Chemistry, Department of


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A THESIS Presented to the Faculty of The Graduate College in the University of Nebraska In Partial Fulfillment of Requirements For the Degree of Master of Science, Major: Chemistry, Under the Supervision of Professor Stephen G. DiMagno. Lincoln, Nebraska: August, 2010
Copyright 2010 Joseph W. Graskemper


Positron Emission Tomography (PET) is a valuable clinical, research, and diagnostic technique for human and animal organ imaging. The current market for PET in the United States is $500 million per year and is projected to be $5.4 billion per year globally by 2015. To synthesize labeled radiotracers, we are most interested in using 18F as the isotope of choice because it is a nearly ideal positron emitting radionuclide.

Electron-rich aromatic substrates can be particularly difficult to fluorinate. We show that reductive elimination of I(III) diaryliodonium salts provide increased fluorination of electron-rich aromatic substrates. Modest yields of fluorinated product were initially observed due to the lack of regioselectivity in the reductive elimination process. It seemed clear that a better directing group would be needed if extremely electron-rich rings are to be fluorinated in high chemical (or radiochemical) yields using diaryliodonium salts. The use of [2.2]paracyclophane as a directing ligand has been shown by computational and experimental data to provide an increase in steric demand above the plane of the aromatic ring; therefore, destabilizing a reductive elimination transition state. This effect is sufficiently large to provide stereoelectronic control of unidirectional reductive elimination (SECURE) for most nucleophiles; however, benzyne chemistry was observed when fluorine and 2,2,2-trifluoroethoxide were used as nucleophiles.

To address the benzyne issue, we have shown that the choice of a judiciously substituted cyclophane substituent on I(III) can provide perfect regioselectivity for reductive elimination of iodocyclophanes and fluorination of electron-rich arenes. This work constitutes the first example of regiospecific fluorination of electron-rich aromatic rings using diaryliodonium fluorides. We believe this discovery paves the way for the synthesis of highly elaborated radiotracers from Ar2IF salts.

Advisor: Stephen G. DiMagno