Developing Greener Methods for the Synthesis of Privileged Structural Motifs and Nitrogen Heterocycles
| dc.contributor.advisor | Kürti, László | en_US |
| dc.creator | Lovato, Kaitlyn | en_US |
| dc.date.accessioned | 2021-08-16T18:17:06Z | en_US |
| dc.date.available | 2022-08-01T05:01:12Z | en_US |
| dc.date.created | 2021-08 | en_US |
| dc.date.issued | 2021-06-07 | en_US |
| dc.date.submitted | August 2021 | en_US |
| dc.date.updated | 2021-08-16T18:17:06Z | en_US |
| dc.description.abstract | Efforts towards the development of novel and sustainable methods for the synthesis of privileged scaffolds that are often found in biologically active compounds are described. With the rising interest in green chemistry, the projects highlighted in Part One focused on developing atom economic protocols that minimized the use of transition metal catalysts and eliminated the utilization of harsh/hazardous reaction conditions. In Chapter 1, the investigation of transition metal-free conditions for the α-arylation of activated C(sp3)–H bonds in ester, nitrile, amide, sulfone and diaryl methane substrates is described. The substrate scope of this transformation was thoroughly explored, and a pKa-based reactivity guide was developed. In Chapter 2, the ability for O-cyclopropyl hydroxylamines to function as atom economic, [3,3]-rearrangement precursors for the construction of various classes of heterocycles is presented. An efficient route towards functionalized O-cyclopropyl hydroxylamines and a base-mediated rearrangement protocol for the construction of tetrahydroquinolines are described. Chapter 3 discusses a study conducted in collaboration with Dr. Carolyn Cannon’s group, which reveals naturally occurring biaryl compounds and their structural analogues as potential antimicrobial agents for further investigation. The straightforward synthesis of promising biaryl compounds via an atom economic, organocatalytic and scalable protocol is described. The projects highlighted in Part Two focused on the development of robust methods for the synthesis of nitrogen heterocycles, which are one of the most pervasive structural components in pharmaceutical compounds. Chapter 4 describes a Ti-mediated coupling of oxime ethers and primary alkyl Grignard reagents under Kulinkovich-like conditions to construct previously unreported four-membered nitrogen heterocycles. This work established a one-step protocol for the synthesis of NH-azetidines, which have demonstrated utility in drug discovery and development. In Chapter 5, an investigation into the design and synthesis of a bicyclic scaffold that could function as a next generation para-disubstituted arene molecular mimic is described. A robust protocol for the synthesis of N-substituted bicyclic carbamate scaffolds was developed and these fragments were found to possess comparable substituent geometry to para-disubstituted arenes. This moiety could possess improved aqueous solubility compared to its all-carbon BCP counterpart and has been presented as a promising and novel structural mimic. | en_US |
| dc.embargo.terms | 2022-08-01 | en_US |
| dc.format.mimetype | application/pdf | en_US |
| dc.identifier.citation | Lovato, Kaitlyn. "Developing Greener Methods for the Synthesis of Privileged Structural Motifs and Nitrogen Heterocycles." (2021) Diss., Rice University. <a href="https://hdl.handle.net/1911/111187">https://hdl.handle.net/1911/111187</a>. | en_US |
| dc.identifier.uri | https://hdl.handle.net/1911/111187 | en_US |
| dc.language.iso | eng | en_US |
| dc.rights | Copyright is held by the author, unless otherwise indicated. Permission to reuse, publish, or reproduce the work beyond the bounds of fair use or other exemptions to copyright law must be obtained from the copyright holder. | en_US |
| dc.subject | Methods Development | en_US |
| dc.subject | Arylation | en_US |
| dc.subject | [3,3]-Rearrangement | en_US |
| dc.subject | Biaryls | en_US |
| dc.subject | Nitrogen Heterocycles | en_US |
| dc.subject | Azetidines | en_US |
| dc.subject | Bioisosteres | en_US |
| dc.title | Developing Greener Methods for the Synthesis of Privileged Structural Motifs and Nitrogen Heterocycles | en_US |
| dc.type | Thesis | en_US |
| dc.type.material | Text | en_US |
| thesis.degree.department | Chemistry | en_US |
| thesis.degree.discipline | Natural Sciences | en_US |
| thesis.degree.grantor | Rice University | en_US |
| thesis.degree.level | Doctoral | en_US |
| thesis.degree.major | Organic Chemistry | en_US |
| thesis.degree.name | Doctor of Philosophy | en_US |
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