Ground-State Flavin-Dependent Enzymatic Catalysis for Formal Hydrophosphinylation of Alkenes

Abstract Organophosphorus compounds constitute an important class of functional molecules with broad relevance in synthesis, catalysis, and medicinal chemistry. Despite their importance, biocatalytic C–P bond formation remains rare, with only a limited number of examples identified from natural product biosynthesis. Here we report a previously unexplored biocatalytic platform for C–P bond construction through flavin-dependent enzyme-catalyzed intermolecular radical coupling involving phosphinoyl radical intermediates. The transformation is directly driven by ground-state FMNhq, and protein engineering enables stereodivergent control over the formal hydrophosphinylation of aryl-substituted alkenes, acrylate-derived electron-deficient alkenes, and representative unactivated alkenes. This work brings phosphinoyl radical chemistry into flavin-dependent radical biocatalysis and provides a new strategy for the asymmetric synthesis of organophosphorus compounds.