Bioinspired Peptide‐Phosphonium Salt Catalysis Unlocks Asymmetric Desymmetrization of Phosphoryl Acids: Programmable Synthesis of P(V)‐Stereogenic Molecules

作者：Yang Siqun, Xingjie Luo, Zanjiao Liu, Siqiang Fang, Jia‐Hong Wu, Tianli Wang · 发表于：Angewandte Chemie International Edition · 年份：2025 · DOI：10.1002/anie.202510513 · 被引用次数：10 · 研究领域：Chemical Synthesis and Analysis、Asymmetric Hydrogenation and Catalysis、Asymmetric Synthesis and Catalysis

Enantioselective desymmetrization of prochiral phosphorus(V) compounds represents a pivotal strategy for constructing P(V)-stereogenic skeletons, yet existing methods face limitations in structural diversification and metal-free catalytic systems. Here we disclose that a bioinspired peptide-phosphonium salt (PPS) catalytic system successfully enables precise desymmetrization of phosphinic acids through synergistic ion-pairing and hydrogen-bonding interactions. This strategy affords multifunctional platform molecules bearing P(V)-stereocenters with excellent enantiocontrol and broad compatibility (43 examples, up to 92% yield, up to >99% ee) at very low catalyst loading (1 mol%). Furthermore, the P(V)-chiral building blocks undergo stereospecific derivatization to access structurally diverse phosphinates (27 examples, up to 75% yield, up to >99% ee) and tertiary phosphine oxides (10 examples). Mechanistic studies reveal that the stereochemical origin is from a semi-enclosed chiral cavity, where dynamic electrostatic and hydrogen-bonding interactions synergistically orchestrate the stereodetermining transition state. The two-stage desymmetrization-derivatization process establishes a versatile platform for modular synthesis of valuable P(V)-stereogenic pharmaceuticals and functional molecules.