Ni-Catalyzed Synthesis of Trisubstituted Hydrazones via Cascade Dehydrogenative Coupling of Alcohol

Trisubstituted hydrazones are important motifs in medicinal chemistry and organic synthesis, but conventional methods often require multistep sequences and stoichiometric reagents. In this report, a phosphine-free, air-stable Ni(II)-catalyzed approach is utilized for the acceptorless dehydrogenative coupling of hydrazines, alcohols, and halides for the efficient synthesis of trisubstituted hydrazones. The method proceeds via a tandem sequence under mild conditions, generating only H₂ and H₂O as byproducts. This sustainable approach enables direct C-N bond formation from readily available feedstocks with high selectivity and atom economy. We also detected two potential intermediates in the catalytic cycle using an ESI-MS analysis. Based on these studies and control experiments, a catalytic mechanism was proposed. The synthetic utility of the hydrazones is demonstrated by their transformation into Fischer indole, benzimidazole derivatives, and the one-pot synthesis of optodynamer precursors. CHEM21 green metrics indicate that nickel-catalyzed C-N coupling is highly efficient and atom-economic.