Catalytic Asymmetric Intramolecular Pauson-Khand...
Transcript of Catalytic Asymmetric Intramolecular Pauson-Khand...
Catalytic Asymmetric Intramolecular Pauson Khand and Pauson Khand TypePauson-Khand and Pauson-Khand-Type
Reactions
Steven BallmerCHEM 535 S iCHEM 535 Seminar
October 9, 2008University of Illinois at Urbana-Champaign
Copyright © 2008 by Steven Ballmer
Co-Mediated [2+2+1] Cycloaddition1
Co Co
R1 R2
OC
OC
OCCO
CO
COO
HH
R2R1
+60-70 °C, 4 h
tolueneR2R1
Co2(CO)8
H H Ph EtH
hexacarbonyldicobaltalkyne complex
cyclopentenone
OHH
MeH
OHH
PhH
OHH
PhPh
OHH
EtEt
OHH
HH
43% 33% 45% 28% 23%
Co Co
OC CO
COR2
R1
R1
Side Products
CO
COOC
Co Co
OC
C COOC
CoOC CO
cyclopentadienylcobalt
(retro Diels Alder)norbornadiene
complexesO
HH
R2R1
O
OHH O
HR2
HHR2
diketones
Pauson and coworkers J. Chem. Soc., Perkin Trans. 1 1973, 977.
Pauson and coworkers J. Chem. Soc., Perkin Trans. 1 1973, 975.
CO
COOC(retro Diels-Alder) complexesHH H R1
Proposed Mechanism
Co Co
OC
C
COCO
CO
OCOC
OCCo Co
R1
OC
OC COCo Co
R1
OCCO
COdissociationX
R1 XR
XR
alkynecomplexation
CO
COOC OCOC
COCO OC CO
CO
R1
R
X X
COenyne
2CO
Co Co
R1
OCOC
CO
CO
CO
RCo Co
R1
OCOC
CO
CO
CO
RCo Co
R1
OC
OCCO
CO
COR
alkenecoordination isomerization
alkeneinsertion
X
OC OC CO
R1 Co(CO)3CO reductive
li i tireductive
lialkyl
XXX
Co Co
R
OCCO
CO
CO
R
OO
R R1
OC
OC
O
R R1
Co( )3
COCO
Co2(CO)6
eliminationcouplingmigration
+ CO
bicyclicc clopentenone
Magnus, P.; Principe, L. M. Tetrahedron Lett. 1985, 26, 4851.
Magnus and coworkers Tetrahedron 1985, 41, 5861.
cyclopentenone
Mechanistic Calculations
DFT (VWN/PW91xc) methodology
ethylenecoordination
acetylenecomplex
Pericàs and coworkers Pure Appl. Chem. 2002, 74, 167.
Support for Proposed Mechanism
Co CoOC
OCCO
CO
CO
SMe OC
bishomopropargylic sulfide complexMixed Ar/N2 Matrix
bishomopropargylic sulfide complex
NMO H2O,DCM, rt, 5 d
Co CoOC
S
CO
CO
CO
Me
10-6 mbar12 K
OC CO
isolable pentacarbonyl complex
O
SMe
Gordon and coworkers J. Organomet. Chem. 1998, 554, 147.Krafft and coworkers J. Am. Chem. Soc. 1993, 115, 7199.
bishomoallylic sulfide
MS Support for Proposed MechanismH Ph
ESI collision-activated reaction (CAR) MS/MS- CO dissociation occurs first
Co CoOC
Ph2PCO
CO
PPh2
OC
H Ph
m/z = 716.0Idppm
Co Co
H Ph
OC CO
CO
Co CoOC
Ph2PCO
CO
PPh2 Ea = 34 kcal/molPh2P PPh2
m/z = 781.1
H Ph
[Idppm - H - CO]-
DFT calculations(B3LYP/LANL2DZ*)
Co CoOC
Ph2PCO
CO
PPh2
[Idppm - H - 2CO]-Ea = 12 kcal/mol
Gimbert and coworkers Org. Lett. 2003, 5, 4073.
X-Ray Crystal Support for Mechanism
OHOH
Co
Co
OCCO
OCOC
OCCo Co
OC CO
CO COOC
CO
hexacarbonyl alkyne complex η2-alkene pentacarbonyl alkyne complex
COCC
COH
Ph
HO Ph
Co2(CO)8
THF, rt, 15h
CoOC CO
OC
COPh O Ph
Evans and coworkers Angew. Chem. Int. Ed. 2007, 46, 2907.
η2-alkene pentacarbonyl alkyne complex (viewed down Co-Co bond)
Catalytic and Intramolecular Pauson-KhandFirst Intramolecular
First Catalytic
Schore, N. E.; Croudace, M. C. J. Org. Chem. 1981, 46, 5436.
Jeong and coworkers J. Am. Chem. Soc. 1994, 116, 3159.
Asymmetric Catalytic CycleCO
RO Cl M
P
OC MPP
CO
Cl
reductive*
*
chiralcatalyst
metallacyclohexenone+ CO
- CO
R
MX
PP
Cl
R
Cl MPelimination
-
*
* *
carbonX O
R R
XCOinsertion
complexationCO * enyne
bicycliccyclopentenone
monoxide
X MPP
Cl
RX M P
PCl
RX
oxidativeaddition
*
**
*
catalyst/enynecomplex
metallacyclpentene
+ CO
- COX M P
COCl
P*complex
CO pressure-dependenceti t d ith i d CO-reaction rate decreases with increased CO pressure
-enantioselectivity decreases with increased CO pressure
Reagent-Directed StereocontrolR
P filledfilled
open
open
Ph Ph
Co
COCOCO
CO
Open/ClosedQuadrantsP
P
Ph Ph
Ph
CoCo
XH
((S)-BINAP)Co2CO6
P filled open
PhPh
Co
COCO
CO
PhP P
PhCo Co
PhPhCO ligandsnot shown
CO ligands not shown
X O
R
X O
R
Ph Ph COCO
HHR isomer S isomer
Co CoP PPh
Ph
P
P
PhPh
Co
Co
CO
COCO
CO
filledfilledopen
open
Open/ClosedQuadrants
((R) BINAP)Co CO P
Ph PhR
CO ligandst h
Ph
CO ligands not shownfilledopen((R)-BINAP)Co2CO6 P
P
Ph Ph
CoCo
not shown
HX
Substrate-Directed StereocontrolH
CoR1R2
H H
(CO)3 R2
R1
O
R
H
R1R2
H H
RCo2(CO)8
R1
HH H
HH
Co
H
R
R(CO)2
O
R
H
R1
R2H
RR2
RH
chairconformer
favoredolefin rotamer
R isomerR
R1
R2
olefin rotamer
R2
R1
O
R
H
R1R2
H
H
disfavoredolefin rotamer
Co1
H
(CO)3
Co2(CO)8
R1H H
H
O
RR1
R2
H
R RR
H
Co
H
R1R2
R(CO)2
HCo2(CO)8H
R2 Rchairconformer
H
H
H
HS isomer
Development of Cobalt Catalysts
RX
20 mol %((S)-BINAP)Co2CO6 X O
R
DME, reflux,1 atm CO H1 atm CO
14 h 24 h 24 h 15 h60% i ld
14 h
O
H
HMeO2CMeO2C
O
H
MeMeO2CMeO2C
O
Me
MeMeO2CMeO2C TsN O
H
H
TsN O
H
Me
14 h53% yield90% ee
31% yield63% ee
90% yield0% ee
60% yield93% ee
13% yield62% ee
P
Ph PhR
HPh Ph
R
R
H Me Me
R P
P
PhPh
CoCo
CO ligandsnot shown
X
HP
P
PhPh
CoCo
XX O
H
favored
H
disfavoredX O
R
H
Hiroi and coworkers Tetrahedron Lett. 2000, 41, 891.Hiroi and coworkers Tetrahedron: Asymmetry 2000, 11, 797.
Development of Titanium Catalysts
Buchwald and coworkers J. Am. Chem. Soc. 1996, 118, 9450.Buchwald and coworkers J. Am. Chem. Soc. 1996, 118, 11688.
Expansion of Substrate Scope
XR
•
X
RR1
R
MeO2C
MeO2C
R2R1
allenynes dienenesdienynes
X O
R
X
R
OX O
H
HR
R1X O
H
HR
R1
MeO2CMeO2C
R
O
HR2
R1
dienylcyclopentenones
-methylenecyclopentenones
R1R2
vinylcyclopentenones
vinylcyclopentanones
-methylenecyclopentanones
X
• R2
R3
X O
R3R2
H
H
X•
PhO2S
OX
SO2Ph
RRH H
-methylene vinylcyclopentanones
allenenes cyclopenteonesdiene-allenes
Bicyclic Dienones from Allenynes
XR
•
XR
•MM X
R
•XX
R
O O
RCOCO M M
bi li di ll
non-catalyticnon-asymmetric
bicyclic dienone -methylenecyclopentenone
allenyne
non asymmetric
X•
MeS
X O
MeS
Fe(CO)5, TMANO, THF
rt, h (100 W)
O O OHO Ph Ph
O
MeS 60%
O
SMe
OO
SMeSMe
O
SMe45%15% 30%19%
Fe(CO)3
cyclopentadienoneiron complex
Narasaka, K.; Shibata, T. Chem. Lett. 1994, 315.
iron complex
α-Methylene Cyclopentenones from Allenynesy
XR
•
XR
•MM X
R
•XX
R
O O
RCOCO M M
non-catalytic
bicyclic dienone -methylenecyclopentenone
allenyne
non-asymmetricMo(CO)6 (1.2 equiv), DMSO
PhMe, 100 °C, 3 hX O
TMS
XTMS
•
triquinane sesquiterpenesmethylenomycin antitumor agents
O
TMS
O
TMS
O
TMS
O
TMS
MeMe
HO Me68% 47% 30% 0%
no cycloaddition
TMS
•
Me
Brummond and coworkers Tetrahedron Lett. 1995, 36, 2407.
-no cycloaddition-starting material decompostion
Vinyl Cyclopentenones from DienynesRR
MeO2C
MeO2C
R2
[RhCl(CO)(PPh3)2], AgSbF6
DCE, CO
R1
MeO2CMeO2C
R
O
HR2
R1
MeO2C
Me
OMeO2C
TMS
OMeO2C
O
89% 85% 43%1 mol% Rh, Ag1 atm COrt, 14 h
2 mol% Rh, Ag2 atm COrt 12 h
1 mol% Rh, Ag1 atm COrt, 40 h
MeO2CO
HMeO2C
O
HMeO2C
O
Hi-Pr i-Pr i-Pr
rt, 12 h
5 l% Rh A 1 mol% Rh Ag
MeO2CMeO2C
Me
O
H
MeO2CMeO2C
O
H
96% 45% 42%MeO2CMeO2C
O
H Me
1 mol% Rh, Ag1 atm COrt, 24 h
5 mol% Rh, Ag1 atm COrt, 32 h
1 mol% Rh, Ag1 atm COrt, 30 h
MeO2CM O C
Me
O MeO2C
Me
OMeO2C
Me
O
86% 90% 96%2.5 mol% Rh, Ag2 atm CO40 °C, 12 h
2.5 mol% Rh, Ag1 atm CO40 °C, 12 h
2.5 mol% Rh, Ag2 atm CO40 °C, 10 h
Wender and coworkers Angew. Chem. Int. Ed. 2003, 42, 1853.
MeO2CH
MeO2CH
MeO2CHMe Me
α-Methylene Cyclopentanones from Diene-Allenes
Wender and coworkers Angew. Chem. Int. Ed. 2006, 45, 2459.
Bicyclo[5.3.0]decenones from AllenenesPhO2S
SO PhSO Ph
X•
OX
SO2Ph
OX
SO2Phisomerization to, -unsaturated
ketone
[RhCl(CO)2]2, CO
PhMe, 120 °C
H
OO
H
SO2PhSO2Ph
MeO2CMeO2CPhO2S
PhO2S49%36%
73%25:75
5 mol% Rh10 atm CO
82%35:65
10 mol% Rh10 atm CO
47%60 40
10 mol% Rh10 atm CO
H H
SO2Ph SO2PhSO2Ph
49%15:85
cis:trans
36%60:40
cis:trans2.5 mol% Rh5 atm CO
5 mol% Rh10 atm CO
25:75cis:trans
35:65cis:trans
60:40cis:trans
TsN OO OO
H HH
SO2Ph SO2Ph2
33%93:7
cis:trans
73%80:20
cis:trans
30%100:0
cis:trans
10 mol% Rh10 atm CO10 mol% Rh
10 atm CO10 mol% Rh10 atm CO
SO2Ph
cis:trans10 atm CO
•PhO2S
MeO2CM O C
•PhO2S
MeO2CM O C
[2+2]adduct
5 mol% [RhCl(CO)2]2,5 atm CO
Mukai and coworkers Org. Lett. 2006, 8, 1217.
MeMeMeO2C
MeO2C
68%Me
MeO2C
Me
MeO2CMe
adductPhMe, 120 °C
olefin isomerizationRh
Synthesis of Isocarbacyclin
OO
MeMe
1 atm CO,5 mol% (CO)6Co2-(2-methyl-3-butyn-2-ol)
OO
H
MeMe
10 mol% Et3SiH 10 mol% CyNH21+
O O
OHHO
H
OHHO
TMS O
TMS
H10 mol% Et3SiH, 10 mol% CyNH2,DME, 65 °C, 15 min;
1, reflux, 6 h
(CO) C (2 th l 3 b t 2 l)
1
51%
33%OHHO
L-ascorbic acid
Livinghouse conditions(CO)6Co2-alkyne complexes
as Co2(CO)8 surrogates
(CO)6Co2-(2-methyl-3-butyn-2-ol)
HO MeMe
(OC)6Co2
H H Me
CO2H
4
3Me
HMe
(CO)3Me
(CO)3
OHOH
isocarbacyclinCo
Co
H
O
O HMe
TMS(CO)2
Co
Co
H
O
OMe
TMS(CO)2
H
Saito and coworkers J. Org. Chem. 2004, 69, 8133.
-Prostacyclin (PGI2) analogue-metabolically stable
Synthesis of (-)-Pentalenene
-unnatural enantiomer of triquinane
Fox and coworkers Org. Lett. 2007, 9, 5625.
natural product-bio precursors to pentalenolactone
antiobiotics
Synthesis of Tricyclic Sesquiterpenoids
MeTBSO
MOMO•
CO Me
O
MeTBSO
MOMO5 mol% [RhCO(dppp)2]Cl,
1 atm CO, PhMe,reflux, 1 h
74%
HOHO
Me
H
MOMO CO2Me CO2Me
H RhLO
H H
H
H
H
Me CO2Me
MOMOTBSO
RhLn
O
O
HO
OMeMeMe
equatorial chair
MOMO HMe MeH
AcO
Ac2O, TEA, DMAP,DCM, 0 °C to rt
HOO
equatorial, chair
H
MeO2COTBS
RhLn
H
MOMORhLnTBSO
CO2Me
AcOMe
H H
H
dimethylD-tartrate
HO
HO
OMeOMe
Oaxial, chair equatorial, boat
Mukai and coworkers Org. Lett. 2008, 10, 2385.
isolated from Jatropha neopauciflora
Conclusion and Future Directions
• The Pauson-Khand reaction is a highly versatile and efficient transformation for the synthesis of cyclopentenones.
• The Pauson-Khand reaction enables construction of complex molecules in a convergent and atom economic fashion from structurally simple precursors.
• The catalytic, asymmetric, intramolecular variant is highly enabling for the synthesis of stereodefined bicyclic cyclopentenones.
• Reagent-directed stereocontrol absent in context of complex g pmolecule synthesis.
• Further research must seek out more general conditions for the catalytic, asymmetric, intramolecular Pauson-Khand reaction.y , y ,