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

Abstract

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.

Keywords

• acyl fluorides
• deoxyfluorination
• fluorine
• solvent-free
• trifluoromethyl group