Bioinspired Fe-Porphyrin Sites in a Porous Organic Polymer for Aerobic Oxidative Cyclization of Bioactive 2-Aminobenzoxazole

A cytochrome P450-mimetic monodispersed Fe-porphyrin-based porous framework is designed and synthesized via a FeCl3-assisted Friedel-Crafts reaction, to combine the advantages of heterogeneous systems with enzymatic reactivity. Specifically, the Fe-porphyrin site in this material mimics the heme-center in cytochrome P450, which efficiently catalyzes the aerobic oxidative cyclization of 2-aminophenols with isothiocyanates in water, affording a broad range of biologically relevant 2-aminobenzoxazoles in yields of up to 94% under mild conditions without the need for any external oxidants. Controlled experiments demonstrate the crucial role of molecular oxygen, indicating a radical-mediated reaction pathway. XAS provides insights into the local atomic structure, unravelling the key Fe(III)-active site influencing the reaction mechanism. Thermodynamically favorable formation of redox-active ligand and detailed mechanistic insights into the electron-transfer-mediated catalytic transformation are gained from quantum-chemical calculations. Oxygen activation forms peroxide-like species, followed by a sequence of radical steps ultimately leading to the product formation. Spin-density variation in these steps is well consistent with Fe(III)/Fe(II) redox-cycling. This work combining experiments and quantum simulations establishes a Fe-porphyrin-engineered porous organic polymer as an effective oxidative catalyst and highlights the potential of single-site bioinspired porous materials for sustainable aerobic oxidation chemistry.