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Copper‐Catalyzed Intramolecular C(sp 3 )H and C(sp 2 )H Amidation by Oxidative Cyclization
Author(s) -
Wang Zhen,
Ni Jizhi,
Kuninobu Yoichiro,
Kanai Motomu
Publication year - 2014
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201311105
Subject(s) - chemistry , intramolecular force , catalysis , medicinal chemistry , yield (engineering) , kinetic isotope effect , substrate (aquarium) , sulfoxide , copper , alkyl , stereochemistry , organic chemistry , deuterium , materials science , physics , oceanography , quantum mechanics , metallurgy , geology
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 CH bond activation is the rate‐determining step. The 5‐methoxyquinolyl directing group could be removed by oxidation.