A General Photocatalytic Strategy for Nucleophilic Amination of Primary and Secondary Benzylic C–H Bonds
Madeline E. Ruos, R. Garrison Kinney, Oliver T. Ring, Abigail G. Doyle
Abstract
We report a visible-light photoredox-catalyzed method that enables nucleophilic amination of primary and secondary benzylic C(sp 3 )–H bonds. A novel amidyl radical precursor and organic photocatalyst operate in tandem to transform primary and secondary benzylic C(sp 3 )–H bonds into carbocations via sequential hydrogen atom transfer (HAT) and oxidative radical-polar crossover. 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(sp 3 )–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(sp 3 )–H bonds to a library of aminated products.