I2-catalyzed tandem sp3 C–H oxidation and annulation of aryl methyl ketones with amidoximes for the synthesis of 5-aroyl-1,2,4-oxadiazoles†

Abstract

A metal-free, iodine-catalyzed protocol has been developed for constructing biologically significant 5-aroyl 1,2,4-oxadiazole scaffolds using aryl methyl ketones and amidoximes. The strategy produces structurally diverse 5-aroyl 1,2,4-oxadiazoles in good to excellent yields, with a broad substrate scope that includes drug derived substrates. The reaction proceeds through iodine/DMSO-mediated oxidation of aryl methyl ketones, followed by imine formation and subsequent cyclization to yield the desired products. Additionally, this protocol has successfully produced the carbonyl analogs of ataluren and tioxazafen and has facilitated some intriguing late-stage transformations.