香港大学黄重行团队报道了丙二酸酯的催化还原不对称反应。相关研究成果于2021年6月10日发表在《自然—化学》。

完全取代的含一对对映体官能团碳的去对称化是合成四元立体中心的一种实用策略，因为它划分了对映体选择和CC键形成的任务。二取代丙二酸酯作为去对称化反应的底物，由于其制备简单、模块化，以及手性单酯产物的高合成值，特别具有吸引力。

该文中，研究人员报道了一种带有四酸配体的双核锌配合物可以选择性地将丙二酸酯中的一个羰基氢化，从而得到α-季β-羟基酯，为不对称水解主题化羧酸酯酶提供了一个有前途的替代品。不对称还原具有良好的对映体控制性，可以区分空间相似的取代基和高选择性的双酯基序的底物。再加上丙二酸酯底物的多功能制备和还原后衍生化，非对称还原使得合成具有独特结构特征的各种四元立体中心成为可能。

附：英文原文

Title: Catalytic reductive desymmetrization of malonic esters

Author: Pengwei Xu, Zhongxing Huang

Issue&Volume: 2021-06-10

Abstract: Desymmetrization of fully substituted carbons with a pair of enantiotopic functional groups is a practical strategy for the synthesis of quaternary stereocentres, as it divides the tasks of enantioselection and CC bond formation. The use of disubstituted malonic esters as the substrate of desymmetrization is particularly attractive, given their easy and modular preparation, as well as the high synthetic values of the chiral monoester products. Here, we report that a dinuclear zinc complex with a tetradentate ligand can selectively hydrosilylate one of the carbonyls of malonic esters to give α-quaternary β-hydroxyesters, providing a promising alternative to the desymmetric hydrolysis using carboxylesterases. The asymmetric reduction features excellent enantiocontrol that can differentiate sterically similar substituents and high chemoselectivity towards the diester motif of substrates. Together with the versatile preparation of malonic ester substrates and post-reduction derivatization, the desymmetric reduction has enabled the synthesis of a diverse array of quaternary stereocentres with distinct structural features.

DOI: 10.1038/s41557-021-00715-0

Source: https://www.nature.com/articles/s41557-021-00715-0