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, which facilitates the necessary radical anion formation and stabilization, is challenging and limits the use of this chemistry to simple cyanopyridines. We discovered that pyridylphosphonium salts, installed directly and 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 pyridylphosphonium salts over cyanopyridines.

Automated summary

Radical couplings of cyanopyridine radical anions offer a valuable technology for functionalizing pyridines in pharmaceuticals, agrochemicals, and materials. This study demonstrates that pyridylphosphonium salts can be useful alternatives to cyanopyridines in radical-radical coupling reactions, expanding the scope of complex pyridines. Additionally, late-stage functionalization of pharmaceuticals is highlighted as an advantage of pyridylphosphonium salts over cyanopyridines.