Photochemical C3-Amidation of Pyridines via Zincke Imine Intermediates

Selective skeletal and peripheral editing of the pyridine moiety broadly expanded the chemical space. While CH functionalizations at the positions C2 and C4 are enabled by the inherent reactivity of this heteroarene, selective derivatization at C3 has long posed a significant challenge. Recently, based on dearomatization-rearomatization sequence, involving Zincke imine intermediates, selective halogenation (-Br, -Cl, -I) and isotopic labelling was accomplished. Here, we report a mild and regioselective method for C3 amination that relies on the photochemical reaction of Zincke imine with an amidyl radical generated from N-aminopyridinium salts. Mechanistic and theoretical studies confirmed radical intermediates involved and explains C-3 regioselectivity of the reaction.