Enantioconvergent Alkylations of Amines by Alkyl Electrophiles: Copper-Catalyzed Nucleophilic Substitutions of Racemic α-Halolactams by Indoles
Enantioconvergent Alkylations of Amines by Alkyl Electrophiles: Copper-Catalyzed Nucleophilic Substitutions of Racemic α-Halolactams by Indoles
复制标题
DOI：
10.1021/jacs.9b07875
复制
发表时间：
2019-09-18
影响因子：
15
通讯作者：
Fu, Gregory C.
中科院分区：
文献类型：
--
作者：
Bartoszewicz, Agnieszka;Matier, Carson D.;Fu, Gregory C.
过渡金属催化有潜力解决经典S(N)2反应中胺与烷基亲电试剂在反应活性和对映选择性方面的缺点。在这项研究中，我们描述了一种用户友好的方法的发展（反应在室温下，与市售的催化剂成分），以吲哚取代外消旋仲烷基卤化物（α -碘内酰胺）的对映会聚亲核。机理研究与铜(I)-吲哚基配合物的形成一致，该配合物与亲电试剂的两个对映体以不同的速率反应，在反应条件下相互转化（动态动力学分辨率）。这项研究补充了早期关于光诱导对映收敛的工作，支持了这一重要挑战可以通过一系列策略来解决的前提。
Transition-metal catalysis has the potential to address shortcomings in the classic S(N)2 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 (alpha-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 photoinduced enantioconvergent supporting the premise that this important challenge can be addressed by a range of strategies.