Development of Highly Reactive Sulfone Iminium Fluoride Reagents and Their Application in Fluorine Methodologies

<p>Organofluorines are important molecules that have found great use in the pharmaceutical industry. Deoxyfluorination is an appealing methodology available to synthetic chemists for forming carbon-fluorine bonds. In the first part of this work, we report the synthesis of sulfone iminium fluorides (SIFs), a new and highly reactive sulfur (VI) fluoride reagent class. A small library of these compounds was synthesized in five simple, modular steps from cheap starting materials. The SIF reagents successfully convert alcohols and carboxylic acids into their corresponding fluorinated moieties in high yields at room temperature with unprecedented reaction speed, requiring just 60 seconds. Furthermore, the SIF reagents were applied in sulfur fluoride exchange (SuFEx), creating the first charged SuFEx adducts and in similar speed.</p> <p>In the second part of this project, we utilize SIFs to perform deoxyfluorination on more challenging substrates, namely phosphinic acids and related P(V)-OH molecules to generate phosphorus(V)-fluoride molecules at room temperature in just 60 seconds. The reaction exhibits excellent yields and broad substrate scope, with low sensitivity to steric congestion. Formation of phosphinic fluorides was also possible from the corresponding phosphine oxides albeit at a slower reaction rate.</p> <p>In the third part of this work, we explore a modified Beckmann rearrangement using SIFs. We find that the reaction of a range of ketoximes with SIF rapidly produces imidoyl fluorides in 60 seconds. These fluorinated molecules have low stability but serve as useful ii i precursors for the synthesis of amidines and imidates when reacted with amines and alcohols, respectively.</p> <p>In the final part of this project, we synthesize fluoroformamidines via the rearrangement of in situ-generated amidoximes using SIFs. The stable fluorinated products are created in 60 seconds under mild conditions and this methodology represents a significant improvement over previous protocols for their formation. Additionally, fluoroformamidines serve as precursors for the synthesis of ureas and carbamimidates when treated with water and phenols.</p> <p>Altogether, this work presents a variety of transformations involving novel SIF reagents.</p>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Open Access

Discipline thesis:degree_discipline

Chemistry

Year

2026

Author dc:creator

• Vogel, James

Repository record dc:identifier

https://repository.brynmawr.edu/dissertations/268

OAI identifier oai:identifier

oai:repository.brynmawr.edu:dissertations-1284