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Updated: Oct 25, 2026

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives
Published on: January 19, 2016
Radical Fluoroalkoxylation of α-Mono/Trihalo Ketones
Qiyan Sun1, Yinke Huang1, Ruoyu Wang1
1Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), Guangxi Key Laboratory of Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin, Guangxi541004, P. R. China.
Abstract:
Herein we report a photocatalytic radical fluoroalkoxylation of α-mono/trihalo ketones via selective C-X (X = F, Cl, Br) bond activation. The protocol affords diverse α,α-difluoromonofluoromethoxy ketones from readily available α-halo ketones under mild conditions with broad substrate scope and excellent functional group tolerance. It is amenable to one-pot synthesis and late-stage diversification of pharmaceuticals and bioactive molecules. The strategy is further applicable to trifluoroethoxylation and alkoxylation, demonstrating the versatility of this radical fluoroalkoxylation platform. Mechanistic studies, including EPR and radical-trapping experiments, support an O-centered radical pathway.
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