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

Article abstract of DOI:10.1016/S0040-4039(99)00728-5

Using chiral bicyclic lactams, containing an α,β-unsaturation, the key precursor of (-)-indolizomycin was obtained in optically pure form. The sequence involved a >20:1 diastereoselective cyclopropanation of the unsaturated lactam 5 employing sulfoxonium methylide. TiCl₄ mediated addition of allyltrimethylsilane afforded pyrrolidone 7 in a diastereomeric ratio of >20:1. The appropriately substituted pyrrolidone 2 was prepared by debenzylation and subsequent alkylation with 3-bromoproponic ester. The six step sequence from commercially available starting materials was performed in 26% overall yield.