Homogeneous Iron Catalyzed C−H Amination

Iron-catalyzed C-H amination is emerging as an attractive and sustainable method to install amine functionalities into organic compounds. Amination of C(sp3)-H bonds is usually mediated by an iron-nitrene intermediate via a Hydrogen Atom Abstraction/Radical Recombination mechanism reminiscent of biomimetic C-H oxidation. Accordingly, this transformation can be catalyzed by engineered iron enzymes, heme and nonheme iron complexes as well as iron salts, although it is often limited to intramolecular reactions and/or activated positions. Aromatic C(sp2)-H amination is mediated by addition of electrophilic iron nitrenes or protonated N-radical intermediates (produced with Fe catalysts) to aromatic systems. Again, high selectivity is obtained via (pseudo) intramolecular reactions. From a mechanistic perspective, several iron nitrene intermediates have been isolated and characterized over the years in different ligand scaffolds and iron oxidation states. Structure-activity correlations have been drawn only in few cases and point to a key role of the spin density on the nitrene ligand and of the iron oxidation state. This review describes the state of the art for homogeneous iron catalyzed C(sp3)-H and C(sp2)-H amination focusing on the last 5 years (2019-2023) from a mechanism-driven catalyst design perspective.Homogeneous iron catalysts are emerging as an attractive and sustainable method for the amination of C(sp3)-H bonds and aromatic rings, mainly via high-valent iron-nitrene intermediates. This review describes the advancements in this field during the last 5 years (2019-2023) from a mechanism-driven catalyst design perspective. image