Regioselective Spirocyclopropyl C–C Cleavage and Ketene–Imine-Triggered Skeletal Rearrangement for the Synthesis of α-Carboline

A reaction of regioselective spirocyclopropyl ring opening coupled with a specific pathway of a cascade transformation sequence governed by in situ-generated ketene-imine has been discovered, which enables efficient construction of poly-substituted/functionalized α-carbolines. Although controlling the regioselectivity of cyclopropyl C-C bond cleavage is always challenging and a spirocyclopropyl-iminoindoline skeleton is susceptible to undergoing minimally four reaction pathways, our developed reaction method mediated by BF₃·OEt₂ promotes regioselective C-C bond cleavage and molecular skeleton rearrangement and produces α-carbolines in up to 92% yield, while exhibiting a broad substrate scope. With control experiments and spectroscopic and spectrometric studies, a mechanism of the reaction has been proposed. The extended synthetic applications of the reaction for the preparation of drug motif-containing skeletons and installation of synthesized products into drug molecules have been explored.