Synthesis of Fluorinated Heterocycles via Prins Cyclization in Ionic Liquids

Significance

Described is the synthesis of fluorinated tetrahydropyrans, thiacyclohexanes and piperidines via Prins cyclization using ionic liquid˙HF salts as the solvent and fluoride source. Several different ionic liquid˙HF salts were screened, with Et₄NF˙5HF found to be the best protic acid catalyst. Prins cyclization of both aliphatic and aromatic aldehydes 1 with homoallylic alcohols 2 rapidly gave cis-tetrahydropyrans 3 in excellent yields. Extension to the reaction of 1 with homoallylic thiol 4 and amine 6 to give thiacyclohexanes 5 and piperidines 7, respectively, was achieved although the stereoselectivity is slightly reduced in these cases. The reusability of the ionic liquid was demonstrated without loss of product yield for up to five runs.