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Palladium/Norbornene-Catalyzed Direct Vicinal Di-Carbo-Functionalization of Indoles: Reaction Development and Mechanistic Study |
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| Authors: | Xin Liu Yun Zhou Xiaotian Qi Renhe Li Peng Liu Guangbin Dong |
| Institution: | 1. Department of Chemistry, University of Chicago, Chicago, IL 60637 USA
These authors contributed equally to this work.;2. Department of Chemistry, University of Pittsburgh, Pittsburgh, PA 15260 USA These authors contributed equally to this work.;3. Department of Chemistry, University of Chicago, Chicago, IL 60637 USA;4. Department of Chemistry, University of Pittsburgh, Pittsburgh, PA 15260 USA |
| Abstract: | 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. |
| Keywords: | Arylation Difunctionalization Indole Norbornene Palladium |