Asymmetric Transformations by Deprotonation Using Chiral Lithium Amides

Abstract

Lithium dialkylamides, especially lithium diisopropylamide (LDA), are valuable bases in organic synthesis but it is only since 1980 that their chiral counterparts have found application in reactions that can be broadly defined as asymmetric deprotonations. This chapter provides a comprehensive overview of all selective deprotonation processes mediated by chiral lithium amides, including desymmetrizations, kinetic resolutions, and other applications such as regioselective enolizations of chiral substrates. The chapter covers the entire substrate scope of chiral lithium amide deprotonation reactions, which includes rearrangement of epoxides to allylic alcohols, enolizations of carbonyl compounds (principally, but not exclusively, cyclic ketones), and metalations of organometallics (especially tricarbonyl(η6-arene)chromium(0) complexes) and miscellaneous phosphorous- or sulfur-containing compounds. It is possible to perform some benchmark reactions under “catalytic conditions,” i.e., using substoichiometic quantities of chiral lithium amide, particularly epoxide rearrangements. The capability of deprotonations, mediated by chiral lithium amides, to deliver non-racemic intermediates with acceptable selectivity for target synthesis is amply illustrated by the examples included in the review. In particular, the desymmetrization of conformationally biased prochiral cyclic ketones has become a well-established strategy for organic synthesis, and has seen significant application in target-oriented synthesis. Keywords: enantioselectivity; stereochemistry; asymmetric deprotonation; lithiation; rearrangements; lithium amides; epoxides; cyclic ketones; enolates; cyclic imides; bridgehead substitution; tricarbonyl(η6-arene)chromium(0) complexes; kinetic resolution; catalysis; polymeric reagents