Exploring Synthetic Strategies for 1H‐Indazoles and Their N‐Oxides: Electrochemical Synthesis of 1H‐Indazole N‐Oxides and Their Divergent C−H Functionalizations

Abstract The selective electrochemical synthesis of 1 H ‐indazoles and their N ‐oxides and the subsequent C−H functionalization of the 1 H ‐indazole N ‐oxides are described. The electrochemical outcomes were determined by the nature of the cathode material. When a reticulated vitreous carbon cathode was used, a wide range of 1 H ‐indazole N ‐oxides were selectively synthesized, and the electrosynthesis products were deoxygenated to N‐heteroaromatics, owing to cathodic cleavage of the N−O bond via paired electrolysis, when a Zn cathode was used. The scope of this electrochemical protocol is broad, as both electron‐rich and electron‐poor substrates were tolerated. The potency of this electrochemical strategy was demonstrated through the late‐stage functionalization of various bioactive molecules, making this reaction attractive for the synthesis of 1 H ‐indazole derivatives for pharmaceutical research and development. Detailed mechanistic investigations involving electron paramagnetic resonance spectroscopy and cyclic voltammetry suggested a radical pathway featuring iminoxyl radicals. Owing to the rich reactivity of 1 H ‐indazole N ‐oxides, diverse C−H functionalization reactions were performed. We demonstrated the synthetic utility of 1 H ‐indazole N ‐oxides by synthesizing the pharmaceutical molecules lificiguat and YD (3); key intermediates for bendazac, benzydamine, norepinephrine/serotonin reuptake inhibitors, SAM‐531, and gamendazole analogues; and a precursor for organic light‐emitting diodes.