Copper-Catalyzed Remote C–H Functionalizations of Naphthylamides through a Coordinating Activation Strategy and Single-Electron-Transfer (SET) Mechanism

 http://pubs.acs.org/doi/abs/10.1021/acscatal.6b03671

Copper-Catalyzed Remote C–H Functionalizations of Naphthylamides through a Coordinating Activation Strategy and Single-Electron-Transfer (SET) Mechanism

Jun-Ming Li†, Yong-Heng Wang†, Yang Yu, Rui-Bo Wu, Jiang Weng^*, and Gui Lu^*

Institute of Medicinal Chemistry, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, People’s Republic of China

ACS Catal., 2017, 7, pp 2661–2667

DOI: 10.1021/acscatal.6b03671

Publication Date (Web): February 27, 2017

Copyright © 2017 American Chemical Society

Abstract

Achieving p-C_Ar–H site selectivity is one of the major challenges in direct carbon–hydrogen (C–H) functionalization reactions. Herein, the copper-catalyzed and picolinamide-assisted remote p-C–H sulfonylation of 1-naphthylamides was realized. The synthetic utility of this method was further examined by sequential functionalizations and the efficient synthesis of the pharmaceutically useful 5-HT₆ serotonin receptor ligand. This approach also provided a general strategy for other p-C–H bond functionalization, such as highly selective constructions of C–O, C–Br, C–I, C–C, and C–N bonds. Control experiments and theoretical calculations suggested that this C–H sulfonylation reaction might proceed through a single-electron-transfer process.