Harnessing the reactivity of captodative radicals: photocatalytic α-pyridination of glycyl derivatives through reversible radical coupling

Abstract

Captodative radicals that are highly stabilized by the presence of both electron-donating and electron-withdrawing groups exhibit unique reactivity in organic syntheses. These radicals are known to be less reactive towards radical–radical coupling reactions due to the presence of a shielding occupied molecular orbital. Herein we describe a photocatalytic synthetic strategy for the coupling of two different captodative radicals, which are generated from glycyl derivatives and 4-cyanopyridines. An aromatization is incorporated as the driving force after a reversible radical–radical coupling process. This method can be applied to a wide variety of peptides, providing pharmaceutically relevant pyridyl-functionalized products under mild reaction conditions.