BF3-Catalyzed Intramolecular Fluorocarbamoylation of Alkynes: Synthesis of 3-Fluoromethylene Oxindoles and γ-Lactams



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. Our proposed mechanism involves fluoride addition to the alkyne via a nucleophilic fluoroborate species, followed by cyclization onto the carbamoyl moiety with concomitant release of fluoride. The developed method provides access to 3-fluoromethylene oxindoles and γ-lactams with excellent stereoselectivity, including fluorinated derivatives of known protein kinase inhibitors.


Supplementary material

Supporting Information
Reaction optimization tables, experimental procedures for synthesis of starting materials and products, mechanistic studies, copies of 1H, 13C, and 19F NMR spectra for new com-pounds, and single crystal X-ray crystallography data for 2a¸ 4a, and 5aa (PDF).