Synthesis of cis,cis-6-aminospiro[4.4]nonan-1-ol and application of its derivatives as chiral ligands and auxiliaries

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dc.contributor.advisorKeay, Brian A.
dc.contributor.authorLait, Susan M.
dc.date.accessioned2005-08-19T20:54:28Z
dc.date.available2005-08-19T20:54:28Z
dc.date.issued2004
dc.descriptionBibliography: p. 192-204, 217-220en
dc.description.abstractA review showed that 1,3-amino-alcohols and their derivatives had proven useful as sources of chiral induction in organic synthesis and that there was much room for research in this area. Of particular interest was a cis,cis-spiro-1,3-amino-alcohol in which two spirocyclic pentacycles offered structural rigidity and the cis,cis geometry of the molecule held the amino and hydroxy moieties in close proximity. A synthesis of (1RS,5RS,6RS)-6-aminospiro[4.4 ]nonan-1-ol is reported in which only one diastereomer was produced in 22% yield over 6 steps. The structure of this amino-alcohol was confirmed by X-ray crystallography of the pivalamido-p­bromobenzoate derivative. Resolution of this amino-alcohol was achieved by co­crystallization with 0.5 equiv. mandelic acid in acetonitrile to give material that which appeared enantiopure by chiral GC. Conversion of (1R,5R,6R)-6-aminospiro[ 4.4]nonan-1-ol to (lR,5R,6R)-N-( 6-hydroxyspiro[ 4.4 ]non-1-yl)-2,2-dimethylpropionamide was accomplished in 1 step with 97% yield, and this amido-alcohol was used as a chiral auxiliary in BCh-catalyzed Diels­Alder reactions. Dienophiles were prepared in 1 step, in 74-77% yield, from (1R,5R,6R)­N-( 6-hydroxyspiro[ 4.4 ]non-l-yl)-2,2-dimethylpropionamide, and reaction of these dienophiles with a variety of dienes in the presence of 2 equiv. BCl₃ at -78°C gave Diels-Alder adducts with 77 to >98% de. The amido-alcohol auxiliary was readily cleaved from the Diels-Alder adducts by saponification and could be recovered in sufficient quantity and purity to warrant recycling. (1S,5S,6.5)-6-Aminospiro[4.4 ]nonan-1-ol was converted to phosphino-oxazine ligand (3aS,6aS,9aS)-5-(2-diphenylphosphanylphenyl)-1,2,3,3a,6a, 7,8,9-octahydro-4- oxa-6-azacyclopenta[ d]indene in 90% yield over 2 steps. Its structure was confirmed by X-ray crystallography of the ZnCh complex. The phosphino-oxazine was used as a ligand for asymmetric Pd-catalyzed alkylation of dimethyl malonate with 1,3-diphenyl acetate to give product with up to 91 % ee.en
dc.format.extentxxvi, 200 leaves : ill. ; 30 cm.en
dc.identifier.citationLait, S. M. (2004). Synthesis of cis,cis-6-aminospiro[4.4]nonan-1-ol and application of its derivatives as chiral ligands and auxiliaries (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/12784en_US
dc.identifier.doihttp://dx.doi.org/10.11575/PRISM/12784
dc.identifier.isbnAC1 .T484 2004 L35en
dc.identifier.lccAC1 .T484 2004 L35en
dc.identifier.urihttp://hdl.handle.net/1880/42583
dc.language.isoeng
dc.publisher.institutionUniversity of Calgaryen
dc.publisher.placeCalgaryen
dc.rightsUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.
dc.titleSynthesis of cis,cis-6-aminospiro[4.4]nonan-1-ol and application of its derivatives as chiral ligands and auxiliaries
dc.typedoctoral thesis
thesis.degree.disciplineChemistry
thesis.degree.grantorUniversity of Calgary
thesis.degree.nameDoctor of Philosophy (PhD)
ucalgary.item.requestcopytrue
ucalgary.thesis.accessionTheses Collection 58.002:Box 1514 520492031
ucalgary.thesis.notesUARCen
ucalgary.thesis.uarcreleaseyen
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