Synthesis of trifluoromethylated tetrahydropyrans from ene reaction products of trifluoromethyl ketones: synthesis of fluorine analogues of sesquiterpenes

Abstract

Ene reaction of trifluoromethyl ketones were investigated extensively, 1) and the ene reaction products were transformed to many types of trifluoromethyl compounds. 2) Among these research, the ene reaction products of trifluoromethyl ketones were converted to α-trifluoromethylated tetrahydrofurans. In this study, derivatization of the ene reaction products to α-trifluoromethylated tetrahydropyrans were accomplished. Therefore, treatment of esters of 3,4-unsaturated alcohols with trifluoromethyl ketones gave α-(trifluoromethyl)homoallyl alcohol derivatives, which were hydrolyzed to 2,3-unsaturated 1,5-diol compounds. These were oxidized to δ-ketoalcohols. Hydrogenation of these alcohols, followed by treatment with Grignard reagents, gave trifluoromethylated 1,5-diols, which were dehydrated and cyclized to α- trifluoromethylated tetrahydropyran derivatives, some of which are fluorine analogues of curcumene ether, a sesquiterpene.