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Updated: Aug 12, 2025

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives
Published on: January 19, 2016
Nickel-catalyzed alkyl-arylation of 3,3,3-trifluoropropene
Chang Xu1, Ming-Kuan Wang1, Shu Zhang2
1Key Laboratory of Organofluorine Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Road, Shanghai, 200032, China.
Abstract:
Owing to the versatile synthetic utility of its carbon-carbon double bond, low-cost industrial chemical 3,3,3-trifluoropropene (TFP) represents one of the most straightforward and cost-efficient precursors to prepare trifluoromethylated compounds. However, only limited methods for the efficient transformations of TFP have been reported so far. Here, we report a nickel-catalyzed dicarbofunctionalization of TFP. The reaction uses inexpensive NiCl2·6H2O as the catalyst and 4,4'-biMeO-bpy and PCy2Ph as the ligands, allowing the alkyl-arylation of TFP with a variety of tertiary alkyl iodides and arylzinc reagents in high efficiency. This nickel-catalyzed process overcomes the previous challenges by suppressing β-H and β-F eliminations from TFP, rendering this strategy effective for the transformations of TFP into medicinal interest trifluoromethylated compounds.
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