Defluorinative C−O Coupling between Trifluoromethylarenes and Alcohols via Copper Photoredox Catalysis

Abstract

Fluorine-containing compounds have shown unparalleled impacts in the realm of functional molecules, and the ability to prepare novel structures has been crucial in unlocking new properties for pharmaceutical and materials science. Herein, we report a copper-catalyzed, photoinduced defluorinative C‒O coupling between trifluoromethylarenes and alcohols. This method allows for direct access to a wide selection of difluorobenzylether (ArCF2OR) molecules, including a com-pound displaying liquid crystal behavior. Through slight modification of the protocol, we were able to generate ArCF2I products, another class of synthetically useful fluorine-bearing molecules. Comprehensive mechanistic investigations first suggested ArCF2I as a reservoir to steadily supply the key ArCF2• radical species. Furthermore, experimental evi-dence supported a mechanism consisting of two collaborative cycles: C‒F activation operated by a homoleptic Cu(I) co-ordinated by two bisphosphine ligands as the photocatalyst and C‒O coupling promoted by a Cu(I) ligated by a single bisphosphine ligand. The critical roles of the two salt additives, lithium iodide and zinc acetate, in orchestrating the two cycles were also elucidated. This dual-role copper catalyst demonstrates the power of base metal photoredox catalysis in achieving both substrate activation and chemical bond formation via a single catalytic system.