ENANTIOSELECTIVE SYNTHESIS OF THE HEXAHYDRONAPHTHALENE NUCLEUS OF (-)-COMPACTIN FROM ETHYL (1R,2S)-2-METHYL-4-OXOCYCLOHEXANECARBOXYLATE AND2-(3-NITROPROPYL)-1,3-DIOXOLANE AS 4 CARBON BIFUNCTIONAL ANNELATING AGENT

An enantioselective approach to the synthesis of the hexahydronapththa lene nucleus of natural compactin is described. The key elements of th e synthesis are as follows: (i) the preparation of the chiral starting material through enzymatic resolution of the readily available cis 2- methyl-4-oxocyclohexane carboxylic acid, (ii) conversion into the suit ably protected 4S,5S)-4-hydroxymethyl-5-methyl-2-cyclohexen-2-one by r egioselective introduction of the alpha,beta-carbon-carbon double bond by Pd(II)-catalyzed dehydrosilylation, (iii) construction of the new six-membered ring into the preexisting carbon skeleton using 2-(3-nitr opropyl)-1,3-dioxolane as a four carbon bifunctional annelating reagen t, (iv) elaboration of the derived hexahydronaphthalenone to an advanc ed precursor already taken to the natural target by functional group m anipulation, including conversion of the nitro group to the oxygenated function at C-1 and dehydration of an allylic alcohol precursor to th e required 1,3-diene moiety.