BF3‑Catalyzed Intramolecular Fluorocarbamoylation of Alkynes via Halide Recycling
| dc.contributor.author | McKnight, E. Ali | |
| dc.contributor.author | Arora, Ramon | |
| dc.contributor.author | Pradhan, Ekadashi | |
| dc.contributor.author | Fujisato, Yuriko H. | |
| dc.contributor.author | Ajayi, Ayonitemi, J. | |
| dc.contributor.author | Lautens, Mark | |
| dc.contributor.author | Zeng, Tao | |
| dc.contributor.author | Le, Christine M. | |
| dc.date.accessioned | 2023-06-02T16:43:36Z | |
| dc.date.available | 2023-06-02T16:43:36Z | |
| dc.date.issued | 2023-05-12 | |
| dc.description.abstract | 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, 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. | en_US |
| dc.identifier.citation | J. Am. Chem. Soc. 2023, 145, 20, 11012–11018 | en_US |
| dc.identifier.uri | 10.1021/jacs.3c03982 | en_US |
| dc.identifier.uri | http://hdl.handle.net/10315/41193 | |
| dc.language.iso | en | en_US |
| dc.publisher | American Chemical Society | en_US |
| dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 International | * |
| dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
| dc.subject | fluorocarbamoylation, Lewis acid, halide recycling | en_US |
| dc.title | BF3‑Catalyzed Intramolecular Fluorocarbamoylation of Alkynes via Halide Recycling | en_US |
| dc.type | Article | en_US |