Record Broken: A Copper Peroxide Complex with Enhanced Stability and Faster Hydroxylation Catalysis

Abstract

Tyrosinase model systems pinpoint pathways to translating Nature's synthetic abilities for useful synthetic catalysts. Mostly, they use N-donor ligands which mimic the histidine residues coordinating the two copper centres. Copper complexes with bis(pyrazolyl)methanes with pyridinyl or imidazolyl moieties are already reported as excellent tyrosinase models. Substitution of the pyridinyl donor results in the new ligand HC(3-tBuPz) (4-CO MePy) which stabilises a room-temperature stable μ-η :η -peroxide dicopper(II) species upon oxygenation. It reveals highly efficient catalytic activity as it hydroxylates 8-hydroxyquinoline in high yields (TONs of up to 20) and much faster than all other model systems (max. conversion within 7.5 min). Stoichiometric reactions with para-substituted sodium phenolates show saturation kinetics which are nearly linear for electron-rich substrates. The resulting Hammett correlation proves the electrophilic aromatic substitution mechanism. Furthermore, density functional theory (DFT) calculations elucidate the influence of the substituent at the pyridinyl donor: the carboxymethyl group adjusts the basicity and nucleophilicity without additional steric demand. This substitution opens up new pathways in reactivity tuning.

Copper‐Catalyzed Monooxygenation of Phenols: Evidence for a Mononuclear Reaction Mechanism

“…The formation and detection of corresponding intermediates as well as their impact on catalytic activity thus have always been of central importance in TY model chemistry. [6,12,15,17,19,20] In order to obtain more information about the factors influencing the performance of the catalysts, our group focused on the improvement of TY model compounds based on mononuclear copper(I) complexes. Within this project steric and electronic effects of primarily applied bidentate N-donor ligands were investigated in detail.…”

“…The fundamental mechanism of TY activity, proceeding via a μ‐η 2 :η 2 ‐peroxo‐dicopper(II) species, has been firmly rooted in the literature for decades (Scheme 1a). The formation and detection of corresponding intermediates as well as their impact on catalytic activity thus have always been of central importance in TY model chemistry [6, 12, 15, 17, 19, 20] . In order to obtain more information about the factors influencing the performance of the catalysts, our group focused on the improvement of TY model compounds based on mononuclear copper(I) complexes.…”

Fluorescent Bis(guanidine) Copper Complexes as Precursors for Hydroxylation Catalysis

“…The most notable feature is the hydroxylation activity for the special substrate 8-hydroxyquinoline. Up to now, only some bis(pyrazolyl)methane stabilized peroxido species are able to hydroxylate this challenging substrate to its corresponding quinone [19,37,38]. It must be noted that the hydroxylation velocity seems to be enormous since the reaction is accomplished in a few seconds at −80 • C. Further kinetic analysis was prevented by the limited stability of the Cu 2 O 2 species.…”

“…If a stable peroxido or bis(µ-oxido) species is obtained, usually the next step involves testing the activity of the reaction system in the hydroxylation of substrates. Workgroups with major advancements in synthesizing catalytically active model systems are Tuczek et al [4,18,23,30,31], Lumb and Ottenwaelder et al [32][33][34], Casella et al [10,35,36], and Herres-Pawlis et al [19,25,37,38]. Tuczek et al developed tyrosinase model systems based on pyridine-imines [18,39].…”

“…The group of Herres-Pawlis et al presented efficient hydroxylation catalysis with bis(pyrazoly)methane copper complexes [19,25]. Recently a room-temperature stable bis(pyrazolyl) (pyridinyl)methane copper complex, proved to be the fastest catalyst in such an environment [38].…”