Photoinduced Palladium-Catalyzed Defluorinative Cascade Reaction of Unactivated Alkenes with Trifluoromethylarenes

The development of efficient protocols for the construction of difluoromethylene (CF2) units has remained at the forefront of synthetic organic chemistry, owing to their widespread applications in pharmaceuticals, organic synthesis, and material science. Herein, we report a palladium-catalyzed redox-neutral difluoromethylation reaction of N-indolyl-tethered unactivated alkenes, via a visible-light-promoted defluorinative cascade of readily available trifluoromethylarenes. Mechanistic studies suggested that the reaction is likely to proceed through an efficient homolytic cleavage of a C(sp3)-F bond in ArCF3 by photoexcited palladium(0) species, to generate the corresponding difluorobenzyl radical that undergoes a rapid radical addition to the terminal alkenyl carbon, with the resulting carbon-centered radical being trapped by the tethered indolyl unit via a 5-exo-trig cyclization process. Notably, this methodology features a broad substrate scope, good functional group tolerance, and excellent regioselectivity, thus providing straightforward access to a diverse array of medicinally interesting ArCF2-functionalized polycyclic indoles under mild conditions.