The Synthesis of 3-Vinylindolines by the Palladium-Catalyzed Intramolecular Allylic Alkylation of Cinnamyl Acetates and the Synthesis of Polyphenolic 4-Aryl-3,4-dihydrocoumarins by Domino Friedel-Crafts Reactions
| dc.contributor.author | Rydzik, Jordan | |
| dc.date.accessioned | 2018-10-24T19:56:42Z | |
| dc.date.available | 2019-10-25T04:50:12Z | |
| dc.date.issued | 2018-10-24 | |
| dc.date.submitted | 2018-10-22 | |
| dc.description.abstract | Historically, the alkylation of allylic acetates with non-stabilized C(sp3) nucleophiles has been challenging. The metal-catalyzed alkylation of allylic acetates and carbonates with organotin and organoboron reagents has significantly increased the scope of nucleophiles available to participate in such reactions; however, the generation of C(sp3)-C(sp3) bonds in this manner remains difficult. We therefore designed a substrate in order to explore the intramolecular transition metal-catalyzed alkylation of an allylic acetate with a C(sp3) organotin nucleophile. From this substrate we were able to successfully synthesize a number of 3-vinylindolines in modest to good yields in as little as seven steps through the palladium-catalyzed intramolecular allylic alkylation of cinnamyl acetates with tethered organotin nucleophiles. To the best of our knowledge this represents the first example of such a transformation, resulting in the formation of novel C(sp3)-C(sp3) bonds. It has been shown that polyphenolic procyandins, members of the flavonoid class of compounds, possess moderate affinity for a synthetic model of a proline rich region of the microtubule associated protein tau. The phosphorylation of this region of tau is thought to be correlated with the development of intraneuronal protein deposits, a hallmark of Alzheimer’s disease physiopathology. In the second part of this thesis, we set out to utilize the domino Friedel-Crafts alkylation/acylation of benzylidene Meldrum’s acids with phenols previously developed in our group for the synthesis of a number of polyphenolic 4-aryl-3,4-dihydrocoumarins, members of the neoflavonoid class of compounds. By synthesizing a library of polyphenolic neoflavonoids in this manner, which possessed variation in the number and position of hydroxyl groups about the aromatic rings, a systematic survey of the structure-activity relationship was to be conducted. This would allow us gain a better understanding of potential therapeutic agents that may be able to attenuate the formation of these intraneuronal protein deposits in the treatment of Alzheimer’s disease. | en |
| dc.identifier.uri | http://hdl.handle.net/10012/14059 | |
| dc.language.iso | en | en |
| dc.pending | false | |
| dc.publisher | University of Waterloo | en |
| dc.subject | Organic chemistry | en |
| dc.subject | Synthetic chemistry | en |
| dc.subject | Allylic alkylation | en |
| dc.subject | Palladium | en |
| dc.subject | Friedel-Crafts alkylation | en |
| dc.subject | Friedel-Crafts acylation | en |
| dc.subject | Tsuji-Trost | en |
| dc.subject | Indoline | en |
| dc.subject | Indole | en |
| dc.subject | Coumarin | en |
| dc.subject | Alzheimer's disease | en |
| dc.subject | Polyphenols | en |
| dc.title | The Synthesis of 3-Vinylindolines by the Palladium-Catalyzed Intramolecular Allylic Alkylation of Cinnamyl Acetates and the Synthesis of Polyphenolic 4-Aryl-3,4-dihydrocoumarins by Domino Friedel-Crafts Reactions | en |
| dc.type | Master Thesis | en |
| uws-etd.degree | Master of Science | en |
| uws-etd.degree.department | Chemistry | en |
| uws-etd.degree.discipline | Chemistry | en |
| uws-etd.degree.grantor | University of Waterloo | en |
| uws-etd.embargo.terms | 1 year | en |
| uws.contributor.advisor | Fillion, Eric | |
| uws.contributor.affiliation1 | Faculty of Science | en |
| uws.peerReviewStatus | Unreviewed | en |
| uws.published.city | Waterloo | en |
| uws.published.country | Canada | en |
| uws.published.province | Ontario | en |
| uws.scholarLevel | Graduate | en |
| uws.typeOfResource | Text | en |