ADAPTATION OF OXYANIONIC SIGMATROPY TO THE CONVERGENT ENANTIOSELECTIVE SYNTHESIS OF AMBERGRIS-TYPE ODORANTS

(-)-(1S,4R)-5,8,8-Trimethylbicyclo[2.2.2]oct-5-en-2-one has been prepared in high optical purity in order to adapt its beta,gamma-unsaturated ketone component to an anionic oxy-Cope strategy aimed at several labdane-like tricyclic ethers. Condensation reactions with the dichloro cerate derivatives of 2,3-dihydrofuran and dihydropyran proceeded regioselectively from the less hindered pi-surface, thereby setting the stage for anionically accelerated [3,3] sigmatropic shift. The resulting enolate anions are electronically destabilized relative to their tautomers, which are consequently formed efficiently. These are captured by reaction with phenylselenenyl chloride. Once selenoxide elimination and reduction with NaBH4-CeCl3 had been accomplished, the stage was set for installation of trans A/B ring stereochemistry. Direct saturation of the original dienones led instead to the cis A/B isomers. The enantioselective syntheses were completed by conversion to the respective xanthates and reduction of these intermediates under free-radical conditions. The results indicate that a practical route to certain potent olfactory agents has been developed.