Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao, 266071, China.
University of Chinese Academy of Sciences, Beijing, 101408, China.
Angew Chem Int Ed Engl. 2021 Jun 14;60(25):13871-13876. doi: 10.1002/anie.202103395. Epub 2021 May 11.
Palladium-catalyzed direct C-H activation of indole benzenoid moiety has been achieved in the past decade. However, palladium-catalyzed remote C-H activation of indoles is rare. Herein, we report a challenging palladium-catalyzed remote C4-H phosphonylation of indoles by a radical approach. The method provides access to a series of C4-phosphonylated indoles, including tryptophan and tryptophan-containing dipeptides, which are typically inaccessible by direct C4-H activation due to its heavy reliance on C3 directing groups. Notably, unexpected C6-phosphonylated indoles were obtained through blocking of the C4 position. The preliminary mechanistic studies indicated that the reactions may proceed via a C7-palladacycle/remote-activation process. Based on the strategy, examples of remote C4-H difluoromethylation with BrCF COOEt are also presented, suggesting that the strategy may offer a general blueprint for other cross-couplings.
过去十年中，钯催化吲哚苯并部分的直接 C-H 活化已经实现。然而，钯催化吲哚的远程 C-H 活化很少见。在此，我们报告了一种通过自由基途径实现的具有挑战性的钯催化吲哚远程 C4-H 膦酰化反应。该方法可用于一系列 C4-膦酰化吲哚，包括色氨酸和色氨酸二肽，由于其严重依赖 C3 导向基团，直接 C4-H 活化通常无法获得这些化合物。值得注意的是，通过阻断 C4 位还获得了意想不到的 C6-膦酰化吲哚。初步的机理研究表明，反应可能通过 C7-钯环/远程活化过程进行。基于该策略，还展示了用 BrCF COOEt 进行远程 C4-H 二氟甲基化的例子，这表明该策略可能为其他交叉偶联反应提供了一个通用蓝图。
