Copper‐Catalyzed Highly Stereoselective Trifluoromethylation and Difluoroalkylation of Secondary Propargyl Sulfonates. Issue 12 (21st February 2018)

• Record Type: Journal Article
• Authors: Gao, Xing; Xiao, Yu‐Lan; Wan, Xiaolong; Zhang, Xingang
• Is Part Of: Angewandte Chemie international edition. Volume 57:Issue 12(2018)
• Page Start: 3187
• Page End: 3191
• Publication Date: 2018-02-21
• Subjects: asymmetric catalysis -- copper -- difluoroalkylation -- propargyl sulfonates -- trifluoromethylation; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201711463
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: It is challenging to stereoselectively introduce a trifluoromethyl group (CF3 ) into organic molecules. To date, only limited strategies involving direct asymmetric trifluoromethylation have been reported. Herein, we describe a new strategy for direct asymmetric trifluoromethylation through the copper‐catalyzed stereospecific trifluoromethylation of optically active secondary propargyl sulfonates. The reaction enables propargylic trifluoromethylation with high regioselectivity and stereoselectivity. The reaction could also be extended to stereospecific propargylic difluoroalkylation. Transformations of the resulting enantiomerically enriched fluoroalkylated alkynes led to a variety of chiral fluoroalkylated compounds, thus providing a useful protocol for applications in the synthesis of fluorinated complexes. Abstract : Just the beginning : The title reaction enables propargylic trifluoromethylation and difluoroalkylation with high regioselectivity and stereoselectivity (see scheme) to provide versatile building blocks that undergo a wide variety of transformations. Inversion of configuration was observed for the copper‐catalyzed process, thus demonstrating that SN 2‐type oxidative addition of copper to the secondary propargyl sulfonate may be involved in the reaction.