Tunable molecular editing of indoles with fluoroalkyl carbenes

Building molecular complexity from simple feedstocks through peripheral and skeletal editing is central to modern organic synthesis. Nevertheless, a controllable strategy that can modify both the core skeleton and periphery of an aromatic heterocycle with a common substrate remains undeveloped, despite its potential to maximize structural diversity and applications. Here we report a fluoroalkyl carbene-initiated chemodivergent molecular editing of indoles, allowing both skeletal and peripheral editing by trapping electrophilic fluoroalkyl carbene generated in situ from fluoroalkyl N-triftosylhydrazones. A variety of fluorine-containing N-heterocyclic scaffolds could be efficiently achieved through the tunable chemoselective editing reactions at skeleton or periphery of the indole, including one-carbon insertion, C3−H gem-difluoroolefination, tandem cyclopropanation/N1−H gem-difluoroolefination, and cyclopropanation. Mechanistic experiments and computations have probed the reaction mechanism and the origins of chemo- and regioselectivity.