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Updated: Oct 9, 2025

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives
Published on: January 19, 2016
TMSCF2 Br-Enabled Fluorination-Aminocarbonylation of Aldehydes: Modular Access to α-Fluoroamides
An Liu1, Chuanfa Ni1, Qiqiang Xie1
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 Ling-Ling Road, Shanghai, 200032, China.
Abstract:
A protocol for the modular assembly of the α-fluoroamide motif has been developed, which provides a practical method for the efficient synthesis of structurally diverse α-fluoroamides from easily available aldehydes and tertiary amines through a three-component fluorination-aminocarbonylation process. The key to the success of this process is taking advantage of the multiple roles of the unique difluorocarbene reagent TMSCF2 Br (TMS=trimethylsilyl). The mechanism of the process involves the 1,2-fluorine and oxygen migrations of the in situ formed TMS-protected α-aminodifluoromethyl carbinol intermediates, which represents a new type of deoxyfluorination reaction.
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