Copper(II)‐Mediated Aromatic ortho‐Hydroxylation: A Hybrid DFT and Ab Initio Exploration

Abstract

Mechanistic pathways for the aromatic hydroxylation by [CuII(L1)(TMAO)(O)](-) (L1=hippuric acid, TMAO=trimethylamine N-oxide), derived from the O--N bond homolysis of its [CuII(L1)(TMAO)2] precursor, were explored by using hybrid density functional theory (B3LYP) and highly correlated ab initio methods (QCISD and CCSD). Published experimental studies suggest that the catalytic reaction is triggered by a terminal copper-oxo species, and a detailed study of electronic structures, bonding, and energetics of the corresponding electromers is presented. Two pathways, a stepwise and a concerted reaction, were considered for the hydroxylation process. The results reveal a clear preference for the concerted pathway, in which the terminal oxygen atom directly attacks the carbon atom of the benzene ring, leading to the ortho-selectively hydroxylated product. Solvent effects were probed by using the PCM and CPCM solvation models, and the PCM model was found to perform better in the present case. Excellent agreement between the experimental and computational results was found, in particular also for changes in reactivity with derivatives of L1.

Quantum mechanical calculations suggest that lytic polysaccharide monooxygenases use a copper-oxyl, oxygen-rebound mechanism

“…Thus, we consider C-H oxidation by a Cu(II)-oxyl ROS, dubbed the "oxyl mechanism" (Fig. 3) as this species has been previously predicted to exhibit a more strongly oxidative character than Cu(II)-superoxo (31,32 (20,33,34). From this system, we test two different geometries for oxidative attack at the C1 and C4 carbons to evaluate different enzyme-substrate poses (SI Appendix, Fig.…”

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

“…Overall catalytic reaction and proposed mechanism for the hydroxylation of benzoate derivatives (TMAO is trimethylamine- N- oxide) (ref 121). …”

“…120,121 DFT calculations employed to analyze this process suggested that homolytic scission of the N–O bond in a copper(II) complex of trimethylamine- N -oxide (TMAO) yielded a copper(II)-oxyl intermediate. 121 A concerted pathway for hydroxylation of the aromatic ring by this intermediate was found to be favored relative to a stepwise hydrogen atom abstraction/rebound process. Copper(II)-oxyl species have also been proposed in other catalytic reactions.…”

Copper–dioxygen complex mediated C–H bond oxygenation: relevance for particulate methane monooxygenase (pMMO)

“…The species has not been observed in any molecular or enzymatic system, but indirect evidence has led several researchers to suggest such a species as a reactive intermediate. Several instances – experimental and theoretical – of intramolecular arene hydroxylation have been proposed to be promoted by a cupryl [58-60]. For example, oxygenation of a mononuclear Cu(I)-α-ketocarboxylate complex leads to intramolecular hydroxylation of a pyridyl phenyl arm (Figure 10) .…”