Recent advances in iodine–DMSO mediated C(sp3)–H functionalization of methyl-azaarenes via Kornblum oxidation

Abstract

N-aromatic heterocycles (azaarenes) are useful molecules found in many natural products and pharmaceuticals. Their methyl derivatives (methyl azaarenes) are a unique class of molecules. The methyl group can be converted into an aldehyde group in the iodine–DMSO medium via Kornblum oxidation. The heteroaromatic aldehydes generated are of prime importance in medicinal chemistry and can be isolated or can be trapped by nucleophiles to construct diverse azaarene-linked scaffolds. The whole process can be summed up as functionalization of C(sp³)–H to form aldehydes, which are further functionalized to form an array of diversely functionalized azaarenes. This particular reaction system has gained popularity in recent years. In this reaction system, the methyl azaarene first gets iodinated. The alkyl iodide generated in situ meets the requirements of Kornblum oxidation in the presence of DMSO. Kornblum oxidation is one of the most popular and most preferred reactions of oxidation of alkyl halides because of its non-toxic and metal-free nature and mild reaction conditions. Thus, we present a collection of literature, which cover the reports available in the last decade for the C(sp³)–H functionalization of methyl azaarenes in the iodine–DMSO medium during 2013–2023.