Acid-free Synthesis Of Highly Functionalized Diacetoxyiodoarenes And Diaryliodonium Salts

Diaryliodonium salts, have wide applications in organic synthesis as a kind ofmild and non-toxic arylation reagent for a large variety of organic and inorganicnucleophiles.They are also useful as initiators for cationic polymerization forgenerating protons upon exposure tolight.Recently, highly functionalizeddiaryliodonium salts have been shown to be useful precursors for the synthesis ofradiopharmaceuticals for positron emission tomography (PET).Several methods have been reported for synthesis of diaryliodonium saltsdirectly from iodoarenes (Ar-I).All of these oxidation requiredacidic conditions andsuffered from poor yield and selectivity when applied to highly electron-richsubstrates with multiple functional groups, especially acid-sensitive groups.Recently,the lack of universally available methods for direct n.c.a. radiofluorination of complexiodides (III) limits the wide use of18F-labelled radio tracers. According to currentsituations, we proposed an innovative method to synthesis diaryliodonium salts offormula ArIX2in acid-free conditions. N-F reagents were used as the oxidants andTMSX were added to tame the intermidates so thatstable iodides (III) could beobtained.Firstly, NMR scale reactions were carried out to investigate theoxidation of ArIby with a combination of five N-F reagents and four TMSX salts at differenttemperatures.4-Iodoanisole and5-iodo-2,3-dihydrobenzofuran were selected asmodel compounds. The results were compared in terms of percentage of substrateconversion. The optimal oxidation conditions were determined to beusing thecombination of Selectfluor and TMSOAc at45C. A mechanism for the N-Freagents/TMSX oxidation of iodoarenes is proposed. The optimized oxidation conditions were applied to fourteen more aryl iodidesfeaturing variousfunctionalities.The results showed eleven out of sixteen iodoarenes were successfullyconverted to the corresponding diacetoxyiodo arenes with NMR yields ranging from85%to96%. The scope and limitations of the Selectfluor/TMSOAc oxidation werediscussed.Some of thediacetoxyiodo arenes could not be isolated without beingdecomposed.In order to obtainisolable ArI(III) species, thediacetoxyiodoarenesformedwere converted in situ to the corresponding diaryliodoniumhexaflourophosphatesby reacting with potassiumbenzenetrifluoroborate in thepresence of trimethylsilyl trifluoroacetate followed by ion-exchangeingwithpotassium hexaflourophosphate. The expected products were obtained inexcellent isolated yield. Seven out of eleven diaryliodonium hexafluorophosphateshadnever been reported before.The structures of all compounds were confirmed by1H-NMR/13C-NMR/Mass spectra.In summary, iodoarenes bearing various functionalities could be selectively andefficiently converted to the corresponding diacetoxyiodoarenes using a mixture ofSelectFluor and TMSOAc. The role of TMSOAc is likely to be reacting with andtaming the highly reactive I(III) intermediate from oxidative addition of iodine to theN-F bond. The method is compatible with acid labile substrates and generally offershigher selectivity and yields compared with widely adopted procedures usingH2O2/Ac2O and NaBO3/AcOH as oxidants. The diacetoxyiodoarenes could be furtherstabilized by being converted to the corresponding diaryliodonium salts for easyisolation and purification..