dc.creator | Sprague, Daniel James | |
dc.date.accessioned | 2020-08-22T20:32:11Z | |
dc.date.available | 2018-08-04 | |
dc.date.issued | 2016-08-04 | |
dc.identifier.uri | https://etd.library.vanderbilt.edu/etd-07222016-145717 | |
dc.identifier.uri | http://hdl.handle.net/1803/13464 | |
dc.description.abstract | 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.
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. | |
dc.format.mimetype | application/pdf | |
dc.subject | aza-Henry | |
dc.subject | nitro Mannich | |
dc.subject | organocatalysis | |
dc.subject | amino acid | |
dc.subject | brevianamide | |
dc.subject | Diels-Alder | |
dc.subject | Biomimetic | |
dc.title | Chiral Proton Catalysis: New Applications in Enantioselective Hetero-Diels-Alder Reactions, Amino Acid Synthesis, and Tetrahydroisoquinoline Alkaloid Synthesis | |
dc.type | dissertation | |
dc.contributor.committeeMember | Ned A. Porter, Ph.D. | |
dc.contributor.committeeMember | Janet E. Macdonald, Ph.D. | |
dc.contributor.committeeMember | Timothy P. Hanusa, Ph.D. | |
dc.type.material | text | |
thesis.degree.name | PHD | |
thesis.degree.level | dissertation | |
thesis.degree.discipline | Chemistry | |
thesis.degree.grantor | Vanderbilt University | |
local.embargo.terms | 2018-08-04 | |
local.embargo.lift | 2018-08-04 | |
dc.contributor.committeeChair | Jeffrey N. Johnston, Ph.D. | |