Synthesis of trifluoromethyl ketones by nucleophilic trifluoromethylation of esters under a fluoroform/KHMDS/triglyme system

A straightforward method that enables the formation of biologically attractive trifluoromethyl ketones from readily available methyl esters using the potent greenhouse gas fluoroform (HCF3, HFC-23) was developed. The combination of fluoroform and KHMDS in triglyme at -40 degrees C was effective for this transformation, with good yields as high as 92%. Substrate scope of the trifluoromethylation procedure was explored for aromatic, aliphatic, and conjugated methyl esters. This study presents a straightforward trifluoromethylation process of various methyl esters that convert well to the corresponding trifluoromethyl ketones. The tolerance of various pharmacophores under the reaction conditions was also explored.

Automated summary

A method utilizing fluoroform to synthesize biologically attractive trifluoromethyl ketones from methyl esters was developed, achieving high yields of up to 92% at -40 degrees C. The study explored the substrate scope of trifluoromethylation procedure for various aromatic, aliphatic, and conjugated methyl esters, as well as the tolerance of different pharmacophores under the reaction conditions.