Aza Analogs of Arene Oxygenase Metabolization via Iron Catalysis

Oxidative transformations of arenes catalyzed by oxygenases constitute the core metabolism of aromatic compounds in living organisms. The intriguing hydroxylative dearomatization and arene hydroxylation reactions inherent to these processes have been successfully adapted for organic synthesis, inspiring the development of small-molecule catalysts that mimic these enzymatic reactivities. However, the aza analogs of such arene metabolic pathways, aimed at constructing the valuable C-N bonds, remain elusive in both enzymatic systems and biomimetic catalysis. In this work, we demonstrate that an iron-aminyl radical can emulate the iron-oxo core of oxygenases in arene transformations, enabling the dearomative amino-etherification and an NIH shift-type amination of benzamides. The dearomatization reaction selectively yields 1,3-cyclohexadienes, facilitating the construction of diverse three-dimensional architectures; the NIH shift-type amination offers a divergent approach to accessing constitutional isomers of 2-anilinobenzamides, which are valuable synthetic intermediates for pharmaceutically relevant heterocycles.