Electronic Theses and Dissertations

Date of Award


Document Type


Degree Name

Ph.D. in Pharmaceutical Sciences

First Advisor

David Colby

Second Advisor

John Rimoldi

Third Advisor

Robert Doerksen

Relational Format



Methods for creating fluorinated organic molecules are highly valuable in drug discovery and synthetic organic chemistry. Fluorine has been found to enhance desirable properties of organic molecules, leading to an increasing number of pharmaceuticals containing fluorine. The research studies in this dissertation center around the synthetic utility of pentafluoro-gem-diols, which are precursors of fluorinated building blocks. Using pentafluoro-gem-diols, we have discovered new synthetic methods to create valuable fluorinated molecules such as difluoro-β-amino ketones, difluoroethanols, pentafluorohemiketals, and pentafluoroisopropanols. Prior methods for making α,α-difluoro-β-amino ketones required multiple steps and the use of an unstable starting material. We have developed a one-step method that avoids the use of the unstable starting material to synthesize α,α-difluoro-β-amino ketones. Although fluorinated alcohols such as trifluoroethanol and hexafluoroisopropanol are valuable solvents, the methods to make different fluorinated alcohols are currently lacking. We successfully developed a method to synthesize 2,2-difluoroethanols, which are analogues of trifluoroethanol, and identified the conditions to produce pentafluoroisopropanols, which are analogues of hexafluoroisopropanol. During the development of synthetic methods using pentafluoro-gem-diols, we discovered the formation of transient pentafluorohemiketals when alcohols were used as solvents. We further identified a way to convert transient hemiketals into stable fluorinated molecules, and this method can be used to create complex fluorinated structures. Overall, our discoveries contribute to the development of new synthetic methods for creating valuable fluorinated compounds with potential applications in medicinal chemistry.

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