Visible-Light-Mediated C(sp ³ )–Se Coupling: Synthesis of GPx-Mimic Unsymmetrical Aryl–Secondary Alkyl Selenoether Antioxidants

We report a visible-light-mediated, metal- and base-free C(<i>sp</i>³)-Se cross-coupling of Hantzsch esters with diaryl diselenides, providing straightforward access to biologically potent unsymmetrical aryl-<i>secondary</i> alkyl selenoethers. Such compounds often cannot be accessed by conventional TM-catalyzed or base-mediated methods, which are largely limited to simple aryl-<i>primary</i> alkyl selenoethers due to steric hindrance at the Se center and poor functional group tolerance. Moreover, the efficiency of this open-air protocol even under sunlight and the greener ethyl acetate solvent makes it a practical and sustainable alternative to the traditional approaches. Mechanistic studies reveal that the inexpensive organic photocatalyst-induced <i>secondary</i> alkyl radicals add to diaryl diselenides, a pathway that could not be accessed under traditional methods because of steric crowding at the Se center. The resulting selenoethers were further evaluated as glutathione peroxidase (GPx) mimics, efficiently catalyzing reduction of hydrogen peroxide with benzenethiol and exhibiting efficient GPx-like activity compared to benchmark Se-antioxidants: diphenyl diselenide and ebselen.