Asymmetric deprotonation reactions using enantiopure lithium amide bases

Abstract

Lithium diisopropylamide (LDA), one of a family of dialkyllithium amides, is firmly established as the most important strong base used in organic synthesis. Bearing in mind the significance of such bases in deprotonation reactions of weak carbon acids, especially carbonyl compounds, sulphones and sulphoxides, and the tremendous effort that has been applied to the development of asymmetric reactions, it is surprising that asymmetric deprotonation chemistry has been so little developed. Indeed, prior to the report in 1986 of the asymmetric deprotonation of cis-2, 6-dimethylcyclohexanone using enantiopure lithium amide bases*, only a handful of reports concerning the chemistry of these reagents had appeared. Since that time, enantiopure lithium amides have been developed extensively as reagents for organic synthesis, both as powerful bases and as chiral nucleophiles. This brief review will focus on reactions of enantiopure lithium amides as bases in which the deprotonation reaction is the key asymmetric step and will deal primarily with reactions of ketones.1†