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

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.