The marine natural product Popolohuanone E has been the target for total synthesis. This C42 marine sponge metabolite, which contains two identical cis-decalin moieties, was first approached by a route starting from 3,4-dimethylcyclohex-2-enone via two stereospecific cuprate addition reactions. The known decalin (+/-)-3,4,4abeta,5,6,7,8,8a-octahydro-1beta-hydroxymethyl-5,6,8abeta-trimethyl-5beta-vinyl-2(1H)-naphthalenone was synthesised by this route and subsequent elaboration carried out. After deoxygenation of the carbonyl group and further manipulation, the novel aldehyde, (+/-)-1,2,3,4,4abeta,5,6,7,8,8a-decahydro-1beta-tert-butyldimethylsilyloxymethyl-5,6,8abeta-trimethyl-5beta-formyl naphthalene, was obtained. Further elaboration of the aldehyde to the pseudo-monomeric carbon skeleton of popolohuanone E was not possible. Secondly a new route to the cis-decalin moiety was attempted. This involved synthesis of 1-iodo-3,4-dimethyl-6-trimethylsilylhex-4-ene from tiglic aldehyde by a route involving an Eschenmoser-Claisen rearrangement. Unfortunately due to time constraints the coupling of this iodide with the ketal of 2-bromo-l-cyclohex-2-enone and the subsequent intramolecular Hosomi-Sakurai cyclization were not accomplished. Finally attention was turned to developing a reliable route to the pseudo-monomer utilising a benzylic cuprate addition. Even after extensive experimentation with various enones, the desired adducts proved to be elusive
