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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. [ABSTRACT FROM AUTHOR]

A new reaction mode of palladium/norbornene (Pd/NBE) cooperative catalysis is reported involving the selective coupling of two different carbon‐based electrophiles for vicinal double C‐H functionalization of five‐membered heteroarenes in a site‐selective and redox‐neutral manner. The key is to use alkynyl bromides as the second electrophile, which allows vicinal difunctionalization of a wide range of heteroarenes including pyrroles, thiophenes and furans at their C4 and C5 positions. One‐ or two‐step tetrafunctionalizations of simple pyrrole and thiophene have also been realized. The C2‐substituted NBEs prove most effective in these reactions, and the mechanistic exploration discloses the origin of the high selectivity of this transformation. Synthetic utility of this method has been exemplified in the concise preparations of thiophene‐containing organic materials and a protein kinase inhibitor analogue. Preliminary success has also been achieved in a direct annulation event, using a tethered ketone as the second electrophile. [ABSTRACT FROM AUTHOR]