贵州大学伍星星研究团队报道了制备P(V)-立体性磷化合物的有机催化不对称缩合法。相关研究成果发表在2024年11月26日出版的《美国化学会杂志》。

富含对映体的磷（V）-立体化合物，以五价磷原子为立体中心，在各种天然产物、药物、生物活性分子和催化剂/配体中至关重要。虽然已经开发了一些立体选择性合成方法，但通过催化产生磷（V）-杂原子键来实现磷原子的直接立体控制仍然是一个艰巨的挑战。

该文中，研究人员报道了一种有机催化不对称缩合策略，该策略采用了一种新的稳定原料次膦酸活化模式，通过形成混合次膦酸酐作为反应物种，以促进进一步的催化剂控制的不对称P-O键形成，包括通过辛可宁衍生的双功能催化剂与醇亲核试剂进行动态动力学不对称转化（DYKAT）过程。

由此产生的H-次膦酸酯中间体能够进一步的立体特异性衍生化，提供模块化路径获得具有显著抗菌活性的手性膦酸酯和膦酰胺酸酯的多样化库。此外，该合成平台促进了P-O/N与各种天然产物和药物的偶联，为医学和农用化学品的发现提供了有价值的工具。

附：英文原文

Title: Synthesis of P(V)-Stereogenic Phosphorus Compounds via Organocatalytic Asymmetric Condensation

Author: Fengrui Che, Junyuan Hu, Minghong Liao, Zhongfu Luo, Hongyan Long, Benpeng Li, Yonggui Robin Chi, Xingxing Wu

Issue&Volume: November 26, 2024

Abstract: Enantioenriched phosphorus(V)-stereogenic compounds, featuring a pentavalent phosphorus atom as the stereogenic center, are crucial in various natural products, drugs, bioactive molecules, and catalysts/ligands. While a handful of stereoselective synthetic approaches have been developed, achieving direct stereocontrol at the phosphorus atom through catalytic generation of phosphorus(V)-heteroatom bonds continues to be a formidable challenge. Here, we disclose an organocatalytic asymmetric condensation strategy that employs a novel activation mode of stable feedstock phosphinic acids by the formation of mixed phosphinic anhydride as the reactive species to facilitate further catalyst-controlled asymmetric P–O bond formations, involving a dynamic kinetic asymmetric transformation (DYKAT) process with alcohol nucleophiles via a cinchonidine-derived bifunctional catalyst. The resulting H-phosphinate intermediates allow further stereospecific derivatizations, affording modular access to a diverse library of chiral phosphonates and phosphonamidates with notable antibacterial activity. Furthermore, this synthetic platform facilitates P–O/N coupling with various natural products and drugs, presenting a valuable tool for medicine and agrochemical discovery.

DOI: 10.1021/jacs.4c11956

Source: https://pubs.acs.org/doi/abs/10.1021/jacs.4c11956