Stereogenic P(V) platform construction via streamlined installation

Molecules bearing a fully heteroatom-substituted phosphorus(V) stereocenter exist ubiquitously in medicines, agroscience and catalysis fields. Due to the lack of efficient and robust catalytic asymmetric methods, approaches to achieve fully heteroatom-substituted phosphorus(V) stereocenters usually rely on conventional chiral auxiliary control and resolution pathways. Recent catalytic protocols are built on tedious stepwise synthesis from complex P(V) precursors. Here, we report a streamlined installation strategy to achieve various fully heteroatom-substituted P(V) stereocenters from simple POCl₃. Thirteen types of N-, O-, and S-based nucleophiles are adopted for the preparation of six types of P(V) stereocenters. Over 100 examples are provided to show the generality and reliability of the synthetic method. This protocol is also applied to the concise synthesis of twelve bioactive molecules and analogs. The antifungal evaluations of the prepared compounds reveal two new fungicide candidates and also suggest the importance of the stereochemistry for bioactivity.