Hydroformylations, Hydrovinylations, and Hydrocyanations - Carbohydrates: Tools for Stereoselective Synthesis - page 201

catalyst (1 mol%):
[(allyl)NiBr] 2 / ligand 68a (ratio 1:2)
additive: AgSbF 4 (1 mol%)

Me

74 75

Br CH 2 Cl 2 Br

H 2 CCH 2

89%ee

98%

(dppp)NiCl 2
(1.6 mol%)
i BuMgCl
Et 2 O

95%

Me Me

( R )-ibuprofen

1.) O 3 , MeOH, then Me 2 S
2.) KMnO 4 , acetone

CO 2 H

66%

i Bu 77 i Bu 76

89%ee
controlled by chiral GC
of (-)-menthyl ester

Scheme 9.12 Asymmetric synthesis of (R) -ibuprofen via asymmetric hydrovinylation of
4-bromostyrene.

9.3
Hydrocyanation Reactions

The catalytic addition of hydrogen cyanide to an olefin, also called hydrocyanation
[32], offers potentially easy access to nitriles, which can be elaborated into a host
synthetically valuable compounds such as aldehydes, carboxylic acids, and amines.
Therefore, an efficient asymmetric version of this transformation is highly desir-
able. The reaction proceeds mainly with activated alkenes such as vinylarenes and
dienes as substrates and nickel(0) compounds make the most important catalysts
(Scheme 9.13). As with the previously described addition processes across olefinic
double bonds, an undesired achiral side product ( 80 ) may be formed along with
the chiral addition product ( 79 ) and, thus, apart from high stereoselectivity, the
catalyst has to provide a control of the regioselectivity.

HCN

Me

R 1

Ni(COD) + ligand *

∗ CN

CN

R 1 Ar 1

78 +

79 80

(undesired)

R 1 = aryl, alkenyl

Scheme 9.13

Nickel-catalyzed asymmetric hydrocyanation of activated alkene substrates.

9.3.1
Diphosphinite Ligands

After the initial work by Elms and Jackson on asymmetric hydrocyanation of
norbornene as a substrate [33], it was again the group of RajanBabu who employed
a highly useful series of ligands based on carbohydrates, giving unprecedented