Epton Ryan G, Unsworth William P, Lynam Jason M
Department of Chemistry, University of York, Heslington, York, YO10 5DD, U.K.
Organometallics. 2022 Feb 28;41(4):497-507. doi: 10.1021/acs.organomet.2c00035. Epub 2022 Feb 10.
A convenient and mild protocol for the gold-catalyzed intermolecular coupling of substituted indoles with carbonyl-functionalized alkynes to give vinyl indoles is reported. This reaction affords 3-substituted indoles in high yield, and in contrast to the analogous reactions with simple alkynes which give indolemethanes, only a single indole is added to the alkyne. The protocol is robust and tolerates substitution at a range of positions of the indole and the use of ester-, amide-, and ketone-substituted alkynes. The use of 3-substituted indoles as substrates results in the introduction of the vinyl substituent at the 2-position of the ring. A combined experimental and computational mechanistic study has revealed that the gold catalyst has a greater affinity to the indole than the alkyne, despite the carbon-carbon bond formation step proceeding through an η(π)-alkyne complex, which helps to explain the stark differences between the intra- and intermolecular variants of the reaction. This study also demonstrated that the addition of a second indole to the carbonyl-containing vinyl indole products is both kinetically and thermodynamically less favored than in the case of more simple alkynes, providing an explanation for the observed selectivity. Finally, a highly unusual gold-promoted alkyne dimerization reaction to form a substituted gold pyrylium salt has been identified and studied in detail.
报道了一种简便温和的方法，用于金催化取代吲哚与羰基官能化炔烃的分子间偶联反应，以生成乙烯基吲哚。该反应能高产率地得到3-取代吲哚，与简单炔烃发生类似反应生成吲哚甲烷不同，该反应中仅向炔烃中添加了一个吲哚。该方法具有较强的适应性，能耐受吲哚一系列位置上的取代以及酯基、酰胺基和酮基取代炔烃的使用。使用3-取代吲哚作为底物会导致乙烯基取代基引入到环的2-位。一项结合实验和计算的机理研究表明，尽管碳-碳键形成步骤是通过η(π)-炔烃配合物进行的，但金催化剂对吲哚的亲和力比对炔烃的更大，这有助于解释该反应分子内和分子间变体之间的显著差异。该研究还表明，与更简单的炔烃相比，向含羰基的乙烯基吲哚产物中添加第二个吲哚在动力学和热力学上都不太有利，这为观察到的选择性提供了解释。最后，已鉴定并详细研究了一种非常特殊的金促进炔烃二聚反应，该反应生成一种取代的金吡喃鎓盐。
