Lit t R t 2012 06 12Literature Report 2012-06-12

Duan, Y. Checker: Chen, M.-W.

Lindsay, D. M. et al

Chem. Commun. 2010, 46, 2474

Selected resonance structures and simplified orbital pictures

dipp dipp dipp

N

Npp

dippN

N

dippN

Ndipp

dippdipp pp

dipp-imd (1)

dipp dipp dipp

N

Ndipp

dipp

BH3N

NHdipp

dipp

BH3N

Ndipp

dipp

B

dipp dipp pp

dipp-imd-BH3 (2)

NHC-boranes, do not readily hydroborate themselvesy y

The synthesis of NHC-boranes

N i-Pri-Pr

a) KOt Bu THF N i-Pri-Pr

N

NH

i-Pri-Pr

Cl- a) KOt-Bu, THF

b) BH3-THF N

NBH3

i-Pri-Pri Pr

Yield: 60%

R Ar Ar

Select examples of NHC-boranes

N

N

R

BH3N

N

Ar

BH3N

N

Ar

BH3

R

RR Ar Ar

R = CH(CH3)2R = adamantyl

Ar = 4-ClC6H4Ar = 4-t-Bu-2,6-Me2C6H2

R = CNR = Cl

N

NMes

BH3N

Ndipp

BH3N

NMe

BH3N(CH2)nCH=CH2

n = 1, 2

Ndipp

NR

R = CH2CH=CH2R = CH3

NO

i-Pr

N NMe

N NPh

N

NBH3

Oi-Pr

N

N

NBH3

Me

N

NBH3

X ray crystallographic studyX-ray crystallographic study

Clyburne J A C et al Chem Commun 2003 1722Clyburne, J. A. C. et al Chem. Commun. 2003, 1722

A new class of boron centered radical

S BH2NHC

A new class of boron-centered radical

R R'

O SCH3

S

+ NHC-BH2

R R'

O SCH3

SBH2NHC

R R R R

SBH2NHC

BH2NHC

R R'

O SCH3 R R' +S

SCH3O

BH2NHC

R R' + NHC-BH3H

+ NHC-BH2

Curran D P et al J Am Chem Soc 2009 131 11256

R R 3R R'

2

Curran, D. P. et al J. Am. Chem. Soc. 2009, 131, 11256

J. Am. Chem. Soc. 2010, 132, 2350

Entry RX equiv solvent T (oC) Prod, X = yield11B NMR(CDCl3, δ)

1 C12H25Cl 1 PhCF3 140 Cl ND -18.7

2 CCl4 64 CCl4/CDCl3 80 Cl 84 -18.7

3 C12H25Br 1.5 toluene 140 Br 70 -23.0

4 CBr4 1 C6D6 80 Br 56 -23.0

5 C12H25I 1 C6D6 180 I 90 -33.0

6 C4H9I 1 PhH 180 I 100 -33.0

7 C12H25OTs 1.5 toluene 140 OTs 70 -11.4

8 C12H25OMs 1.5 toluene 140 OMs 60 -11.0

Lacote, E. et al J. Am. Chem. Soc. 2010, 132, 15072

9 C12H25OTf 1.5 1,4-dioxane 25 OTf ND -8.8

Estimated rate constants for hydrogen abstraction

Lacote, E. et al Org. Lett. 2010, 12, 2998

The rate constants kH for hydrogen-atom transfer

Deoxygenations of Xanthates and Thionocarbonates

N

NBH3R

OX

diMe-Imd-BH3 R-H

EtBnO(H2C)5

OXEtBnO(H2C)5

14, X = C(S)SMe

14, X = C(S)SMe

A

B

19, 79%

19, 81%

BnO(H2C)5

OX

BnO(H2C)5 (CH2)2Y20, Y = H21, Y = SC(=O)SMe

A ) 1 equiv of AIBN, 80 oC, 2 h.

B ) 1 equiv of Et3B, rt, 2 h.

15, X = C(S)SMe

15, X = C(S)SMe

A

B

20, 52%; 21, 17%

20, 63%; 21, 22%

, SC( O)S e

HO C6H13

OX

HO C6H13

HA

Lacote, E. et al Org. Lett. 2010, 12, 3002

X = C(=S)OPh 68%

N-Heterocyclic carbene boranes are good hydride donorsy g y

Entry Equiv HOAc Equiv 2 T Yield (%)

1 0 1.3 24 h --

2 1.3 1.3 1.5 h 84%

3 1 0.7 16 h 86%

4 1 0.5 16 h 94%

5 1 0.33 3 d 86%

Mayr, H. et al Org. Lett. 2012, 14, 82

Nucleophilicity parameters N of some hydride donors

Mayr H et al Org Lett 2012 14 82Mayr, H. et al Org. Lett. 2012, 14, 82

Scope of the palladium-mediated reduction of Csp2-X bonds

Curran, D. P. et al Chem. Eur. J. 2009, 15, 12937

Curran, D. P. et al Chem. Eur. J. 2009, 15, 12937

Applications in the asymmetric reduction of ketones

N N

OO

N N

B Ht-Bu t-Bu

R R1

O

R R1

OH

BF3.OEt2, -90 oC

CH2Cl2, 15 hUp to 85% ee

Lindsay, D. M. et al Chem. Commun. 2010, 46, 2474

Synthesis of NHC–borane complexes

Entry NHC.HX Base NHC.BH3 Yield (%)y 3 ( )

1 3⋅HPF6 KHMDS 3⋅BH3 88

2 4⋅HOTf n-BuLi 4⋅BH3 96

3 5⋅HOTf n-BuLi 5⋅BH3 95

4 6⋅HOTf n-BuLi 6⋅BH3 46

Reduction of acetophenone with NHC borane complexes

O OH

Reduction of acetophenone with NHC–borane complexes

ONHC.BH3, CH2Cl2

15-16 h

OH

Entry NHC.HX Lewis acid T/oC Yield (%) Ee: (%)Entry NHC HX Lewis acid T/ C Yield (%) Ee: (%)

1 3⋅BH3 -- rt -- --

2 3⋅BH3 -- 40 -- --3

3 4⋅BH3 -- rt 44 14

4 4⋅BH3 -- 0 10 36

5 4⋅BH3 Sc(OTf)3 -78 95 42

6 5⋅BH3 Sc(OTf)3 -78 92 50

7 6 BH Sc(OTf) 78 60 757 6⋅BH3 Sc(OTf)3 -78 60 75

A t i k t d ti i NHC di lk lb lAsymmetric ketone reduction using NHC–dialkylborane complexes

Entry NHC.BHR2 T/oC t/h Yield (%) Ee: (%)

1 3⋅9-BBNa rt 24 15 --

2 4⋅9-BBNb rt 15 40 34

3 4⋅9-BBNc 0 4 90 56

4 4⋅9-BBNc -78 15 82 60

5 5 9 BBNc 78 15 80 845 5⋅9-BBNc -78 15 80 84

6 6⋅9-BBNc -78 15 45 10

N L i id ddi i b 1 i S (OTf) 1 i BF OEa No Lewis acid additive. b 1 equiv. Sc(OTf)3. c 1 equiv BF3.OEt2

OO

Asymmetric ketone reduction

N N

OO

B Ht-Bu t-Bu

O OH

B H

R R1 R R1BF3

.OEt2, -90 oCCH2Cl2, 15 h

Up to 85% ee

OH OH OH OH

Ee: 84% (80%) Ee: 85% (76%)

F MeO

Ee: 59% (74%) Ee: 71% (87%)

OH OH OH

Ph

OH OH

Ee: 63% (82%) Ee: 24% (65%) Ee: 0 (68%) Ee: 70% (88%) Ee: 62% (62%)

Summary

ONHC.BH3 CH2Cl2

OHNHC BH3, CH2Cl2

15-16 h

展 望

O N+

N N

NN

NN N N

Ndipp

HX CDCl Ndipp

N

NBH3

dipp

HX, CDCl3

T N

NBH2X

dipp

dipp-Imd-BH3 dipp-Imd-BH2X

Entry HX pKa T Prod, X = yield11B NMR(CDCl δ)y p , y (CDCl3, δ)

1 TfOH -14 0 OTf NMR -8.8

2 HBr 9 0 Br NMR 23 02 HBr -9 0 Br NMR -23.0

3 HCl -8 0 Cl 81 -18.7

4 TsOH 2 6 60 OTs NMR 11 24 TsOH -2.6 60 OTs NMR -11.2

5 MsOH -2.6 0 OMs 88 -11.0

6 CF COOH 0 6 25 OCOCF 85 11 46 CF3COOH -0.6 25 OCOCF3 85 -11.4

7 Cl2CHCOOH 1.3 60 OCOCHCl2 67 -11.1

8 NCCH COOH 2 5 60 OCOCH CN 24 11 9

Lacote, E. et al J. Am. Chem. Soc. 2010, 132, 15072

8 NCCH2COOH 2.5 60 OCOCH2CN 24 -11.9

dipp dipp

N

NBH3

dipp

HX, CDCl3

T N

NBH2X

dippdipp dipp

dipp-Imd-BH3 dipp-Imd-BH2X

For more than 40 years, there has been intense interest in the study of N-

heterocyclic carbenes (NHCs) initially focused on empirical researchheterocyclic carbenes (NHCs), initially focused on empirical research,

which led to the isolation of NHCs, and their concomitant impact in

catalysis for organic synthesis. The ligating ability of NHCs equals orcatalysis for organic synthesis. The ligating ability of NHCs equals or

surpasses that of phosphanes in a range of transition metal-catalysed

reactions, and the Lewis- and Brønsted basicity of NHCs has enabled their, y

use as powerful organocatalysts.

In summary, we have synthesised a range of chiral and achiral NHC–

borane and –organoborane complexes, and shown, in the firstg p , ,

example of asymmetric synthesis using structurally well-defined

chiral NHC–main group complexes, their potential in the asymmetric

reduction of ketones. Work in our laboratory is ongoing to identify

more effective chiral NHCs to apply the methodology to other C=X

systems and to develop a catalytic, asymmetric variant of the

reaction, and these studies will be described in due course.