SYNTHESIS OF (+/-)-PISIFERIN, (+/-)-PISIFEROL, AND RELATED-COMPOUNDS BY INTRAMOLECULAR [4 + 2]CYCLOADDITION

Thermolysis of the olefinic benzocyclobutene (17) afforded the tricyclic compounds (18a) and (18b), whose sequential reduction, via the aldehyde (19), gave rise to the pisiferol derivatives (20a) and (20b). Since (20a) was transformed into pisiferol (2), pisiferic acid (3), and methyl pisiferate (4), this synthesis constitutes their formal synthesis. Wolff-Kishner reduction of the hydrazone of (19b) yielded the known tricyclic compound (21), which has previously been transformed into xanthoperyl methyl ether (22). Furthermore, the predominantly cis used mixture of compound (18) (a/b = 1:4) was converted into the predominantly trans-fused mixture (a/b = 3:1) using catalytic hydrogenation of the enone (24) as a key reaction. Finally, a skeletal rearrangement of an abietane-type into a 9(10→20)abeo-abietane-type compound was demonstrated. Dehydration of the alcohol (20a) afforded the methyl ether (26) and its isomer (27) in the ratio of 3:1 as an inseparable mixture. Demethylation of the mixture (26) and (27) provided pisiferin (1) and compound (28). Interestingly, rearrangement of the cis-fused compound (20b) formed the methyl ether (27) as a sole product, which was converted into isopisiferin (29).