中国科学院上海有机化学研究所麻生明团队近日研究了经由配体接力策略DACH-ZYC-Phos/钯催化的仲膦氧化物高烯丙基化不对称反应。2025年7月7日出版的《美国化学会志》发表了这项成果。

手性烯丙基膦氧化物在有机合成中具有重要的应用价值，可作为高效的催化剂、配体和多用途合成子。然而，过渡金属催化这些化合物的不对称合成的发展仍未得到探索，主要是因为膦氧化物容易变异构成三价R¹R²P-OH，这可能会通过强配位相互作用严重失活过渡金属催化剂。

研究组采用配体接力策略解决了Pd催化丙炔苯甲酸酯与仲磷氧化物（SPO）的对映选择性偶联反应中的这一挑战，从而获得了手性高ee的三取代烯基膦氧化物。配体接力方案包括钯催化剂与现成的三苯基膦的初始配位，随后与可拉伸的手性配体DACH-ZYC-Phos-C1 （L26）进行动态配体交换，而PPh3在这种转化中不作为钯催化剂的非手性配体。

研究组通过对烯基膦氧化物的还原，得到了高ee的手性三价有机膦。力学研究揭示了动力学分辨的本质。DFT计算为观察到的高对映选择性和优越的催化效率提供了机制基础，这是由配体L26通过空间排斥力选择性地破坏不利的氧化加成过渡态来控制的。

附：英文原文

Title: DACH-ZYC-Phos/Pd-Catalyzed Enantioselective Allenylation of Secondary Phosphine Oxides via Ligand Relay

Author: Zhaoqiang Chen, Huanan Wang, Ping Du, Jiaao Zhao, Xue Zhang, Hui Qian, Junliang Zhang, Shengming Ma

Issue&Volume: July 7, 2025

Abstract: Chiral allenyl phosphine oxides hold significant application value in organic synthesis, serving as efficient catalysts, ligands, and versatile synthons. However, the development of transition metal-catalyzed asymmetric synthesis for these compounds remains unexplored, primarily due to the facile tautomerization of phosphine oxides into trivalent R1R2P–OH species, which may severely deactivate transition metal catalysts through strong coordination interactions. Herein, a ligand relay strategy has been applied to address this challenge in the Pd-catalyzed enantioselective coupling reactions of propargylic benzoates and secondary phosphine oxides (SPOs) to afford chiral trisubstituted allenyl phosphine oxides with high ee. The ligand relay protocol involves the initial coordination of a palladium catalyst with readily available triphenylphosphine, followed by dynamic ligand exchange with the stretchable chiral ligand DACH-ZYC-Phos-C1 (L26), while PPh3 does not work as a nonchiral ligand for palladium catalysts in this transformation. Chiral trivalent organophosphines with high ee have been obtained upon the reduction of allenyl phosphine oxides. Mechanistic studies revealed the nature of the kinetic resolution. DFT calculations provide a mechanistic rationale for the observed high enantioselectivity and superior catalytic efficiency, which is governed by the ligand L26 through steric repulsions that selectively destabilize the disfavored oxidative addition transition states.

DOI: 10.1021/jacs.5c07465

Source: https://pubs.acs.org/doi/abs/10.1021/jacs.5c07465