A general photocatalytic strategy for nucleophilic amination of primary and secondary benzylic C–H bonds

Abstract

We report a visible-light photoredox-catalyzed method that enables nucleophilic amination of primary and secondary benzylic C(sp3)–H bonds. A novel amidyl radical precursor and organic photocatalyst operate in tandem to transform primary and secondary benzylic C(sp3)–H bonds into carbocations via sequential hydrogen atom transfer (HAT) and oxidative radical-polar crossover (ORPC). The resulting carbocation can be intercepted by a variety of N centered nucleophiles, including nitriles (Ritter reaction), amides, carbamates, sulfonamides, and azoles for the construction of pharmaceutically-relevant C(sp3)–N bonds under unified reaction conditions. Mechanistic studies indicate that HAT is amidyl radical-mediated and that the photocatalyst operates via a reductive quenching pathway. These findings establish a mild, metal-free, and modular protocol for the rapid diversification of C(sp3)–H bonds to a library of aminated products.