BF3-Catalyzed Intramolecular Fluorocarbamoylation of Alkynes via Halide Recycling

19 April 2023, Version 2
This content is a preprint and has not undergone peer review at the time of posting.


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.


Lewis acid catalysis
carbamoyl fluorides

Supplementary materials

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


Comments are not moderated before they are posted, but they can be removed by the site moderators if they are found to be in contravention of our Commenting Policy [opens in a new tab] - please read this policy before you post. Comments should be used for scholarly discussion of the content in question. You can find more information about how to use the commenting feature here [opens in a new tab] .
This site is protected by reCAPTCHA and the Google Privacy Policy [opens in a new tab] and Terms of Service [opens in a new tab] apply.