ENANTIOSELECTIVE FORMATION OF AN ALPHA,BETA-EPOXY ALCOHOL BY REACTIONOF METHYL 13(S)-HYDROPEROXY-9(Z),11(E)-OCTADECADIENOATE WITH TITANIUMISOPROPOXIDE

Methyl 11(R),12(R)-epoxy-13(S)-hydroxy-9(Z)-octadecenoate (three isome r) was generated from linoleic acid by the sequential action of an enz yme and two chemical reagents. Linoleic acid was treated with lipoxyge nase to yield its corresponding hydroperoxide [13(S)-hydroperoxy-9(Z), 11(E)-octadecadienoic acid]. After methylation with CH2N2, the hydrope roxide was treated with titanium (IV) isopropoxide [Ti(O-i-Pr)(4)] at 5 degrees C for 1 h. The products were separated by normal-phase high- performance liquid chromatography and characterized with gas chromatog raphy-mass spectrometry, infrared spectroscopy, and nuclear magnetic r esonance spectroscopy. Approximately 30% of the product was methyl 13( S)-hydroxy-9(Z),11(E)-octadecadienoate. Over 60% of the isolated produ ct was methyl 1(R),12(R)-epoxy-13(S)-hydroxy-9(Z)-octadecenoate. After quenching Ti(O-i-Pr)(4) with water, the spent catalyst could be remov ed from the fatty products by partitioning between CH2Cl2 and water. T hese results demonstrate that Ti(O-i-Pr)(4) selectively promotes the f ormation of an a-epoxide with the threo configuration. It was critical ly important to start with dry methyl 13(S)-hydroperoxy-9(Z),11(E)-oct adecadienoate because the presence of small amounts of water in the re action medium resulted in the complete hydrolysis of epoxy alcohol to trihydroxy products.