Direct Conversion of Carboxylic Acids to Trifluoromethyl Ketones

19 March 2007

A recent publication from workers at Boehringer-Ingelheim* describes a direct method for the direct conversion of primary and secondary carboxylic acids to trifluoromethyl ketones by reaction with trifluoroacetic anhydride (TFAA) and pyridine in toluene. Tertiary carboxylic acids are not mentioned in the report, but since a pyridinium enolate is proposed as an intermediate, it seems that the presence of at least one α–proton is necessary and so tertiary arboxylic acids will not react.

In a typical reaction the carboxylic acid is reacted with 4.5 equivalents of TFAA and 6 equivalents of pyridine in toluene at 60C for 8 hours (for primary carboxylic acids) or 75-100C for 24-48 hours for secondary carboxylic acids. Yields of 55-82% are achieved with primary carboxylic acids, and 41-66% for secondary carboxylic acids.

*J.T. Reeves et al., Tetrahedron Letters 2007, 48, 189-192.