1,1,2,2-Tetrafluoroethyl-N,N-dimethylamine (TFEDMA) for Nucleophilic Fluorination

Mark Redlich

1,1,2,2-Tetrafluoroethyl-N,N-dimethylamine (TFEDMA) is a mild, and selective nucleophilic fluorination reagent for fluorination of alcohols and activated carbonyl compounds.¹ In contrast to the similar Yarovenko–Raksha reagent (2-chloro-1,1,2-trifluoroethyl- N,N-diethylamine), the material is stable at ambient temperature with unlimited shelf life as long as it is contained in polyethylene, polytetrafluoroethylene (PTFE), or metal containers.

Reactions of TFEDMA with primary alcohols provide the corresponding alkyl fluorides in good to excellent yields (Scheme 1). Secondary and tertiary alcohols are more reactive towards TFEDMA, though in some cases provide the elimination product in addition to the fluoride (Scheme 2). Aldehydes and ketones can also react with TFEDMA to yield the gem-difluorides, and carboxylic or sulfonic acids produce the corresponding acyl or sulfonyl fluorides. The amide byproduct of TFEDMA in fluorination reactions is water-soluble and can usually be washed from the reaction mixture, simplifying reaction workup.

Scheme 1

Scheme 2

References

1. Petrov VA. 2001. Reaction of imines of fluorinated ketones and perfluoronitriles with carbon tetrachloride. A new route to polyfluorinated imines. Journal of Fluorine Chemistry. 109(2):123-128. https://doi.org/10.1016/s0022-1139(01)00361-x