Page 160 - Advanced Organic Chemistry Part A - Structure and Mechanisms, 5th ed (2007) - Carey _ Sundberg

140 alcohol or the acylation reagent is enantiopure. The enantioselectivity is a result of
differential interactions in the TS (transition structure) and the reactions are carried to
CHAPTER 2 partial conversion to achieve kinetic resolution. These reactions presumably proceed
Stereochemistry, via the typical addition-elimination mechanism for acylation (see Section 7.4) and
Conformation,
and Stereoselectivity do not have the benefit of any particular organizing center such as a metal ion.
The observed enantioselectivities are quite high, and presumably depend primarily on
steric differences in the diastereomeric TSs. Entries 4 and 5 involve enantioselective
catalysts. Entry 4, is an oxidative cleavage that involves a complex of Ti(IV) with the
chiral ligand, diisopropyl tartrate. It is sufficiently selective to achieve 95% e.e. at the
point of about 67% completion. The other enantiomer is destroyed by the oxidation.
Entry 5 uses a hydrogenation reaction with the chiral BINAP ligand (see p. 130 for
structure). The S-enantiomer is preferentially hydrogenated and the R-enantiomer is
obtained in high e.e. In both of these examples, the reactant coordinates to the metal
center through the hydroxy group prior to reaction. The relatively high e.e. that is
observed in each case reflects the high degree of order and discrimination provided by
the chiral ligands at the metal center. Entry 6 is the oxidative formation of a sulfoxide,
using BINOL (see p. 130) as a chiral ligand and again involves a metal center in a
chiral environment. We discuss enantioselective catalysis further in Section 2.5.
Enzymes constitute a particularly important group of enantioselective catalysts, 11
as they are highly efficient and selective and can carry out a variety of transformations.
Enzyme-catalyzed reactions can be used to resolve organic compounds. Because the
enzymes are derived from L-amino acids, they are chiral and usually one enantiomer
of a reactant (substrate) is much more reactive than the other. The interaction with each
enantiomer is diastereomeric in comparison with the interaction of the enzyme with
the other enantiomer. Since enzymatic catalysis is usually based on a specific fit to an
“active site,” the degree of selectivity between the two enantiomers is often very high.
For enzymatic resolutions, the enantioselectivity can be formulated in terms of two
12
reactants in competition for a single type of catalytic site. Enzymatic reactions can be
described by Michaelis-Menten kinetics, where the key parameters are the equilibrium
constant for binding at the active site, K, and the rate constant, k, of the enzymatic
reaction. The rates for the two enantiomers are given by

v = k R /K and = k S /K S (2.6)
R
S
S
R
R
In a resolution with the initial concentrations being equal, S = R the enantiomeric
selectivity ratio E is the relative rate given by
k /K S
S
E = (2.7)
k /K R
R
Figure 2.9 shows the relationship between the e.e. of unreacted material and product
as a function of the extent of conversion and the value of E.
The most generally useful enzymes catalyze hydrolysis of esters and amides
(esterases, lipases, peptidases, acylases) or interconvert alcohols with ketones and
aldehydes (oxido-reductases). Purified enzymes can be used or the reaction can be
done by incubating the reactant with an organism (e.g., a yeast) that produces an

11 J. B. Jones, Tetrahedron, 42, 3351 (1986); J. B. Jones, in Asymmetric Synthesis, J. D. Morrison, ed.,
Vol. 5, Academic Press, Chap. 9; G. M. Whitesides and C.-H. Wong, Angew. Chem. Int. Ed. Engl., 24,
617 (1985).
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C.-S. Chen, Y. Fujimoto, G. Girdaukas, and C. J. Sih, J. Am. Chem. Soc., 104, 7294 (1982).