Catalytic Enantioselective Nucleophilic Desymmetrization at Phosphorus(V): A Three-Phase Strategy for Modular Preparation of Phosphoramidates
Xiao‐kang Nie, Shiqi Zhang, Xuyang Wang, Wanting Yang, Zhang Xia, Shaofeng Chen, Xin Cui, Zhuo Tang, Guangxun Li
Abstract
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.