Site-Selective Electrochemical Benzylic C-H Amination

Abstract

C-H/N-H cross-coupling is an ideal strategy to synthesize various amines but remains challenging owing to the requirement for sacrificial chemical oxidants and the difficulty in controlling the regio- and chemo-selectivity. Herein we report a site-selective electrochemical amination reaction that can convert benzylic C-H bonds into C-N linkages via H₂ evolution without need for external oxidants or metal catalysts. The synthetic strategy involves anodic cleavage of benzylic C-H to form a carbocation intermediate, which is then trapped with an amine nucleophile leading to C-N bond formation. Key to the success is to include HFIP as a co-solvent to modulate the oxidation potentials of the alkylbenzene substrate and the aminated product to avoid overoxidation of the latter.

Keywords: C−H amination; C−H functionalization; cross-dehydrogenative coupling; electrochemistry; oxidation.