Solid‐Supported Iodonium Salts for Fluorinations

Abstract

Solid‐supported iodonium salt precursors have been prepared and used for the production of fluoroarenes. The importance of the resin functionality for the attachment of the iodonium salt moieties has been demonstrated. Furthermore, the production of new iodonium salt precursors for fluorination has been achieved by an alternative and improved method with respect to those previously described. The successful radiofluorination of a simple solid‐supported precursor with no‐carrier‐added (n.c.a.) [18F]fluoride shows the suitability of the method for the production of useful PET synthons.

Enabling Efficient Positron Emission Tomography (PET) Imaging of Synaptic Vesicle Glycoprotein 2A (SV2A) with a Robust and One-Step Radiosynthesis of a Highly Potent 18F-Labeled Ligand ([18F]UCB-H)

“…However, some of those precursors have, at this stage of their development, physicochemical properties that make them less suited than others for automated and cGMP productions of PET tracers. Iodonium salts, for their part, have repeatedly been shown to be efficient and stable late-stage radiofluorination precursors from their first reported [ 18 F]-radiolabeling in 1995, which prompted us to develop such an iodonium-based precursor for the one-step radiosynthesis of [ 18 F] 7 . − To this day, little information has been made available on the routine, high-activity [ 18 F]-labeling of iodonium salts in the framework of cGMP productions; filling that gap was also one of the objectives of this project. We also tackled what may have represented a major drawback of iodonium [ 18 F]-radiolabelings in a cGMP perspective, which is the use of the genotoxic radical scavenger TEMPO ((2,2,6,6-tetramethyl­piperidin-1-yl)­oxy) for controlling the radical side reactions occurring during the radiolabeling and increasing the yield and reproducibility thereof. ,, …”

Synthesis of Aryl(2,4,6-trimethoxyphenyl)iodonium Trifluoroacetate Salts

“…While these methods have been a primary driving force for the utilization of diaryl­iodonium salts in novel arylation reactions, direct access to diaryl­iodonium salts incorporating other counteranions are relatively limited. Specifically, although diaryl­iodonium trifluoro­acetates are useful salts in their own right, we were surprised to find that a well-established synthesis from aryl iodides has not been reported, , although they are suggested as intermediates in the synthesis of diaryl­iodonium triflates with trifluoro­acetic acid as solvent. , Given empirical evidence for the importance of counteranion identity on reactivity, the development of methods that deliver diaryl­iodonium trifluoro­acetates directly, without recourse to anion exchange, would enable reaction development with these reagents.…”

Base/Cryptand/Metal‐Free Automated Nucleophilic Radiofluorination of [18F]FDOPA from Iodonium Salts: Importance of Hydrogen Carbonate Counterion

“…These modifications could explain the lower yield obtained (36 %) compared to the reported procedure (63 %). Alternatively, to this time‐consuming and relatively complex one‐pot reaction, we turned our attention to the recent development described by Wirth and co‐workers for solid‐supported synthesis of iodonium salts. This strategy required the synthesis of trimethylstannane 7 from aryl iodine derivative 4 using hexamethylditin and Pd(PPh 3 ) 4 as catalyst.…”