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Dissertation
Making and Breaking Double Bonds: Adventures with Isocyanoalkenes and Benzonitriles
Doctor of Philosophy (Ph.D.), Drexel University
Jun 2024
DOI:
https://doi.org/10.17918/00010666
Abstract
The diversity of affordable isocyanides is skewed and underrepresented. Isocyanoalkenes can be easily prepared from benzonitriles and are valuable precursors for the formation of diverse isocyanides. The discovery of a copper-catalyzed isocyanide conjugate addition will be discussed, readily forming C-S, C-N, and C-C bonds to provide [beta]-functionalized isocyanides. Through a deep mechanistic understanding, the catalytic cycle can be interrupted to afford cyclopropylisocyanides, which are then demonstrated to be productive MCR candidates. The conjugate addition mode can be further elaborated to afford heterocycles through a unique conjugate addition-cyclization cascade. The thesis will also cover a counterintuitive interrupted SNAr-alkylation dearomatization of benzonitriles with lithiated nitrile and isocyanide nucleophiles. The dearomatization was found to be solventpromoted, rapidly providing diastereoselective 1,4-cyclohexadiene carbocyclic frameworks in a single step from commercially available benzonitriles. Setting the stage for the subsequent chemistry, the first chapter describes carbocyclic dearomatizations, providing an overview of available dearomatization strategies with a focus on the advancements made between 2020-2024. Chapter 2 describes a mild dearomatization approach using lithiated nitriles or isocyanides in SNAr-type additions,creating [sigma]-complexes that lead to diastereoselective, efficient dearomatizations. The third chapter serves as an introduction to isocyanides, covering the formation, structure, and reactivity of metalated isocyanides. Chapter 4 describes a method to prepare functionalized isocyanides though a novel copper iodide-Pyox catalyzed conjugate addition of sulfur, nitrogen, and carbon nucleophiles to isocyanoalkenes. Chapter 5 elaborates on the utility of chapter 4, exploring an addition-cyclization-decarboxylation cascade reaction, providing heterocyclic products.
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Details
- Title
- Making and Breaking Double Bonds
- Creators
- John-Paul Ryan Marrazzo
- Contributors
- Fraser F. Fleming (Advisor)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- xv, 357 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- College of Arts and Sciences; Chemistry; Drexel University
- Other Identifier
- 991021890212804721