Abstract
This thesis describes our efforts towards the total synthesis of dihydroisochamaecynone (25), a natural product containing a cis-decalin carbon skeleton core, using a polyene cyclization strategy recently developed in our laboratories. Towards this end, bicyclic enone (76),a projected advanced synthetic intermediate, has been synthesized staring with the readily available ethoxy enone (52). Stork-Danheiser alkylations of enone (52), first with methyl iodide and then with 4-bromo-1-butene, gave the dialkylated product (54). Reduction of enone (54) with lithium aluminumhydride followed by acid hydrolysis of the ensuing ethoxy enol then afforded the 4,4-disubstituted cyclohexenone (55). Enone (55) was then subjected to carbomethoxylation using dimethylcarbonate followed by dehydrogenation with 2.3-dichloro-5,6-dicyanoqutnone to give the polyene cyclization precursor (16). Treatment of dienone (16) with zinc iodide in diethyl ether afforded bicyclic enone (20), the key intermediate of our synthetic strategy. Treatment of the sodium enolate of bicyclic enone (20) with methyl iodide then gave the bicyclic conjugated dienyl product (59) which was then subjected to reduction by lithium aluminumhydride and acidic workup to afford bicyclic dienone (73). Finally, catalytic hydrogenation of bicyclic dienone (73) using Wilkinson,s catalyst gave bicyclic enone (76), the advanced intermediate of our synthetic sequence.