Trifluoroacetylation of unsymmetrical ketone acetals. A convenient route to obtain alkyl side chain trifluoromethylated heterocycles

A convenient method to obtain beta-alkyl-beta-methoxyvinyl trifluoromethyl ketones [CF3COCH=C(OMe)R, where R = Et, n-Pr, i-Pr, i-Bu, t-Bu, -(CH2)(2)OM e] from the regiospecific acylation of kinetic enol ether generated in situ is reported. The unsymmetrical ketone dimethyl acetals react with trifluor oacetic anhydride in the presence of pyridine using dry chloroform as solve nt with a temperature range of 25-60 degrees C. These acetals [R-C(OMe)(2)M e] are obtained from the reaction of alkyl methyl ketones with trimethyl or thoformate in the presence of p-toluenesulfonic acid as catalyst in pure me thanol as solvent. The new acetylated enol ethers proved to be versatile bu ilding blocks for the construction of interesting alkyl trifluoromethyl sub stituted heterocycles. Thus, examples of isoxazoline, pyrazoline, pyrazole and pyrimidinone have been obtained in good yields (62-79%). (C) 1999 Elsev ier Science S.A. All rights reserved.