A general intramolecular Diels-Alder approach to tricyclic sesquiterpenes: stereoselective total syntheses of (±)-sinularene and (±)-5-epi-sinularene

Stereoselective total syntheses of (±)-sinularene and (±)-5-epi-sinularene are described. The sequence employs a "blocked" cyclopentadiene in which the cyclopropane unit also serves as a latent methyl group. Thus intramolecular [4 + 2] cycloaddition of the substituted methyl spiro[2.4]hepta-4,6-dien-1-yl-2-pentenoate 13 c affords 5-benzyloxy-6-isopropyl-8-carbomethoxytetracyclo[5.4.0 1,7 .0 2,4 .0 2,9 ]undec-10-ene ( 14 c), which after selective hydrogenolysis generates the tricyclo[4.4.0 1,6 .0 2,8 ]decane (sinularene) ring system. Removal of the secondary hydroxyl function by elimination and hydrogenation (Ph 3 P/CCl 4 /CH 3 CN; H 2 /Pd/C), reduction of the methyl ester (LiAlH 4 ), and introduction of the exocyclic double bond (acetate pyrolysis, 550 °C) completes the synthesis of (±)-sinularene in 12 steps from aldehyde 7 . A parallel series of reactions employing the isopropyl triene epimer 13 a affords (±)-5-epi-sinularene. X-ray analyses of the triene 13 a and the adduct 14 a are also reported.