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.