Trifluoromethylation of aliphatic halogen compounds

Abstract

Aryl, heteroaryl or vinyl halides can be trifluoromethylated using CF₃CO₂Na–Cul. With alkyl iodides, however, the method fails, yielding trifluoroacetyl esters instead. Allylic halogens can be substituted with Burton's reagent, obtained from dihalogenodifluoromethane via CF₃CdHal and transmetallation with Cul. A new access to trifluoropropionic acid is thereby found. Prop-2-ynyl bromide produces trifluoromethylallene. Attempts at trifluoromethylation of bromoacetate with CF₃CO₂Na–Cul in NMP (N-methyl-2-pyrrolidone) solution led to formation of the trifluoroacetoxy derivative and of a formal adduct of hexafluoroacetone to the α position of NMP.