Page 209 - Advanced Organic Chemistry Part A - Structure and Mechanisms, 5th ed (2007) - Carey _ Sundberg

2.5. Enantioselective Reactions 189

SECTION 2.5
Enantioselectivereactionsareaparticularcaseofstereoselectivereactionsthatshow
Enantioselective
a preference for one of a pair of enantiomers. As noted in Section 2.1.8, no reaction can
Reactions
produceanexcessofoneenantiomerunlessthereisatleastonechiralcomponentinvolved.
Enantiospecific reactions are a special case of stereoselective reactions in which the
mechanism ensures that the configuration of reactant, reagent, or catalyst determines that
of the product. A simple example is S 2 substitution, where the back-side displacement
N
mechanismdictatesinversionofconfiguration.Inthenextseveralsubsections,wediscuss
examples of enantioselective and enantiospecific reactions.

2.5.1. Enantioselective Hydrogenation
Most catalytic hydrogenations are carried out under heterogeneous conditions
using finely dispersed transition metals as catalysts. Such reactions take place on
the catalyst surface (heterogeneous hydrogenation) and are not normally enantiose-
lective, although they may be stereoselective (see Section 2.4.1.1). In addition, certain
soluble transition metal complexes are active hydrogenation catalysts. 132 Many of
these catalysts include phosphine ligands, which serve both to provide a stable soluble
complex and to adjust the reactivity of the metal center. Hydrogenation by homoge-
neous catalysts is believed to take place through a complex of the unsaturated
compound. The metals also react with molecular hydrogen and form metal hydrides.
The addition of hydrogen to the metal can occur before or after complexation of the
alkene. An alkylmetal intermediate is formed by transfer of hydrogen from the metal
to the carbon. This intermediate can break down to alkane by reductive elimination or
in some cases by reaction with a proton source.

H 2
H
n
X-M L m X-M n+2 L m
reductive
H RCH CH +M L
n
RC CH 2 H elimination 2 3 m
R H 2 RCH 2 CH 2 M n+2 L m
H
n
M L m R H
M n+2 L m protonolysis n+2
RCH 2 CH 3 + M L m
H
n = charge on metal
alkene-dihydridometal
m = number of ligands
The process of homogeneous catalytic hydrogenation can be made enantiose-
lective by establishing a chiral environment at the catalytic metal center. Most of the
successful cases of enantioselective hydrogenation involve reactants having a potential

132
A. J. Birch and D. H. Williamson, Org.Reactions, 24, 1 (1976); B. R. James, Homogeneous Hydro-
genation, Wiley, New York, 1973; B. R. James, in Comprehensive Organometallic Chemistry,
G. Wilkinson, F. G. A. Stone, and E. W. Abel, eds., Pergamon Press, Oxford, 1982, Vol. 8, Chap. 51;
P. A. Chaloner, M. A. Esteruelas, F. Joo, L. A. Oro, Homogeneous Hydrogenation, Kluwer Academic,
Dordrecht, 1994.