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. 2015 Aug 21;80(16):8449-57.
doi: 10.1021/acs.joc.5b01343. Epub 2015 Aug 11.

Copper-Catalyzed Synthesis of Trifluoroethylarenes from Benzylic Bromodifluoroacetates

Brett R Ambler  1 , Lingui Zhu  1 , Ryan A Altman  1
Affiliations

Copper-Catalyzed Synthesis of Trifluoroethylarenes from Benzylic Bromodifluoroacetates

Brett R Ambler et al. J Org Chem. .

Abstract

Trifluoroethylarenes are found in a variety of biologically active molecules, and strategies for accessing this substructure are important for developing therapeutic candidates and biological probes. Trifluoroethylarenes can be directly accessed via nucleophilic trifluoromethylation of benzylic electrophiles; however, current catalytic methods do not effectively transform electron-deficient substrates and heterocycles. To address this gap, we report a Cu-catalyzed decarboxylative trifluoromethylation of benzylic bromodifluoroacetates. To account for the tolerance of sensitive functional groups, we propose an inner-sphere mechanism of decarboxylation.

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Figures

Figure 1
Figure 1
Iodide plays an essential role in benzylic trifluoromethylation
Scheme 1
Scheme 1
Trifluoromethylation of Benzylic Electrophiles Typically Requires Stoichiometric Copper
Scheme 2
Scheme 2
Previously proposed mechanism involves generation of free −CF3
Scheme 3
Scheme 3
Copper-catalyzed reaction improves access to target compounds
See this image and copyright information in PMC

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