BF₃-Catalyzed Intramolecular Fluorocarbamoylation of Alkynes via Halide Recycling

A BF3-catalyzed atom-economical fluorocarbamoylationreaction of alkyne-tethered carbamoyl fluorides is reported. The catalystacts as both a fluoride source and Lewis acid activator, thereby enablingthe formal insertion of alkynes into strong C-F bonds througha halide recycling mechanism. The developed method provides accessto 3-(fluoromethylene) oxindoles and gamma-lactams with excellentstereoselectivity, including fluorinated derivatives of known proteinkinase inhibitors. Experimental and computational studies supporta stepwise mechanism for the fluorocarbamoylation reaction involvinga turnover-limiting cyclization step, followed by internal fluoridetransfer from a BF3-coordinated carbamoyl adduct. For methyleneoxindoles, a thermodynamically driven Z-E isomerizationis facilitated by a transition state with aromatic character. In contrast,this aromatic stabilization is not relevant for gamma-lactams, whichresults in a higher barrier for isomerization and the exclusive formationof the Z-isomer.