Syntheses and resolutions of heterobifunctionalized p-stereogenic phosphines: applications as substrate-bound chiral auxiliaries and ligands in asymmetric reactions
| dc.contributor.advisor | Keay, Brian A. | |
| dc.contributor.author | Benoit, Wendy L. | |
| dc.date.accessioned | 2017-12-18T21:26:41Z | |
| dc.date.available | 2017-12-18T21:26:41Z | |
| dc.date.issued | 2007 | |
| dc.description | Bibliography: p. 252-268 | en |
| dc.description | Some pages are in colour. | en |
| dc.description.abstract | P-stereogenic phosphine ligands play an important role m the development of new and effective asymmetric catalysts. A review of the recent literature revealed that Pstereogenic phosphines are challenging synthetic targets, as they do not occur naturally and must therefore be made through asymmetric synthesis. Plans were then devised to test a camphor-derived chiral auxiliary and a spiro-1 ,3-arnino alcohol auxiliary for the asymmetric synthesis of P-stereogenic phosphines for use as ligands in asymmetric catalysis Camphor-derived organoazide [2-(tert-butyl-dirnethyl-si lanyloxy )-7, 7-di??ethylbicyclo[2.2. l ]hept- l-yl]-methanesulfony l azide was attached to a heterobifunctionalized racemic P-stereogenic oxazaphospholidine to give a 1: 1 mixture of diastereomeric phosphinimines that were separated by chromatographic methods. The absolute configuration of each phosphorus center was determined by X-ray crystallography. Efforts to remove the chiral auxiliary were unsuccessful. Thus, the introduction of different functional groups at phosphorus were carried out with the auxiliary attached with up to 77% yield of ring-opened product. However, the tedious chromatography and troublesome later steps forced abandonment of the approach in pursuit of more practical methods. A derivative of spiro 1,3-amino alcohol ( 5R,6R)-6-amino-spiro[ 4.4 ]nonan-1-ol was used as a chiral auxiliary to form a heterobifunctionalized P-stereogenic oxazaphosphorinane in a 2.5: 1 mixture of diastereomers. The major diastereomer was isolated from the mixture via recrystallization in a 36% yield and its absolute stereochemistry was found to be Rp by X-ray crystallography. (SR, 6aR, 9aR)-6-Methyl-5-phenyl-decahydro-4-oxa-6-aza-5-phospha-cyclopenta[ d]indene borane was then reacted with various nucleophiles in efforts to develop a general route to P-stereogenic phosphines. The nucleophilic oxazaphosphorinane ring openings were perfom1ed in up to 77% yield, but unfortunately gave a 50:50 mixture of diastereomeric products. The lack of stereoselectivity prompted efforts to be directed toward using deprotected (SR, 6aR, 9aR)-6-methyl-5-phenyl-decahydro-4-oxa-6-aza-5-phospha-cyclopenta[ d]indene borane as a P-stereogenic catalyst precursor. After failed attempts at using (SR, 6aR, 9aR)-6-methyl-5-phenyl-decahydro-4- oxa-6-aza-5-phospha-cyclopenta[ d]indene borane as a P-stereogenic organocatalyst, conditions were developed to remove the borane protecting group and use (SR, 6aR, 9aR)-6-methyl-5-phenyl-decahydro-4-oxa-6-aza-5-phospha-cyclopenta[ d]indene as a Pstereogenic ligand for transition metal catalysis. Poor results from this led to the synthesis of a chelating spiro oxazaphosphorinane derivative. Rhodium-catalyzed hydrogenation of methyl 2-acetamidoacrylate usmg the dimerized sp1ro oxazaphosphinane ligand was performed with up to 15% ee. Extreme sensitivity of the oxazaphosphinane ligands toward oxidation prevented further optimization of the enantioselectivity. | |
| dc.format.extent | xxiv, 280 leaves : ill. ; 30 cm. | en |
| dc.identifier.citation | Benoit, W. L. (2007). Syntheses and resolutions of heterobifunctionalized p-stereogenic phosphines: applications as substrate-bound chiral auxiliaries and ligands in asymmetric reactions (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/1367 | en_US |
| dc.identifier.doi | http://dx.doi.org/10.11575/PRISM/1367 | |
| dc.identifier.uri | http://hdl.handle.net/1880/102368 | |
| dc.language.iso | eng | |
| dc.publisher.institution | University of Calgary | en |
| dc.publisher.place | Calgary | en |
| dc.rights | University 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.title | Syntheses and resolutions of heterobifunctionalized p-stereogenic phosphines: applications as substrate-bound chiral auxiliaries and ligands in asymmetric reactions | |
| dc.type | doctoral thesis | |
| thesis.degree.discipline | Chemistry | |
| thesis.degree.grantor | University of Calgary | |
| thesis.degree.name | Doctor of Philosophy (PhD) | |
| ucalgary.item.requestcopy | true | |
| ucalgary.thesis.accession | Theses Collection 58.002:Box 1701 520492218 | |
| ucalgary.thesis.notes | UARC | en |
| ucalgary.thesis.uarcrelease | y | en |
Files
Original bundle
1 - 1 of 1
Loading...
- Name:
- thesis_Benoit_2007.pdf
- Size:
- 111.77 MB
- Format:
- Adobe Portable Document Format
- Description:
- Thesis