Synthesis of guaia-4(5)-en-11-ol, guaia-5(6)-en-11-ol, aciphyllene, 1-epi-melicodenones C and E, and other guaiane-type sesquiterpenoids via the diastereoselective epoxidation of guaiol.

The diastereomeric ratio of epoxidation of the internally bridged carbon-carbon double bond of guaiol (1a) is strongly influenced by the combined effects of the types of remote protecting groups on the hydroxyisopropyl side chain, choice of solvent, and epoxidizing reagent. This observation has allowed us to devise concise stereoselective syntheses of a range of guaiane-type sesquiterpenoids via an epoxidation, ring-opening/elimination, and functionality manipulation sequence. Natural products guaia-4(5)-en-11-ol (2a), guaia-5(6)-en-11-ol (3), and aciphyllene (4a) and epimers of the recently isolated natural products, 1-epi-guaia-4(5)-en-11-ol (2b), 1-epi-aciphyllene (4b), and 1-epi-melicodenones C (5a) and E (6a), were synthesized in good yields in relatively few steps.