Liu Xin, Zhou Yun, Qi Xiaotian, Li Renhe, Liu Peng, Dong Guangbin
Department of Chemistry, University of Chicago, Chicago, IL 60637, USA.
Department of Chemistry, University of Pittsburgh, Pittsburgh, PA 15260, USA.
Angew Chem Int Ed Engl. 2023 Oct 23;62(43):e202310697. doi: 10.1002/anie.202310697. Epub 2023 Sep 15.
Methods that can simultaneously install multiple different functional groups to heteroarenes via C-H functionalizations are valuable for complex molecule synthesis, which, however, remain challenging to realize. Here we report the development of vicinal di-carbo-functionalization of indoles in a site- and regioselective manner, enabled by the palladium/norbornene (Pd/NBE) cooperative catalysis. The reaction is initiated by the Pd(II)-mediated C3-metalation and specifically promoted by the C1-substituted NBEs. The mild, scalable, and robust reaction conditions allow for a good substrate scope and excellent functional group tolerance. The resulting C2-arylated C3-alkenylated indoles can be converted to diverse synthetically useful scaffolds. The combined experimental and computational mechanistic study reveals the unique role of the C1-substituted NBE in accelerating the turnover-limiting oxidative addition step.
通过碳氢键官能化反应同时向杂芳烃中引入多个不同官能团的方法，对于复杂分子的合成具有重要价值，但实现起来仍具有挑战性。在此，我们报道了一种以位点和区域选择性方式实现吲哚邻位双碳官能化的方法，该方法由钯/降冰片烯（Pd/NBE）协同催化实现。反应由钯（II）介导的C3金属化引发，并由C1取代的降冰片烯特异性促进。温和、可扩展且稳健的反应条件使得该反应具有良好的底物范围和出色的官能团耐受性。所得的C2芳基化C3烯基化吲哚可转化为多种具有合成用途的骨架。结合实验和计算的机理研究揭示了C1取代的降冰片烯在加速限速氧化加成步骤中所起的独特作用。
