Stereoselective synthesis of α-bulnesene, 4-epi-α-bulnesene, and 5-epi-α-bulnesene

Lithium–ammonia reduction of the hydroguaiazulene derivative 6, followed by oxidation of the resulting diol 13, gave, in a highly stereoselective manner, the keto alcohol 14. The latter was converted into 5-epi-α-bulnesene (2). In a similar sequence of reactions, 4-epi-α-bulnesene (3) was obtained from compound 9. Photochemical rearrangement of the previously obtained dienone 25 gave the hydroguaiazulene derivative 27. Successive subjection of the latter to acetylation, hydrogenation, and sodium borohydride reduction gave a mixture of the epimeric diols 31 and 32. When this mixture was treated with p-toluenesulfonic acid in pyridine, and the resulting olefinic diester 35 was sequentially subjected to hydrogenation [tris(triphenylphosphine)chlororhodium] and lithium aluminum hydride reduction, the crystalline diol 37 was obtained. The latter was converted into α-bulnesene (1) by standard reactions.