Functionalization of Aromatic Organic Molecules by Anhydrous Flourides and by Reductive Elimination of Iodine(III)

Authors

Bijia Wang, University of Nebraska - LincolnFollow

Date of this Version

4-2010

Comments

A DISSERTATION Presented to the Faculty of The Graduate College at the University of Nebraska In Partial Fulfillment of Requirements For the Degree of Doctor of Philosophy, Major: Chemistry, Under the Supervision of Professor Stephen G. DiMagno. Lincoln, Nebraska: May, 2010
Copyright (c) 2010 Bijia Wang

Abstract

Solution phase reactivity of nucleophilic fluoride reagents is attenuated by ion-pairing interactions. ¹H-¹⁹F HOESY competition experiments permit generation of a fluoride ion affinity scale in the weak-binding regime. Direct DFT calculations of ion pair interaction energies as well as calculated cation electrostatic potential maps can be used to predict solution phase ion pairing tendencies for closely related ammonium cations. It was found by studying the decomposition of tetra-substituted ammonium cations by fluoride that: 1) rates of E2 decomposition is faster than the S_N2 pathway; 2) aryl substituents destabilize the cations; 3) steric strain tends to promote decomposition. This led us to prepare anhydrous trineopentylmethylammonium fluoride as a fluorinating regent with superior thermal stability.

We show that the reagent combination of PhIF₂/TBAF* is a convenient and effective dehydrating agent for anhydrous fluoride salts. In conjunction with ¹⁹F NMR spectroscopy, this reagent combination can be used as a rapid, convenient, general, and exquisitely sensitive aquametry method.

Fluorination via reductive elimination of diaryliodonium salts is investigated. Use of non-polar solvents suppresses disproportionation and leads to significant improvements in total fluorination yields. Fluoride promotes aryl ligand exchange processes of diaryliodonium species, which lowers the apparent regioselectivity of aryl fluoride extrusion from diaryliodonium fluorides under stoichiometric conditions, but this problem disappears at low fluoride ion concentration. A computational study shows that the regioselectivity is determined by transition state stability. We also show that ¹⁸F-DOPA can be synthesized in good yield with our improved procedures.

Diaryliodine(III) species can also be used to functionalize arenes with a variety of nucleophiles. Aryl azide formation is found to be a robust reaction that is insensitive to change of solvent, and which offers fast access to various azido aromatic compounds. Lastly, we show that an increase in steric demand above the plane of the aromatic ring leads to a high degree of regioselectivity in reductive elimination reactions of Ar₂I(III) salts. This effect is sufficiently large to provide stereoelectronic control of unidirectional reductive elimination (SECURE).

Adviser: Stephen G. DiMagno