Rearrangement Approaches to Cyclic Skeletons. XIII. Total Synthesis of 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

Article abstract of DOI:10.1246/bcsj.71.231

A reaction of 1,4-dimethoxybicyclo[2.2.2]oct-5-en-2-one and R¹MgX, followed by treatment with p-toluenesulfonic acid in benzene, gave the 5-methoxybicyclo[3.2.1]oct-6-en-2-one having a substituent (R¹) at the C-1 bridgehead. This ketone was converted into the 5-methoxybicyclo[3.2.1]oct-3-en-2-one, By treatment with Li[CuR₂], a second bridgehead substituent (R) was introduced at the C-4 position of the conjugated ketone. The product was converted into the corresponding α,β-unsaturated ketone, and then treated with R²Li or DIBAL-H (R²= H). Acid treatment of the resulting allyl alcohols gave the bicyclo[2.2.2]oct-5-en-2-one having substituents R, R¹, and R² at the C-1, 4, and 5 positions, respectively. This procedure was successfully applied to a formal total synthesis of (±)-modhephene, a propellane-type triquinane sesquiterpene, and that of (±)-isocomene, an angular triquinane sesquiterpene, on the basis of an oxa-di-π methane rearrangement of the bicyclo[2.2.2]oct-5-en-2-ones.