Deoxyfluorination of acyl fluorides to trifluoromethyl compounds by FLUOLEAD®/Olah’s reagent under solvent-free conditions

• Main Authors: Yumeng Liang, Akihito Taya, Zhengyu Zhao, Norimichi Saito, Norio Shibata
• Format: Article
• Language: English
• Published: Beilstein-Institut 2020-12-01
• Series: Beilstein Journal of Organic Chemistry
• Subjects: acyl fluorides; deoxyfluorination; fluorine; solvent-free; trifluoromethyl group
• Online Access: https://doi.org/10.3762/bjoc.16.254

A new protocol enabling the formation of trifluoromethyl compounds from acyl fluorides has been developed. The combination of FLUOLEAD® and Olah’s reagent in solvent-free conditions at 70 °C initiated the significant deoxyfluorination of the acyl fluorides and resulted in the corresponding trifluoromethyl products with high yields (up to 99%). This strategy showed a great tolerance for various acyl fluorides containing aryloyl, (heteroaryl)oyl, or aliphatic acyl moieties, providing good to excellent yields of the trifluoromethyl products. Synthetic drug-like molecules were also transformed into the corresponding trifluoromethyl compounds under the same reaction conditions. A reaction mechanism is proposed.