Trimerization Products of Trifluoroacetone: Critical Solvent Effect on Position and Kinetics of Anomeric Equilibria

In the presence of bases, trifluoroacetone is known to trimerize leading to configurationally labile 6-methyl-2,4,6-tris(trifluoromethyl)tetrahydro-2H-pyran-2,4-diols 1a,b and 2a,b, structurally close to fluorinated
carbohydrates. We report herein a complete study of their behavior in solution. The remarkable solvent
effect on the two equilibria (1a ⇔ 1b; 2a ⇔ 2b) was rationalized using solvent basicity measures and
polarity scales. Solvents of weak donor number were found to favor the diastereoisomers 1a and 2a,
which were subsequently isolated. According to their X-ray analyses, they both possess a concave structure
with 1,3-cis-diaxial hydroxyl groups. A complementary kinetic study illustrated that acidic conditions
can drastically reduce the equilibration rate, allowing the use of a wide range of solvents. Finally, a
reexamination of previously published trimerization conditions using sodium or magnesium amalgam
revealed that, contrary to the suggestion by two independent reports, 1,3,5-tris(trifluoromethyl)cyclohexane-1,3,5-triol 3/4 was neither formed as the principal product in place of 1a,b and 2a,b nor could it be
detected as a minor product.