Amine Oxidative N‑Dealkylation via Cupric Hydroperoxide Cu-OOH Homolytic Cleavage Followed by Site-Specific Fenton Chemistry

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 CuII-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 CuII-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 CuII-OOH entity could be ruled out. It is concluded that the chemistry proceeds by rate limiting Cu-O homolytic cleavage of the CuII-(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 CuIOOH species undergoes O–O homolytic cleavage to yield a hydroxyl radical and CuIIOH rather than heterolytic cleavage to yield water and a CuII-O•– species.