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Dissertation
Cyclizations with Nitriles and Isocyanides via Cascade Sequences
Doctor of Philosophy (Ph.D.), Drexel University
Sep 2023
DOI:
https://doi.org/10.17918/00001851
Abstract
[beta]-Oxoalkenenitriles are potent Michael acceptors which react with a variety of nucleophiles to generate complex heterocyclic and carbocyclic molecular frameworks. These core frameworks are embedded within numerous classes of natural products and pharmaceutical drugs making them attractive synthetic targets. As a class, the reactivity of [beta]-Oxoalkenenitriles is akin to that of superglue, [alpha]-cyanoacrylate! Therefore, the challenge has been to develop methods amenable to small molecule synthesis and to circumvent polymerization. The focus of this dissertation is to discuss novel methodologies developed to harness the unique reactivity of [beta]-Oxoalkenenitriles towards the synthesis of highly functionalizes heterocyclic and carbocyclic frameworks with an emphasis on mechanistic perspectives. As such the thesis is a summary of four distinct areas of research. The first chapter is a review, focused on the Lewis acid catalyzed addition of two or more isocyanide molecules in multi-component type reactions. The review surveys the reactivity of isocyanides, reaction conditions and outcomes leading to successful multicomponent reactions. Chapter 2 discusses a first in class multicomponent reaction in which the Lewis acid SiCl4 promotes the conjugate addition of tertiary isocyanides to cyclic oxonitriles triggering a double isocyanide insertion-cascade enabling the rapid assembly of a novel class of 3-acylpyrroles. An analogous addition of tertiary and benzyl isocyanides to acyclic oxonitriles affords 2-aminofurans; which rapidly oxidize to pyrrolidinones upon exposure to air! Chapter 3 discusses a DMSO oxidation-cyclization cascade to generate highly oxidized bicyclic carbocycles. Lastly, Chapter 4 discusses future directions towards the synthesis of formamides promoted by SiCl4. Collectively, the thesis demonstrates several novel methodologies for the rapid assembly of heterocyclic and carbocyclic frameworks initiated by cascade reaction with oxonitriles.
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Details
- Title
- Cyclizations with Nitriles and Isocyanides via Cascade Sequences
- Creators
- John Kornfeind
- Contributors
- Fraser F. Fleming (Advisor)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- xiii, 199 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- College of Arts and Sciences; Chemistry; Drexel University
- Other Identifier
- 991021230111904721