The resolution of racemic hydroperoxides: a chromatography-based separation of perketals derived from arachidonic, linoleic, and oleic acid hydroperoxides

In spite of the importance of optically pure unsaturated hydroperoxides in biology, chemistry, and medicine, no general method for synthesizing these labile compounds has been reported. We have developed a chiral vinyl ether that reacts with racemic hydroperoxides to give diastereomeric perketals in high yield. These perketals can be separated by liquid chromatography and the chiral group removed to provide highly enriched hydroperoxide enantiomers (greater than 99% enantiomeric excess). The chiral reagent that has been most successful in our hands is the 2-propenyl ether derived from trans-2-phenylcyclohexanol. By use of this vinyl ether, perketals are readily formed from hydroperoxides, they are stable to normal- and reverse-phase chromatography, and the hydroperoxide is regenerated from the perketal without racemization in high yield with mild acid. Several chiral hydroperoxides have been resolved by this procedure: alpha-phenethyl hydroperoxide, 2-octyl hydroperoxide, and a number of hydroperoxides derived from oleic, linoleic, and arachidonic acids.