Regiospecific Syntheses of Functionalized Diaryliodonium Tosylates via [Hydroxy(tosyloxy)iodo]arenes Generated in Situ from (Diacetoxyiodo)arenes

Abstract

Ready access to 18F-labeled aryl synthons is required for preparing novel radiotracers for molecular imaging with positron emission tomography. Diaryiodonium salts react with cyclotron-produced no-carrier-added [18F]fluoride ion to produce [18F]aryl fluorides. We aimed to prepare functionalized diaryliodonium salts to serve as potential precursors for producing useful 18F-labeled aryl synthons, such as 18F-labeled halomethylbenzenes, benzaldehydes and benzoic acid esters. Such salts were designed to have one functionalized aryl ring, one relatively electron-rich ring, such as 4-methoxyphenyl or 2-thienyl, and a non-fluorine containing weakly nucleophilic anion. Generation of a [hydroxy(tosyloxy)iodo]arene from a functionalized (diacetoxyiodo)arene in situ followed by treatment with an electron-rich arene, such as anisole or thiophene, or with a functionalized arylstannane gave expedient regiospecific access to a wide range of functionally diverse diaryliodonium tosylates in moderate to high yields (44–98%). The described methodology broadens the scope for producing new functionalized diaryliodonium salts for diverse applications.

Trimethoxyphenyl (TMP) as a Useful Auxiliary for in situ Formation and Reaction of Aryl(TMP)iodonium Salts: Synthesis of Diaryl Ethers

“…Diaryliodonium salts contain an aryliodonium leaving group that leads to mechanistic advantages over traditional halides: facile oxidative addition to first-row metals (i. e., copper) and increased scope in metal-free reactions (Scheme 1b). [7][8][9] We have an ongoing interest in the development of reactions to synthesize [10,11] and use [7b-d] aryl(TMP)iodonium salts, and herein we describe a methods to generate and use them in situ for phenol arylation. A potential solution is to form the diaryliodonium in situ and exploit the aforementioned advantages of the iodonium leaving group while using more readily abundant starting materials (Scheme 1c).…”

Single‐Step Radiosynthesis of “18F‐Labeled Click Synthons” from Azide‐Functionalized Diaryliodonium Salts

“…Recently, we have reported success in preparing functionalized diaryliodonium tosylates by generating reactive [hydroxy(tosyl)iodo]arenes in situ for reaction with activated arenes or arylstannanes. [17] Yamamoto and Togo [18] have reported the syntheses of [hydroxy(sulfonyloxy)iodo]arenes from iodoarenes and m CPBA ( m -chloroperbenzoic acid) in the presence of various sulfonic acids. Because this method uses a mild oxidizing agent under ambient temperature, we were attracted to its use for preparing azide-bearing [hydroxy(tosyloxy)iodo]arenes that might then be converted in situ into the target diaryliodonium tosylates by treatment with anisole or thiophene (Figure 3).…”

Single-step syntheses of no-carrier-added functionalized [18F]fluoroarenes as labeling synthons from diaryliodonium salts

“…We have previously reported 17 the syntheses of most of the functionalized diaryliodonium tosylates used in this study, based on two methods, A and B (Fig. 2).…”

“…The required (diacetoxyiodo)arenes were themselves obtained as white crystalline solids by oxidation of the corresponding iodoarenes with 32 wt% peracetic acid in acetic acid. 17 …”