Intramolecular cycloadditions of azides with olefins: Synthetic approaches to pyrrolizidine and indolizidine alkaloids.
dc.contributor.author | Williams, John Patrick | en_US |
dc.contributor.advisor | Pearson, William | en_US |
dc.date.accessioned | 2014-02-24T16:28:08Z | |
dc.date.available | 2014-02-24T16:28:08Z | |
dc.date.issued | 1991 | en_US |
dc.identifier.other | (UMI)AAI9124139 | en_US |
dc.identifier.uri | http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqm&rft_dat=xri:pqdiss:9124139 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/105472 | |
dc.description.abstract | Alkyl azides were found to undergo intramolecular cycloadditions with various olefins to provide 4,5-dihyro-3H-pyrroles, 2,3,5,6,7,7a-hexahydro-1H-pyrrolines (pyrrolizidines) and 1,2,3,5,6,7,8,8a-octahydroindolizines (indolizidines). Thermolysis of racemic mixtures of (Z)-7-azido-5-(methoxy)methoxy-3-phenylthio-1,3-heptadiene and (Z)-8-azido-5-(methoxy)methoxy-3-phenylthio-1,3-octadiene provided racemic mixtures of (1R*,7aR*)-2,3,5,7a-tetrahydro-1-(methoxy)methoxy-7-phenylthio-$ 1$H-pyrrolizine and (8R*,8aR*)-3,5,6,7,8,8a-hexahydro-8-(methoxy)methoxy-$ 1$-(phenylthio)indolizidine. The cyclization of these chiral substrates proceeded with high diastereoselectivity to produce materials closely related to the naturally occurring alkaloids heliotridine and swainsonine. Preparation of (Z)-7-azido-5-(methoxy)methoxy-3-phenylthio-1,3-heptadiene and (Z)-8-azido-5-(methoxy)methoxy-3-phenylthio-1,3-octadiene relied on the reduction of propargyl alcohols with sodium bis-(2-methoxy)ethoxy aluminum hydride followed by treatment with phenylsulfenyl chloride. Heating (S)-5-azido-3- ((benzyl)oxy) methoxypentene, which was derived from (S)-malic acid, at 120$\sp\circ$C. gave (S)-3- ((benzyl)oxy) methoxy-4,5-dihydro-2-methyl-3H-pyrrole. Treatment of this compound with butyllithium followed by 3-chloro-(2-chloromethyl)proprene and NaBH$\sb4$ provided (1S,8aS)-1- ((benzyl)oxy) methoxy-1,2,3,5,6,7,8,8a-octahydro-6-(methylene)indolizidine. This compound was closely related to the indolizidine alkaloid slaframine. The synthesis of slaframine from (1S,8aS)-1- ((benzyl)oxy) methoxy-1,2,3,5,6,7,8,8a-octahydro-6-(methylene)indolizidine was impossible due to the apparent instability of subsequent intermediate compounds. | en_US |
dc.format.extent | 200 p. | en_US |
dc.subject | Chemistry, Organic | en_US |
dc.title | Intramolecular cycloadditions of azides with olefins: Synthetic approaches to pyrrolizidine and indolizidine alkaloids. | en_US |
dc.type | Thesis | en_US |
dc.description.thesisdegreename | PhD | en_US |
dc.description.thesisdegreediscipline | Chemistry | en_US |
dc.description.thesisdegreegrantor | University of Michigan, Horace H. Rackham School of Graduate Studies | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/105472/1/9124139.pdf | |
dc.description.filedescription | Description of 9124139.pdf : Restricted to UM users only. | en_US |
dc.owningcollname | Dissertations and Theses (Ph.D. and Master's) |
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