Zheng Chenxu, Jiang Zhi-Jiang, Jin Ke, Wang Qian, Bai Jian-Fei, Xu Gang, Gao Zhanghua
NingboTech-Cuiying Joint Laboratory of Stable Isotope Technology, School of Biological and Chemical Engineering, NingboTech University, Ningbo 315100, P. R. of China.
School of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310058, P. R. of China.
J Org Chem. 2023 Dec 15;88(24):17164-17171. doi: 10.1021/acs.joc.3c02030. Epub 2023 Nov 22.
As a representative scaffold of alkaloids, indoles have been extensively subjected to deuteration, but the regioselective C4 labeling has not been achieved due to its low reactivity. In this work, a Pd-catalyzed deuterium labeling at the indole's C4 position has been developed under the strategy of transient directing, using DO as a deuterium source. The substituent effect is found to be crucial in facilitating this H/D exchange process, where the reversing C-D bond formation favors an electron-enriched ligation contrary to its C-H halogenation counterpart.
作为生物碱的代表性骨架，吲哚已被广泛地进行氘代，但由于其低反应活性，尚未实现区域选择性的C4标记。在这项工作中，利用DO作为氘源，通过瞬态导向策略开发了一种钯催化的吲哚C4位氘代反应。发现取代基效应对于促进这种H/D交换过程至关重要，其中C-D键的反向形成有利于电子富集的连接，这与其C-H卤化反应相反。
