Prins Cyclization in Ionic Liquid Hydrogen Fluoride Salts: Facile and Highly Efficient Synthesis of 4-Fluorinated Tetrahydropyrans, Thiacyclohexanes, and Piperidines
Prins cyclization of homoallylic alcohols with various aldehydes was investigated in ionic liquid hydrogen fluoride (HF) salts, which played roles as a reaction medium, a catalyst, and a fluorine source. The reaction afforded the corresponding 4-fluorinated tetrahydropyrans in excellent yields with a high stereoselectivity (cis form exclusively). When benzaldehydes having a strongly electron-donating group at the para position were used, the stereoselectivity was lost in this system. In order to apply this method to the synthesis of other 4-fluorinated heterocyclic compounds, we also carried out thia-Prins and aza-Prins cyclization in HF salt and successfully obtained 4-fluorinated thiacyclohexanes and piperidines, respectively.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)