Regiospecific α-hexafluoroisopropylidenation of ketones using hexafluoroacetone

Hexafluoroacetone (HFA) reacted regiospecifically with various enol silyl ethers at −30 to −35°C in the presence of a Lewis acid to give HFA aldols, or α-bis(trifluoromethyl)hydroxymethyl carbonyl compounds, in good yields. The reaction of HFA with dienol silyl ethers, on the other hand, cleanly proceeded even in the absence of a Lewis acid to provide [4+2]cycloadducts, or bistrifluoromethylated tetrahydropyran-4-one derivatives, quantitatively. The former HFA aldols were converted in excellent yields into α-hexafluoroisopropylidene ketones by the action of methyl chlorosulfite and pyridine.