Synthesis of Trifluoromethyl-Substituted Tetrahydropyrans

Abstract

Reported is a one-pot l-proline-catalyzed synthesis of substituted tetrahydro-2H-pyran-3-carboxylate derivatives by the three-component condensation of cinnamaldehyde, anilines and 4,4,4-trifluoroacetoacetate. The reaction proceeds well with non-bulky electron-rich anilines but in lower yields with electron-withdrawing or bulky anilines. The tetrahydropyran derivatives were obtained as racemic mixtures and the ste­reochemistry was established by X-ray crystallographic analysis on one derivative. A reasonable mechanism as shown was suggested without evidence.