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

Achieving p-CAr–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.