One-pot C(sp3)–H difluoroalkylation of tetrahydroisoquinolines and isochromans via electrochemical oxidation and organozinc alkylation

Abstract

The C(sp³)–H difluoroalkylation for the introduction of carbonylated CF₂ groups into tetrahydroisoquinolines (THIQs) and isochromans has been achieved by using electrochemical oxidation and organozinc alkylation. This one-pot process proceeded smoothly under transition-metal catalyst- and chemical oxidant-free conditions, and the desired products were obtained in good to high yields with a broad scope, except for N-Boc-THIQ. In addition, the gram-scale experiment successfully demonstrated the promising scalability. This is the first example of an electrochemical method for C(sp³)–H difluoroalkylation of amines and ethers.