A Novel One-Step Diastereo- and Enantioselective Formation of <i>trans</i>-Azetidinones and Its Application to the Total Synthesis of Cholesterol Absorption Inhibitors

Abstract

An efficient and practical asymmetric process was developed for the synthesis of azetidinone-based cholesterol absorption inhibitors. Key to this synthesis was the discovery of a novel one-step diastereo- and enantioselective formation of trans beta-lactams starting from commercially available 3(S)-hydroxy-gamma-lactone. Various trans beta-lactams can be prepared in good yields and with better than 95:5 enantio- and diastereoselctivity. A Lewis acid-catalyzed aldol condensation and a highly enantioselective oxazaborolidine-catalyzed chiral reduction completes the side chain.