Asymmetric Synthesis of Diverse P(V) Compounds Bearing a C–P Bond via Desymmetrization of Phosphonic Dichlorides Catalyzed by a Chiral Bicyclic Imidazole

Chiral phosphorus(V) compounds bearing one or two C-P bonds exhibit significant utility in pharmacy and catalysis. Although several established methods enable stereoselective access to these P-stereogenic compounds, achieving direct enantiocontrol at phosphorus via catalytic P(V)-heteroatom bond formation remains challenging. Herein, we present a highly efficient strategy to synthesize such chiral P(V) compounds through the asymmetric desymmetrization of phosphonic dichlorides catalyzed by a readily accessible bifunctional chiral bicyclic imidazole. The synergistic combination of Lewis base catalysis and hydrogen bond catalysis is responsible for the high reactivity and stereoselectivity. The one-pot sequential process combining the catalytic desymmetrization and the enantiospecific SN2 displacement delivers a large number of chiral P(V) compounds with excellent yields and enantioselectivities. This protocol establishes a versatile platform for the concise synthesis of structurally diverse P-chirogenic motifs relevant to high-value bioactive molecules.