美国哈佛大学Jacobsen, Eric N.团队报道了阴离子结合法实现对映选择性过渡金属催化。相关研究成果发表在2023年2月14日出版的国际知名学术期刊《自然》。

不对称过渡金属催化是获取对映体富集分子的有力策略。用过渡金属催化剂诱导对映体选择性的经典策略依赖于手性配体的直接络合，以产生空间受限的反应性金属位点，该位点能够形成主要产物对映体，同时通过空间排斥有效抑制到次要对映体的途径。手性配体策略已被证明适用于多种高度对映选择性的过渡金属催化反应，但存在限制其成功适应的重要场景。

该文中，研究人员报告了一种在过渡金属催化反应中诱导对映体选择性的新方法，该方法依赖于中性氢键供体（HBD），其结合阳离子过渡金属配合物的阴离子，通过与其他非共价相互作用协同的离子配对实现对映体控制和速率增强。手性双硫脲HBD的协同阴离子结合效应被证明在分子内钌催化的炔丙基取代反应中导致高对映体选择性（高达99%对映体过量）。实验和计算机制研究揭示了HBD中缺少电子的芳烃组分与作为对映体诱导和加速效应基础的金属络合物之间的吸引人的相互作用。

附：英文原文

Title: Enantioselective Transition-Metal Catalysis via an Anion-Binding Approach

Author: Ovian, John M., Vojkov, Petra, Jacobsen, Eric N.

Issue&Volume: 2023-02-14

Abstract: Asymmetric transition-metal catalysis represents a powerful strategy for accessing enantiomerically enriched molecules1–3. The classical strategy for inducing enantioselectivity with transition-metal catalysts relies on direct complexation of chiral ligands to produce a sterically constrained reactive metal site that allows formation of the major product enantiomer while effectively inhibiting the pathway to the minor enantiomer through steric repulsion4. The chiral-ligand strategy has proven applicable to a wide variety of highly enantioselective transition-metal-catalyzed reactions, but important scenarios exist that impose limits to its successful adaptation. Here, we report a new approach for inducing enantioselectivity in transition-metal-catalyzed reactions that relies on neutral hydrogen-bond donors (HBDs)5,6 that bind anions of cationic transition-metal complexes to achieve enantiocontrol and rate enhancement through ion pairing in concert with other noncovalent interactions7–9. A cooperative anion-binding effect of a chiral bis-thiourea HBD is demonstrated to lead to high enantioselectivity (up to 99% enantiomeric excess) in intramolecular ruthenium-catalyzed propargylic substitution reactions10. Experimental and computational mechanistic studies reveal the attractive interactions between electron-deficient arene components of the HBD and the metal complex that underlie enantioinduction and the acceleration effect.

DOI: 10.1038/s41586-023-05804-3

Source: https://www.nature.com/articles/s41586-023-05804-3