The proton is the smallest Lewis acid and has been utilized in nature by enzymes for catalysis and stereocontrol of a variety of reactions long before chemistry was pursued as the discipline it is today. This precedent notwithstanding, there are very few examples of asymmetric catalysis which utilize a polar ionic hydrogen bond (essentially, a chiral proton complex). We have developed bifunctional Bis(AMidine) (BAM) catalysts that are efficient chiral proton catalysts for several mechanistically distinct transformations.
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This dissertation explores a rationally designed extension of BAM catalysis to an aza-Henry reaction employing α-nitro esters as pronucleophiles. This allows for the enantio- and diastereoselective synthesis of α,β-diamino acid derivatives. A reagent-controlled diastereodivergence is observed from the selectivity typically observed in BAM catalysis and is further explored with preliminary computational analysis. This methodology was applied to the synthesis of a potent heterocyclic proteasome inhibitor. Additionally, a chiral proton chaperoned biomimetic hetero-Diels-Alder reaction was effected with moderate enantioselectivity, and preliminary results towards the synthesis of fluorinated tetrahydroisoquinoline alkaloids are reported.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-07222016-145717 |
| Date | 04 August 2016 |
| Creators | Sprague, Daniel James |
| Contributors | Ned A. Porter, Ph.D., Janet E. Macdonald, Ph.D., Timothy P. Hanusa, Ph.D., Jeffrey N. Johnston, Ph.D. |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu/available/etd-07222016-145717/ |
| Rights | restricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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