BASE-INDUCED AND BASE-DIRECTED REARRANGEMENTS OF 4-MONOTOSYLATED PERHYDRONAPHTHALENE-1,4-DIOLS - SYNTHESIS OF (+/-)-5-EPI-NARDOL

The utility of perhydronaphthalene precursors for the synthesis of sesquiterpenes which possess a cis-fused perhydroazulene skeleton with an exocyclic methylene unit has been examined. For this purpose the tosylates 3, 4, 28, and 29 were prepared, and their behavior under basic conditions was studied. Upon treatment with sodium tert-amylate in refluxing benzene, the tosylate 3 gave the desired selective formation of the exo 8-olefin 11 (90%). When the tosylate 4 was treated this way a lesser selectivity (58%) was observed. The tosylates 28 and 29 showed a slow rearrangement with no selectivity and no reaction at all, respectively. The role of the hydroxyl group, the solvent, the base strength, and the metal cation has been investigated. A mechanism for this selective skeletal rearrangement (3—11) has been proposed. As an application of this intramolecular base-induced rearrangement the unnatural C-5 epimer of nardol (33) has been prepared in 11 steps from the monoprotected trans-fused dione 5 in an overall yield of 25%. In the synthesis of 33 again the rearrangement (34—33) proceeded selectively and in high yield (90%). © 1990, American Chemical Society. All rights reserved.