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

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 S-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.