Nonheme iron catalyst mimics heme-dependent haloperoxidase for efficient bromination and oxidation

The [Fe]/H2O2 oxidation system has found wide applications in chemistry and biology. Halogenation with this [Fe]/H2O2 oxidation protocol and halide (X-) in the biological system is well established with the identification of heme-iron-dependent haloperoxidases. However, mimicking such halogenation process is rarely explored for practical use in organic synthesis. Here, we report the development of a nonheme iron catalyst that mimics the heme-iron-dependent haloperoxidases to catalyze the generation of HOBr from H2O2/Br- with high efficiency. We discovered that a tridentate terpyridine (TPY) ligand designed for Fenton chemistry was optimal for FeBr3 to form a stable nonheme iron catalyst [Fe(TPY)Br3], which catalyzed arene bromination, Hunsdiecker-type decarboxylative bromination, bromolactonization, and oxidation of sulfides and thiols. Mechanistic studies revealed that Fenton chemistry ([Fe]/H2O2) might operate to generate hydroxyl radical (HO•), which oxidize bromide ion [Br-] into reactive HOBr. This nonheme iron catalyst represents a biomimetic model for heme-iron-dependent haloperoxidases with potential applications in organic synthesis, drug discovery, and biology.