Catalysis

Asymmetric Defluoroallylation of 4-Trifluoromethylpyridines Enabled by Umpolung C-F Bond Activation

Authors

Abstract

Carbon-fluorine bond activation reaction of the trifluoromethyl group represent an important approach to fluorine-containing molecules. While selective defluorofunctionalization reactions of CF3-containing substrates have been achieved by invoking difluorocarbocation, difluorocarboradical, or difluoroorganometallic species as the key intermedi-ate, the transformations via fluorocarbanion mechanism remained a limited success. Furthermore, the enantioselective defluorotransformation of CF3 group has not yet been realized. Herein, we report a defluorofunctionalization reaction of 4-trifluoromethylpyridines involving pyridyldifluoromethyl anion as the key intermediate, which was developed based upon our previous studies on the N-boryl pyridyl anion chemistry. When combined with Ir-catalysis, asymmetric defluoroallylation of 4-trifluoromethylpyridines could be achieved to forge a difluoroalkyl-substituted chiral center. The present work opens up a new opportunity for the defluorofunctionalization of CF3 group, and provides new insights into the N-boryl pyridyl anion chemistry.

Content

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Supplementary material

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Supporting Information for Asymmetric Defluoroallylation of 4-Trifluoromethylpyridines Enabled by Umpolung C-F Activation Strategy
Experimental procedures, characterization data, and copies of NMR spectra.