Acid Catalysis of a Linoleic Acid Hydroperoxide: Formation of Epoxides by an Intramolecular Cyclization of Hydroperoxide Group

Article abstract of DOI:10.1021/jo00177a024

Acid catalysis (0.1 M H2SO4) of (13S)-(9Z,11E)-13 hydroperoxy-9,11-octadecadienoic acid (1) in methanol-water (9:1) did not afford appreciable yields of anticipated products, hexanal and (Z)-12-oxo-9-dodecenoic acid, via the known Hock rearrangement of hydroperoxides.Instead, intramolecular rearrangement of the 13-hydroperoxide into 12,13-epoxides, accompanied by solvent substitution, was the primary course of reaction (all products were isolated after conversion to methyl esters).Three isomeric methyl (Z)-12,13-epoxy-11-methoxy-9-octadecenoates were isolated in 20.2 mol percent yield; methyl (11R,12R,13S)-(Z)-12,13-epoxy-11-methoxy-9-octadecenoate (2a) comprised 81percent of the three.The stereoselectivity observed in the formation of 2a implied anchimeric assistance by the epoxide group in substitution by methanol.Kinetic evidence, as well as a 20.4 mol percent yield of stereoisomers of methyl (E)-13-hydroxy-9,12-dimethoxy-10-octadecenoates, was indicative of intermediate (E)-12,13-epoxy-9-methoxy-10-octadecenoic acids.These allylic epoxides could not be isolated, presumably because they solvolyzed rapidly in the presence of acid.On the other hand, the nonallylic epoxides 2a-c solvolyzed more slowly.The following reaction mechanism is proposed: (a) a conjugate acid forms by addition of a proton to a hydroperoxy group; (b) electrophilic attack on C-12 by a partially positive-charged α-oxygen of the hydroperoxy group affords a 12,13-epoxy-9,11-allylic cation; (c) C-9 or C-11 undergoes substitution from methanol; (d) the products of the substitution, isomeric epoxymethoxyoctadecenoic acids, are solvolyzed further to hydroxydimethoxyoctadecenoic acids.The possibility that heterolysis of 1, as well as of other hydroperoxides of polyunsaturated fatty acids, may have significance in biological transformations is dicussed.