Copper-Catalyzed Synthesis of Trifluoroethylarenes from Benzylic Bromodifluoroacetates
Brett R Ambler1, Lingui Zhu1, Ryan A Altman1
1Department of Medicinal Chemistry, The University of Kansas, Lawrence, Kansas 66045, United States.
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.
Related Concept Videos
Electrophilic Aromatic Substitution: Fluorination and Iodination of Benzene
Electrophilic Aromatic Substitution: Chlorination and Bromination of Benzene
Electrophilic Aromatic Substitution: Friedel–Crafts Acylation of Benzene
Electrophilic Aromatic Substitution: Friedel–Crafts Alkylation of Benzene
Diazonium Group Substitution with Halogens and Cyanide: Sandmeyer and Schiemann Reactions
Reactions at the Benzylic Position: Halogenation


![[DPEPhosbcpCu]PF6: A General and Broadly Applicable Copper-Based Photoredox Catalyst](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F59739.jpg&w=3840&q=50)