BF3-Catalyzed Intramolecular Fluorocarbamoylation of Alkynes via Halide Recycling

A BF3-catalyzed atom-economical fluorocarbamoylation reaction of alkyne-tethered carbamoyl fluorides is reported. The catalyst acts as both a fluoride source and Lewis acid activator, enabling the formal insertion of alkynes into strong C–F bonds through a halide recycling mechanism. The developed method provides access to 3-(fluoromethylene)oxindoles and γ-lactams with excellent stereoselectivity, including fluorinated derivatives of known protein kinase inhibitors. Experimental and computational studies support a stepwise mechanism for the fluorocarbamoylation reaction involving a turnover-limiting cyclization step, followed by internal fluoride transfer from a BF3-coordinated carbamoyl adduct. For methylene oxindoles, a thermodynamically driven Z-E isomerization is facilitated by a transition state with aromatic character. In contrast, this aromatic stabilization is not relevant for γ-lactams, resulting in a higher barrier for isomerization and the exclusive formation of the kinetic Z-isomer.