Copper‐Catalyzed Intramolecular C(sp³)H and C(sp²)H Amidation by Oxidative Cyclization

Abstract

Abstract The first copper‐catalyzed intramolecular C(sp 3 )H and C(sp 2 )H oxidative amidation has been developed. Using a Cu(OAc) 2 catalyst and an Ag 2 CO 3 oxidant in dichloroethane solvent, C(sp 3 )H amidation proceeded at a terminal methyl group, as well as at the internal benzylic position of an alkyl chain. This reaction has a broad substrate scope, and various β‐lactams were obtained in excellent yield, even on gram scale. Use of CuCl 2 and Ag 2 CO 3 under an O 2 atmosphere in dimethyl sulfoxide, however, leads to 2‐indolinone selectively by C(sp 2 )H amidation. Kinetic isotope effect (KIE) studies indicated that CH bond activation is the rate‐determining step. The 5‐methoxyquinolyl directing group could be removed by oxidation.