Bioinspired oxidation reactions of phenols with dinuclear copper complexes

Abstract

This thesis is focused on the understanding of the cooperative effects in di- and oligonuclear transition metal complexes and their further application as catalysts for the oxidation of phenol substrates. In nature, two or more proximate metal ions are useful for inter alia multi-electron redox transformations of substrate molecules. This is particularly important for reactions involving aerial dioxygen. A prominent example are the so-called type 3 copper centers, which contain two copper ions within their active site (mainly Catechol Oxidase and Tyrosinase). In order to mimic the active site of type 3 copper centers we apply pyrazole-based ligands, where the anionic pyrazolate unit has a high tendency to span two metal ions in a exo-bidentate fashion. A range of copper complexes were successfully prepared and moreover, the coordination spheres of the individual copper ions as well as the intramolecular metal-metal separation were properly tuned. Well-characterized copper complexes with desirable properties were applied as catalysts in different types of oxidation reactions of phenolic substrates. In particular, it was shown that certain dicopper complex catalyzes the unusual oxidative C-C coupling of 2,4,6-trimethylphenol (TMP) to yield 3,3',5,5'-tetramethylstilbene-4,4'-quinone (TMSQ). Moreover, the mechanism of formation and structure of intermediates in the catalytic reactions of TMP were elucidated by means of various spectroscopic methods. On the basis of these studies it was shown that C-C coupling of TMP is taking place only in the presence of dicopper complex and dioxygen as oxidant. Dicopper(II)-phenolate complexes with 4-hydroxybenzamide and pentafluorophenol substrates that are inert to any oxidation reaction were successfully prepared, which revealed a mode of interaction between phenols and dicopper complex. In addition, it was shown that, depending on the reaction conditions applied, dicopper catalyst can catalyze the 1,6-nucleophilic addition of several small molecules such as MeOH to TMP.All these above-mentioned studies provided a better understanding of the principles that govern the catalytic activity towards phenols of pyrazolate-based complexes reminiscent of type 3 dicopper sites, allowed to propose a preliminary mechanism for the oxidative C-C coupling of TMP and provide the significant background necessary to advance future studies on bioinspired phenol oxidation reactions.