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Updated: Sep 8, 2025

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives
Published on: January 19, 2016
A practical photocatalytic strategy for radical (deuterio)difluoromethylation using imidazolium reagents
Chao Sun1, Yinpu Shen1, Heyin Li1
1State Key Laboratory of Coordination Chemistry, Jiangsu Key Laboratory of Advanced Organic Materials, Collaborative Innovation Center of Advanced Microstructures, School of Chemistry and Chemical Engineering, Nanjing University Nanjing 210023 China yiwang@nju.edu.cn.
Abstract:
The difluoromethyl group (CF2H) has garnered significant interest in medicinal chemistry owing to its unique biochemical and physicochemical properties. Its deuterated counterpart (CF2D), building on the established utility of CF2H, exhibits multifaceted potential for advancing biomedical research and therapeutic development. While the incorporation of the difluoromethyl group (CF2H) into drug molecules has matured, efficient installation of its deuterated counterpart (CF2D) remains a formidable challenge in medicinal chemistry. This study reports a novel (deuterio)difluoromethyl imidazolate reagent IMDN-SO2CF2X (X = D, H), which is used to successfully construct various highly selective (deuterio)difluoromethyl compounds in the form of (deuterio)difluoromethyl radicals while maintaining high deuteration rates, achieving >99% isotopic purity in deuterium incorporation. The reagent enables precise CF2D and CF2H installation in natural products and synthetic bioactive compounds, showing broad substrate compatibility. This establishes a robust deuteration platform for drug discovery.
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