Department of Chemistry and Shenzhen Grubbs Institute, Guangdong Provincial Key Laboratory of Catalysis, Southern University of Science and Technology, 518055, Shenzhen, China.
Nat Commun. 2022 Jun 7;13(1):3276. doi: 10.1038/s41467-022-31026-8.
Molecular recognition and self-assembly are often mediated by intermolecular forces involving aromatic π-systems. Despite the ubiquity of such interactions in biological systems and in the design of functional materials, the elusive nature of aromatic π interaction results in that they have been seldom used as a design element for promoting challenging chemical reactions. Described here is a well-engineered catalytic system into which non-covalent π interactions are directly incorporated. Enabled by a lone pair-π interaction and a π-π stacking interaction operating collectively, efficient chiral recognition is successfully achieved in the long-pursued dihydroxylation-based kinetic resolution. Density functional theory calculations shed light on the crucial role played by the lone pair-π interaction between the carbonyl oxygen of the cinchona alkaloid ligand and the electron-deficient phthalazine π moiety of the substrate in the stereoselectivity-determining transition states. This discovery serves as a proof-of-principle example showing how the weak non-covalent π interactions, if ingeniously designed, could be a powerful guide in attaining highly enantioselective catalysis.
分子识别和自组装通常是由涉及芳环π系统的分子间力介导的。尽管这种相互作用在生物系统和功能材料的设计中无处不在，但由于芳环π相互作用的难以捉摸的性质，它们很少被用作促进具有挑战性的化学反应的设计元素。这里描述的是一个经过精心设计的催化体系，其中直接包含非共价π相互作用。通过单独的一对-π相互作用和π-π堆积相互作用的共同作用，成功地实现了在长期追求的基于二羟化的动力学拆分中高效的手性识别。密度泛函理论计算揭示了手性金鸡纳生物碱配体的羰基氧和底物的缺电子酞嗪π部分之间的孤对-π相互作用在立体选择性决定过渡态中所起的关键作用。这一发现提供了一个原理性的例子，表明如果巧妙地设计弱的非共价π相互作用，它们可以成为获得高对映选择性催化的有力指导。
