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Updated: Jun 11, 2025

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives
Published on: January 19, 2016
Iridium-Catalyzed Enantioselective Propargylic C-H Trifluoromethylthiolation and Related Processes
Jiao Yu1, Yue Xia1, Shalini Dey1
1Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, United States.
Abstract:
The trifluoromethylthio group (SCF3) has gained increasing prominence in the field of drug design and development due to its unique electronic properties, remarkable stability, and high lipophilicity, but its derivatives remain challenging to access, especially in an enantioselective manner. In this Communication, we present an enantioselective iridium-catalyzed trifluoromethylthiolation of the propargylic C(sp3)-H bonds of alkynes. This protocol demonstrates its efficacy across a diverse array of alkyne substrates, including B- and Si-protected terminal alkynes as well as those derived from natural products and pharmaceuticals, to give trifluoromethyl thioethers with good to excellent yield and stereoselectivity. Moreover, this protocol could be modified to access enantioenriched difluoromethyl and chlorodifluoromethyl thioethers (SCF2H and SCF2Cl derivatives), significantly expanding the space of synthetically accessible enantioenriched fluoroorganic compounds.
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