Aromatic Hydroxylation in a Copper Bis(imine) Complex Mediated by a μ‐η²:η² Peroxo Dicopper Core: A Mechanistic Scenario

Abstract

Detailed mechanistic studies on the ligand hydroxylation reaction mediated by a copper bis(imine) complex are presented. Starting from a structural analysis of the CuI complex and the CuII product with a hydroxylated ligand, the optical absorption and vibrational spectra of starting material and product are analyzed. Kinetic analysis of the ligand hydroxylation reaction shows that O2 binding is the rate-limiting step. The reaction proceeds much faster in methanol than in acetonitrile. Moreover, an inverse kinetic isotope effect (KIE) is evidenced for the reaction in acetonitrile, which is attributed to a sterically congested transition state leading to the peroxo adduct. In methanol, however, no KIE is observed. A DFT analysis of the oxygenation reaction mediated by the micro-eta2:eta2 peroxo core demonstrates that the major barrier after O2 binding corresponds to electrophilic attack on the arene ring. The relevant orbital interaction occurs between the sigma* orbital of the Cu2O2 unit and the HOMO of the ligand. On the basis of the activation energy for the rate-limiting step (18.3 kcal mol(-1)) this reaction is thermally allowed, in agreement with the experimental observation. The calculations also predict the presence of a stable dienone intermediate which, however, escaped experimental detection so far. Reasons for these findings are considered. The implications of the results for the mechanism of tyrosinase are discussed.

Copper–Oxygen Complexes Revisited: Structures, Spectroscopy, and Reactivity

“…275,276 In several cases, no oxygenated intermediate was observed, 181,277 and in some of these instances a ( μ - η 2 : η 2 -peroxo)dicopper species was proposed on the basis of precedent or DFT calculations. 278,279 In other cases, a ( μ - η 2 : η 2 -peroxo)-dicopper was observed by spectroscopy and insights into the kinetics and thermodynamics of its formation and/or intramolecular hydroxylation reactivity were attained. 280–282 For example, kinetic studies of the oxygenation and subsequent intramolecular hydroxylation reactions of Cu(I) complexes of L58g and L58h and the asymmetric ligand L50a were performed.…”

Synthesis, Molecular Structure, and Physical Properties of the Complexes [{PhB(pz)2(CH2SMe)}2M] (M = MnII, FeII; pz = pyrazol‐1‐yl) Containing a Novel [N,N,S]‐Heteroscorpionate Ligand

“…[10] One focus of our own interests is the development of artificial analogs of the copper-containing enzymes dopamine β-monooxygenase (DβM) and peptidylglycine α-hydroxylating monooxygenase (PHM) as well as the detailed mechanistic understanding of the reactivity patterns of such species. [13][14][15][16] The O 2 binding mechanism of the active sites of mononuclear copper enzymes was successfully modeled by use of the strongly deactivating, tripodal tetradentate Ndonor ligands derived from superbasic peralkyl guanidines. [17][18][19][20] However, a more realistic ligand to mimic the protein pocket of the O 2 -binding copper ion in DβM and PHM (two histidine residues, one methionine side chain) would be the yet missing scorpionate [RB(pz) 2 (CH 2 SRЈ)] -(x = 2; R = Ph, RЈ = Me; see above).…”

Das erste katalytische Tyrosinasemodell basierend auf einem einkernigen Kupfer(I)‐Komplex: Kinetik und Mechanismus

“…Die Hydroxylierung wird dabei durch das s*-Orbital des koordinierten Peroxids vermittelt. [16] Im stöchiometrischen Modus ist die Reaktion auf der Stufe von 4 beendet. Ein weiteres wichtiges Resultat ist die Tatsache, dass die Zugabe von DTBP-H/NEt 3 im Überschuss zu 4 unter anaeroben Bedingungen zur Freisetzung des Substrats als Chinon führt (Schema 3 und Abbildung 2, Kurve c).…”