Palladium-catalyzed synthesis of indole-3-alkynones via direct carbonylation of indoles

A new method has been developed for the Pd-catalyzed direct carbonylation of indoles with phenylacetylenes. The process involved the initial iodination of the indole to afford the corresponding 3-iodo-indole, which was subsequently carbonylated with a variety of different alkynes using Pd(0) to yield the indole-3-alkynones. In contrast to the traditional Pd-catalyzed oxidative carbonylation strategy, which involves the Pd(II)-mediated activation of the aromatic C-H bonds, the aromatic C-H bonds in the current process were activated by iodine oxidation, eliminating the problems associated with the reduction of Pd(II) to Pd(0) under the CO atmosphere. Following an extensive screening process, Pd(OAc)2/CuI was identified as the most efficient catalyst system for the reaction in the presence of a base and iodine as an oxidant under mild conditions (0.2 MPa CO, 90 °C). The reaction provided the desired products in moderate to excellent isolated yields (up to 94%) and good tolerance to a variety of different functional groups. The structure of a representative alkynone product (3he) was unambiguously verified by X-ray single crystal structure analysis. Furthermore, the carbonylation products underwent a three-component reaction with sodium azide and benzyl bromide to give the corresponding 1,2,3-triazole analogues in the absence of any catalyst, thus expanding the synthetic application of the current methodology.

摘要 采用共合成法制备了一系列不同硅氨基含量的介孔氧化硅 SBA-15, 在其孔道中引入 Keggin 型钨磷酸, 且其含量随硅氨基含量的增加而增加. 考察了不同处理温度下杂多酸的热稳定性, 发现焙烧后钨物种能在 SBA-15 孔道内高度分散. 以 H2O2 为氧化剂, 研究了该催化剂在环己烯环氧化反应中的催化活性, 考察了杂多酸负载量和焙烧温度对催化活性的影响. 结果表明, 400 °C 处理后的钨磷酸催化剂具有高的反应活性和重复使用性能.

Graphical abstractAn efficient strategy has been developed for the synthesis of indole-3-alkynones involving sequential oxidative iodination and Pd(0)-catalyzed carbonylation processes. The products could be further applied to the synthesis of triazole derivatives.Figure optionsDownload full-size imageDownload as PowerPoint slide