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Copper/O2-Mediated Oxidative C-C Activation of Nitriles for Selective Acylation-Bromination of Anilines
1Key Laboratory of Synthetic and Biological Colloids, Ministry of Education, School of Chemical and Material Engineering, Jiangnan University, Wuxi, Jiangsu 214122, China.
Abstract:
This study reports selective dual amino acylation and C-H bromination of aniline compounds enabled by Cu/O2 catalyst systems. This method involves crucial oxidation-induced C-CN bond cleavage of α-methylene nitriles to generate an acylcyanide intermediate that is facilely intercepted by anilines. After amino acylation, the Cu(II) precatalyst in combination with NBS generates Cu(III)-Br in situ that engages in selective electrophilic para- or ortho-C-H bromination. The substrate scope, mechanistic aspects, and late-stage functionalization of biologically active anilines are studied. This study shows the synthetic potential of oxidative C-CN bond activation of nitriles for the development of valuable reactions.
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