Divergent Synthesis of Functionalized Indazole N-Oxides with Anticancer Activity via the Cascade Reaction of N-Nitrosoanilines with Diazo Compounds and HFIP

Presented herein is a novel and divergent synthesis of indazole N-oxides based on the one pot cascade reaction of N-nitrosoanilines with diazo compounds and HFIP. By using this method, indazole N-oxides tethered with diversely functionalized benzoyl or phenylacrylate moiety as well as CF3 unit were obtained in an atom-economical, effective and concise manner. The formation of product involves an intriguing cascade procedure consisting nitroso-directed C−H bond alkylation of N-nitrosoaniline with diazo compound as the carbene precursor, followed by enol nucleophilic addition onto the nitroso group, HFIP-assisted ring-opening and aromatization-driven dehydrogenation. In addition, the decent anti-proliferative activity of the products thus obtained against three human cancer cell lines demonstrated their prospects as lead compounds.