Uses of Diaryliodonium Salts and Methods for their Synthesis

Diaryliodonium salts have been studied continuously since the first report of their synthesis in 1894. Diaryliodonium salts are I(III) derivatives that are air- and moisturestable. The reactivity of these compounds resembles the organometallic chemistry of heavy transition metal ions such as Pb(IV), Hg(II), Th(III), and Pd(II). A significant advantage of diaryliodonium salts is that they can carry undergo many of the aryl functionalization reactions of heavy metal organometallic complexes, yet they have little to no toxicity and they are relatively inexpensive to prepare. The DiMagno laboratory uses diaryliodonium salts as precursors in the final synthetic step of radiopharmaceuticals; given that radiotracer prepared in this manner need to be injected into humans shortly after their synthesis, it is a virtual requirement that precursors and labeling reactions do not generate potentially toxic byproducts in radiotracer preparations. This thesis comprises to two distinct projects. The first is the discussion of the synthesis of the highly electron-rich diaryliodonium salts in which one of the rings is an indole. Diaryliodonium salts featuring indole substituents constitute a relatively uncommon and poorly characterized class of compounds to date. The chapter will discuss the synthesis of diaryliodonium salts that feature 2- and 5-indole substituents, and will report nucleophilic substitution of these compounds with a variety of nucleophiles. Progress towards synthesizing diaryliodonium salts that could serve as precursors to radiofluorinated or radioiodinated serotonin, tryptamine, and tryptophan derivatives, along with model studies that provide insight into the nature of nucleophilic substitution for these substrates, will be reported. Because of the electron-rich nature of the C-2 position of indole, conventional methods to synthesize diaryliodonium salts featuring this moiety failed. Here I discuss application of a novel synthetic approach to diaryliodonium salts, developed by Dr. Bao Hu in our group, which features condensation of Grignard reagents with aryl iodonium precursors. This reaction proved to be an extremely useful tool for the synthesis of extremely electron rich diaryliodonium salts that we were unable to prepare using the oxidative coupling methodology developed in our laboratory. The second part of this thesis will discuss the synthesis of diaryliodonium salts on solid-phase resins, and the potential for using solid phase techniques for radiopharmaceutical synthesis Very little previous work has been done in synthesizing diaryliodonium salts on a solid support, so this work is quite new, and not fully developed at this time. Advisor: Stephen G. DiMagn