Site-selective arene C–H amination with iron-aminyl radical

Homolytic aromatic substitution is an enabling strategy for arene C–H functionalization with numerous important synthetic applications. However, despite notable advances, exerting control over site selectivity remains a formidable challenge. Here we report a unified highly site-selective arene C–H amination of various electronically distinct arenes using an iron-aminyl radical. Unlike the conventionally employed free nitrogen-centred radicals, the metal-supported aminyl radical possesses a general attractive interaction with diverse inherent functional groups in arene substrates, engendering extraordinary regioselectivity through substrate chelation. Importantly, this approach has the ability to override the inherent influences of polar and steric effects that typically dictate regiochemical control in homolytic aromatic substitution, leading to high site selectivity. The broad scope of applicable directing groups renders this method a powerful tool to streamline the synthesis of various important aniline building blocks and pharmaceuticals, and allows for the late-stage C–H amination of structurally diverse drugs and other bioactive molecules.