Organic Chemistry

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.


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Supplementary material

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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).