McKnight, E. AliArora, RamonPradhan, EkadashiFujisato, Yuriko H.Ajayi, Ayonitemi, J.Lautens, MarkZeng, TaoLe, Christine M.2023-06-022023-06-022023-05-12J. Am. Chem. Soc. 2023, 145, 20, 11012–1101810.1021/jacs.3c03982http://hdl.handle.net/10315/41193A 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, thereby 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, which results in a higher barrier for isomerization and the exclusive formation of the Z-isomer.enAttribution-NonCommercial-NoDerivatives 4.0 Internationalfluorocarbamoylation, Lewis acid, halide recyclingArticle