Proline catalyzed enantioselective retro-aldol reaction
| dc.contributor.advisor | Ward, Dale E. | en_US |
| dc.contributor.committeeMember | Gravel, Michel | en_US |
| dc.contributor.committeeMember | Scott, Robert W. | en_US |
| dc.creator | Cheng, Muxi | en_US |
| dc.date.accessioned | 2015-05-15T12:00:12Z | |
| dc.date.available | 2015-05-15T12:00:12Z | |
| dc.date.created | 2013-12 | en_US |
| dc.date.issued | 2015-05-14 | en_US |
| dc.date.submitted | December 2013 | en_US |
| dc.description.abstract | In the Ward Group, stereoselective aldol reactions of thiopyran derived templates play an important role in polypropionate natural product syntheses. Central to this approach is the diastereo- and enantioselective synthesis of all possible aldol adducts 3 arising from tetrahydro-4H-thiopyran-4-one (1) and 1,4-dioxa-8-thiaspiro[4.5] decane-6- carboxaldehyde (2). There are four possible diastereomers of 3 indicated by the relative configurations at positions 3 and 1’ (syn or anti) and positions 1’ and 6’ (syn or anti). Up to date, the asymmetric aldol reaction of 1 with 2 catalyzed by L-proline or its tetrazole analogue 12 provides efficient access to 3,1’-anti-1’,6’-syn-3 (3-AS) without need for chromatography (>40 g scale; 75% yield, >98% ee) and 3,1’-syn-1’,6’-syn-3(3-SS) (via isomerization of 3-AS; >75% yield, 2 cycles); however, the preparation of enantiopure 3,1’-anti-1’,6’-anti-3 (3-AA) and 3,1’-anti-1’,6’-syn-3 (3-SA) still requires the use of enantiopure aldehyde 2 in a diastereoselective synthesis. Without a simple and scalable route, access to enantioenriched iterative aldol adducts and polypropionate natural products that are based on 3-AA and 3-SA skeletons are hindered. It was observed that conducting the asymmetric aldol synthesis of 3-AS on large scale gave enantioenriched 3-AA as a very minor product. This observation triggered the hypothesis of using L-proline to resolve racemic 3-AA via a retro-aldol reaction.In this thesis, the development, optimization, and application of an unprecedented L-proline catalyzed enantioselective retro-aldol reaction is described. Interesting mechanistic insights were uncovered. An unexpected isomerization process between 3-AA and 3-SA occurs in parallel with the retro-aldol process. The method was demonstrated to be a robust, flexible, and readily scalable process to access highly enantioenriched 3-AA (ee > 95%) and 3-SA (ee > 95%). To the best of our knowledge, this reaction represents the only reported enantioselective retro-aldol reaction catalyzed by L-proline. | en_US |
| dc.identifier.uri | http://hdl.handle.net/10388/ETD-2013-12-1320 | en_US |
| dc.language.iso | eng | en_US |
| dc.subject | L-proline | en_US |
| dc.subject | enantioselective | en_US |
| dc.subject | retro-aldol | en_US |
| dc.subject | asymmetric catalysis | en_US |
| dc.subject | polypropionate | en_US |
| dc.subject | aldol | en_US |
| dc.title | Proline catalyzed enantioselective retro-aldol reaction | en_US |
| dc.type.genre | Thesis | en_US |
| dc.type.material | text | en_US |
| thesis.degree.department | Chemistry | en_US |
| thesis.degree.discipline | Chemistry | en_US |
| thesis.degree.grantor | University of Saskatchewan | en_US |
| thesis.degree.level | Masters | en_US |
| thesis.degree.name | Master of Science (M.Sc.) | en_US |