title: Copper-catalyzed intramolecular C(sp³)-H and C(sp²)-H amidation by oxidative cyclization.
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 Ag2CO3 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 CuCl2 and Ag2CO3 under an O2 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.
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan).
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.forename: Jizhi
authors.initials: J
authors.lastname: Ni
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Kuninobu
authors.forename: Motomu
authors.initials: M
authors.lastname: Kanai
mesh_terms: D002384:Catalysis; D003300:Copper / Q000737:chemistry*; D003500:Cyclization; D015394:Molecular Structure; D010084:Oxidation-Reduction
chemical_list: D003300:Copper
keywords: CH activation; copper; cyclization; heterocycles; lactams