Reaction of Enolates - Carbohydrates: Tools for Stereoselective Synthesis - page 58

provides an efficient enantioselective synthesis of chiral tertiary aldols, which are
often difficult to prepare. Essentially, a single diastereoisomer was obtained in
70-97% yield by the reaction of 55 with several silyl enol ethers or silyl ketene
acetals in the presence of SnCl 4 . The chiral auxiliary was easily removed from the
aldol adduct by simple base-promoted hydrolysis of 56 [26].
Tadano et al. have used propionyl ester 27 in the 1,4-addition to -unsaturated

methyl crotonate (Scheme 3.19). The anti- Michael adduct 57 was obtained as a
single product in 75% yield and 90% diastereoselectivity. The synthetic usefulness
of the approach was demonstrated by a three-step asymmetric synthesis of the
acyclic monoterpene (-)-lasiol 58, a sex attracting pheromone of the ant Lasius
meridionalis. As before the high diastereoselectivity was accounted for by invoking
the formation of (Z) -enolate 28 and the subsequent approach of the methyl cro-
tonate from the Si face (Scheme 3.19) [27].

α , β

D- gluco

O O

O

1) NaHMDS

3 Steps

H 3 C

THF, -78 to 0 °C
2)

O

O

MeO O

O

TBSO

TBSO

O

TBSO

TBSO

OMe

OMe

57

OMe

27

OH

(-)-lasiol

58

Scheme 3.19 Asymmetric synthesis of (-)-lasiol using methyl 6-deoxy-2,3-di- O-
( t -butyldimethylsilyl)- α -d-glucopyranoside as chiral auxiliary.

3.4
Concluding Remarks

From the examples presented in this section some concluding remarks can be
drawn. As stated in the introduction, auxiliary-based aldol condensation has
reached great sophistication, efficiency, and reliability in predicting the stereo-
chemical outcome of the reaction. As a result, this approach is commonly employed
by pharmaceutical companies at the preclinical and clinical stage to efficiently and
rapidly produce enantiopure APIs on a kilogram scale. An illustrative example of
such applications is the impressive large-scale synthesis of the anticancer natural
compound discodermolide by Novartis [28]. The approach is based on an Evans
aldol reaction using an oxazilidinone as chiral auxiliary, which was, importantly,