Pyridylphosphonium Salts as Alternatives to Cyanopyridines in Radical-Radical Coupling Reactions

Radical couplings of cyanopyridine radical anions represent a valuable technology for functionalizing pyridines, which are prevalent throughout pharmaceuticals, agrochemicals, and materials. Installing the cyano group, necessary for radical anion stabilization, is challenging and limits the use of this chemistry to simple cyanopyridines. We discovered that pyridyl phosphonium salts, installed regioselectively from C-H precursors, are useful alternatives to cyanopyridines in radical-radical coupling reactions, expanding the scope of this reaction manifold to complex pyridines. Methods for both alkylation and amination of pyridines mediated by photoredox catalysis are described. Additionally, we demonstrate late-stage functionalization of pharmaceuticals, highlighting an advantage of pyridyl phosphonium salts over cyanopyridines.