Electroreductive Cross-Electrophile Coupling of Polyfluoroarenes for the Synthesis of Polyfluoroarylmethanes and Polyfluorinated Biaryls

Abstract

Polyfluoroarenes are essential motifs in pharmaceuticals, agrochemicals, and materials science, yet their direct functionalization remains challenging due to the high inertness of C–F bonds and the frequent requirement for harsh or costly conditions. Herein, we report a scalable, noble-metal-free electrochemical cross-electrophile coupling (eXEC) method that enables direct coupling of polyfluoroarenes with diverse electrophiles under mild conditions. This strategy allows the construction of structurally diverse polyfluoro di-, tri-, and tetraarylmethanes via the coupling of polyfluoroarenes with arylmethanols or benzylic (pseudo)halides. Furthermore, nickel-catalyzed electrochemical C(sp²)–C(sp²) coupling expands the method’s applicability to aryl electrophiles, affording valuable polyfluorinated biaryls. The protocol exhibits broad substrate scope, excellent functional group tolerance, suitability for late-stage modification, and scalability to 10 g scale. This work provides a versatile platform for accessing highly functionalized polyfluoroarenes with significant potential in drug discovery, materials development, and industrial synthesis.