Synthetic studies of occidenol and synthetic and kinetic studies on substituted cyclohexadienones

When attacked by microorganisms, certain plants produce secondary metabolites called phytoalexins. Many phytoalexins are oxygenated terpenes. One of these is occidenol, a sesquiterpene of questionable stereochemistry found in tobacco plants invaded by P. Solanacearum, the tobacco mosaic virus, and in Thuja occidentalis, the eastern white cedar. A a stereo controlled synthesis of occidenol would not only be the first synthesis of a natural product with a dihydrooxipin ring, but would also allow the correct stereochemistry to be determined through spectral comparisons of the synthesized compound with an authentic sample. Previous attempts at the synthesis of occidenol have failed. Two new routes were tried.

The acid-catalyzed rearrangements of carbocations has long been an area of intensive study. The migrating group is often hydrogen, aryl, or alkyl. In a 4-methoxy-4-alkylcyclohexadienone system rearranging in aqueous sulfuric acid, an ethyl group migrates faster than a methyl group by a factor of two hundred and sixty-one times. It was predicted that an isopropyl group would migrate faster than an ethyl group by the same factor. Also, in a 4-methyl-4-alkyl-cyclohexadienone system, an ethyl group migrates faster than a methyl group by a factor of about fifty times. It was predicted that an isopropyl group would migrate fifty times as fast as an ethyl group. The two compounds with the isopropyl groups had to be synthesized for the first time. The predictions were validated by kinetics studies. This is the first case of an apriori prediction of migration rates as a function of the structure of the migrating group.

Thioester groups are known to migrate well, while amides show poor migration tendencies. Two 4-methyl-4-R-cyclohexadienones, one with a thioester group and the other with an amide group as the potential migrating group, were synthesized for the first time. These compounds did not rearrange in aqueous sulfuric acid, but rather cleaved.