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

Abstract

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-l-yl-2-pentenoate 13c affords 5-benzyloxy-6-isopropyl- 8-carbomethoxytetracyclo[5.4.01,7.02,4.02,9]undec-10-ene (14c), which after selective hydrogenolysis generates the tri- cyclo[4.4.01,6.02,8]decane (sinularene) ring system. Removal of the secondary hydroxyl function by elimination and hydrogenation (Ph3P/CCl4/CH3CN; H2/Pd/C), reduction of the methyl ester (LiAlH4), 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 13a affords (±)-5-epi-sinularene. X-ray analyses of the triene 13a and the adduct 14a are also reported.