Aerobic oxidative condensation for the synthesis of phenoxazinone and phenazine derivatives catalyzed by an iron-porphyrin complex with a pendant imidazole ligand

Abstract

Phenoxazinone and phenazine represent privileged N-heteroaromatic scaffolds that are ubiquitously prevalent in natural products, bioactive molecules, and advanced functional materials. Conventional synthetic methodologies for constructing these complex heterocyclic frameworks have relied heavily on stoichiometric amounts of strong oxidants. However, these classical approaches are inevitably accompanied by severe environmental and efficiency issues, including poor functional group tolerance, harsh reaction conditions. Inspired by the active site architecture of natural heme-containing metalloenzymes like cytochrome c oxidase, we designed and synthesized a novel biomimetic iron-porphyrin complex featuring a covalently tethered pendant imidazole. This imidazole acts as an axial ligand, perfectly mimicking the natural enzyme's confined microenvironment. This catalyst exhibits outstanding activity for the aerobic oxidative cyclocondensation of o-aminophenols and o-phenylenediamines. The system demonstrates broad functional group tolerance, affording diverse phenoxazinone and phenazine derivatives in excellent yields using air as the terminal oxidant. This study offers a highly efficient, sustainable paradigm for biomimetic oxidation catalysis.