Synthetic Studies in the Sesquiterpene Field

Part I: The synthesis of (+/-) cuparene and (+/-) cuparenic acid was achieved starting from 3-methylcyclohex-2-enone. A Friedel Crafts reaction with toluene gave 3-methyl-3-p-tolyleyclohexanone. The mono-furfurylidene derivative of this ketone was bis-alkylated to give 2-furfurylidene-5:6:6-trimethyl-5-p-tolylcyclohexanone which was subjected to ozonolysis, cyclization, and reduction to give (+/-) cuparene which was then oxidized to (+/-) cuparenic acid. Two unsuccessful synthetic approaches to cuparene are also described. Acid treatment of an alpha-ketol, 3:3 dimethyl-2-hydroxy-2-p-tolylcyclopentanone, brought about a novel 1:3-hydride shift leading to 4:4-dirnethyl-5-p-tolylcyclopentenone. The mechanism of enol-chloride formation of unsymmetrical cyclohexan-1:3-diones is also discussed. Part II: A novel approach to the spiro-[5:4]-decane system encountered in acorone was undertaken by 1:4 addition of acetylenic Grignard reagents to the cyclohexylidene malononitrile system. The ethynyl dinitrilea, so formed were found to undergo basic Internal hydration, Construction of the spiro system was effected by an internal Michael cyclization of ethyl 5-(4-methyl-3-oxo-cyclohexenyl)-3-oxo-hexanoate. The product of this cyclization was elaborated to the gross structure of acorone