Electron-rich Alkynes and Azodicarboxylates Chemistry Towards Vicinal Diamine Motif Containing Small Molecules and N-Heterocycles
Date of Award
Doctor of Philosophy (PhD)
Daniel C. Whitehead
William T. Pennington
Heterocyclic molecules that contain nitrogens and consist of four, five and six-membered rings such as azetidinones (eg: β-lactams), pyrroles, indoles, azoles, triazoles, oxadiazines, and oxadiazinones, etc. are ubiquitous in the use of pharmaceutical fields. This also reflected in the recently FDA approved unique small-molecule pharmaceuticals, where about 90% of those molecules contain a nitrogen heterocycle. Particularly, the vicinal diamino motif has been appeared in leading drug directing candidates such as penicillin, cephalosporins, and oseltamivir (Tamiflu) over the past years.
Historically, there has been minimal interest in synthesizing a broad scope of vicinal diamino motif-containing small molecules and heterocyclic compounds for the purpose of using them in the medicinal fields. Therefore, synthesizing the vicinal diamino motif in a few synthetic steps with a broad substrate scope has remained challenging. In this work, we assess the potential to access the vicinal diamino skeleton through the reactivity of various azodicarboxylates (as the main nitrogen source) with various electron-rich alkynes. With further investigations, this chemistry leads us to develop novel methods to generate several classes of vicinal diamino motif-containing products, such as diazacyclobutenes (four-membered heterocyclic compound) and 2-iminothioimidates (acyclic vicinal diimino compounds), and highly substituted tetrahydroindoles (fused bicyclic compound consist of a five-membered N-heterocycle) in good yields with a broad substrate scope.
Additionally, with the divergent reactivity of this chemistry under the catalytic environment; a novel compound consist of a 6-membered 1,3,4-oxadiazin-2-one heterocyclic skeleton was produced. This dissertation further discloses the substrate dependent reactivity, divergent reactivity, mechanistic investigations and variable temperature dynamic NMR studies of these novel compounds.
In overall, this electron-rich alkynes and azodicarboxylates chemistry described in this document has been validated a novel protocol to rapidly access diverse vicinal diamino motif containing acyclic and cyclic compounds which have potential utility in organic synthesis and medicinal chemistry.
Last part of this dissertation describes the development of a protocol for the in-house synthesis of the cellulose nanocrystals, optimization and scale up synthesis of the poly(etheleneimne) functionalized cellulose nanocrystals to investigate the possibility of reducing the cost of the synthesis while maintaining the environmental remediation properties of these functionalized materials at the same efficiency.
Narangoda, Chandima Jeewantha, "Electron-rich Alkynes and Azodicarboxylates Chemistry Towards Vicinal Diamine Motif Containing Small Molecules and N-Heterocycles" (2020). All Dissertations. 2711.