Copper-Stabilized Nitrene Radical in N─N Coupling: Facile Synthesis of Hydrazides and Pyrazole.

Despite extensive studies of electrophilic copper-nitrenoid species in nitrene transfer chemistry, the formation and application of Cu-nitrene radicals remain elusive and underdeveloped. Nitrene radicals, being highly reactive, actively participate in radical-type amination reactions under mild conditions. Using a well-defined Cu(II)-catalyst [Cu(L)Cl] (1) bearing 2,6-bis(phenyldiazenyl)pyridine (L) as a ligand, the otherwise copper-stabilized electrophilic nitrenoid species has been transformed to a nitrene radical species via selective catalyst to nitrene single electron transfer. The copper-stabilized nitrene radical species facilitates the selective formation of N─N bonds, resulting in N-acyl hydrazides. Catalyst 1 exhibits a broad substrate scope, smoothly functionalizing dioxazolone derivatives derived from long-chain fatty acids, including palmitic, stearic, oleic, and erucic acids, as well as biologically relevant acids such as 1-adamantane acetic acid, α-lipoic acid, and glutamic acid. Important N-heterocyclic amines, such as quinolines, carbazoles, and azepines, were also successfully functionalized. Catalyst 1 is also compatible with intramolecular N─N coupling, enabling the direct synthesis of pyrazoles in a single step, thereby emphasizing the method's synthetic versatility. The reaction is scalable, affording excellent yields in gram-scale synthesis. Detailed mechanistic investigations, control experiments, and EPR analysis, including DFT calculations, confirm the existence of a radical-mediated pathway.