Synthesis Of Aryl Methyl Sulfones From Aryl Halides And DMSO: Copper-catalyzed Aerobic Oxidation And C-S Bond Cleavage/Formation

The synthesis of aryl sulfones has attracted much attention due to theirpromosing antibacterial, antifungal and antitumor activities. The synthesis of arylsulfones occupies a place of quite importance in organic and pharmaceuticalsynthesis. Although numerous types of method have been reported, convenient andenvironmentally benign methods for the oxidation of sulfides or sulfoxides are stillrequired. Air （atmospheric oxygen） is a green, safe and economical oxidant. Usingair as the sole oxidant still remains a challenge in this field. To our knowledge, it isthe first example of using atmospheric oxygen as the oxidant, DMSO and arylhalides as substrates to prepare aryl methyl sulfones.Firstly, with DMSO and PhI as substrates, we carefully examined the effect ofcatalysts, ligand, base, solvent, reaction temperature and time on the reaction. Theoptimized reaction conditions are summarized as follows: the catalyst Cu₂O, the ligandacetyl, base t-BuOK, DMSO as substrate as well as the solvent, reaction temperature100¹200C and reaction time20³6h. Under the optimized condition, phenyl methyl sulfonecould be obtained in a high isolated yield （92%）. We further examined the scope andlimitation of this method. The experimental results showed that Ar-X （X=I, Br） with eitherelectron-donating group or electron-withdrawing group could afford the correspondingtarget product in moderate to good yields. However, with halogenated alkane and othersulfoxides as substrates except DMSO, the corresponding sulfones could be not obtained atall. In order to confirm the molecular structures, the products were characterized by GC-MS,HR-MS,¹H NMR and¹³C NMR.In order to probe the reaction mechanism, the isotopic labeling experiments withH₂¹⁸O and¹⁸O₂were performed. The isotopic labeling studies demonstrated clearlythat the additional oxygen atom of aryl methyl sulfones originated from molecular O₂instead of H₂O. The copper-catalyzed the aerobic oxidation plays an important role inthe formation of aryl methyl sulfones. In addition, based on the control experimentalresults, we deduce that the formation of aryl methyl sulfones may undergo twoprocesses. Namely, DMSO is oxidized by oxygen to dimethyl sulfone, and then the coupling reaction of iodobenzene with dimethyl sulfone affords the target product arylmethyl sulfone. The t-BuO-probably as the nucleophile plays a key role in the cleavageof the C-S bond.In conclusion, we have developed a novel method for the synthesis of arylmethyl sulfones from aryl halides and dimethyl sulphoxide. The methodology cantolerate many important functional groups. The air instead of toxic or expensivecompounds as the oxidant and Cu₂O as the catalyst make the present syntheticroute show a potential application in organic and pharmaceutical synthesis.