Page 69 - Advanced Organic Chemistry Part B - Reactions & Synthesis

1.2.6. Control of Enantioselectivity in Alkylation Reactions 41
The alkylation of an enolate creates a new stereogenic center when the - SECTION 1.2
substituents are nonidentical. In enantioselective synthesis, it is necessary to control Alkylation of Enolates
the direction of approach and thus the configuration of the new stereocenter.
O – O O
2
R Z R Z CH R
R + RCH 2 X R CH R or R R Z
2
R E
R E R E
Enantioselective enolate alkylation can be done using chiral auxiliaries. (See
Section 2.6 of Part A to review the role of chiral auxiliaries in control of reaction stereo-
89
chemistry.) The most frequently used are the N-acyloxazolidinones. The 4-isopropyl
and 4-benzyl derivatives, which can be obtained from valine and phenylalanine, respec-
tively, and the cis-4-methyl-5-phenyl derivatives are readily available. Another useful
auxiliary is the 4-phenyl derivative. 90
O O O O
C C C C
O NH O NH O NH O NH

CH(CH ) CH 2 Ph Ph CH 3 Ph
3 2
Several other oxazolidinones have been developed for use as chiral auxiliaries. The
4-isopropyl-5,5-dimethyl derivative gives excellent enantioselectivity. 91 5,5-Diaryl
derivatives are also quite promising. 92

O O O
C
C O NH C
O NH O NH
CH 3 Ph ) Naph
)
CH 3 CH(CH ) Ph CH(CH 3 2 Naph CH(CH 3 2
3 2
The reactants are usually N-acyl derivatives. The lithium enolates form chelate
structures with Z-stereochemistry at the double bond. The ring substituents then govern
the preferred direction of approach.

Li + R'X
Li +
O O – O O – O
R R' O O O
C R'X C R R R
O N O N C R'X C R'
H O N O N
CH(CH ) ) H
3 2
12 CH(CH 3 2 Ph CH 3 R'X Ph CH
13 3
89
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