Issue 28, 2025

Electrochemical trifluoromethylation of alkenyl oximes for the synthesis of isoxazolines and cyclic nitrones via radical annulation

Abstract

A highly efficient and environmentally friendly approach to access fluorine-containing isoxazoline and cyclic nitrone derivatives without any oxidant addition is reported. In this electrochemical system, sodium trifluoromethanesulfonate (CF3SO2Na) serves as a practical and inexpensive trifluoromethyl source, enabling electrochemically induced radical addition and oxidative cyclization with a variety of β,γ- or γ,δ-alkenyl oxime substrates. This protocol proceeds smoothly under mild conditions and exhibits broad substrate compatibility, tolerating both electron-donating and electron-withdrawing substituents. Mechanistic studies and cyclic voltammetry experiments indicate that the trifluoromethyl radical is preferentially initiated under electrochemical conditions. The desired products are obtained in moderate to good yields. Furthermore, the synthetic utility of this methodology was demonstrated by a gram-scale reaction, which furnished the target compound with slightly reduced efficiency. This work provides a green and scalable platform for the construction of CF3-functionalized heterocycles, offering valuable insights into sustainable radical fluorination strategies.

Graphical abstract: Electrochemical trifluoromethylation of alkenyl oximes for the synthesis of isoxazolines and cyclic nitrones via radical annulation

Supplementary files

Article information

Article type
Paper
Submitted
28 Apr 2025
Accepted
23 Jun 2025
First published
24 Jun 2025

Org. Biomol. Chem., 2025,23, 6808-6813

Electrochemical trifluoromethylation of alkenyl oximes for the synthesis of isoxazolines and cyclic nitrones via radical annulation

J. Chen, M. Yan, M. Wu, X. Jiang, J. Wan, Z. Ren, M. Yuan, K. Zhou, C. Shi and S. Guo, Org. Biomol. Chem., 2025, 23, 6808 DOI: 10.1039/D5OB00694E

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements