Direct α-C−H Heteroarylation of Unprotected Primary Amines

High Resolution Image Download MS PowerPoint Slide Primary alkylamines are widely used in chemical synthesis, yet their high reactivity at nitrogen has made selective α-C−H functionalization almost always dependent on preinstalled protecting or directing groups, compromising atom- and step-economy. Here we report the α-C−H heteroarylation of unprotected, non-benzylic primary alkylamines, enabling a direct, catalytic, and scalable synthesis of unprotected α-azolyl primary amines, including sterically congested α-tertiary motifs. The transformation proceeds via photoredox-catalyzed hydrogen-atom transfer to achieve chemoselective C−H activation and heteroaryl coupling. Notably, a representative case study demonstrates that low-temperature continuous-flow photochemistry enables a reaction with a highly electrophilic azolyl chloride that is impossible under batch conditions, illustrating how flow can kinetically divert reactivity from nitrogen to carbon in unprotected amines.