Division of Chemistry and Chemical Engineering , California Institute of Technology , Pasadena , California 91125 , United States.
J Am Chem Soc. 2019 Sep 18;141(37):14864-14869. doi: 10.1021/jacs.9b07875. Epub 2019 Sep 9.
Transition-metal catalysis has the potential to address shortcomings in the classic S2 reaction of an amine with an alkyl electrophile, both with respect to reactivity and to enantioselectivity. In this study, we describe the development of a user-friendly method (reaction at room temperature, with commercially available catalyst components) for the enantioconvergent nucleophilic substitution of racemic secondary alkyl halides (α-iodolactams) by indoles. Mechanistic studies are consistent with the formation of a copper(I)-indolyl complex that reacts at different rates with the two enantiomers of the electrophile, which interconvert under the reaction conditions (dynamic kinetic resolution). This investigation complements earlier work on enantioconvergent N-alkylation, supporting the premise that this important challenge can be addressed by a range of strategies.
过渡金属催化有可能解决经典的胺与烷基亲电试剂的 S2 反应的缺点，无论是在反应性还是对映选择性方面。在这项研究中，我们描述了一种用户友好的方法（在室温下反应，使用商业可得的催化剂成分）的发展，用于通过吲哚对消旋仲烷基卤化物（α-碘代内酰胺）进行对映选择性亲核取代。 机理研究与铜（I）-吲哚络合物的形成一致，该络合物以不同的速率与亲电试剂的两种对映异构体反应，在反应条件下（动态动力学拆分）相互转化。 这项研究补充了早期关于对映选择性 N-烷基化的工作，支持了这样一个前提，即这一重要挑战可以通过一系列策略来解决。
