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 moieties and CF₃ units were obtained in an atom-economical, effective and concise manner. The formation of products involves an intriguing cascade procedure consisting of nitroso-directed C–H bond alkylation of N-nitrosoaniline with a 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.