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Keywords:

  • C[BOND]H activation;
  • copper;
  • cyclization;
  • heterocycles;
  • lactams

Abstract

The first copper-catalyzed intramolecular C(sp3)[BOND]H and C(sp2)[BOND]H oxidative amidation has been developed. Using a Cu(OAc)2 catalyst and an Ag2CO3 oxidant in dichloroethane solvent, C(sp3)[BOND]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)[BOND]H amidation. Kinetic isotope effect (KIE) studies indicated that C[BOND]H bond activation is the rate-determining step. The 5-methoxyquinolyl directing group could be removed by oxidation.