Deciphering the Role of Crown‐ether Receptor Orientation in C‐H Oxidation Catalyzed by Supramolecular Nonheme Fe^IV(O) Complexes

The outstanding efficiency and selectivity of enzymatic reactions, such as C-H oxidation by nonheme iron oxygenases, stems from a precise control of substrate positioning inside the active site. The resulting proximity between a specific moiety (a certain C-H bond) and the reactant (a Fe^IV(O) active species) translates into higher rates and selectivity, that can be in part replicated also with artificial supramolecular catalysts. However, structural modification of the position and orientation of the binding site both in enzymes and in artificial catalysts often leads to significant variations in reactivity that can be difficult to rationalize due to the system's complexity. Herein, we quantitatively analyzed the impact of such a structural modification (namely receptor orientation) on the C-H oxidation reactivity (kinetics, Effective Molarity) and selectivity by comparing simple supramolecular Fe^IV(O) models. Overall, we did not observe significant differences in reaction rates, but we noticed slight changes in the selectivity profile. These results indicate that, when a crown-ether is employed as a recognition site, the key ingredient for enhanced reactivity is the presence of the supramolecular receptor itself rather than its exact orientation, providing a guide for the rational design of supramolecular catalysts.