Nucleophilic Fluorination with Aqueous Bifluoride Solution: Effect of the Phase-Transfer Catalyst

Nucleophilic fluorination of sulfonyl chlorides, acyl chlorides, and alkyl sulfonates with saturated aqueous solution of potassium bifluoride (KHF2) was studied under liquid–liquid two-phase conditions. Original “on-water” procedure, reported by Sharpless et al. ( J. Org. Chem. 2016, 81, 11360−11362, DOI: 10.1021/acs.joc.6b01423), was tested on model 1-octanesulfonyl chloride in the presence of phase transfer catalysts, some of which appeared to be beneficial for the reaction rate. Despite the high hydration energy of the fluoride ions, the catalytic system displayed numerous features typical for interfacial transportation of the nucleophilic species, being controlled by amount and structure of the catalyst, lipophilicity of the catalyst’s counterion, and rate of stirring. Besides for synthesis of acyl fluorides presence of 1 mol % of tetrabutylammonium chloride affected the selectivity of the reaction by minimizing formation of carboxylic acids and anhydrides. The presented results suggest that aqueous solutions of bifluorides (or synthetically equivalent systems accessible by acidification of alkali metal fluoride solutions) can be efficient sources of the fluoride ions under two-phase conditions, provided that rate of the intrinsic reaction is sufficiently high. The methodology supplements family of nucleophilic fluorinations, delivering a more reactive form of the solvated anions.