Document Type


Date of Award


Degree Name

Doctor of Philosophy (PhD)



First Advisor

Haoran Sun


Fluorination is a ubiquitous in modern materials and pharmaceuticals due to organofluorine compounds possessing unique physicochemical properties. However, this process is a demanding task due to difficulty in handling key reagents for selective fluorination. One strategy is the usage of deoxyfluorination reagents due to the wide availability of oxygen in many functional moieties. These reagents have allowed to production of new fluorinated materials and pharmaceuticals, yet the costs of several reagents and instabilities for others lead to restricted conditions, functional group tolerance, and safety risks for both users and the environment. Reported here is the culmination of a new hypothesis driven deoxyfluorination methodology that utilizes safe commercially available reagents with anion-π interactions to activate fluoride salts, achieve leaving group conversion, and successfully deoxyfluorinate aldehydes, alcohols, and phenols. Using tetrafluorophthalonitrile with anhydrous tetramethylammonium fluoride, difluoromethyl, monofluoromethyl, and aromatic fluorides were prepared in moderate to excellent yields. In addition, a selection of electron deficient fluoroaromatics were used in a comparison study to ascertain the degree of deoxyfluorination would be possible. These data were correlated with computational investigations using electrostatic potential maps, HOMO and LUMO modeling, and based on the corresponding phenoxide-based byproduct’s gas phase acidity, pKa, and fluoride-π interactions between each fluoroaromatic. Joint experimental and theoretical investigations have revealed the threshold for strong deoxyfluorination and laid the groundwork for synthetically preparing new fluoroaromatics to expand the scope of this methodology to a wider selection of substrates.

Subject Categories



Fluorination, Electron

Number of Pages



University of South Dakota

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