Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan).
Angew Chem Int Ed Engl. 2014 Mar 24;53(13):3496-9. doi: 10.1002/anie.201311105. Epub 2014 Feb 24.
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.
首次发展了铜催化的分子内 C(sp(3))-H 和 C(sp(2))-H 氧化酰胺化反应。在二氯乙烷溶剂中，使用 Cu(OAc)2 催化剂和 Ag2CO3 氧化剂，C(sp(3))-H 酰胺化在末端甲基以及烷基链的内部苄基位置进行。该反应具有广泛的底物范围，即使在克级规模下，也能以优异的收率得到各种β-内酰胺。然而，在二甲基亚砜中使用 CuCl2 和 Ag2CO3 在氧气气氛下，通过 C(sp(2))-H 酰胺化则选择性得到 2-吲哚啉酮。动力学同位素效应（KIE）研究表明，C-H 键活化是速率决定步骤。5-甲氧基喹啉基导向基团可以通过氧化去除。
