Shi Qin, Hu Haiyan, Du Minxing, Sun Yajun, Li Yudong, Li Yuehui
State Key Laboratory for Oxo Synthesis and Selective Oxidation, Lanzhou Institute of Chemical Physics (LICP), Chinese Academy of Sciences, Lanzhou 730000, P. R. China.
University of Chinese Academy of Sciences, Beijing 100049, P. R. China.
Org Lett. 2023 Oct 6;25(39):7100-7104. doi: 10.1021/acs.orglett.3c02406. Epub 2023 Sep 28.
C-H methylation of heteroarenes (e.g., indoles, pyrroles, etc.) is frequently applied in the synthesis of drug/biorelated compounds. We herein report the use of CO/H as a methylation reagent for selective C-H methylation of indoles and pyrroles in the presence of cobalt/B(CF) cocatalysts. The Lewis acidic additive B(CF) is essential to achieving good reactivity for a broad scope of substituted indoles and pyrroles (20 examples, up to 92% yields). The C-H methylation is accomplished via the CO reduction/C-C bond formation/reduction sequence. Water is the only byproduct. This system based on the use of non-noble metal catalysts features an environmentally benign alternative for C-H methylation.
杂芳烃（如吲哚、吡咯等）的C-H甲基化常用于药物/生物相关化合物的合成。我们在此报道，在钴/B（CF）共催化剂存在下，使用CO/H作为甲基化试剂对吲哚和吡咯进行选择性C-H甲基化。路易斯酸性添加剂B（CF）对于实现广泛取代的吲哚和吡咯的良好反应性至关重要（20个例子，产率高达92%）。C-H甲基化通过CO还原/C-C键形成/还原序列完成。水是唯一的副产物。这种基于使用非贵金属催化剂的体系为C-H甲基化提供了一种环境友好的替代方法。
