Applications of iodonium salts and iodonium ylides as precursors for nucleophilic fluorination in Positron Emission Tomography

Abstract

This review summarizes the applications of iodonium compounds in the rapidly developing field of Positron Emission Tomography (PET). Reactions of diaryliodonium salts with fluoride anion have found wide practical application in PET as a fast and convenient method for the introduction of the radioactive [18 F]-fluoride into radiotracer molecules. The best synthetic methods for the preparation of iodonium precursors for PET are described, the mechanistic aspects of nucleophilic fluorination reaction are discussed, and specific examples of the preparation of PET radioligands are provided.

Copper-Catalyzed [18F]Fluorination of (Mesityl)(aryl)iodonium Salts

“…The first involves radiofluorination of powerful electrophiles such as diaryliodonium salts. 5 Diaryliodonium salts bearing the 2-thienyl group have been shown to react with [ 18 F]KF at elevated temperatures (often ≥150 °C) to afford [ 18 F]fluororarenes (Scheme 1 a). 6 In these systems, the 2-thienyl group directs radiofluorination to the other aromatic ligand on iodine with moderate to good selectivity.…”

“… 3 , 4 However, despite decades of research, there is no routine automated synthesis of 18 F-DOPA in clinical use . 5 , 6 To further demonstrate the utility of this method, we have performed the automated synthesis of 15 from the shelf stable salt 14-OTs . Under our standard conditions, 14-OTs afforded 17 ± 2% RCC of 15 with a SA of 4000 ± 2000 Ci/mmol ( n = 2).…”

Application of Hypervalent Iodine Compounds in Advanced Green Technologies (In Press)

“…In recent years, reactions of aryliodonium compounds with fluoride anion have found important practical application in Positron Emission Tomography (PET) as a fast and convenient method for the introduction of the radioactive [18F]-fluoride into radiotracer molecules [10,[61][62][63]. PET is a powerful method of molecular imaging based on the use of radiopharmaceuticals labeled with the short-lived positron-emitting radioisotopes 11 C, 18 F, 15 O, and 13 N. Fluorine-18 is the most commonly used in PET radioisotope owing of its a short positron linear range in tissue (2.3 mm) which gives the highest resolution PET images of all the available positron emitters.…”

“…Hypervalent iodine compounds are widely used as mild and selective oxidants and electrophilic group transfer reagents in organic synthesis. Iodonium salts have found widespread industrial application as initiators of polymerization [9], as well as precursors to [18F]fluorinated radiotracers in the Positron Emission Tomography (PET) [10]. The present review provides a summary of industrial applications of inorganic and organic polyvalent iodine compounds with emphasis on the applications of iodonium salts.…”

Cu-Mediated C–H 18F-Fluorination of Electron-Rich (Hetero)arenes

“…As shown in Scheme 2 , ArI III X 2 salts are known to participate in site-selective S E Ar reactions with electron-rich (hetero)arenes. 11 − 13 Furthermore, these transformations yield diaryliodonium salts, which we have shown to undergo Cu-catalyzed radiofluorination with [ 18 F]KF. 3a , 14 While electron-rich diaryliodonium salts are notoriously unstable, 5a , 15 this approach offers the advantage that they are generated in situ from stable and readily available C–H starting materials.…”