Lei, Bo (1989) Total synthesis of (+)-longifolene by an intramolecular Diels-Alder strategy. Doctoral (PhD) thesis, Memorial University of Newfoundland.
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The total synthesis of the sesquiterpene (+)-longifolene by an intramolecular Diels-Alder cycloaddition strategy is described. The route utilized an addition initiated ring closure involving methyllithium and epoxyfulvene 80. The cyclopentadienyl anion 81 that resulted cyclized in an exo-tet manner to generate a substituted spiro[2.4]hepta-4,6-diene 82 in which the cyclopropane ring blocked the 1,5-sigmatropic rearrangement and acted as a latent methylene group. Oxidation with active Mn02 afforded cyclopropyl aldehyde 83, which was condensed with the anion derived from methyl 3,3-dimethyIacryIate 97 in the presence of cadmium chloride. These conditions resulted in selective v substitution and were a consequence of isomerization to the thermodynamically most favored product This procedure was shown to be general for related systems. -- The resulting alcohol-protected triene 100 was cyclized directly to tetracyclic adduct 103 under thermal conditions in a microwave oven. Modification of the functional groups gave cyclopropyl ketone 118, which opened to the longifolene ring system by lithium/ammonia reduction. -- The route to optically active material followed a different pathway which involved the Lewis acid catalyzed addition of methanol to the optically active spirocyclopropane-cyclopentadiene 134. The product 137 was capable of rapid sigmatropic rearrangement, which in principle could give rise to several different Diels-Alder adducts. In practice, because of the constrained nature of the cyclic dienophile, the lowest energy path led to the adduct 138 with the tricyclic nucleus required for (+)-longifolene. This was the only product isolated and represented the first successful synthesis of a cycloheptane directly from a cyclopentadiene in a carbocyclic precursor. In order to complete the synthesis the lactone 138 was reduced and the primary alcohol converted selectively to its acetate 144. Sequential removal of the secondary hydroxyl functions was accomplished under free radical conditions. Pyrolysis of the acetate 146 at 525°C provided (+)-longifolene.
|Item Type:||Thesis (Doctoral (PhD))|
|Additional Information:||Bibliography: leaves 146-150|
|Department(s):||Science, Faculty of > Chemistry|
|Library of Congress Subject Heading:||Terpenes--Synthesis; Diels-Alder reaction|
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