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.