Type of Document Dissertation Author Wang, Aimin URN etd-04052005-180434 Title Synthetic Studies towards the Total Syntheses of the Tetracyclic Diquinane Lycopodium Alkaloids Magellanine and Magellaninone Degree Doctor of Philosophy Department Chemistry and Biochemistry, Department of Advisory Committee
Advisor Name Title Kenneth A. Goldsby Committee Member Laura R. Keller Committee Member Marie E. Krafft Committee Member Martin A. Schwartz Committee Member Robert A. Holton Committee Member Keywords
Date of Defense 2005-03-29 Availability unrestricted AbstractThe synthetic studies towards the total synthesis of the tetracyclic diquinane Lycopodium alkaloids magellanine and magellaninone were designed around utilizing two intramolecular Pauson-Khand reactions to deliver the magellanane skeleton. The model study went relatively well, but when the same reaction conditions were applied to substrates 48, 53, 54, 55, 56, 57, 58, 59, 61, 62, 63, 64, none of them produced the corresponding enone products. Our explanation is that additional substitution at the allylic and homoallylic position interferes with the insertion of the alkene pi-bond into one of the formal cobalt-carbon bonds of the alkyne complex to form the cobalt metallocycle. Because of the failure of this crucial Pauson-Khand step we could not move forward although we spent a lot of time and screened a variety of conditions known in the literature.
After a switch to an alternative route, an intramolecular Pauson-Khand reaction and domino Heck reaction have been successfully utilized to deliver the magellanane skeleton. As anticipated for substrate 115 the second C-Pd/C=C insertion was favored over beta-hydride elimination. This domino Heck reaction is not favorable when the new sigma-alkylpalladium species has a hydrogen atom as is evident from the result with substrate 124. For substrate 115 the second C-Pd/C=C insertion was favored over beta-hydride elimination. Possibly chelate formation prevents proper alignment between the syn-beta-hydrogen and the carbon-palladium beta-bond. Another possibility is that the beta-hydride elimination produces a highly strained ring system and in situ hydropalladation regenerates the sigma-alkylpalladium so the second C-Pd/C=C insertion can take over.
We haven't optimized the conditions for the domino Heck reaction yet. By fine tuning the precatalyst, solvent and base we believe the intermolecular reactions and the beta-hydride elimination may be largely suppressed and the smooth second C-Pd/C=C insertion will deliver the tetracyclic magellanane skeleton in higher yield. Further transformation of the diene to enone and oxidative cleavage of the cyclopentane ring followed by the double reductive amination will finalize the total synthesis of the tetracyclic diquinane Lycopodium alkaloids magellanine and magellaninone.
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