Copper-catalyzed intramolecular C(sp³)-H and C(sp²)-H amidation by oxidative cyclization

The first copper-catalyzed intramolecular C(sp³)-H and C(sp ²)-H oxidative amidation has been developed. Using a Cu(OAc) ₂ catalyst and an Ag₂CO₃ oxidant in dichloroethane solvent, C(sp³)-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 CuCl₂ and Ag₂CO₃ under an O₂ atmosphere in dimethyl sulfoxide, however, leads to 2-indolinone selectively by C(sp²)-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. Silver ox: By using a Cu(OAc)₂ catalyst and an Ag₂CO₃ oxidant in dichloroethane solvent, C(sp³)-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 a gram scale. Use of CuCl₂ and Ag₂CO₃ under an O₂ atmosphere led to 2-indolinone selectively synthesized by C(sp²)-H amidation. DMSO=dimethylsulfoxide.