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

Abstract

Stereoselective total synthesis 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 11 affords 5-benzyloxy-6-isopropyl-8-carbomethoxytetracyclo[5.4.0 1,7 .0 2,4 .0 2,9 ]undec-10-ene (12) 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 (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 14 steps from cyclopentadiene. A parallel series of reactions employing the isopropyl epimer of 12 affords (±)-5-epi-sinularene.