Synthesis of bicyclic γ-lactam derivatives by intramolecular carbene insertion and aza-Wittig reaction

Abstract

A comparative study of the various methodologies to construct bicyclic γ-lactams is reported. Thus RhII-catalyzed decomposition of 2-pyrrolidone and pyrrolidine derived diazomalonates were attempted to synthesize fused γ-lactams. Spectral evidences revealed the formation of diastereomeric alcohols instead of desired C-H or N-H insertion products, indicating significant conformational bias towards insertion process. On the other hand, the method involving the N-H insertion onto the lactam nitrogen of 2-pyrrolidone ring was successful. Intramolecular aza-Wittig reaction was also successfully explored to construct bicyclic γ-lactam scaffolds. All the bicyclic analogues showed weak antibacterial activity against S. aureus and E. coli.