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postgraduate thesis: Investigations on the intramolecular (4+3) cycloadditions of epoxy enolsilanes, and applications towards the asymmetric synthesis of himandrine

TitleInvestigations on the intramolecular (4+3) cycloadditions of epoxy enolsilanes, and applications towards the asymmetric synthesis of himandrine
Authors
Issue Date2017
PublisherThe University of Hong Kong (Pokfulam, Hong Kong)
Citation
He, J.. (2017). Investigations on the intramolecular (4+3) cycloadditions of epoxy enolsilanes, and applications towards the asymmetric synthesis of himandrine. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR.
AbstractThe intramolecular (4+3) cycloadditions of epoxy enolsilane substrates 1.89 generated polycyclic cycloadducts 1.90 having bicyclo[5.3.0]decane frameworks, a skeleton which is common among terpenoid natural products (Scheme 1). Each cycloadduct has been fully characterized, and two cycloaddition models have been proposed to rationalize their formation. Epimerization has been observed to generate an additional diastereomer which did not directly result from cycloaddition. Cycloaddition of optically enriched (+)-1.89b produced 1.90b with conserved ee. Tethered pyrroles having a range of N-protecting groups and substituents have been synthesized and their cycloadditions examined (Scheme 2). The intramolecular (4+3) cycloadditions of pyrrolyl enolsilanes such as 2.171 has been observed to proceed with good yields and diastereoselectivities. The endo cycloadducts (type i) were the major diastereomers in all cycloadditions, except when the pyrrole is substituted at C3. Cycloaddition models have been proposed to explain the stereochemical outcomes. Cycloaddition of enantiomerically pure (+)-2.106 also provided (–)-2.113a and (+)-2.114 with conserved ee. Based on these results, we have pursued the asymmetric synthesis of 3.77, the BCDEF rings of himandrine, a Type II Galbulimima alkaloid. The intramolecular (4+3) cycloaddition of optically enriched pyrrole (+)-3.127 to generate cycloadduct (–)-3.138ii, was the key step to construct the BCF ring system of the himandrine core (Scheme 3). From (–)-3.138ii, the methoxycarbonyl group was introduced by a palladium-catalyzed carbonylation, and further transformations provided cyclic amine (–)-3.159. Ring E was formed by the aza-Michael/Mukaiyama aldol sequence, and the resultant alcohols 3.167 were reduced by a Barton-McCombie deoxygenation. For constructing ring D, a metal-halogen exchange and intramolecular carbonyl addition were employed. Finally, the target molecule (–)-3.77 has been successfully achieved in 19 (or 20) steps.
DegreeDoctor of Philosophy
SubjectOrganic compounds - Synthesis
Dept/ProgramChemistry
Persistent Identifierhttp://hdl.handle.net/10722/241419
HKU Library Item IDb5864168

 

DC FieldValueLanguage
dc.contributor.authorHe, Jiayun-
dc.date.accessioned2017-06-13T02:07:48Z-
dc.date.available2017-06-13T02:07:48Z-
dc.date.issued2017-
dc.identifier.citationHe, J.. (2017). Investigations on the intramolecular (4+3) cycloadditions of epoxy enolsilanes, and applications towards the asymmetric synthesis of himandrine. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR.-
dc.identifier.urihttp://hdl.handle.net/10722/241419-
dc.description.abstractThe intramolecular (4+3) cycloadditions of epoxy enolsilane substrates 1.89 generated polycyclic cycloadducts 1.90 having bicyclo[5.3.0]decane frameworks, a skeleton which is common among terpenoid natural products (Scheme 1). Each cycloadduct has been fully characterized, and two cycloaddition models have been proposed to rationalize their formation. Epimerization has been observed to generate an additional diastereomer which did not directly result from cycloaddition. Cycloaddition of optically enriched (+)-1.89b produced 1.90b with conserved ee. Tethered pyrroles having a range of N-protecting groups and substituents have been synthesized and their cycloadditions examined (Scheme 2). The intramolecular (4+3) cycloadditions of pyrrolyl enolsilanes such as 2.171 has been observed to proceed with good yields and diastereoselectivities. The endo cycloadducts (type i) were the major diastereomers in all cycloadditions, except when the pyrrole is substituted at C3. Cycloaddition models have been proposed to explain the stereochemical outcomes. Cycloaddition of enantiomerically pure (+)-2.106 also provided (–)-2.113a and (+)-2.114 with conserved ee. Based on these results, we have pursued the asymmetric synthesis of 3.77, the BCDEF rings of himandrine, a Type II Galbulimima alkaloid. The intramolecular (4+3) cycloaddition of optically enriched pyrrole (+)-3.127 to generate cycloadduct (–)-3.138ii, was the key step to construct the BCF ring system of the himandrine core (Scheme 3). From (–)-3.138ii, the methoxycarbonyl group was introduced by a palladium-catalyzed carbonylation, and further transformations provided cyclic amine (–)-3.159. Ring E was formed by the aza-Michael/Mukaiyama aldol sequence, and the resultant alcohols 3.167 were reduced by a Barton-McCombie deoxygenation. For constructing ring D, a metal-halogen exchange and intramolecular carbonyl addition were employed. Finally, the target molecule (–)-3.77 has been successfully achieved in 19 (or 20) steps. -
dc.languageeng-
dc.publisherThe University of Hong Kong (Pokfulam, Hong Kong)-
dc.relation.ispartofHKU Theses Online (HKUTO)-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.rightsThe author retains all proprietary rights, (such as patent rights) and the right to use in future works.-
dc.subject.lcshOrganic compounds - Synthesis-
dc.titleInvestigations on the intramolecular (4+3) cycloadditions of epoxy enolsilanes, and applications towards the asymmetric synthesis of himandrine-
dc.typePG_Thesis-
dc.identifier.hkulb5864168-
dc.description.thesisnameDoctor of Philosophy-
dc.description.thesislevelDoctoral-
dc.description.thesisdisciplineChemistry-
dc.description.naturepublished_or_final_version-

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