Forging structural complexity: diastereoselective synthesis of densely substituted β-lactams with dual functional handles for enhanced core modifications

Abstract

The preparation of the β-lactam motif containing both C–Br and N–O bonds as functional handles remains an unmet synthetic challenge. Described herein is a novel and highly diastereoselective NBS-mediated cyclization of N-alkoxy α,β-unsaturated silyl imino ethers to furnish nearly three dozen α-bromo N-alkoxy β-lactams. The reaction gives rapid and convenient access to structurally diverse monocyclic, spirocyclic and fused β-lactams in moderate to good yields. The two functional handles were shown to be useful for the further elaboration of the β-lactam core.