Two annulation strategies have been examined as a potential route to highly functionalised, oxygenated decalins of the type embodied in natural product azadirachtin. Both approaches employ a Michael addition of a latently functionalised nucleophile to an $ alpha, beta$-unsaturated keto ester to assemble the annulation precursor. / One approach deploys the in-house developed 4C siloxy diene, 1-trimethylsiloxy-1-methoxy-3-phenylthio-1,3-butadiene as the nucleophilic component in a Lewis acid mediated 1,4 conjugate addition to triethyl 4-oxo-2-cyclohexen-1,1,3-tricarboxylate. The potential of the keto ester moiety in the E Michael adduct, to function as the nucleophilic component, in a Claisen condensation in the conventional sense was examined. Cyclisation onto the tethered electrophile was achieved with an acyl chloride as the electrophilic partner. The stereochemistry of this kinetically controlled, essentially irreversible closure was found to lead exclusively to cis product geometry. The method provides a concise route to highly functionalised cis decalins incorporating a latent angular hydroxymethylene equivalent. Access to the corresponding trans series was explored. / A second strategy designed to examine three modes of cyclisation to a functionalised decalin intermediate required the development of metallo-cuprate chemistry. A convenient, operationally simple route to the higher-order homo bis trimethylstannyl cyano cuprate was invented through the intermediacy of a novel bis amido cuprate. Bis trimethylstannyl cuprate was shown to add to acetylene to provide the desired cuprate trimethylstannylvinyl cyano cuprate in synthetically useful yields. The conjugate addition of this cuprate to enones and enone-esters alike was compared with similar addition of other mixed stannylvinyl cuprates. Two novel mixed trimetylstannyl and trimethylstannylvinyl amido cuprates, requiring only one equivalent of valuable tin reagent for their preparation are described and briefly evaluated as selective tin transfer reagents. Finally BSA was shown to efficiently promote conjugate addition of homo bis trimethylstannylyinyl cuprate to enone and enone esters alike without unwanted side-reactions. The method was successfully used to generate a key Michael adduct in 92% yield. The activating potential of this reagent (BSA) as a newly discovered $ pi$ Lewis donnor was assessed, relative to other conventional activating agents. / A second study designed to more easily access transfused decalins, employed a cis trimethylstannylvinyl cuprate as the Michael donnor in 1,4-conjugate addition to triethyl 4-oxo-7-cyclohexen-1.1.3-tricarboxyiate. The trimethylstannylvinyl residue in the resulting adduct was evaluated as a latent nuclcophile in the synthesis of several cyclisation precursors. None were found suitable in this capacity. The most expedient route to a promising annulation precursor retained the vinyl stannane moiety and employed a Claisen rearangement to install the C$ sb2$ electrophilic centre with complete control of relative stereochemistry of three contiguous stereogenic centres.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.40423 |
| Date | January 1996 |
| Creators | Pereira, Oswy Zeno. |
| Contributors | Chan, T. H. (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Department of Chemistry.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001536642, proquestno: NN19763, Theses scanned by UMI/ProQuest. |
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