Max-Planck-Institut für Kohlenforschung , Kaiser-Wilhelm Platz 1, Mülheim an der Ruhr 45470, Germany.
J Am Chem Soc. 2016 Nov 9;138(44):14740-14749. doi: 10.1021/jacs.6b09179. Epub 2016 Oct 25.
The heterodimerizing self-assembly between a phosphoric acid catalyst and a carboxylic acid has recently been established as a new activation mode in Brønsted acid catalysis. In this article, we present a comprehensive mechanistic investigation on this activation principle, which eventually led to its elucidation. Detailed studies are reported, including computational investigations on the supramolecular heterodimer, kinetic studies on the catalytic cycle, and a thorough analysis of transition states by DFT calculations for the rationalization of the catalyst structure-selectivity relationship. On the basis of these investigations, we developed a kinetic resolution of racemic epoxides, which proceeds with high selectivity (up to s = 93), giving the unreacted epoxides and the corresponding protected 1,2-diols in high enantiopurity. Moreover, this approach could be advanced to an unprecedented stereodivergent resolution of racemic α-chiral carboxylic acids, thus providing access to a variety of enantiopure nonsteroidal anti-inflammatory drugs and to α-amino acid derivatives.
磷酸催化剂和羧酸之间的杂二聚自组装最近被确立为 Brønsted 酸催化中的一种新的激活模式。在本文中，我们对这一激活原理进行了全面的机理研究，最终阐明了这一原理。详细的研究包括对超分子杂二聚体的计算研究、催化循环的动力学研究以及通过 DFT 计算对过渡态的深入分析，以合理推断催化剂结构选择性关系。在此基础上，我们开发了一种对映选择性动力学拆分外消旋环氧化物的方法，该方法具有很高的选择性（高达 s = 93），可得到高对映纯度的未反应环氧化物和相应的保护 1,2-二醇。此外，该方法可以进一步扩展到前所未有的外消旋α-手性羧酸的立体发散拆分，从而获得各种手性非甾体抗炎药和α-氨基酸衍生物。
