Enantioselective Reduction of Cyclic-1, 2-dicarboxylic Anhydrides and 1, 2-Dicarboximides: Asymmetric Synthesis of Bicyclic Lactones and Hydroxylactams

Abstract

Chiral bicyclic lactones (3, 8, 9) and bicyclic hydroxylactams (10—13) were synthesized by highly enantioselective reduction of meso-cyclic-1, 2-dicarboxylic anhydrides (1, 4) and meso-cyclic-1, 2-dicarboximides (2) with lithium aluminum hydride (LiAlH4)-alcohol(ROH)-(R)- or (S)-1, 1‘-bi-2-naphthol complex [(R)- or (S‘)-BINAL-H(ROH)]. Treatment of the hydroxylactams (10—13) with triethylsilane (Et3SiH) and trifluoroacetic acid (CF3CO2H) gave chiral bicyclic lactams (14, 15) in quantitative yields. Removal of the N-4-methoxyphenyl group of the lactams (14, 15) with cerium(IV) ammonium nitrate (CAN) proceeded smoothly to give the corresponding N-unsubstituted lactams (16, 17) in high optical purity. © 1994, The Pharmaceutical Society of Japan. All rights reserved.