A Mild and General One‐Pot Synthesis of Densely Functionalized Diaryliodonium Salts

Abstract

Diaryliodonium salts are powerful and widely used arylating agents in organic chemistry. Here we report a scalable, synthesis of densely functionalized diaryliodonium salts from aryl iodides under mild conditions. This two-step, one-pot process has remarkable functional group tolerance, is compatible with commonly employed acid-labile protective group strategies, avoids heavy metal and transition metal reagents, and provides a direct route to stable precursors to PET imaging agents.

Efficient Pathway for the Preparation of Aryl(isoquinoline)iodonium(III) Salts and Synthesis of Radiofluorinated Isoquinolines

“…[5k,5l] Diaryliodonium salts have also shown to be useful in the production of PET radiotracers, including [ 18 F]TFB, [5d] [ 18 F]flumazenil, [6] [ 18 F]mFBG, [7] [ 18 F]6-fluorodopamine, [5g,8] [ 18 F]FPhe, [5g] [ 18 F]DAA1106, [5g] and [ 18 F]6-F-DOPA. [5e,9] Despite the significant role of radiofluorination using iodonium methods in the PET tracer development, the preparation of these hypervalent iodine precursors [10] necessitates oxidation of iodoarene in acid media [11] or exchange with organometallic species, [12] for example stannylated/boronated compounds, which are prepared from “Miyaura borylation” type cross-coupling reactions with the corresponding aryl halides (Scheme 1a). These common procedures have potential risks of contamination, if heavy metal reagents, for example tin, is utilized or show incompatibility with oxidation conditions in the presence of sensitive functionalities, including alkene and nitrogenous compounds.…”

Hypervalent aryliodine compounds as precursors for radiofluorination

“…Recently, a method has been developed for synthesizing (diacetoxyiodo)arenes in the absence of protic acids . This method is based on treating a substituted iodoarene with Selectfluor ( N ‐chloromethyl‐ N ′‐fluorotriethylenediammonium bis(tetrafluoroborate); F‐TEDA‐BF 4 ) and TMSOAc (Figure ).…”

“…Diaryliodonium salts are generally stable to air and moisture and may be prepared on a multigram scale . Several diaryliodonium salts are now commercially available.…”

“…31 Recently, a method has been developed for synthesizing (diacetoxyiodo)arenes in the absence of protic acids. 39 This method is based on treating a substituted iodoarene with Selectfluor (N-chloromethyl-N′-fluorotriethylenediammonium bis(tetrafluoroborate); F-TEDA-BF 4 ) and TMSOAc ( Figure 6). This method is applicable to electron-rich and electron-poor iodoarenes and tolerates both acid-and base-sensitive functional groups.…”

“…Diaryliodonium salts are generally stable to air and moisture and may be prepared on a multigram scale. 39 Several diaryliodonium salts are now commercially available. Our laboratory's experience is that diaryliodonium salts can be stored for months, even years, in the cold and dark without decomposition.…”