Catalytic Enantioselective Nucleophilic Desymmetrization at Phosphorus(V): A Three-Phase Strategy for Modular Preparation of Phosphoramidates

作者：Xiao‐kang Nie, Shiqi Zhang, Xuyang Wang, Wanting Yang, Zhang Xia, Shaofeng Chen, Xin Cui, Zhuo Tang, Guangxun Li · 发表于：Journal of the American Chemical Society · 年份：2025 · DOI：10.1021/jacs.4c15587 · 被引用次数：37 · 研究领域：Asymmetric Hydrogenation and Catalysis、Organophosphorus compounds synthesis、Asymmetric Synthesis and Catalysis

Chiral phosphoramidates characterized by at least a P-N bond without a P-C bond demonstrate a significant applicative value within nucleoside phosphoramidate prodrugs. Despite the availability of methodologies for the selective construction of diverse chiral organophosphorus entities, achieving P-stereocenters solely substituted by heteroatoms often relies on diastereomeric synthesis. Here, we present a catalytic enantioselective desymmetrization strategy using an electrophilic phosphorus reagent with three leaving groups as a substrate, enabling a three-phase nucleophilic attack with various alcohols and amines. By generating a broad range of possible substituent combinations around phosphorus atoms, this synthetic strategy may expedite the synthesis and screening of biologically active phosphoramidates.