN

Fe

Me2N

PPd

SiCl3NN

Fe

PPdSiCl3

NN

Fe

NMe2

PPd

SiCl3NN

Fe

Me2N

48

00

08

03

16

-172

-155

exo

endo


68


DD

D

D5

HndashSiCl3 [PdL]

DD

D

D5

HO H DD

H

D5

HO H DH

H

D5

HO H DD

D

D5

HO D

oxid workup

+ + +


MeD1

MeD2

13C-1H-HZQCNMR

MeD2

MeD11 equivsilane

5 equivsilane

EI-MS


69





70


Energy(kcalmol)

(at rt)


(kcalmol)

(at rt)

ee

endo-syn -103 123

75 (S)[65 (S)]

endo-syn -172 859

81 (R)[64 (R)]

endo-anti -81 03 75 (S)[65 (S)]


75 (S)[65 (S)] exo-syn -155 48

81 (R)[64 (R)]

exo-anti -106 669

75 (S)[65 (S)]

exo-anti -153 35

81 (R)[64 (R)]


71

Conclusions




72














47


Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



Ph Ph

OCOOEt

Ph Ph

N



NH

Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



48

N

Me

N

Fe

PPh2

Ph Ph

OCO2Et

Ph Ph

NHCH2Ph

[Pd(dba)2 ]+ Ligand





991 (220)

67 (11)

33 (2)

987 (153)

gt995 (gt400)



3 mol Pd-catalyst

PF6- Selectivity

Killer




49

Ph

Ph

P

NPd

+

endo-syn-syn

+

exo-syn-syn

Ph

PhP

NPd

Ph Ph

OCOOEt

Ph Ph



Slow with PF6-

(tight ion pairs )

Fast with F-

(Coordination)

R-Product S-Product

more stable


S R


50










51

E N Jacobsen et al



NN

OMn

OCl

X X

HHX = OMe 96 ee

X = NO2 22 ee

52




MeO MeO

CN

OOOPh

OPhOPAr2

OAr2P CF3F3C MeMe

HCN [Ni(COD)2] L

Ar =

91 eeL

16 ee

53





OCO O

++

nn2 3

4

1


Δ

54

([α]D=-450)




Polymer)50 220 370 1800


PCy2Me

Fe P

CF3

CF32

PCy2Me

Fe P

OMe

OMe2

PCy2Me

Fe P

H

H2

PCy2Me

Fe P

CH3

CH32

55


Markus Baumann


NMeN

Fe

Me

Me

Me

P

O+ PhOTf



O Ph O Ph O

Ph

+ +

2

Rn

Rn=(m-CF3)2

Rn=(m-SiMe3)2

Rn=(p-OMe)

Rn=(p-CF3)

1 (34ee)

8 (62ee)

1 (46ee)

1 (10ee)

94 (88ee)

90 (95ee)

97 (96ee)

96 (95ee)

5

2

2

3

56



NMeN

Fe

PMe Me

F3C

F3CNMeN

Fe

PMe Me

CF3

F3CF3C

F3C

NMeN

Fe

PF3C CF3

MeO

MeO

NMeN

Fe

PMe Me

MeO

MeO

NMeN

Fe

PF3C CF3

NMeN

Fe

PMe Me

NMeN

Fe

PMe Me

Me2N

Me2NNMeN

Fe

PF3C CF3

F3C

F3C

95 ee985 ee

5 ee72 ee

33 ee

98 ee90 ee

40 ee

the worst

and the best

57





NMeN

Fe

Me

Me

Me

PPh2


2) Oxidative Workup

OH

NMeN

Fe PPh2

NMeN

Fe PPh2

Me

39ee 76ee 99ee

Catalytic activity

NMeN

Fe

MeO

OMe

OMe

PPh2

NMeN

Fe

Me

Me

Me

P

CF3

CF3

2

82ee 91ee

58


X

Fe PPh2

N N

Mes

Me

X

1) cat PdCl2(L)

2) Oxidation


= L

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=078rsup2=0996

NMe₂

OMe

Me

ClH


Fe P X

N N

Mes

Me

1) cat PdCl2(L)

2) Oxidation


2

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=014rsup2=0986

NMe₂OMe

Me HCl


59



Fe P X

N N

Mes

Me

OH1) cat PdCl2(L)

2) Oxidation


2

60



X

Fe PPh2

N N

Mes

Me

X

OH1) cat PdCl2(L)

2) Oxidation

= L

61


PdN

P

Cl

Cl

PdN

P H

SiCl3

R

PdN

P

R

SiCl3

N

PdP

HCl3Si

N

Pd

P

Cl3Si

R

R





Unclear formation

σp

σp+


62


TK Woo

HH P

PdSiCl3SiCl3

NNH H

HH

HH P

PdSiCl3SiCl3

NNH H

FeP

PdSiCl3SiCl3

NN

FeP

PdSiCl3SiCl3

NN

HH P

PdSiCl3SiCl3

NNH H

HH P

PdSiCl3SiCl3

NN

H3CH

HH

H

Model 1

Model 2


63






PPd

H

SiCl3NN

HH

PPd

HSiCl3

NN

HH

PPd

HSiCl3

NN

HH

PPd

SiCl3NN

HH PPd

SiCl3NN

HH

1900

22

-02

-83

141

52

PPd

SiCl3NN

HH

PPd

Cl3SiNN

HH

64


endoendo-syn

PPdH

SiCl3NN

Fe

PPd HSiCl3NN

FeFe P

Pd

SiCl3NN

PPd HSiCl3NN

Fe

Cl3Si

PPd

SiCl3N

Fe

N

PPd

Cl3SiNN

Fe

PPdH

SiCl3NN

Fe

PPd

NN

Fe

Cl3Si

R

-35

09

TS1

TS2

-205

+-103

+styrene

00

42+48

61

Dagger Dagger


65





FeP

PdH

SiCl3NN

PPd

HSiCl3

NN

Fe


66


PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPd

H

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPdSiCl3NN

Fe

PPd

SiCl3NN

Fe

48

00

1609

51

-103

-113



endo-syn

exo-synendo

exo


kcalmol

67



endo-syn

exo-syn

NMe2

PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

NMe2

PPd

SiCl3NN

Fe

NMe2

PPdH

SiCl3NN

Fe

Me2N

PPd

SiCl3NN

Fe

PPdSiCl3

NN

Fe

NMe2

PPd

SiCl3NN

Fe

Me2N

48

00

08

03

16

-172

-155

exo

endo


68


DD

D

D5

HndashSiCl3 [PdL]

DD

D

D5

HO H DD

H

D5

HO H DH

H

D5

HO H DD

D

D5

HO D

oxid workup

+ + +


MeD1

MeD2

13C-1H-HZQCNMR

MeD2

MeD11 equivsilane

5 equivsilane

EI-MS


69





70


Energy(kcalmol)

(at rt)


(kcalmol)

(at rt)

ee

endo-syn -103 123

75 (S)[65 (S)]

endo-syn -172 859

81 (R)[64 (R)]

endo-anti -81 03 75 (S)[65 (S)]


75 (S)[65 (S)] exo-syn -155 48

81 (R)[64 (R)]

exo-anti -106 669

75 (S)[65 (S)]

exo-anti -153 35

81 (R)[64 (R)]


71

Conclusions




72


Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



Ph Ph

OCOOEt

Ph Ph

N



NH

Ph Ph

OCOOEt

NH2

Ph Ph

NHCH2Ph



48

N

Me

N

Fe

PPh2

Ph Ph

OCO2Et

Ph Ph

NHCH2Ph

[Pd(dba)2 ]+ Ligand





991 (220)

67 (11)

33 (2)

987 (153)

gt995 (gt400)



3 mol Pd-catalyst

PF6- Selectivity

Killer




49

Ph

Ph

P

NPd

+

endo-syn-syn

+

exo-syn-syn

Ph

PhP

NPd

Ph Ph

OCOOEt

Ph Ph



Slow with PF6-

(tight ion pairs )

Fast with F-

(Coordination)

R-Product S-Product

more stable


S R


50










51

E N Jacobsen et al



NN

OMn

OCl

X X

HHX = OMe 96 ee

X = NO2 22 ee

52




MeO MeO

CN

OOOPh

OPhOPAr2

OAr2P CF3F3C MeMe

HCN [Ni(COD)2] L

Ar =

91 eeL

16 ee

53





OCO O

++

nn2 3

4

1


Δ

54

([α]D=-450)




Polymer)50 220 370 1800


PCy2Me

Fe P

CF3

CF32

PCy2Me

Fe P

OMe

OMe2

PCy2Me

Fe P

H

H2

PCy2Me

Fe P

CH3

CH32

55


Markus Baumann


NMeN

Fe

Me

Me

Me

P

O+ PhOTf



O Ph O Ph O

Ph

+ +

2

Rn

Rn=(m-CF3)2

Rn=(m-SiMe3)2

Rn=(p-OMe)

Rn=(p-CF3)

1 (34ee)

8 (62ee)

1 (46ee)

1 (10ee)

94 (88ee)

90 (95ee)

97 (96ee)

96 (95ee)

5

2

2

3

56



NMeN

Fe

PMe Me

F3C

F3CNMeN

Fe

PMe Me

CF3

F3CF3C

F3C

NMeN

Fe

PF3C CF3

MeO

MeO

NMeN

Fe

PMe Me

MeO

MeO

NMeN

Fe

PF3C CF3

NMeN

Fe

PMe Me

NMeN

Fe

PMe Me

Me2N

Me2NNMeN

Fe

PF3C CF3

F3C

F3C

95 ee985 ee

5 ee72 ee

33 ee

98 ee90 ee

40 ee

the worst

and the best

57





NMeN

Fe

Me

Me

Me

PPh2


2) Oxidative Workup

OH

NMeN

Fe PPh2

NMeN

Fe PPh2

Me

39ee 76ee 99ee

Catalytic activity

NMeN

Fe

MeO

OMe

OMe

PPh2

NMeN

Fe

Me

Me

Me

P

CF3

CF3

2

82ee 91ee

58


X

Fe PPh2

N N

Mes

Me

X

1) cat PdCl2(L)

2) Oxidation


= L

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=078rsup2=0996

NMe₂

OMe

Me

ClH


Fe P X

N N

Mes

Me

1) cat PdCl2(L)

2) Oxidation


2

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=014rsup2=0986

NMe₂OMe

Me HCl


59



Fe P X

N N

Mes

Me

OH1) cat PdCl2(L)

2) Oxidation


2

60



X

Fe PPh2

N N

Mes

Me

X

OH1) cat PdCl2(L)

2) Oxidation

= L

61


PdN

P

Cl

Cl

PdN

P H

SiCl3

R

PdN

P

R

SiCl3

N

PdP

HCl3Si

N

Pd

P

Cl3Si

R

R





Unclear formation

σp

σp+


62


TK Woo

HH P

PdSiCl3SiCl3

NNH H

HH

HH P

PdSiCl3SiCl3

NNH H

FeP

PdSiCl3SiCl3

NN

FeP

PdSiCl3SiCl3

NN

HH P

PdSiCl3SiCl3

NNH H

HH P

PdSiCl3SiCl3

NN

H3CH

HH

H

Model 1

Model 2


63






PPd

H

SiCl3NN

HH

PPd

HSiCl3

NN

HH

PPd

HSiCl3

NN

HH

PPd

SiCl3NN

HH PPd

SiCl3NN

HH

1900

22

-02

-83

141

52

PPd

SiCl3NN

HH

PPd

Cl3SiNN

HH

64


endoendo-syn

PPdH

SiCl3NN

Fe

PPd HSiCl3NN

FeFe P

Pd

SiCl3NN

PPd HSiCl3NN

Fe

Cl3Si

PPd

SiCl3N

Fe

N

PPd

Cl3SiNN

Fe

PPdH

SiCl3NN

Fe

PPd

NN

Fe

Cl3Si

R

-35

09

TS1

TS2

-205

+-103

+styrene

00

42+48

61

Dagger Dagger


65





FeP

PdH

SiCl3NN

PPd

HSiCl3

NN

Fe


66


PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPd

H

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPdSiCl3NN

Fe

PPd

SiCl3NN

Fe

48

00

1609

51

-103

-113



endo-syn

exo-synendo

exo


kcalmol

67



endo-syn

exo-syn

NMe2

PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

NMe2

PPd

SiCl3NN

Fe

NMe2

PPdH

SiCl3NN

Fe

Me2N

PPd

SiCl3NN

Fe

PPdSiCl3

NN

Fe

NMe2

PPd

SiCl3NN

Fe

Me2N

48

00

08

03

16

-172

-155

exo

endo


68


DD

D

D5

HndashSiCl3 [PdL]

DD

D

D5

HO H DD

H

D5

HO H DH

H

D5

HO H DD

D

D5

HO D

oxid workup

+ + +


MeD1

MeD2

13C-1H-HZQCNMR

MeD2

MeD11 equivsilane

5 equivsilane

EI-MS


69





70


Energy(kcalmol)

(at rt)


(kcalmol)

(at rt)

ee

endo-syn -103 123

75 (S)[65 (S)]

endo-syn -172 859

81 (R)[64 (R)]

endo-anti -81 03 75 (S)[65 (S)]


75 (S)[65 (S)] exo-syn -155 48

81 (R)[64 (R)]

exo-anti -106 669

75 (S)[65 (S)]

exo-anti -153 35

81 (R)[64 (R)]


71

Conclusions




72

N

Me

N

Fe

PPh2

Ph Ph

OCO2Et

Ph Ph

NHCH2Ph

[Pd(dba)2 ]+ Ligand





991 (220)

67 (11)

33 (2)

987 (153)

gt995 (gt400)



3 mol Pd-catalyst

PF6- Selectivity

Killer




49

Ph

Ph

P

NPd

+

endo-syn-syn

+

exo-syn-syn

Ph

PhP

NPd

Ph Ph

OCOOEt

Ph Ph



Slow with PF6-

(tight ion pairs )

Fast with F-

(Coordination)

R-Product S-Product

more stable


S R


50










51

E N Jacobsen et al



NN

OMn

OCl

X X

HHX = OMe 96 ee

X = NO2 22 ee

52




MeO MeO

CN

OOOPh

OPhOPAr2

OAr2P CF3F3C MeMe

HCN [Ni(COD)2] L

Ar =

91 eeL

16 ee

53





OCO O

++

nn2 3

4

1


Δ

54

([α]D=-450)




Polymer)50 220 370 1800


PCy2Me

Fe P

CF3

CF32

PCy2Me

Fe P

OMe

OMe2

PCy2Me

Fe P

H

H2

PCy2Me

Fe P

CH3

CH32

55


Markus Baumann


NMeN

Fe

Me

Me

Me

P

O+ PhOTf



O Ph O Ph O

Ph

+ +

2

Rn

Rn=(m-CF3)2

Rn=(m-SiMe3)2

Rn=(p-OMe)

Rn=(p-CF3)

1 (34ee)

8 (62ee)

1 (46ee)

1 (10ee)

94 (88ee)

90 (95ee)

97 (96ee)

96 (95ee)

5

2

2

3

56



NMeN

Fe

PMe Me

F3C

F3CNMeN

Fe

PMe Me

CF3

F3CF3C

F3C

NMeN

Fe

PF3C CF3

MeO

MeO

NMeN

Fe

PMe Me

MeO

MeO

NMeN

Fe

PF3C CF3

NMeN

Fe

PMe Me

NMeN

Fe

PMe Me

Me2N

Me2NNMeN

Fe

PF3C CF3

F3C

F3C

95 ee985 ee

5 ee72 ee

33 ee

98 ee90 ee

40 ee

the worst

and the best

57





NMeN

Fe

Me

Me

Me

PPh2


2) Oxidative Workup

OH

NMeN

Fe PPh2

NMeN

Fe PPh2

Me

39ee 76ee 99ee

Catalytic activity

NMeN

Fe

MeO

OMe

OMe

PPh2

NMeN

Fe

Me

Me

Me

P

CF3

CF3

2

82ee 91ee

58


X

Fe PPh2

N N

Mes

Me

X

1) cat PdCl2(L)

2) Oxidation


= L

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=078rsup2=0996

NMe₂

OMe

Me

ClH


Fe P X

N N

Mes

Me

1) cat PdCl2(L)

2) Oxidation


2

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=014rsup2=0986

NMe₂OMe

Me HCl


59



Fe P X

N N

Mes

Me

OH1) cat PdCl2(L)

2) Oxidation


2

60



X

Fe PPh2

N N

Mes

Me

X

OH1) cat PdCl2(L)

2) Oxidation

= L

61


PdN

P

Cl

Cl

PdN

P H

SiCl3

R

PdN

P

R

SiCl3

N

PdP

HCl3Si

N

Pd

P

Cl3Si

R

R





Unclear formation

σp

σp+


62


TK Woo

HH P

PdSiCl3SiCl3

NNH H

HH

HH P

PdSiCl3SiCl3

NNH H

FeP

PdSiCl3SiCl3

NN

FeP

PdSiCl3SiCl3

NN

HH P

PdSiCl3SiCl3

NNH H

HH P

PdSiCl3SiCl3

NN

H3CH

HH

H

Model 1

Model 2


63






PPd

H

SiCl3NN

HH

PPd

HSiCl3

NN

HH

PPd

HSiCl3

NN

HH

PPd

SiCl3NN

HH PPd

SiCl3NN

HH

1900

22

-02

-83

141

52

PPd

SiCl3NN

HH

PPd

Cl3SiNN

HH

64


endoendo-syn

PPdH

SiCl3NN

Fe

PPd HSiCl3NN

FeFe P

Pd

SiCl3NN

PPd HSiCl3NN

Fe

Cl3Si

PPd

SiCl3N

Fe

N

PPd

Cl3SiNN

Fe

PPdH

SiCl3NN

Fe

PPd

NN

Fe

Cl3Si

R

-35

09

TS1

TS2

-205

+-103

+styrene

00

42+48

61

Dagger Dagger


65





FeP

PdH

SiCl3NN

PPd

HSiCl3

NN

Fe


66


PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPd

H

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPdSiCl3NN

Fe

PPd

SiCl3NN

Fe

48

00

1609

51

-103

-113



endo-syn

exo-synendo

exo


kcalmol

67



endo-syn

exo-syn

NMe2

PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

NMe2

PPd

SiCl3NN

Fe

NMe2

PPdH

SiCl3NN

Fe

Me2N

PPd

SiCl3NN

Fe

PPdSiCl3

NN

Fe

NMe2

PPd

SiCl3NN

Fe

Me2N

48

00

08

03

16

-172

-155

exo

endo


68


DD

D

D5

HndashSiCl3 [PdL]

DD

D

D5

HO H DD

H

D5

HO H DH

H

D5

HO H DD

D

D5

HO D

oxid workup

+ + +


MeD1

MeD2

13C-1H-HZQCNMR

MeD2

MeD11 equivsilane

5 equivsilane

EI-MS


69





70


Energy(kcalmol)

(at rt)


(kcalmol)

(at rt)

ee

endo-syn -103 123

75 (S)[65 (S)]

endo-syn -172 859

81 (R)[64 (R)]

endo-anti -81 03 75 (S)[65 (S)]


75 (S)[65 (S)] exo-syn -155 48

81 (R)[64 (R)]

exo-anti -106 669

75 (S)[65 (S)]

exo-anti -153 35

81 (R)[64 (R)]


71

Conclusions




72

Ph

Ph

P

NPd

+

endo-syn-syn

+

exo-syn-syn

Ph

PhP

NPd

Ph Ph

OCOOEt

Ph Ph



Slow with PF6-

(tight ion pairs )

Fast with F-

(Coordination)

R-Product S-Product

more stable


S R


50










51

E N Jacobsen et al



NN

OMn

OCl

X X

HHX = OMe 96 ee

X = NO2 22 ee

52




MeO MeO

CN

OOOPh

OPhOPAr2

OAr2P CF3F3C MeMe

HCN [Ni(COD)2] L

Ar =

91 eeL

16 ee

53





OCO O

++

nn2 3

4

1


Δ

54

([α]D=-450)




Polymer)50 220 370 1800


PCy2Me

Fe P

CF3

CF32

PCy2Me

Fe P

OMe

OMe2

PCy2Me

Fe P

H

H2

PCy2Me

Fe P

CH3

CH32

55


Markus Baumann


NMeN

Fe

Me

Me

Me

P

O+ PhOTf



O Ph O Ph O

Ph

+ +

2

Rn

Rn=(m-CF3)2

Rn=(m-SiMe3)2

Rn=(p-OMe)

Rn=(p-CF3)

1 (34ee)

8 (62ee)

1 (46ee)

1 (10ee)

94 (88ee)

90 (95ee)

97 (96ee)

96 (95ee)

5

2

2

3

56



NMeN

Fe

PMe Me

F3C

F3CNMeN

Fe

PMe Me

CF3

F3CF3C

F3C

NMeN

Fe

PF3C CF3

MeO

MeO

NMeN

Fe

PMe Me

MeO

MeO

NMeN

Fe

PF3C CF3

NMeN

Fe

PMe Me

NMeN

Fe

PMe Me

Me2N

Me2NNMeN

Fe

PF3C CF3

F3C

F3C

95 ee985 ee

5 ee72 ee

33 ee

98 ee90 ee

40 ee

the worst

and the best

57





NMeN

Fe

Me

Me

Me

PPh2


2) Oxidative Workup

OH

NMeN

Fe PPh2

NMeN

Fe PPh2

Me

39ee 76ee 99ee

Catalytic activity

NMeN

Fe

MeO

OMe

OMe

PPh2

NMeN

Fe

Me

Me

Me

P

CF3

CF3

2

82ee 91ee

58


X

Fe PPh2

N N

Mes

Me

X

1) cat PdCl2(L)

2) Oxidation


= L

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=078rsup2=0996

NMe₂

OMe

Me

ClH


Fe P X

N N

Mes

Me

1) cat PdCl2(L)

2) Oxidation


2

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=014rsup2=0986

NMe₂OMe

Me HCl


59



Fe P X

N N

Mes

Me

OH1) cat PdCl2(L)

2) Oxidation


2

60



X

Fe PPh2

N N

Mes

Me

X

OH1) cat PdCl2(L)

2) Oxidation

= L

61


PdN

P

Cl

Cl

PdN

P H

SiCl3

R

PdN

P

R

SiCl3

N

PdP

HCl3Si

N

Pd

P

Cl3Si

R

R





Unclear formation

σp

σp+


62


TK Woo

HH P

PdSiCl3SiCl3

NNH H

HH

HH P

PdSiCl3SiCl3

NNH H

FeP

PdSiCl3SiCl3

NN

FeP

PdSiCl3SiCl3

NN

HH P

PdSiCl3SiCl3

NNH H

HH P

PdSiCl3SiCl3

NN

H3CH

HH

H

Model 1

Model 2


63






PPd

H

SiCl3NN

HH

PPd

HSiCl3

NN

HH

PPd

HSiCl3

NN

HH

PPd

SiCl3NN

HH PPd

SiCl3NN

HH

1900

22

-02

-83

141

52

PPd

SiCl3NN

HH

PPd

Cl3SiNN

HH

64


endoendo-syn

PPdH

SiCl3NN

Fe

PPd HSiCl3NN

FeFe P

Pd

SiCl3NN

PPd HSiCl3NN

Fe

Cl3Si

PPd

SiCl3N

Fe

N

PPd

Cl3SiNN

Fe

PPdH

SiCl3NN

Fe

PPd

NN

Fe

Cl3Si

R

-35

09

TS1

TS2

-205

+-103

+styrene

00

42+48

61

Dagger Dagger


65





FeP

PdH

SiCl3NN

PPd

HSiCl3

NN

Fe


66


PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPd

H

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPdSiCl3NN

Fe

PPd

SiCl3NN

Fe

48

00

1609

51

-103

-113



endo-syn

exo-synendo

exo


kcalmol

67



endo-syn

exo-syn

NMe2

PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

NMe2

PPd

SiCl3NN

Fe

NMe2

PPdH

SiCl3NN

Fe

Me2N

PPd

SiCl3NN

Fe

PPdSiCl3

NN

Fe

NMe2

PPd

SiCl3NN

Fe

Me2N

48

00

08

03

16

-172

-155

exo

endo


68


DD

D

D5

HndashSiCl3 [PdL]

DD

D

D5

HO H DD

H

D5

HO H DH

H

D5

HO H DD

D

D5

HO D

oxid workup

+ + +


MeD1

MeD2

13C-1H-HZQCNMR

MeD2

MeD11 equivsilane

5 equivsilane

EI-MS


69





70


Energy(kcalmol)

(at rt)


(kcalmol)

(at rt)

ee

endo-syn -103 123

75 (S)[65 (S)]

endo-syn -172 859

81 (R)[64 (R)]

endo-anti -81 03 75 (S)[65 (S)]


75 (S)[65 (S)] exo-syn -155 48

81 (R)[64 (R)]

exo-anti -106 669

75 (S)[65 (S)]

exo-anti -153 35

81 (R)[64 (R)]


71

Conclusions




72










51

E N Jacobsen et al



NN

OMn

OCl

X X

HHX = OMe 96 ee

X = NO2 22 ee

52




MeO MeO

CN

OOOPh

OPhOPAr2

OAr2P CF3F3C MeMe

HCN [Ni(COD)2] L

Ar =

91 eeL

16 ee

53





OCO O

++

nn2 3

4

1


Δ

54

([α]D=-450)




Polymer)50 220 370 1800


PCy2Me

Fe P

CF3

CF32

PCy2Me

Fe P

OMe

OMe2

PCy2Me

Fe P

H

H2

PCy2Me

Fe P

CH3

CH32

55


Markus Baumann


NMeN

Fe

Me

Me

Me

P

O+ PhOTf



O Ph O Ph O

Ph

+ +

2

Rn

Rn=(m-CF3)2

Rn=(m-SiMe3)2

Rn=(p-OMe)

Rn=(p-CF3)

1 (34ee)

8 (62ee)

1 (46ee)

1 (10ee)

94 (88ee)

90 (95ee)

97 (96ee)

96 (95ee)

5

2

2

3

56



NMeN

Fe

PMe Me

F3C

F3CNMeN

Fe

PMe Me

CF3

F3CF3C

F3C

NMeN

Fe

PF3C CF3

MeO

MeO

NMeN

Fe

PMe Me

MeO

MeO

NMeN

Fe

PF3C CF3

NMeN

Fe

PMe Me

NMeN

Fe

PMe Me

Me2N

Me2NNMeN

Fe

PF3C CF3

F3C

F3C

95 ee985 ee

5 ee72 ee

33 ee

98 ee90 ee

40 ee

the worst

and the best

57





NMeN

Fe

Me

Me

Me

PPh2


2) Oxidative Workup

OH

NMeN

Fe PPh2

NMeN

Fe PPh2

Me

39ee 76ee 99ee

Catalytic activity

NMeN

Fe

MeO

OMe

OMe

PPh2

NMeN

Fe

Me

Me

Me

P

CF3

CF3

2

82ee 91ee

58


X

Fe PPh2

N N

Mes

Me

X

1) cat PdCl2(L)

2) Oxidation


= L

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=078rsup2=0996

NMe₂

OMe

Me

ClH


Fe P X

N N

Mes

Me

1) cat PdCl2(L)

2) Oxidation


2

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=014rsup2=0986

NMe₂OMe

Me HCl


59



Fe P X

N N

Mes

Me

OH1) cat PdCl2(L)

2) Oxidation


2

60



X

Fe PPh2

N N

Mes

Me

X

OH1) cat PdCl2(L)

2) Oxidation

= L

61


PdN

P

Cl

Cl

PdN

P H

SiCl3

R

PdN

P

R

SiCl3

N

PdP

HCl3Si

N

Pd

P

Cl3Si

R

R





Unclear formation

σp

σp+


62


TK Woo

HH P

PdSiCl3SiCl3

NNH H

HH

HH P

PdSiCl3SiCl3

NNH H

FeP

PdSiCl3SiCl3

NN

FeP

PdSiCl3SiCl3

NN

HH P

PdSiCl3SiCl3

NNH H

HH P

PdSiCl3SiCl3

NN

H3CH

HH

H

Model 1

Model 2


63






PPd

H

SiCl3NN

HH

PPd

HSiCl3

NN

HH

PPd

HSiCl3

NN

HH

PPd

SiCl3NN

HH PPd

SiCl3NN

HH

1900

22

-02

-83

141

52

PPd

SiCl3NN

HH

PPd

Cl3SiNN

HH

64


endoendo-syn

PPdH

SiCl3NN

Fe

PPd HSiCl3NN

FeFe P

Pd

SiCl3NN

PPd HSiCl3NN

Fe

Cl3Si

PPd

SiCl3N

Fe

N

PPd

Cl3SiNN

Fe

PPdH

SiCl3NN

Fe

PPd

NN

Fe

Cl3Si

R

-35

09

TS1

TS2

-205

+-103

+styrene

00

42+48

61

Dagger Dagger


65





FeP

PdH

SiCl3NN

PPd

HSiCl3

NN

Fe


66


PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPd

H

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPdSiCl3NN

Fe

PPd

SiCl3NN

Fe

48

00

1609

51

-103

-113



endo-syn

exo-synendo

exo


kcalmol

67



endo-syn

exo-syn

NMe2

PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

NMe2

PPd

SiCl3NN

Fe

NMe2

PPdH

SiCl3NN

Fe

Me2N

PPd

SiCl3NN

Fe

PPdSiCl3

NN

Fe

NMe2

PPd

SiCl3NN

Fe

Me2N

48

00

08

03

16

-172

-155

exo

endo


68


DD

D

D5

HndashSiCl3 [PdL]

DD

D

D5

HO H DD

H

D5

HO H DH

H

D5

HO H DD

D

D5

HO D

oxid workup

+ + +


MeD1

MeD2

13C-1H-HZQCNMR

MeD2

MeD11 equivsilane

5 equivsilane

EI-MS


69





70


Energy(kcalmol)

(at rt)


(kcalmol)

(at rt)

ee

endo-syn -103 123

75 (S)[65 (S)]

endo-syn -172 859

81 (R)[64 (R)]

endo-anti -81 03 75 (S)[65 (S)]


75 (S)[65 (S)] exo-syn -155 48

81 (R)[64 (R)]

exo-anti -106 669

75 (S)[65 (S)]

exo-anti -153 35

81 (R)[64 (R)]


71

Conclusions




72

E N Jacobsen et al



NN

OMn

OCl

X X

HHX = OMe 96 ee

X = NO2 22 ee

52




MeO MeO

CN

OOOPh

OPhOPAr2

OAr2P CF3F3C MeMe

HCN [Ni(COD)2] L

Ar =

91 eeL

16 ee

53





OCO O

++

nn2 3

4

1


Δ

54

([α]D=-450)




Polymer)50 220 370 1800


PCy2Me

Fe P

CF3

CF32

PCy2Me

Fe P

OMe

OMe2

PCy2Me

Fe P

H

H2

PCy2Me

Fe P

CH3

CH32

55


Markus Baumann


NMeN

Fe

Me

Me

Me

P

O+ PhOTf



O Ph O Ph O

Ph

+ +

2

Rn

Rn=(m-CF3)2

Rn=(m-SiMe3)2

Rn=(p-OMe)

Rn=(p-CF3)

1 (34ee)

8 (62ee)

1 (46ee)

1 (10ee)

94 (88ee)

90 (95ee)

97 (96ee)

96 (95ee)

5

2

2

3

56



NMeN

Fe

PMe Me

F3C

F3CNMeN

Fe

PMe Me

CF3

F3CF3C

F3C

NMeN

Fe

PF3C CF3

MeO

MeO

NMeN

Fe

PMe Me

MeO

MeO

NMeN

Fe

PF3C CF3

NMeN

Fe

PMe Me

NMeN

Fe

PMe Me

Me2N

Me2NNMeN

Fe

PF3C CF3

F3C

F3C

95 ee985 ee

5 ee72 ee

33 ee

98 ee90 ee

40 ee

the worst

and the best

57





NMeN

Fe

Me

Me

Me

PPh2


2) Oxidative Workup

OH

NMeN

Fe PPh2

NMeN

Fe PPh2

Me

39ee 76ee 99ee

Catalytic activity

NMeN

Fe

MeO

OMe

OMe

PPh2

NMeN

Fe

Me

Me

Me

P

CF3

CF3

2

82ee 91ee

58


X

Fe PPh2

N N

Mes

Me

X

1) cat PdCl2(L)

2) Oxidation


= L

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=078rsup2=0996

NMe₂

OMe

Me

ClH


Fe P X

N N

Mes

Me

1) cat PdCl2(L)

2) Oxidation


2

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=014rsup2=0986

NMe₂OMe

Me HCl


59



Fe P X

N N

Mes

Me

OH1) cat PdCl2(L)

2) Oxidation


2

60



X

Fe PPh2

N N

Mes

Me

X

OH1) cat PdCl2(L)

2) Oxidation

= L

61


PdN

P

Cl

Cl

PdN

P H

SiCl3

R

PdN

P

R

SiCl3

N

PdP

HCl3Si

N

Pd

P

Cl3Si

R

R





Unclear formation

σp

σp+


62


TK Woo

HH P

PdSiCl3SiCl3

NNH H

HH

HH P

PdSiCl3SiCl3

NNH H

FeP

PdSiCl3SiCl3

NN

FeP

PdSiCl3SiCl3

NN

HH P

PdSiCl3SiCl3

NNH H

HH P

PdSiCl3SiCl3

NN

H3CH

HH

H

Model 1

Model 2


63






PPd

H

SiCl3NN

HH

PPd

HSiCl3

NN

HH

PPd

HSiCl3

NN

HH

PPd

SiCl3NN

HH PPd

SiCl3NN

HH

1900

22

-02

-83

141

52

PPd

SiCl3NN

HH

PPd

Cl3SiNN

HH

64


endoendo-syn

PPdH

SiCl3NN

Fe

PPd HSiCl3NN

FeFe P

Pd

SiCl3NN

PPd HSiCl3NN

Fe

Cl3Si

PPd

SiCl3N

Fe

N

PPd

Cl3SiNN

Fe

PPdH

SiCl3NN

Fe

PPd

NN

Fe

Cl3Si

R

-35

09

TS1

TS2

-205

+-103

+styrene

00

42+48

61

Dagger Dagger


65





FeP

PdH

SiCl3NN

PPd

HSiCl3

NN

Fe


66


PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPd

H

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPdSiCl3NN

Fe

PPd

SiCl3NN

Fe

48

00

1609

51

-103

-113



endo-syn

exo-synendo

exo


kcalmol

67



endo-syn

exo-syn

NMe2

PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

NMe2

PPd

SiCl3NN

Fe

NMe2

PPdH

SiCl3NN

Fe

Me2N

PPd

SiCl3NN

Fe

PPdSiCl3

NN

Fe

NMe2

PPd

SiCl3NN

Fe

Me2N

48

00

08

03

16

-172

-155

exo

endo


68


DD

D

D5

HndashSiCl3 [PdL]

DD

D

D5

HO H DD

H

D5

HO H DH

H

D5

HO H DD

D

D5

HO D

oxid workup

+ + +


MeD1

MeD2

13C-1H-HZQCNMR

MeD2

MeD11 equivsilane

5 equivsilane

EI-MS


69





70


Energy(kcalmol)

(at rt)


(kcalmol)

(at rt)

ee

endo-syn -103 123

75 (S)[65 (S)]

endo-syn -172 859

81 (R)[64 (R)]

endo-anti -81 03 75 (S)[65 (S)]


75 (S)[65 (S)] exo-syn -155 48

81 (R)[64 (R)]

exo-anti -106 669

75 (S)[65 (S)]

exo-anti -153 35

81 (R)[64 (R)]


71

Conclusions




72




MeO MeO

CN

OOOPh

OPhOPAr2

OAr2P CF3F3C MeMe

HCN [Ni(COD)2] L

Ar =

91 eeL

16 ee

53





OCO O

++

nn2 3

4

1


Δ

54

([α]D=-450)




Polymer)50 220 370 1800


PCy2Me

Fe P

CF3

CF32

PCy2Me

Fe P

OMe

OMe2

PCy2Me

Fe P

H

H2

PCy2Me

Fe P

CH3

CH32

55


Markus Baumann


NMeN

Fe

Me

Me

Me

P

O+ PhOTf



O Ph O Ph O

Ph

+ +

2

Rn

Rn=(m-CF3)2

Rn=(m-SiMe3)2

Rn=(p-OMe)

Rn=(p-CF3)

1 (34ee)

8 (62ee)

1 (46ee)

1 (10ee)

94 (88ee)

90 (95ee)

97 (96ee)

96 (95ee)

5

2

2

3

56



NMeN

Fe

PMe Me

F3C

F3CNMeN

Fe

PMe Me

CF3

F3CF3C

F3C

NMeN

Fe

PF3C CF3

MeO

MeO

NMeN

Fe

PMe Me

MeO

MeO

NMeN

Fe

PF3C CF3

NMeN

Fe

PMe Me

NMeN

Fe

PMe Me

Me2N

Me2NNMeN

Fe

PF3C CF3

F3C

F3C

95 ee985 ee

5 ee72 ee

33 ee

98 ee90 ee

40 ee

the worst

and the best

57





NMeN

Fe

Me

Me

Me

PPh2


2) Oxidative Workup

OH

NMeN

Fe PPh2

NMeN

Fe PPh2

Me

39ee 76ee 99ee

Catalytic activity

NMeN

Fe

MeO

OMe

OMe

PPh2

NMeN

Fe

Me

Me

Me

P

CF3

CF3

2

82ee 91ee

58


X

Fe PPh2

N N

Mes

Me

X

1) cat PdCl2(L)

2) Oxidation


= L

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=078rsup2=0996

NMe₂

OMe

Me

ClH


Fe P X

N N

Mes

Me

1) cat PdCl2(L)

2) Oxidation


2

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=014rsup2=0986

NMe₂OMe

Me HCl


59



Fe P X

N N

Mes

Me

OH1) cat PdCl2(L)

2) Oxidation


2

60



X

Fe PPh2

N N

Mes

Me

X

OH1) cat PdCl2(L)

2) Oxidation

= L

61


PdN

P

Cl

Cl

PdN

P H

SiCl3

R

PdN

P

R

SiCl3

N

PdP

HCl3Si

N

Pd

P

Cl3Si

R

R





Unclear formation

σp

σp+


62


TK Woo

HH P

PdSiCl3SiCl3

NNH H

HH

HH P

PdSiCl3SiCl3

NNH H

FeP

PdSiCl3SiCl3

NN

FeP

PdSiCl3SiCl3

NN

HH P

PdSiCl3SiCl3

NNH H

HH P

PdSiCl3SiCl3

NN

H3CH

HH

H

Model 1

Model 2


63






PPd

H

SiCl3NN

HH

PPd

HSiCl3

NN

HH

PPd

HSiCl3

NN

HH

PPd

SiCl3NN

HH PPd

SiCl3NN

HH

1900

22

-02

-83

141

52

PPd

SiCl3NN

HH

PPd

Cl3SiNN

HH

64


endoendo-syn

PPdH

SiCl3NN

Fe

PPd HSiCl3NN

FeFe P

Pd

SiCl3NN

PPd HSiCl3NN

Fe

Cl3Si

PPd

SiCl3N

Fe

N

PPd

Cl3SiNN

Fe

PPdH

SiCl3NN

Fe

PPd

NN

Fe

Cl3Si

R

-35

09

TS1

TS2

-205

+-103

+styrene

00

42+48

61

Dagger Dagger


65





FeP

PdH

SiCl3NN

PPd

HSiCl3

NN

Fe


66


PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPd

H

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPdSiCl3NN

Fe

PPd

SiCl3NN

Fe

48

00

1609

51

-103

-113



endo-syn

exo-synendo

exo


kcalmol

67



endo-syn

exo-syn

NMe2

PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

NMe2

PPd

SiCl3NN

Fe

NMe2

PPdH

SiCl3NN

Fe

Me2N

PPd

SiCl3NN

Fe

PPdSiCl3

NN

Fe

NMe2

PPd

SiCl3NN

Fe

Me2N

48

00

08

03

16

-172

-155

exo

endo


68


DD

D

D5

HndashSiCl3 [PdL]

DD

D

D5

HO H DD

H

D5

HO H DH

H

D5

HO H DD

D

D5

HO D

oxid workup

+ + +


MeD1

MeD2

13C-1H-HZQCNMR

MeD2

MeD11 equivsilane

5 equivsilane

EI-MS


69





70


Energy(kcalmol)

(at rt)


(kcalmol)

(at rt)

ee

endo-syn -103 123

75 (S)[65 (S)]

endo-syn -172 859

81 (R)[64 (R)]

endo-anti -81 03 75 (S)[65 (S)]


75 (S)[65 (S)] exo-syn -155 48

81 (R)[64 (R)]

exo-anti -106 669

75 (S)[65 (S)]

exo-anti -153 35

81 (R)[64 (R)]


71

Conclusions




72





OCO O

++

nn2 3

4

1


Δ

54

([α]D=-450)




Polymer)50 220 370 1800


PCy2Me

Fe P

CF3

CF32

PCy2Me

Fe P

OMe

OMe2

PCy2Me

Fe P

H

H2

PCy2Me

Fe P

CH3

CH32

55


Markus Baumann


NMeN

Fe

Me

Me

Me

P

O+ PhOTf



O Ph O Ph O

Ph

+ +

2

Rn

Rn=(m-CF3)2

Rn=(m-SiMe3)2

Rn=(p-OMe)

Rn=(p-CF3)

1 (34ee)

8 (62ee)

1 (46ee)

1 (10ee)

94 (88ee)

90 (95ee)

97 (96ee)

96 (95ee)

5

2

2

3

56



NMeN

Fe

PMe Me

F3C

F3CNMeN

Fe

PMe Me

CF3

F3CF3C

F3C

NMeN

Fe

PF3C CF3

MeO

MeO

NMeN

Fe

PMe Me

MeO

MeO

NMeN

Fe

PF3C CF3

NMeN

Fe

PMe Me

NMeN

Fe

PMe Me

Me2N

Me2NNMeN

Fe

PF3C CF3

F3C

F3C

95 ee985 ee

5 ee72 ee

33 ee

98 ee90 ee

40 ee

the worst

and the best

57





NMeN

Fe

Me

Me

Me

PPh2


2) Oxidative Workup

OH

NMeN

Fe PPh2

NMeN

Fe PPh2

Me

39ee 76ee 99ee

Catalytic activity

NMeN

Fe

MeO

OMe

OMe

PPh2

NMeN

Fe

Me

Me

Me

P

CF3

CF3

2

82ee 91ee

58


X

Fe PPh2

N N

Mes

Me

X

1) cat PdCl2(L)

2) Oxidation


= L

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=078rsup2=0996

NMe₂

OMe

Me

ClH


Fe P X

N N

Mes

Me

1) cat PdCl2(L)

2) Oxidation


2

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=014rsup2=0986

NMe₂OMe

Me HCl


59



Fe P X

N N

Mes

Me

OH1) cat PdCl2(L)

2) Oxidation


2

60



X

Fe PPh2

N N

Mes

Me

X

OH1) cat PdCl2(L)

2) Oxidation

= L

61


PdN

P

Cl

Cl

PdN

P H

SiCl3

R

PdN

P

R

SiCl3

N

PdP

HCl3Si

N

Pd

P

Cl3Si

R

R





Unclear formation

σp

σp+


62


TK Woo

HH P

PdSiCl3SiCl3

NNH H

HH

HH P

PdSiCl3SiCl3

NNH H

FeP

PdSiCl3SiCl3

NN

FeP

PdSiCl3SiCl3

NN

HH P

PdSiCl3SiCl3

NNH H

HH P

PdSiCl3SiCl3

NN

H3CH

HH

H

Model 1

Model 2


63






PPd

H

SiCl3NN

HH

PPd

HSiCl3

NN

HH

PPd

HSiCl3

NN

HH

PPd

SiCl3NN

HH PPd

SiCl3NN

HH

1900

22

-02

-83

141

52

PPd

SiCl3NN

HH

PPd

Cl3SiNN

HH

64


endoendo-syn

PPdH

SiCl3NN

Fe

PPd HSiCl3NN

FeFe P

Pd

SiCl3NN

PPd HSiCl3NN

Fe

Cl3Si

PPd

SiCl3N

Fe

N

PPd

Cl3SiNN

Fe

PPdH

SiCl3NN

Fe

PPd

NN

Fe

Cl3Si

R

-35

09

TS1

TS2

-205

+-103

+styrene

00

42+48

61

Dagger Dagger


65





FeP

PdH

SiCl3NN

PPd

HSiCl3

NN

Fe


66


PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPd

H

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPdSiCl3NN

Fe

PPd

SiCl3NN

Fe

48

00

1609

51

-103

-113



endo-syn

exo-synendo

exo


kcalmol

67



endo-syn

exo-syn

NMe2

PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

NMe2

PPd

SiCl3NN

Fe

NMe2

PPdH

SiCl3NN

Fe

Me2N

PPd

SiCl3NN

Fe

PPdSiCl3

NN

Fe

NMe2

PPd

SiCl3NN

Fe

Me2N

48

00

08

03

16

-172

-155

exo

endo


68


DD

D

D5

HndashSiCl3 [PdL]

DD

D

D5

HO H DD

H

D5

HO H DH

H

D5

HO H DD

D

D5

HO D

oxid workup

+ + +


MeD1

MeD2

13C-1H-HZQCNMR

MeD2

MeD11 equivsilane

5 equivsilane

EI-MS


69





70


Energy(kcalmol)

(at rt)


(kcalmol)

(at rt)

ee

endo-syn -103 123

75 (S)[65 (S)]

endo-syn -172 859

81 (R)[64 (R)]

endo-anti -81 03 75 (S)[65 (S)]


75 (S)[65 (S)] exo-syn -155 48

81 (R)[64 (R)]

exo-anti -106 669

75 (S)[65 (S)]

exo-anti -153 35

81 (R)[64 (R)]


71

Conclusions




72

([α]D=-450)




Polymer)50 220 370 1800


PCy2Me

Fe P

CF3

CF32

PCy2Me

Fe P

OMe

OMe2

PCy2Me

Fe P

H

H2

PCy2Me

Fe P

CH3

CH32

55


Markus Baumann


NMeN

Fe

Me

Me

Me

P

O+ PhOTf



O Ph O Ph O

Ph

+ +

2

Rn

Rn=(m-CF3)2

Rn=(m-SiMe3)2

Rn=(p-OMe)

Rn=(p-CF3)

1 (34ee)

8 (62ee)

1 (46ee)

1 (10ee)

94 (88ee)

90 (95ee)

97 (96ee)

96 (95ee)

5

2

2

3

56



NMeN

Fe

PMe Me

F3C

F3CNMeN

Fe

PMe Me

CF3

F3CF3C

F3C

NMeN

Fe

PF3C CF3

MeO

MeO

NMeN

Fe

PMe Me

MeO

MeO

NMeN

Fe

PF3C CF3

NMeN

Fe

PMe Me

NMeN

Fe

PMe Me

Me2N

Me2NNMeN

Fe

PF3C CF3

F3C

F3C

95 ee985 ee

5 ee72 ee

33 ee

98 ee90 ee

40 ee

the worst

and the best

57





NMeN

Fe

Me

Me

Me

PPh2


2) Oxidative Workup

OH

NMeN

Fe PPh2

NMeN

Fe PPh2

Me

39ee 76ee 99ee

Catalytic activity

NMeN

Fe

MeO

OMe

OMe

PPh2

NMeN

Fe

Me

Me

Me

P

CF3

CF3

2

82ee 91ee

58


X

Fe PPh2

N N

Mes

Me

X

1) cat PdCl2(L)

2) Oxidation


= L

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=078rsup2=0996

NMe₂

OMe

Me

ClH


Fe P X

N N

Mes

Me

1) cat PdCl2(L)

2) Oxidation


2

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=014rsup2=0986

NMe₂OMe

Me HCl


59



Fe P X

N N

Mes

Me

OH1) cat PdCl2(L)

2) Oxidation


2

60



X

Fe PPh2

N N

Mes

Me

X

OH1) cat PdCl2(L)

2) Oxidation

= L

61


PdN

P

Cl

Cl

PdN

P H

SiCl3

R

PdN

P

R

SiCl3

N

PdP

HCl3Si

N

Pd

P

Cl3Si

R

R





Unclear formation

σp

σp+


62


TK Woo

HH P

PdSiCl3SiCl3

NNH H

HH

HH P

PdSiCl3SiCl3

NNH H

FeP

PdSiCl3SiCl3

NN

FeP

PdSiCl3SiCl3

NN

HH P

PdSiCl3SiCl3

NNH H

HH P

PdSiCl3SiCl3

NN

H3CH

HH

H

Model 1

Model 2


63






PPd

H

SiCl3NN

HH

PPd

HSiCl3

NN

HH

PPd

HSiCl3

NN

HH

PPd

SiCl3NN

HH PPd

SiCl3NN

HH

1900

22

-02

-83

141

52

PPd

SiCl3NN

HH

PPd

Cl3SiNN

HH

64


endoendo-syn

PPdH

SiCl3NN

Fe

PPd HSiCl3NN

FeFe P

Pd

SiCl3NN

PPd HSiCl3NN

Fe

Cl3Si

PPd

SiCl3N

Fe

N

PPd

Cl3SiNN

Fe

PPdH

SiCl3NN

Fe

PPd

NN

Fe

Cl3Si

R

-35

09

TS1

TS2

-205

+-103

+styrene

00

42+48

61

Dagger Dagger


65





FeP

PdH

SiCl3NN

PPd

HSiCl3

NN

Fe


66


PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPd

H

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPdSiCl3NN

Fe

PPd

SiCl3NN

Fe

48

00

1609

51

-103

-113



endo-syn

exo-synendo

exo


kcalmol

67



endo-syn

exo-syn

NMe2

PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

NMe2

PPd

SiCl3NN

Fe

NMe2

PPdH

SiCl3NN

Fe

Me2N

PPd

SiCl3NN

Fe

PPdSiCl3

NN

Fe

NMe2

PPd

SiCl3NN

Fe

Me2N

48

00

08

03

16

-172

-155

exo

endo


68


DD

D

D5

HndashSiCl3 [PdL]

DD

D

D5

HO H DD

H

D5

HO H DH

H

D5

HO H DD

D

D5

HO D

oxid workup

+ + +


MeD1

MeD2

13C-1H-HZQCNMR

MeD2

MeD11 equivsilane

5 equivsilane

EI-MS


69





70


Energy(kcalmol)

(at rt)


(kcalmol)

(at rt)

ee

endo-syn -103 123

75 (S)[65 (S)]

endo-syn -172 859

81 (R)[64 (R)]

endo-anti -81 03 75 (S)[65 (S)]


75 (S)[65 (S)] exo-syn -155 48

81 (R)[64 (R)]

exo-anti -106 669

75 (S)[65 (S)]

exo-anti -153 35

81 (R)[64 (R)]


71

Conclusions




72


Markus Baumann


NMeN

Fe

Me

Me

Me

P

O+ PhOTf



O Ph O Ph O

Ph

+ +

2

Rn

Rn=(m-CF3)2

Rn=(m-SiMe3)2

Rn=(p-OMe)

Rn=(p-CF3)

1 (34ee)

8 (62ee)

1 (46ee)

1 (10ee)

94 (88ee)

90 (95ee)

97 (96ee)

96 (95ee)

5

2

2

3

56



NMeN

Fe

PMe Me

F3C

F3CNMeN

Fe

PMe Me

CF3

F3CF3C

F3C

NMeN

Fe

PF3C CF3

MeO

MeO

NMeN

Fe

PMe Me

MeO

MeO

NMeN

Fe

PF3C CF3

NMeN

Fe

PMe Me

NMeN

Fe

PMe Me

Me2N

Me2NNMeN

Fe

PF3C CF3

F3C

F3C

95 ee985 ee

5 ee72 ee

33 ee

98 ee90 ee

40 ee

the worst

and the best

57





NMeN

Fe

Me

Me

Me

PPh2


2) Oxidative Workup

OH

NMeN

Fe PPh2

NMeN

Fe PPh2

Me

39ee 76ee 99ee

Catalytic activity

NMeN

Fe

MeO

OMe

OMe

PPh2

NMeN

Fe

Me

Me

Me

P

CF3

CF3

2

82ee 91ee

58


X

Fe PPh2

N N

Mes

Me

X

1) cat PdCl2(L)

2) Oxidation


= L

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=078rsup2=0996

NMe₂

OMe

Me

ClH


Fe P X

N N

Mes

Me

1) cat PdCl2(L)

2) Oxidation


2

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=014rsup2=0986

NMe₂OMe

Me HCl


59



Fe P X

N N

Mes

Me

OH1) cat PdCl2(L)

2) Oxidation


2

60



X

Fe PPh2

N N

Mes

Me

X

OH1) cat PdCl2(L)

2) Oxidation

= L

61


PdN

P

Cl

Cl

PdN

P H

SiCl3

R

PdN

P

R

SiCl3

N

PdP

HCl3Si

N

Pd

P

Cl3Si

R

R





Unclear formation

σp

σp+


62


TK Woo

HH P

PdSiCl3SiCl3

NNH H

HH

HH P

PdSiCl3SiCl3

NNH H

FeP

PdSiCl3SiCl3

NN

FeP

PdSiCl3SiCl3

NN

HH P

PdSiCl3SiCl3

NNH H

HH P

PdSiCl3SiCl3

NN

H3CH

HH

H

Model 1

Model 2


63






PPd

H

SiCl3NN

HH

PPd

HSiCl3

NN

HH

PPd

HSiCl3

NN

HH

PPd

SiCl3NN

HH PPd

SiCl3NN

HH

1900

22

-02

-83

141

52

PPd

SiCl3NN

HH

PPd

Cl3SiNN

HH

64


endoendo-syn

PPdH

SiCl3NN

Fe

PPd HSiCl3NN

FeFe P

Pd

SiCl3NN

PPd HSiCl3NN

Fe

Cl3Si

PPd

SiCl3N

Fe

N

PPd

Cl3SiNN

Fe

PPdH

SiCl3NN

Fe

PPd

NN

Fe

Cl3Si

R

-35

09

TS1

TS2

-205

+-103

+styrene

00

42+48

61

Dagger Dagger


65





FeP

PdH

SiCl3NN

PPd

HSiCl3

NN

Fe


66


PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPd

H

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPdSiCl3NN

Fe

PPd

SiCl3NN

Fe

48

00

1609

51

-103

-113



endo-syn

exo-synendo

exo


kcalmol

67



endo-syn

exo-syn

NMe2

PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

NMe2

PPd

SiCl3NN

Fe

NMe2

PPdH

SiCl3NN

Fe

Me2N

PPd

SiCl3NN

Fe

PPdSiCl3

NN

Fe

NMe2

PPd

SiCl3NN

Fe

Me2N

48

00

08

03

16

-172

-155

exo

endo


68


DD

D

D5

HndashSiCl3 [PdL]

DD

D

D5

HO H DD

H

D5

HO H DH

H

D5

HO H DD

D

D5

HO D

oxid workup

+ + +


MeD1

MeD2

13C-1H-HZQCNMR

MeD2

MeD11 equivsilane

5 equivsilane

EI-MS


69





70


Energy(kcalmol)

(at rt)


(kcalmol)

(at rt)

ee

endo-syn -103 123

75 (S)[65 (S)]

endo-syn -172 859

81 (R)[64 (R)]

endo-anti -81 03 75 (S)[65 (S)]


75 (S)[65 (S)] exo-syn -155 48

81 (R)[64 (R)]

exo-anti -106 669

75 (S)[65 (S)]

exo-anti -153 35

81 (R)[64 (R)]


71

Conclusions




72



NMeN

Fe

PMe Me

F3C

F3CNMeN

Fe

PMe Me

CF3

F3CF3C

F3C

NMeN

Fe

PF3C CF3

MeO

MeO

NMeN

Fe

PMe Me

MeO

MeO

NMeN

Fe

PF3C CF3

NMeN

Fe

PMe Me

NMeN

Fe

PMe Me

Me2N

Me2NNMeN

Fe

PF3C CF3

F3C

F3C

95 ee985 ee

5 ee72 ee

33 ee

98 ee90 ee

40 ee

the worst

and the best

57





NMeN

Fe

Me

Me

Me

PPh2


2) Oxidative Workup

OH

NMeN

Fe PPh2

NMeN

Fe PPh2

Me

39ee 76ee 99ee

Catalytic activity

NMeN

Fe

MeO

OMe

OMe

PPh2

NMeN

Fe

Me

Me

Me

P

CF3

CF3

2

82ee 91ee

58


X

Fe PPh2

N N

Mes

Me

X

1) cat PdCl2(L)

2) Oxidation


= L

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=078rsup2=0996

NMe₂

OMe

Me

ClH


Fe P X

N N

Mes

Me

1) cat PdCl2(L)

2) Oxidation


2

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=014rsup2=0986

NMe₂OMe

Me HCl


59



Fe P X

N N

Mes

Me

OH1) cat PdCl2(L)

2) Oxidation


2

60



X

Fe PPh2

N N

Mes

Me

X

OH1) cat PdCl2(L)

2) Oxidation

= L

61


PdN

P

Cl

Cl

PdN

P H

SiCl3

R

PdN

P

R

SiCl3

N

PdP

HCl3Si

N

Pd

P

Cl3Si

R

R





Unclear formation

σp

σp+


62


TK Woo

HH P

PdSiCl3SiCl3

NNH H

HH

HH P

PdSiCl3SiCl3

NNH H

FeP

PdSiCl3SiCl3

NN

FeP

PdSiCl3SiCl3

NN

HH P

PdSiCl3SiCl3

NNH H

HH P

PdSiCl3SiCl3

NN

H3CH

HH

H

Model 1

Model 2


63






PPd

H

SiCl3NN

HH

PPd

HSiCl3

NN

HH

PPd

HSiCl3

NN

HH

PPd

SiCl3NN

HH PPd

SiCl3NN

HH

1900

22

-02

-83

141

52

PPd

SiCl3NN

HH

PPd

Cl3SiNN

HH

64


endoendo-syn

PPdH

SiCl3NN

Fe

PPd HSiCl3NN

FeFe P

Pd

SiCl3NN

PPd HSiCl3NN

Fe

Cl3Si

PPd

SiCl3N

Fe

N

PPd

Cl3SiNN

Fe

PPdH

SiCl3NN

Fe

PPd

NN

Fe

Cl3Si

R

-35

09

TS1

TS2

-205

+-103

+styrene

00

42+48

61

Dagger Dagger


65





FeP

PdH

SiCl3NN

PPd

HSiCl3

NN

Fe


66


PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPd

H

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPdSiCl3NN

Fe

PPd

SiCl3NN

Fe

48

00

1609

51

-103

-113



endo-syn

exo-synendo

exo


kcalmol

67



endo-syn

exo-syn

NMe2

PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

NMe2

PPd

SiCl3NN

Fe

NMe2

PPdH

SiCl3NN

Fe

Me2N

PPd

SiCl3NN

Fe

PPdSiCl3

NN

Fe

NMe2

PPd

SiCl3NN

Fe

Me2N

48

00

08

03

16

-172

-155

exo

endo


68


DD

D

D5

HndashSiCl3 [PdL]

DD

D

D5

HO H DD

H

D5

HO H DH

H

D5

HO H DD

D

D5

HO D

oxid workup

+ + +


MeD1

MeD2

13C-1H-HZQCNMR

MeD2

MeD11 equivsilane

5 equivsilane

EI-MS


69





70


Energy(kcalmol)

(at rt)


(kcalmol)

(at rt)

ee

endo-syn -103 123

75 (S)[65 (S)]

endo-syn -172 859

81 (R)[64 (R)]

endo-anti -81 03 75 (S)[65 (S)]


75 (S)[65 (S)] exo-syn -155 48

81 (R)[64 (R)]

exo-anti -106 669

75 (S)[65 (S)]

exo-anti -153 35

81 (R)[64 (R)]


71

Conclusions




72





NMeN

Fe

Me

Me

Me

PPh2


2) Oxidative Workup

OH

NMeN

Fe PPh2

NMeN

Fe PPh2

Me

39ee 76ee 99ee

Catalytic activity

NMeN

Fe

MeO

OMe

OMe

PPh2

NMeN

Fe

Me

Me

Me

P

CF3

CF3

2

82ee 91ee

58


X

Fe PPh2

N N

Mes

Me

X

1) cat PdCl2(L)

2) Oxidation


= L

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=078rsup2=0996

NMe₂

OMe

Me

ClH


Fe P X

N N

Mes

Me

1) cat PdCl2(L)

2) Oxidation


2

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=014rsup2=0986

NMe₂OMe

Me HCl


59



Fe P X

N N

Mes

Me

OH1) cat PdCl2(L)

2) Oxidation


2

60



X

Fe PPh2

N N

Mes

Me

X

OH1) cat PdCl2(L)

2) Oxidation

= L

61


PdN

P

Cl

Cl

PdN

P H

SiCl3

R

PdN

P

R

SiCl3

N

PdP

HCl3Si

N

Pd

P

Cl3Si

R

R





Unclear formation

σp

σp+


62


TK Woo

HH P

PdSiCl3SiCl3

NNH H

HH

HH P

PdSiCl3SiCl3

NNH H

FeP

PdSiCl3SiCl3

NN

FeP

PdSiCl3SiCl3

NN

HH P

PdSiCl3SiCl3

NNH H

HH P

PdSiCl3SiCl3

NN

H3CH

HH

H

Model 1

Model 2


63






PPd

H

SiCl3NN

HH

PPd

HSiCl3

NN

HH

PPd

HSiCl3

NN

HH

PPd

SiCl3NN

HH PPd

SiCl3NN

HH

1900

22

-02

-83

141

52

PPd

SiCl3NN

HH

PPd

Cl3SiNN

HH

64


endoendo-syn

PPdH

SiCl3NN

Fe

PPd HSiCl3NN

FeFe P

Pd

SiCl3NN

PPd HSiCl3NN

Fe

Cl3Si

PPd

SiCl3N

Fe

N

PPd

Cl3SiNN

Fe

PPdH

SiCl3NN

Fe

PPd

NN

Fe

Cl3Si

R

-35

09

TS1

TS2

-205

+-103

+styrene

00

42+48

61

Dagger Dagger


65





FeP

PdH

SiCl3NN

PPd

HSiCl3

NN

Fe


66


PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPd

H

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPdSiCl3NN

Fe

PPd

SiCl3NN

Fe

48

00

1609

51

-103

-113



endo-syn

exo-synendo

exo


kcalmol

67



endo-syn

exo-syn

NMe2

PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

NMe2

PPd

SiCl3NN

Fe

NMe2

PPdH

SiCl3NN

Fe

Me2N

PPd

SiCl3NN

Fe

PPdSiCl3

NN

Fe

NMe2

PPd

SiCl3NN

Fe

Me2N

48

00

08

03

16

-172

-155

exo

endo


68


DD

D

D5

HndashSiCl3 [PdL]

DD

D

D5

HO H DD

H

D5

HO H DH

H

D5

HO H DD

D

D5

HO D

oxid workup

+ + +


MeD1

MeD2

13C-1H-HZQCNMR

MeD2

MeD11 equivsilane

5 equivsilane

EI-MS


69





70


Energy(kcalmol)

(at rt)


(kcalmol)

(at rt)

ee

endo-syn -103 123

75 (S)[65 (S)]

endo-syn -172 859

81 (R)[64 (R)]

endo-anti -81 03 75 (S)[65 (S)]


75 (S)[65 (S)] exo-syn -155 48

81 (R)[64 (R)]

exo-anti -106 669

75 (S)[65 (S)]

exo-anti -153 35

81 (R)[64 (R)]


71

Conclusions




72


X

Fe PPh2

N N

Mes

Me

X

1) cat PdCl2(L)

2) Oxidation


= L

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=078rsup2=0996

NMe₂

OMe

Me

ClH


Fe P X

N N

Mes

Me

1) cat PdCl2(L)

2) Oxidation


2

OH

-08

-06

-04

-02

0

02

04

06

08

-2 -15 -1 -05 0 05

+σp

log[S][R]

ρ=014rsup2=0986

NMe₂OMe

Me HCl


59



Fe P X

N N

Mes

Me

OH1) cat PdCl2(L)

2) Oxidation


2

60



X

Fe PPh2

N N

Mes

Me

X

OH1) cat PdCl2(L)

2) Oxidation

= L

61


PdN

P

Cl

Cl

PdN

P H

SiCl3

R

PdN

P

R

SiCl3

N

PdP

HCl3Si

N

Pd

P

Cl3Si

R

R





Unclear formation

σp

σp+


62


TK Woo

HH P

PdSiCl3SiCl3

NNH H

HH

HH P

PdSiCl3SiCl3

NNH H

FeP

PdSiCl3SiCl3

NN

FeP

PdSiCl3SiCl3

NN

HH P

PdSiCl3SiCl3

NNH H

HH P

PdSiCl3SiCl3

NN

H3CH

HH

H

Model 1

Model 2


63






PPd

H

SiCl3NN

HH

PPd

HSiCl3

NN

HH

PPd

HSiCl3

NN

HH

PPd

SiCl3NN

HH PPd

SiCl3NN

HH

1900

22

-02

-83

141

52

PPd

SiCl3NN

HH

PPd

Cl3SiNN

HH

64


endoendo-syn

PPdH

SiCl3NN

Fe

PPd HSiCl3NN

FeFe P

Pd

SiCl3NN

PPd HSiCl3NN

Fe

Cl3Si

PPd

SiCl3N

Fe

N

PPd

Cl3SiNN

Fe

PPdH

SiCl3NN

Fe

PPd

NN

Fe

Cl3Si

R

-35

09

TS1

TS2

-205

+-103

+styrene

00

42+48

61

Dagger Dagger


65





FeP

PdH

SiCl3NN

PPd

HSiCl3

NN

Fe


66


PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPd

H

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPdSiCl3NN

Fe

PPd

SiCl3NN

Fe

48

00

1609

51

-103

-113



endo-syn

exo-synendo

exo


kcalmol

67



endo-syn

exo-syn

NMe2

PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

NMe2

PPd

SiCl3NN

Fe

NMe2

PPdH

SiCl3NN

Fe

Me2N

PPd

SiCl3NN

Fe

PPdSiCl3

NN

Fe

NMe2

PPd

SiCl3NN

Fe

Me2N

48

00

08

03

16

-172

-155

exo

endo


68


DD

D

D5

HndashSiCl3 [PdL]

DD

D

D5

HO H DD

H

D5

HO H DH

H

D5

HO H DD

D

D5

HO D

oxid workup

+ + +


MeD1

MeD2

13C-1H-HZQCNMR

MeD2

MeD11 equivsilane

5 equivsilane

EI-MS


69





70


Energy(kcalmol)

(at rt)


(kcalmol)

(at rt)

ee

endo-syn -103 123

75 (S)[65 (S)]

endo-syn -172 859

81 (R)[64 (R)]

endo-anti -81 03 75 (S)[65 (S)]


75 (S)[65 (S)] exo-syn -155 48

81 (R)[64 (R)]

exo-anti -106 669

75 (S)[65 (S)]

exo-anti -153 35

81 (R)[64 (R)]


71

Conclusions




72



Fe P X

N N

Mes

Me

OH1) cat PdCl2(L)

2) Oxidation


2

60



X

Fe PPh2

N N

Mes

Me

X

OH1) cat PdCl2(L)

2) Oxidation

= L

61


PdN

P

Cl

Cl

PdN

P H

SiCl3

R

PdN

P

R

SiCl3

N

PdP

HCl3Si

N

Pd

P

Cl3Si

R

R





Unclear formation

σp

σp+


62


TK Woo

HH P

PdSiCl3SiCl3

NNH H

HH

HH P

PdSiCl3SiCl3

NNH H

FeP

PdSiCl3SiCl3

NN

FeP

PdSiCl3SiCl3

NN

HH P

PdSiCl3SiCl3

NNH H

HH P

PdSiCl3SiCl3

NN

H3CH

HH

H

Model 1

Model 2


63






PPd

H

SiCl3NN

HH

PPd

HSiCl3

NN

HH

PPd

HSiCl3

NN

HH

PPd

SiCl3NN

HH PPd

SiCl3NN

HH

1900

22

-02

-83

141

52

PPd

SiCl3NN

HH

PPd

Cl3SiNN

HH

64


endoendo-syn

PPdH

SiCl3NN

Fe

PPd HSiCl3NN

FeFe P

Pd

SiCl3NN

PPd HSiCl3NN

Fe

Cl3Si

PPd

SiCl3N

Fe

N

PPd

Cl3SiNN

Fe

PPdH

SiCl3NN

Fe

PPd

NN

Fe

Cl3Si

R

-35

09

TS1

TS2

-205

+-103

+styrene

00

42+48

61

Dagger Dagger


65





FeP

PdH

SiCl3NN

PPd

HSiCl3

NN

Fe


66


PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPd

H

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPdSiCl3NN

Fe

PPd

SiCl3NN

Fe

48

00

1609

51

-103

-113



endo-syn

exo-synendo

exo


kcalmol

67



endo-syn

exo-syn

NMe2

PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

NMe2

PPd

SiCl3NN

Fe

NMe2

PPdH

SiCl3NN

Fe

Me2N

PPd

SiCl3NN

Fe

PPdSiCl3

NN

Fe

NMe2

PPd

SiCl3NN

Fe

Me2N

48

00

08

03

16

-172

-155

exo

endo


68


DD

D

D5

HndashSiCl3 [PdL]

DD

D

D5

HO H DD

H

D5

HO H DH

H

D5

HO H DD

D

D5

HO D

oxid workup

+ + +


MeD1

MeD2

13C-1H-HZQCNMR

MeD2

MeD11 equivsilane

5 equivsilane

EI-MS


69





70


Energy(kcalmol)

(at rt)


(kcalmol)

(at rt)

ee

endo-syn -103 123

75 (S)[65 (S)]

endo-syn -172 859

81 (R)[64 (R)]

endo-anti -81 03 75 (S)[65 (S)]


75 (S)[65 (S)] exo-syn -155 48

81 (R)[64 (R)]

exo-anti -106 669

75 (S)[65 (S)]

exo-anti -153 35

81 (R)[64 (R)]


71

Conclusions




72



X

Fe PPh2

N N

Mes

Me

X

OH1) cat PdCl2(L)

2) Oxidation

= L

61


PdN

P

Cl

Cl

PdN

P H

SiCl3

R

PdN

P

R

SiCl3

N

PdP

HCl3Si

N

Pd

P

Cl3Si

R

R





Unclear formation

σp

σp+


62


TK Woo

HH P

PdSiCl3SiCl3

NNH H

HH

HH P

PdSiCl3SiCl3

NNH H

FeP

PdSiCl3SiCl3

NN

FeP

PdSiCl3SiCl3

NN

HH P

PdSiCl3SiCl3

NNH H

HH P

PdSiCl3SiCl3

NN

H3CH

HH

H

Model 1

Model 2


63






PPd

H

SiCl3NN

HH

PPd

HSiCl3

NN

HH

PPd

HSiCl3

NN

HH

PPd

SiCl3NN

HH PPd

SiCl3NN

HH

1900

22

-02

-83

141

52

PPd

SiCl3NN

HH

PPd

Cl3SiNN

HH

64


endoendo-syn

PPdH

SiCl3NN

Fe

PPd HSiCl3NN

FeFe P

Pd

SiCl3NN

PPd HSiCl3NN

Fe

Cl3Si

PPd

SiCl3N

Fe

N

PPd

Cl3SiNN

Fe

PPdH

SiCl3NN

Fe

PPd

NN

Fe

Cl3Si

R

-35

09

TS1

TS2

-205

+-103

+styrene

00

42+48

61

Dagger Dagger


65





FeP

PdH

SiCl3NN

PPd

HSiCl3

NN

Fe


66


PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPd

H

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPdSiCl3NN

Fe

PPd

SiCl3NN

Fe

48

00

1609

51

-103

-113



endo-syn

exo-synendo

exo


kcalmol

67



endo-syn

exo-syn

NMe2

PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

NMe2

PPd

SiCl3NN

Fe

NMe2

PPdH

SiCl3NN

Fe

Me2N

PPd

SiCl3NN

Fe

PPdSiCl3

NN

Fe

NMe2

PPd

SiCl3NN

Fe

Me2N

48

00

08

03

16

-172

-155

exo

endo


68


DD

D

D5

HndashSiCl3 [PdL]

DD

D

D5

HO H DD

H

D5

HO H DH

H

D5

HO H DD

D

D5

HO D

oxid workup

+ + +


MeD1

MeD2

13C-1H-HZQCNMR

MeD2

MeD11 equivsilane

5 equivsilane

EI-MS


69





70


Energy(kcalmol)

(at rt)


(kcalmol)

(at rt)

ee

endo-syn -103 123

75 (S)[65 (S)]

endo-syn -172 859

81 (R)[64 (R)]

endo-anti -81 03 75 (S)[65 (S)]


75 (S)[65 (S)] exo-syn -155 48

81 (R)[64 (R)]

exo-anti -106 669

75 (S)[65 (S)]

exo-anti -153 35

81 (R)[64 (R)]


71

Conclusions




72


PdN

P

Cl

Cl

PdN

P H

SiCl3

R

PdN

P

R

SiCl3

N

PdP

HCl3Si

N

Pd

P

Cl3Si

R

R





Unclear formation

σp

σp+


62


TK Woo

HH P

PdSiCl3SiCl3

NNH H

HH

HH P

PdSiCl3SiCl3

NNH H

FeP

PdSiCl3SiCl3

NN

FeP

PdSiCl3SiCl3

NN

HH P

PdSiCl3SiCl3

NNH H

HH P

PdSiCl3SiCl3

NN

H3CH

HH

H

Model 1

Model 2


63






PPd

H

SiCl3NN

HH

PPd

HSiCl3

NN

HH

PPd

HSiCl3

NN

HH

PPd

SiCl3NN

HH PPd

SiCl3NN

HH

1900

22

-02

-83

141

52

PPd

SiCl3NN

HH

PPd

Cl3SiNN

HH

64


endoendo-syn

PPdH

SiCl3NN

Fe

PPd HSiCl3NN

FeFe P

Pd

SiCl3NN

PPd HSiCl3NN

Fe

Cl3Si

PPd

SiCl3N

Fe

N

PPd

Cl3SiNN

Fe

PPdH

SiCl3NN

Fe

PPd

NN

Fe

Cl3Si

R

-35

09

TS1

TS2

-205

+-103

+styrene

00

42+48

61

Dagger Dagger


65





FeP

PdH

SiCl3NN

PPd

HSiCl3

NN

Fe


66


PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPd

H

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPdSiCl3NN

Fe

PPd

SiCl3NN

Fe

48

00

1609

51

-103

-113



endo-syn

exo-synendo

exo


kcalmol

67



endo-syn

exo-syn

NMe2

PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

NMe2

PPd

SiCl3NN

Fe

NMe2

PPdH

SiCl3NN

Fe

Me2N

PPd

SiCl3NN

Fe

PPdSiCl3

NN

Fe

NMe2

PPd

SiCl3NN

Fe

Me2N

48

00

08

03

16

-172

-155

exo

endo


68


DD

D

D5

HndashSiCl3 [PdL]

DD

D

D5

HO H DD

H

D5

HO H DH

H

D5

HO H DD

D

D5

HO D

oxid workup

+ + +


MeD1

MeD2

13C-1H-HZQCNMR

MeD2

MeD11 equivsilane

5 equivsilane

EI-MS


69





70


Energy(kcalmol)

(at rt)


(kcalmol)

(at rt)

ee

endo-syn -103 123

75 (S)[65 (S)]

endo-syn -172 859

81 (R)[64 (R)]

endo-anti -81 03 75 (S)[65 (S)]


75 (S)[65 (S)] exo-syn -155 48

81 (R)[64 (R)]

exo-anti -106 669

75 (S)[65 (S)]

exo-anti -153 35

81 (R)[64 (R)]


71

Conclusions




72


TK Woo

HH P

PdSiCl3SiCl3

NNH H

HH

HH P

PdSiCl3SiCl3

NNH H

FeP

PdSiCl3SiCl3

NN

FeP

PdSiCl3SiCl3

NN

HH P

PdSiCl3SiCl3

NNH H

HH P

PdSiCl3SiCl3

NN

H3CH

HH

H

Model 1

Model 2


63






PPd

H

SiCl3NN

HH

PPd

HSiCl3

NN

HH

PPd

HSiCl3

NN

HH

PPd

SiCl3NN

HH PPd

SiCl3NN

HH

1900

22

-02

-83

141

52

PPd

SiCl3NN

HH

PPd

Cl3SiNN

HH

64


endoendo-syn

PPdH

SiCl3NN

Fe

PPd HSiCl3NN

FeFe P

Pd

SiCl3NN

PPd HSiCl3NN

Fe

Cl3Si

PPd

SiCl3N

Fe

N

PPd

Cl3SiNN

Fe

PPdH

SiCl3NN

Fe

PPd

NN

Fe

Cl3Si

R

-35

09

TS1

TS2

-205

+-103

+styrene

00

42+48

61

Dagger Dagger


65





FeP

PdH

SiCl3NN

PPd

HSiCl3

NN

Fe


66


PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPd

H

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPdSiCl3NN

Fe

PPd

SiCl3NN

Fe

48

00

1609

51

-103

-113



endo-syn

exo-synendo

exo


kcalmol

67



endo-syn

exo-syn

NMe2

PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

NMe2

PPd

SiCl3NN

Fe

NMe2

PPdH

SiCl3NN

Fe

Me2N

PPd

SiCl3NN

Fe

PPdSiCl3

NN

Fe

NMe2

PPd

SiCl3NN

Fe

Me2N

48

00

08

03

16

-172

-155

exo

endo


68


DD

D

D5

HndashSiCl3 [PdL]

DD

D

D5

HO H DD

H

D5

HO H DH

H

D5

HO H DD

D

D5

HO D

oxid workup

+ + +


MeD1

MeD2

13C-1H-HZQCNMR

MeD2

MeD11 equivsilane

5 equivsilane

EI-MS


69





70


Energy(kcalmol)

(at rt)


(kcalmol)

(at rt)

ee

endo-syn -103 123

75 (S)[65 (S)]

endo-syn -172 859

81 (R)[64 (R)]

endo-anti -81 03 75 (S)[65 (S)]


75 (S)[65 (S)] exo-syn -155 48

81 (R)[64 (R)]

exo-anti -106 669

75 (S)[65 (S)]

exo-anti -153 35

81 (R)[64 (R)]


71

Conclusions




72






PPd

H

SiCl3NN

HH

PPd

HSiCl3

NN

HH

PPd

HSiCl3

NN

HH

PPd

SiCl3NN

HH PPd

SiCl3NN

HH

1900

22

-02

-83

141

52

PPd

SiCl3NN

HH

PPd

Cl3SiNN

HH

64


endoendo-syn

PPdH

SiCl3NN

Fe

PPd HSiCl3NN

FeFe P

Pd

SiCl3NN

PPd HSiCl3NN

Fe

Cl3Si

PPd

SiCl3N

Fe

N

PPd

Cl3SiNN

Fe

PPdH

SiCl3NN

Fe

PPd

NN

Fe

Cl3Si

R

-35

09

TS1

TS2

-205

+-103

+styrene

00

42+48

61

Dagger Dagger


65





FeP

PdH

SiCl3NN

PPd

HSiCl3

NN

Fe


66


PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPd

H

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPdSiCl3NN

Fe

PPd

SiCl3NN

Fe

48

00

1609

51

-103

-113



endo-syn

exo-synendo

exo


kcalmol

67



endo-syn

exo-syn

NMe2

PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

NMe2

PPd

SiCl3NN

Fe

NMe2

PPdH

SiCl3NN

Fe

Me2N

PPd

SiCl3NN

Fe

PPdSiCl3

NN

Fe

NMe2

PPd

SiCl3NN

Fe

Me2N

48

00

08

03

16

-172

-155

exo

endo


68


DD

D

D5

HndashSiCl3 [PdL]

DD

D

D5

HO H DD

H

D5

HO H DH

H

D5

HO H DD

D

D5

HO D

oxid workup

+ + +


MeD1

MeD2

13C-1H-HZQCNMR

MeD2

MeD11 equivsilane

5 equivsilane

EI-MS


69





70


Energy(kcalmol)

(at rt)


(kcalmol)

(at rt)

ee

endo-syn -103 123

75 (S)[65 (S)]

endo-syn -172 859

81 (R)[64 (R)]

endo-anti -81 03 75 (S)[65 (S)]


75 (S)[65 (S)] exo-syn -155 48

81 (R)[64 (R)]

exo-anti -106 669

75 (S)[65 (S)]

exo-anti -153 35

81 (R)[64 (R)]


71

Conclusions




72


endoendo-syn

PPdH

SiCl3NN

Fe

PPd HSiCl3NN

FeFe P

Pd

SiCl3NN

PPd HSiCl3NN

Fe

Cl3Si

PPd

SiCl3N

Fe

N

PPd

Cl3SiNN

Fe

PPdH

SiCl3NN

Fe

PPd

NN

Fe

Cl3Si

R

-35

09

TS1

TS2

-205

+-103

+styrene

00

42+48

61

Dagger Dagger


65





FeP

PdH

SiCl3NN

PPd

HSiCl3

NN

Fe


66


PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPd

H

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPdSiCl3NN

Fe

PPd

SiCl3NN

Fe

48

00

1609

51

-103

-113



endo-syn

exo-synendo

exo


kcalmol

67



endo-syn

exo-syn

NMe2

PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

NMe2

PPd

SiCl3NN

Fe

NMe2

PPdH

SiCl3NN

Fe

Me2N

PPd

SiCl3NN

Fe

PPdSiCl3

NN

Fe

NMe2

PPd

SiCl3NN

Fe

Me2N

48

00

08

03

16

-172

-155

exo

endo


68


DD

D

D5

HndashSiCl3 [PdL]

DD

D

D5

HO H DD

H

D5

HO H DH

H

D5

HO H DD

D

D5

HO D

oxid workup

+ + +


MeD1

MeD2

13C-1H-HZQCNMR

MeD2

MeD11 equivsilane

5 equivsilane

EI-MS


69





70


Energy(kcalmol)

(at rt)


(kcalmol)

(at rt)

ee

endo-syn -103 123

75 (S)[65 (S)]

endo-syn -172 859

81 (R)[64 (R)]

endo-anti -81 03 75 (S)[65 (S)]


75 (S)[65 (S)] exo-syn -155 48

81 (R)[64 (R)]

exo-anti -106 669

75 (S)[65 (S)]

exo-anti -153 35

81 (R)[64 (R)]


71

Conclusions




72





FeP

PdH

SiCl3NN

PPd

HSiCl3

NN

Fe


66


PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPd

H

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPdSiCl3NN

Fe

PPd

SiCl3NN

Fe

48

00

1609

51

-103

-113



endo-syn

exo-synendo

exo


kcalmol

67



endo-syn

exo-syn

NMe2

PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

NMe2

PPd

SiCl3NN

Fe

NMe2

PPdH

SiCl3NN

Fe

Me2N

PPd

SiCl3NN

Fe

PPdSiCl3

NN

Fe

NMe2

PPd

SiCl3NN

Fe

Me2N

48

00

08

03

16

-172

-155

exo

endo


68


DD

D

D5

HndashSiCl3 [PdL]

DD

D

D5

HO H DD

H

D5

HO H DH

H

D5

HO H DD

D

D5

HO D

oxid workup

+ + +


MeD1

MeD2

13C-1H-HZQCNMR

MeD2

MeD11 equivsilane

5 equivsilane

EI-MS


69





70


Energy(kcalmol)

(at rt)


(kcalmol)

(at rt)

ee

endo-syn -103 123

75 (S)[65 (S)]

endo-syn -172 859

81 (R)[64 (R)]

endo-anti -81 03 75 (S)[65 (S)]


75 (S)[65 (S)] exo-syn -155 48

81 (R)[64 (R)]

exo-anti -106 669

75 (S)[65 (S)]

exo-anti -153 35

81 (R)[64 (R)]


71

Conclusions




72


PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPd

H

SiCl3NN

Fe

PPd

SiCl3NN

Fe

PPdSiCl3NN

Fe

PPd

SiCl3NN

Fe

48

00

1609

51

-103

-113



endo-syn

exo-synendo

exo


kcalmol

67



endo-syn

exo-syn

NMe2

PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

NMe2

PPd

SiCl3NN

Fe

NMe2

PPdH

SiCl3NN

Fe

Me2N

PPd

SiCl3NN

Fe

PPdSiCl3

NN

Fe

NMe2

PPd

SiCl3NN

Fe

Me2N

48

00

08

03

16

-172

-155

exo

endo


68


DD

D

D5

HndashSiCl3 [PdL]

DD

D

D5

HO H DD

H

D5

HO H DH

H

D5

HO H DD

D

D5

HO D

oxid workup

+ + +


MeD1

MeD2

13C-1H-HZQCNMR

MeD2

MeD11 equivsilane

5 equivsilane

EI-MS


69





70


Energy(kcalmol)

(at rt)


(kcalmol)

(at rt)

ee

endo-syn -103 123

75 (S)[65 (S)]

endo-syn -172 859

81 (R)[64 (R)]

endo-anti -81 03 75 (S)[65 (S)]


75 (S)[65 (S)] exo-syn -155 48

81 (R)[64 (R)]

exo-anti -106 669

75 (S)[65 (S)]

exo-anti -153 35

81 (R)[64 (R)]


71

Conclusions




72



endo-syn

exo-syn

NMe2

PPd

HSiCl3NN

Fe

PPdH

SiCl3NN

Fe

NMe2

PPd

SiCl3NN

Fe

NMe2

PPdH

SiCl3NN

Fe

Me2N

PPd

SiCl3NN

Fe

PPdSiCl3

NN

Fe

NMe2

PPd

SiCl3NN

Fe

Me2N

48

00

08

03

16

-172

-155

exo

endo


68


DD

D

D5

HndashSiCl3 [PdL]

DD

D

D5

HO H DD

H

D5

HO H DH

H

D5

HO H DD

D

D5

HO D

oxid workup

+ + +


MeD1

MeD2

13C-1H-HZQCNMR

MeD2

MeD11 equivsilane

5 equivsilane

EI-MS


69





70


Energy(kcalmol)

(at rt)


(kcalmol)

(at rt)

ee

endo-syn -103 123

75 (S)[65 (S)]

endo-syn -172 859

81 (R)[64 (R)]

endo-anti -81 03 75 (S)[65 (S)]


75 (S)[65 (S)] exo-syn -155 48

81 (R)[64 (R)]

exo-anti -106 669

75 (S)[65 (S)]

exo-anti -153 35

81 (R)[64 (R)]


71

Conclusions




72


DD

D

D5

HndashSiCl3 [PdL]

DD

D

D5

HO H DD

H

D5

HO H DH

H

D5

HO H DD

D

D5

HO D

oxid workup

+ + +


MeD1

MeD2

13C-1H-HZQCNMR

MeD2

MeD11 equivsilane

5 equivsilane

EI-MS


69





70


Energy(kcalmol)

(at rt)


(kcalmol)

(at rt)

ee

endo-syn -103 123

75 (S)[65 (S)]

endo-syn -172 859

81 (R)[64 (R)]

endo-anti -81 03 75 (S)[65 (S)]


75 (S)[65 (S)] exo-syn -155 48

81 (R)[64 (R)]

exo-anti -106 669

75 (S)[65 (S)]

exo-anti -153 35

81 (R)[64 (R)]


71

Conclusions




72





70


Energy(kcalmol)

(at rt)


(kcalmol)

(at rt)

ee

endo-syn -103 123

75 (S)[65 (S)]

endo-syn -172 859

81 (R)[64 (R)]

endo-anti -81 03 75 (S)[65 (S)]


75 (S)[65 (S)] exo-syn -155 48

81 (R)[64 (R)]

exo-anti -106 669

75 (S)[65 (S)]

exo-anti -153 35

81 (R)[64 (R)]


71

Conclusions




72


Energy(kcalmol)

(at rt)


(kcalmol)

(at rt)

ee

endo-syn -103 123

75 (S)[65 (S)]

endo-syn -172 859

81 (R)[64 (R)]

endo-anti -81 03 75 (S)[65 (S)]


75 (S)[65 (S)] exo-syn -155 48

81 (R)[64 (R)]

exo-anti -106 669

75 (S)[65 (S)]

exo-anti -153 35

81 (R)[64 (R)]


71

Conclusions




72

Conclusions




72

How much design is there in asymmetric catalysis ? and ... · How much design is there in...

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