Sponsor
Portland State University. Department of Chemistry
First Advisor
David R. Stuart
Term of Graduation
Spring 2024
Date of Publication
5-29-2024
Document Type
Dissertation
Degree Name
Doctor of Philosophy (Ph.D.) in Chemistry
Department
Chemistry
Language
English
Subjects
Arene, Aryne, Arynophile, Hypervalent, Iodonium
DOI
10.15760/etd.3777
Physical Description
1 online resource (xxiv, 264 pages)
Abstract
Arenes are a ubiquitous structural motif occurring in numerous organic pharmaceuticals, agrochemicals, secondary metabolites, and functional materials. As such, studies on the characterization, functionalization, and properties of arenes have been a central pillar of organic chemistry since its inception. Early methods to synthesize complex benzenoid rings focused on ring functionalization rather than ring construction due to the high accessibility of very simple arenes and the wide range of aromatic substitution reactions discovered in the late 19th century. As the importance of arenes was recognized more methods of building complex arenes emerged. Both classical and modern approaches are still somewhat limited, often suffering from electronic constraints, pre-functionalization hurdles, selectivity issues, and low availability materials. Aryne intermediates have been viewed as having tremendous potential for the synthesis of complex arene rings. Early methods of generating arynes are efficient and often involve deprotonation ortho- a suitable leaving using extremely strong bases, thus lowering chemoselectivity. More chemoselective methods have been developed but they typically require a harsh multistep synthesis of the aryne precursor. This body of work aims to bridge the gap between the synthetic accessibility of aryne precursors and their chemoselectivity.
Described herein are new methods for the efficient and chemoselective generation of arynes starting from abundant chemical feedstocks such as aryl-iodides and simple arenes. The first portion of this work is focused on addressing and overcoming the need for strong base in aryne formation from easily accessible diaryliodonium salt aryne precursors. This is achieved using a potassium phosphate-THF base-solvent system. A quantitative study on the chemoselectivity of the new method and common aryne generating base systems is also provided.
An additional method for the synthesis of arynes by a formal dehydrogenation of simple arenes is also presented. This work capitalizes largely on the electrophilic coupling of simple arenes and λ3-iodanes to form an intermediate diaryliodonium aryne precursor. This approach can be conducted in one or two pots and gives high yields of arynes in a rapid and chemoselective fashion from simple arene C-H bonds. A mechanistic analysis of the salt and aryne forming reactions is provided.
Finally, a new reactivity scale for the reactions of various arynophiles with 3-chlorobenzyne is described. This work aims to remove anecdotal evidence for chemoselectivity in the trapping of arynes with various arynophiles and replace it with a quantitative reactivity parameter we have termed the arynophilicity constant.
Rights
© 2024 Bryan Edward Metze
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Persistent Identifier
https://archives.pdx.edu/ds/psu/42276
Recommended Citation
Metze, Bryan Edward, "Efficient and Chemoselective Access to Highly Functionalized Arenes by C-H Deprotonative Generation of Aryne Intermediates" (2024). Dissertations and Theses. Paper 6645.
https://doi.org/10.15760/etd.3777