REARRANGEMENT APPROACHES TO CYCLIC SKELETONS - XIII - TOTAL SYNTHESISOF TRIQUINANE SESQUITERPENES, (+ -)-MODHEPHENE, AND (+/-)-ISOCOMENE, ON THE BASIS OF FORMAL SUBSTITUTION AT BOTH BRIDGEHEADS OF A BICYCLO[2.2.2]OCT-5-EN-2-ONE/

A reaction of 1,4-dimethoxybicyclo [2.2.2]oct-5-en-2-one and (RMgX)-Mg -1, followed by treatment with p-toluenesulfonic acid in benzene, gave the 5-methoxybicyclo[3.2.1]oct-6-en-2-one having a substituent (R-1) at the C-l bridgehead. This ketone was converted into the 5-methoxybic yclo[3.2.1]oct-3-en-2-one. By treatment with Li[CuR2], a second bridge head substituent (R) was introduced at the C-4 position of the conjuga ted ketone. The product was converted into the corresponding alpha,bet a-unsaturated ketone, and then treated with (RLi)-Li-2 or DIBAL-H (R-2 = H). Acid treatment of the resulting allyl alcohols gave the bicyclo [2.2.2]oct-5-en-2-one having substituents R, R-1, and R-2 at the C-1, 4, and 5 positions, respectively. This procedure was successfully appl ied to a formal total synthesis of (+/-)-modhephene, a propellane-type triquinane sesquiterpene, and that of (+/-)-isocomene, an angular tri quinane sesquiterpene, on the basis of an oxa-di-pi methane rearrangem ent of the bicycle [2.2.2]oct-5-en-2-ones.