Carboxylic Acid Promoted Single-step Indole Construction from Simple Anilines and Ketones via Aerobic Cross-Dehydrogenative Coupling
Carboxylic Acid Promoted Single-step Indole Construction from Simple Anilines and Ketones via Aerobic Cross-Dehydrogenative Coupling
复制标题
羧酸促进简单苯胺和酮通过有氧交叉脱氢偶联一步构建吲哚
DOI：
10.1021/acs.joc.8b02180
复制
发表时间：
2018
影响因子：
3.6
通讯作者：
Zhiyan Xiao
中科院分区：
文献类型：
--
作者：
Long Ren;Guanglei Nan;Yongcheng Wang;Zhiyan Xiao
交叉偶联（CDC）反应是合成吲哚的有效途径。然而，大多数CDC方法需要特殊的底物，并且固有基团的存在限制了进一步转化的通用性。本文开发了一种羧酸促进的有氧催化体系，用于由简单苯胺和酮一步合成吲哚。这种多功能系统的特点是广泛的底物范围和使用环境氧气作为氧化剂，是方便和经济的实验室和工业应用。在C-3位的不稳定氢和在C-2位的高度可转化的羰基的存在使得吲哚在不同背景下成为有机合成的通用构件。基于密度泛函理论（DFT）的计算研究表明，速率决定步骤是羧酸辅助的底物缩合，而不是芳基C-H的官能化。因此，经由亚胺中间体的途径被认为是优选的机制。与一般的推论相反，原位形成的亚胺，而不是其烯胺异构体，被认为参与了α-Me的第一个配体交换和随后的碳钯化，这为这种吲哚化机制提供了新的线索。
The cross-dehydrogenative coupling (CDC) reaction is an efficient strategy for indole synthesis. However, most CDC methods require special substrates, and the presence of inherent groups limits the versatility for further transformation. A carboxylic acid-promoted aerobic catalytic system is developed herein for a single-step synthesis of indoles from simple anilines and ketones. This versatile system is featured by the broad substrate scope and the use of ambient oxygen as an oxidant and is convenient and economical for both laboratory and industry applications. The existence of the labile hydrogen at C-3 and the highly transformable carbonyl at C-2 makes the indoles versatile building blocks for organic synthesis in different contexts. Computational studies based on the density functional theory (DFT) suggest that the rate-determining step is carboxylic acid-assisted condensation of the substrates, rather than the functionalization of aryl C–H. Accordingly, a pathway via imine intermediates is deemed to be the preferred mechanism. In contrast to the general deduction, the in situ formed imine, instead of its enamine isomer, is believed to be involved in the first ligand exchange and later carbopalladation of the α-Me, which shed new light on this indolization mechanism.