Synthesis of 3,5-Disubstituted-(1H-) and (2H-) Heteroaryl-1,2,4-triazoles via an Oxidative Annulation Strategy

1,2,4-Triazole is a ubiquitous heterocycle of significance for pharmaceuticals, materials, and ligand design. A convergent, atom-economical strategy for the construction of this important moiety has been developed, leveraging functionalized heteroaryl hydrazonimides and carbaldehydes via iodine-mediated oxidative annulation in an efficient, scalable, and metal-free manner, providing completely chemoselective 1H- or 2H-3,5-disubstituted-1,2,4-triazoles of relevance to separation science and medicinal chemistry. The twenty-nine-example substrate scope is highlighted by rapid access to sp²- and sp³-hybridized substituents through carbaldehyde selection. Diversely functionalized pyridyl- and heteroaryl components were incorporated through a hydrazonimide synthon with several examples having relevance to unsymmetric, soft-N-donor complexant scaffolds utilized in minor actinide extraction in support of improving the sustainability of the nuclear fuel cycle. Single-crystal X-ray diffraction experiments confirmed the presence of 1H- and 2H-tautomers. Density functional theory computations provided support of a proposed mechanistic hypothesis. Method optimization, substrate scope, scale-up experiments, and a preliminary reaction mechanism are reported herein.