An asymmetric synthesis of the key precursor to (-)-indolizomycin

Using chiral bicyclic lactams, containing an alpha,beta-unsaturation, the k ey precursor of (-)-indolizomycin was obtained in optically pure form. The sequence involved a >20:1 diastereoselective cyclopropanation of the unsatu rated lactam 5 employing sulfoxonium methylide. TiCl4 mediated addition of allyltrimethylsilane afforded pyrrolidone 7 in a diastereomeric ratio of >2 0:1. The appropriately substituted pyrrolidone 2 was prepared by debenzylat ion and subsequent alkylation with 3-bromoproponic ester. The six step sequ ence from commercially available starting materials was performed in 26% ov erall yield. (C) 1999 Elsevier Science Ltd. All rights reserved.