First Advisor

David R. Stuart

Term of Graduation

Spring 2026

Date of Publication

5-20-2026

Document Type

Dissertation

Degree Name

Doctor of Philosophy (Ph.D.) in Chemistry

Department

Chemistry

Language

English

Subjects

arylation, Chemistry, DoE, iodine, iodonium, Synthesis

Physical Description

1 online resource (xvii, 264 pages)

Abstract

Substituted aromatic rings are present in industry in a plethora of organic molecules such as pharmaceuticals, agrochemicals, materials and beyond. Therefore, methods for broadly installing aryl rings into other compounds to create substituted aromatic rings are valuable to many organic chemists. Historically these transformations are achieved through methods such as nucleophilic aromatic substitution and metal catalyzed cross-coupling. Nucleophilic aromatic substitution is a user-friendly method in this space but is limited by reliance on specific electronics. Metal catalyzed cross-coupling reduced the dependence on electronics in this space, but metals are generally unattractive reagents due to high costs, toxicity and challenges with commercial availability of ligands. Diaryliodonium salts have emerged as a desirable alternative to this methodology. By leveraging the metal-like reactivity of hypervalent iodine, these reagents can overcome electron limitations and achieve broad scope while maintaining the affordability and simplicity of nucleophilic aromatic substitution.

Diaryliodonium chemistry is effective for arylation of various nucleophiles but is still actively being developed as it is relatively modern methodology. In prior literature diaryliodonium salts can have issues with chemoselectivity from the use of ineffective auxiliaries and competing reaction pathways. To address this I have used 1,3,5- trimethoxybenzene (TMB) as an auxiliary for chemoselective aryl transfer and applied Design of Experiment (DoE) optimization to develop reactions which arylate cyclic carbamates, phenols and malonates at the nitrogen, oxygen and carbon positions respectively. These reactions are generally high yielding and broadly tolerant of various complex substituents on iodonium salt as well as nucleophile.

This developed methodology also approached arylation via diaryliodonium salts with unique goals to highlight the diversity in applications of iodonium chemistry. In developing the N-arylation of carbamates, the conjugate base of the carbamate nucleophiles caused problematic aryne formation which was strategically limited during optimization (Chapter 2). The O-arylation of phenols by diaryliodonium salts had been previously developed in our group, but was revised here to operate in fully homogenous condition to promote industrial applicability. A new one-pot method towards accessing aryl(TMP)iodonium triflate salts was also developed here to help increase accessibility of iodonium salts which are more soluble in organic solvents (Chapter 3). The arylation of substituted malonates to synthesize benzylic quaternary malonates was developed with the goal to balance high yields with minimizing environmental harm, as seen in the conditions using ethyl acetate and minimal stoichiometry (Chapter 4). This work provides user friendly, high yielding and transition metal-free methodology to make substituted aromatic rings with various nucleophiles. In addition to being practical methodology, this work innovatively approaches developing iodonium chemistry with distinct goals, demonstrating their versatility to inspire more unique reactions in this space.

Rights

© 2026 Joseph Jordan Hatton

In Copyright. URI: http://rightsstatements.org/vocab/InC/1.0/ This Item is protected by copyright and/or related rights. You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s).

Persistent Identifier

https://archives.pdx.edu/ds/psu/44983

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