Amine oxidative N-dealkylation via cupric hydroperoxide Cu-OOH homolytic cleavage followed by site-specific fenton chemistry

Abstract

Copper(II) hydroperoxide species are significant intermediates in processes such as fuel cells and (bio)chemical oxidations, all involving stepwise reduction of molecular oxygen. We previously reported a Cu(II)-OOH species that performs oxidative N-dealkylation on a dibenzylamino group that is appended to the 6-position of a pyridyl donor of a tripodal tetradentate ligand. To obtain insights into the mechanism of this process, reaction kinetics and products were determined employing ligand substrates with various para-substituent dibenzyl pairs (-H,-H; -H,-Cl; -H,-OMe, and -Cl,-OMe), or with partially or fully deuterated dibenzyl N-(CH2Ph)2 moieties. A series of ligand-copper(II) bis-perchlorate complexes were synthesized, characterized, and the X-ray structures of the -H,-OMe analogue were determined. The corresponding metastable Cu(II)-OOH species were generated by addition of H2O2/base in acetone at -90 °C. These convert (t1/2 ≈ 53 s) to oxidatively N-dealkylated products, producing para-substituted benzaldehydes. Based on the experimental observations and supporting DFT calculations, a reaction mechanism involving dibenzylamine H-atom abstraction or electron-transfer oxidation by the Cu(II)-OOH entity could be ruled out. It is concluded that the chemistry proceeds by rate limiting Cu-O homolytic cleavage of the Cu(II)-(OOH) species, followed by site-specific copper Fenton chemistry. As a process of broad interest in copper as well as iron oxidative (bio)chemistries, a detailed computational analysis was performed, indicating that a Cu(I)OOH species undergoes O-O homolytic cleavage to yield a hydroxyl radical and Cu(II)OH rather than heterolytic cleavage to yield water and a Cu(II)-O(•-) species.

Figure 1

(a) X-ray crystal structure of [(L^H,OMe)Cu^II(OClO₃)-(CH₃COCH₃)]⁺ (1^H,OMe) revealing Cu(II) distorted octahedral coordination with three equatorial N and one O_(acetone) donors (Cu–ligand = 1.984 Å_(ave.)) and two elongated axial ligands, one pyridyl group (Cu–Npy = 2.698(2) Å) and a perchlorate O-atom (Cu–O = 2.492(2) Å). (b) UV-vis spectrum of 1^H,OMe (λ_max = 630 nm) and Cu^II-OOH complex 2^H,OMe. (c) EPR spectrum and simulated plot (red) of 1^H,OMe (2 mM, g_|| = 2.205, A_|| = 206 G, g^⊥ = 2.003) and (d) EPR spectrum and simulated plot (red) of 2^H,OMe (2 mM, g_|| = 2.227, A_|| = 205 G, g^⊥ = 2.044); X band (ν = 9.186 GHz) in acetone at 77 K.

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