Copper−Hydroperoxo-Mediated N-Debenzylation Chemistry Mimicking Aspects of Copper Monooxygenases

Abstract

Substantial oxidative N-debenzylation reaction along with PhCH=O formation occurs from a hydroperoxo copper(II) complex which has a dibenzylamino substrate (-N(CH 2 Ph) 2 appended as a substituent on one pyridyl group of its tripodal tetradentate TMPA {≡ TPA ≡ tris(2-pyridylmethyl) amine)} ligand framework. During the course of the (L N(CH 2 Ph) 2 )Cu II ( − OOH) reactivity, formation of a substrate and − OOH (an oxygen atom) derived alkoxo Cu II ( − OR) complex occurs. The observation that the same Cu II ( − OR) species occurs from Cu I /PhIO chemistry suggests the possibility that a copper-oxo (cupryl) reactive intermediate forms during alkoxo species formation, and new ESI-MS data obtained provides some further support for this high-valent intermediate. Net H-atom abstraction chemistry is proposed, based on kinetic isotope effect studies provided here and that previously published for a closely related Cu II ( − OOH) species incorporating dimethylamine (-N (CH 3 ) 2 ) as the internal substrate (J. Am. Chem. Soc. 2007, 129, 6720-6721); the Cu I /PhIO reactivity, with similar isotope effect results, provides further support. The reactivity of these chemical systems closely resembles proposed oxidative N-dealkylation mechanisms effected by the coppermonooxygenases dopamine β-monooxygenase (DβM) or peptidylglycine-α-hydroxylating monooxygenase (PHM).

Transition Metal Complexes and the Activation of Dioxygen

“…Mechanistic studies suggest that these oxidations involve intramolecular HAT from the position α to the N-atom of the ligand, either directly by the Cu(II)-OOH unit or by a [CuO] + moiety formed first via O-O bond homolysis. In indirect support of the latter, similar oxidized products formed in reactions of PhIO with Cu(I) complexes of the supporting ligand in 87a, with electrospray ionization mass spectrometry evidence supporting the involvement of [CuO] + or adduct [CuOIPh] + cores [299]. In related chemistry, hydroxylation at the ortho position of the pendant aryl ring in 87c (Figure 43) occurred upon warming [306].…”

“…Building upon previous work focused primarily on the characterization of monocopper-hydroperoxo and -alkylperoxo complexes [299][300][301][302][303][304], more recent research has emphasized reactivity studies. For example, the complexes 87a, b ( Figure 43) decompose to yield mixtures of products resulting from oxidation of substituents R (e.g., N-alkylation, formation of aldehydes or ketones) [299,305]. Mechanistic studies suggest that these oxidations involve intramolecular HAT from the position α to the N-atom of the ligand, either directly by the Cu(II)-OOH unit or by a [CuO] + moiety formed first via O-O bond homolysis.…”

Ether formation on the tridentate Schiff base ligands of copper(II) complexes

“…Lee et al [53] have determined the structure of a sulfoxide product of the reaction of the Cu(I) compound of a N 2 S tridentate thioether ligand with dioxygen and suggested a similar reaction scheme to that of the hydroxylation reaction reported by Maiti et al [50]. In the presence of excess H 2 O 2 , a sulfone (SO 2 ) product was also formed with their ligand system but there is no evidence of the formation of a sulfone in this work.…”

“…Less common are hydroxylation reactions that occur on the non-aromatic parts instead of aromatic parts of the ligands of copper complexes. This type of reaction [48][49][50][51][52] has been suggested to be a model system of the reactions of copper monooxygenase enzymes such as dopamine β-monooxygenase.…”

“…They then predicted that an intramolecular hydrogen abstraction reaction and direct oxygen insertion mechanism might take place with the bis-μ-oxo Cu(III) compound or with a Cu(II)-oxo radical monomeric species. Maiti et al [50] and Peterson et al Tano et al [52] reported that reaction of phenols on the end of superoxide adduct of the copper(II) complex used in reference 49 produced [LCu(II)OAr] + species in acetone solution at −85°C, but did not report any addition of the OAr groups to their ligand. Figure 9.…”