Honors Theses
Date of Award
Spring 5-7-2026
Document Type
Undergraduate Thesis
Department
Chemistry and Biochemistry
First Advisor
David Colby
Second Advisor
John Rimoldi
Third Advisor
Ryan Fortenberry
Relational Format
Dissertation/Thesis
Abstract
Fluorinated organic molecules have significant and growing importance in medicinal chemistry and drug discovery. The fluorine atom can optimize desired drug-like characteristics of pharmaceuticals. Highly fluorinated functional groups are gaining interest as building blocks in the synthesis of drug-like molecules. A hexafluoroisopropanol (HFIP) group combines extensive levels of fluorination with an adjacent alcohol and can be incorporated into small molecules to improve their biological activity. However, little research has explored the modification and installation of hexafluoroisopropanol groups in medicinal candidates. The goal of this project was to find efficient ways to synthesize diverse hexafluoroisopropanol derivatives. Our laboratory previously discovered that an amidinate salt of hexafluoroacetone hydrate, known as the Colby reagent, reacts with anilines under acidic conditions to produce hexafluoroisopropanols. The reaction scope was expanded using copper-catalyzed reactions with indole derivatives. In addition, the discovery of a novel bipyridine reagent demonstrated promising reactivity as a hydroxyfluoroalkylating reagent. Replacing the Colby reagent with this new bipyridine reagent in both acidic and copper-catalyzed systems increased the yield of the product. Overall, these findings provide an efficient platform for the incorporation of HFIP and expand access to fluorinated building blocks with potential relevance to pharmaceutical development.
Recommended Citation
Arnett, Abigail G., "Synthesis of Derivatives of Hexafluoroisopropanol for Pharmaceutical Design" (2026). Honors Theses. 3400.
https://egrove.olemiss.edu/hon_thesis/3400
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