Regiospecific Intramolecular O-Demethylation of the Ligand by Action of Molecular Dioxygen on a Ferrous Complex: Versatile Coordination Chemistry of Dioxygen in FeCl2 Complexes with (2,3-Dimethoxyphenyl) α-Substituted Tripods in the tris(2-Pyridylmethyl)amine Series

Abstract

We report in this article one of the first examples of a reaction of O-demethylation carried out at a Fe(II) center by molecular dioxygen, in the homogeneous phase in non-porphyrinic chemistry. This reaction parallels at the intramolecular level a very important process found in biology leading to the derivatization and elimination of drugs by oxygen-dependent enzymes that contain nonheme iron centers. To get insight into some reactivity aspects of this reaction, we have used dioxygen and iron complexes coordinated to ligands that are substituted by methoxy groups. We detail in this work the coordination chemistry of FeCl(2) to the series of mono- (L(1)), di- (L(2)), and tris(2,3-dimethoxyphenyl) (L(3)) alpha-substituted ligands in the tris(2-pyridylmethyl)amine series and the behavior of the complexes upon reaction with molecular dioxygen. As main outcomes of this study, we demonstrate that the methoxy group does not need to be coordinated to the metal center to undergo O-demethylation, but needs to be properly orientated close to an oxygenated form of the metal. We also demonstrate the importance of the environment in the reactivity with molecular dioxygen: whereas a regular 18-electron Fe(II) reacts with O(2), a five- coordinate, 16-electron center may be oxygen-stable, if the access of dioxygen to the reaction site is locked.