Sponsor
Portland State University. Department of Chemistry
First Advisor
David R. Stuart
Term of Graduation
Spring 2025
Date of Publication
5-12-2025
Document Type
Dissertation
Degree Name
Doctor of Philosophy (Ph.D.) in Chemistry
Department
Chemistry
Language
English
Subjects
Aryne, C-H functionalization, Iodonium, Thianthrenium
Physical Description
1 online resource (xxiv, 282 pages)
Abstract
The enormous importance of aromatic rings in organic molecules cannot be understated. Aromatic rings are present in the majority of pharmaceuticals, agrochemicals, and consumer products. The way in which these rings are arranged and substituted results in a molecule’s unique properties. Because of this, the current limitations of the chemical methods used to synthesize these molecules results in limited structural diversity and thus missed opportunities for the development of value-added products. To this end, this work demonstrates novel methods of aryne synthesis, aryl thianthrenium synthesis and a unique approach to structural scaffold hopping. The approaches presented herein allow for rapid access to structurally complex molecules.
Current methods of aryne synthesis either suffer from a lack of chemoselectivity or are costly and time intensive to synthesize. To improve access to aryne intermediates, we have developed a formal dehydrogenation of arenes that utilizes site-selective C-H thianthrenation or iodination to generate aryne precursors (Chapter 2). The generation of the aryne intermediate is then triggered by sodium tert-butoxide or lithium bis(trimethylsilyl)amide. This method’s numerous benefits over conventional methods of aryne generation are described.
Arene functionalization via C-H thianthrenation is limited to electron rich arenes. To overcome this limitation, electron-deficient potassium aryl trifluoroborates can be used in lieu of electron-rich arenes (Chapter 3). These reagents are easily accessible from commercially available aryl boronic acids or pinacol esters in a single step. In this study, we compare the reactivity of aryl boronic acids to potassium aryl trifluoroborates andii demonstrate the synthetic utility of electron-deficient aryl thianthrenium salts for metal- catalyzed cross couplings and photoredox catalysis.
Finally, we present efforts toward the use of the formal dehydrogenation methodology reported herein as a valuable synthetic platform for molecular scaffold hopping (Chapter 4). Scaffold hopping methodology is demonstrated by the synthesis of a derivative of the popular beta-blocker Propranolol from a cheap simple arene in a single reaction vessel. Furthermore, this platform is shown to useful for the synthesis of naphthalenes, naphthols and 1,4-naphthoquinones.
Rights
© 2025 Riley Augustus Roberts
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Persistent Identifier
https://archives.pdx.edu/ds/psu/43872
Recommended Citation
Roberts, Riley Augustus, "Enabling New Synthetic Platforms for Aryne Synthesis with Aryl Thianthrenium Reagents" (2025). Dissertations and Theses. Paper 6824.