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

Abstract

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 °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.

Keywords

• fluoroform
• greenhouse gas
• hfc-23
• trifluoromethyl ketones
• trifluoromethylation