Asymmetric synthesis using chiral bases

Abstract

Studies have been made to design chiral bidentate lithium amides and chiral tetradentate amines, and to explore the use of these chiral bases for enantioselective formation and reactions of lithium enolates. Chiral bidentate lithium amides having a chiral amide nitrogen made by virtue of chelation were successfully applied to the enantioselective deprotonation reaction of prochiral cyclic ketones, the kinetic resolution of racemic cyclohexanone derivatives by deprotonation, and the regioselective deprotonation of optically active 3-keto steroids. Structures of some of these chiral bidentate lithium amides in the solid state and in solution were elucidated by X-ray and NMR spectroscopic analyses. By the use of chiral tetradentate amines, enantioselective reactions of lithium enolates with electrophiles, such as alkylation, protonation, and Michael addition, proceeded successfully. Examples of catalytic enantioselective deprotonation, alkylation, and protonation by the present strategy are also presented and discussed.