Additive-Controlled Regioswitching in Ni-Catalyzed Enantioselective Hydrophosphination of Unactivated Alkenes

Transition metal-catalyzed asymmetric hydrophosphination of unsaturated bonds offers the most direct route to chiral organophosphorus compounds. However, unactivated double bonds remain a longstanding challenge in this field due to their inherent low reactivity and the difficulty in achieving precise enantio- and regiocontrol. Herein, we report an amide-assisted asymmetric and regiodivergent hydrophosphination of unactivated alkenes catalyzed by a synergistic Ni(cod)₂/BenzP and Brønsted acid system. Mechanistic studies and density functional theory calculations reveal that the weak noncovalent interactions between the amide substrate and the ligand are critical for selectivity. Diverging from conventional migratory insertion pathways, this strategy leverages distinct hydronickelation pathways mediated solely by pyridine-3-sulfonic acid or 3,5-difluorophenol additives, enabling precise control over enantioselectivity and regioselectivity. All of the branched and linear products are accessed with excellent regiodivergence, showcasing a versatile platform for the modular synthesis of chiral organophosphorus compounds.