1. Catalytic Functionalization of Alkyl Groups Adjacent to Azoles

 

A plethora of bioactive compounds and natural products bear an azole subunit within their complex structural frameworks. A footstep to realize those complex structures in atom economic fashion rely on the direct functionalization of C–H bonds adjacent to an azole group. In addition, the resulting functionalized azole compounds can be simply modified into practically significant genre of a-functionalized carboxylic acids that are otherwise inaccessible through a formal a-functionalization strategy. Despite C(sp3)−H bonds next to an azole ring are somewhat triggered by the electronic influence of the heteroaromatic system, the acidity of those C−H bonds are still low (pKa approx. >25 in DMSO) and require a metal-catalyzed activation. We have studied the scope of functionalizing a methyl and/or methylene group(s) adjacent to an azole ring enabled by late and earth-abundant transition metals under oxidative condition. Collectively, all these approaches have led to access otherwise challenging methoxylated (C–O), chalcogenated (C–S, C–Se), aminated (C–N) and cyanomethylenated (=CHCN) compounds in a rather simpler manner.