Multiphoton photoredox catalysis enables selective hydrodefluorinations

Late-stage modification of complex molecules via site-selective hydrodefluorination is a challenging endeavor. The selective activation of carbon-fluorine (C-F) bonds in the presence of multiple C-F bonds is of importance in organic synthesis and drug discovery. Herein, we describe the activation of C-F bonds via multiphoton photoredox catalysis to selectively produces a series of hydrodefluorinated compounds by simply tuning the reaction conditions. Moreover, this protocol was successfully applied to the late-stage functionalization of different drug-derivatives and the corresponding mono-, di-, and tri-defluorinated products were obtained in good to excellent yields. A detailed mechanistic investigation provides insight into the unprecedented hydrodefluorination pathway. (c) 2024 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.