Chlorine-Free Synthesis of Axially Chiral Organophosphorus Compounds from White Phosphorus

Xinlei Huangfu, Wei Liu, Zhiyi Song, Junnian Wei, and Wen-Xiong Zhang*

Chem 2025, XX, XXXXX–XXXXX.

　　https://doi.org/10.1016/j.chempr.2025.102496

　　Chiral phosphoric acids (CPAs) and their derivatives play a crucial role in various fields, in particular asymmetric catalysis, chiral drug separation, and agrochemistry. However, despite their extensive applications, methods for their synthesis are quite limited. The traditional preparation of such axial chiral organophosphorus compounds (OPCs) predominantly follows a multi-step and environmentally hazardous chlorination pathway, starting from white phosphorus (P₄) through the classical P₄→PCl₃→OPCl₃ or SPCl₃→axial chiral OPCs sequence. The development of practical and mild strategies for the direct functionalization of P₄, bypassing the chlorination step, presents an attractive yet formidable challenge. Herein, we report the first chlorine-free synthesis of CPAs and their derivatives directly from P₄. This chlorine-free method directly from P₄ will innovate the synthesis of chiral OPCs and accelerate the revolution of green manufacturing of OPCs.