Copper-Catalyzed Enantioconvergent Radical C(sp³)–N Cross-Coupling to Access Chiral α-Amino-β-lactams

Abstract

A copper-catalyzed enantioconvergent radical C-(sp 3 )−N cross-coupling of racemic tertiary α-bromo-β-lactams with aromatic amines is developed under mild thermal reaction conditions. The use of a sterically demanded oxazoline-derived sulfonamide N,N,N-ligand is crucial for the reaction initiation and effective enantio-discrimination of the azetidinone-derived cyclic alkyl radicals. The strategy provides an attractive approach to access chiral α-amino-β-lactams, an important structural motif in many biologically active molecules. Preliminary mechanistic studies support the formation of azetidinone-derived alkyl radicals from the L*Cu(I)-amido complex and α-bromo-β-lactams.