Organocatalysis approach to trifluoromethylation with fluoroform

• Organic base catalysis provides an access to trifluoromethylation with fluoroform in good overall efficiency.
• The equilibrium of fluoroform and base shifts to the parent ones, however, to undergo trifluoromethylation of electrophiles.
• The reaction of fluoroform with carbon dioxide is noteworthy to give the trifluoromethylation product even at low temperature.
• Aromatic esters and acid halides provide ketone products in contrast to alcohols with lithium reagents.
• Epoxides surprisingly give internal rather than terminal trifluoromethylation products with quaternary carbon centers.

The organic base methodology exploits an access to generate the “trifluoromethyl anion” for carbonyl, ester, acid halide, epoxide, deuterium donor, and carbon dioxide substrates to afford the trifluoromethylation products with good overall efficiency even in organocatalysis conditions. The NMR analysis of the mixture of fluoroform and P4-base shows no change thereof. However, on addition of electrophiles, the trifluoromethylation products were obtained efficiently.

Organocatalysis approach to trifluoromethylation with fluoroform is presented to give the “trifluoromethyl anion” for carbonyl, ester, acid halide, epoxide, deuterium donor, and carbon dioxide substrates.Figure optionsDownload as PowerPoint slide