Copper(II)‐hydroperoxo species are proposed as key intermediates in the catalytic cycles of copper‐monooxygenase enzymes that perform C–H bond hydroxylation. Herein we report on the oxidation chemistry of a copper(II) complex with a coordinating cryptand based on a peralkylated tetradentate tris(2‐aminoethyl)amine (tren) moiety. X‐ray crystallography of the copper(II) acetate complex of this cryptand revealed that the copper(II) ion is in a square‐pyramidal environment, with the cryptand acting only as a tridentate ligand. This geometry is conserved in solution and likely results from restraints imposed by the semi‐rigid cryptand. Reaction of this complex with basic hydrogen peroxide in methanol led to the decomposition of the complex with an oxygen‐atom transfer to the ligand, as evidenced by mass spectrometry analysis after reaction and demetallation. Low‐temperature stopped‐flow experiments (down to –90 °C) support the formation of a copper(II)‐hydroperoxo intermediate, CuOOH, before ligand oxygenation occurs. It is proposed that this intermediate performs the oxygen‐atom transfer to a weak benzylic C–H bond of the cryptand, thereby mimicking the behavior of dopamine‐β‐hydroxylase.

We report a detailed investigation of the formation and self-decomposition of Cu(ii)-hydroperoxo intermediates under the influence of second-coordination-sphere features provided by a cryptand. In solution, an equilibrium between two copper complexes with square-planar and square-pyramidal geometries was identified. Upon addition of H2O2/Et3N, two copper(ii)-hydroperoxo intermediates formed at different rates. Their decomposition via self-oxidation was probed by deuterating select positions on the cryptand. This led to a small kinetic isotope effect of 1.5. Mass spectrometry analysis of the demetallated organic products is consistent with a direct oxygen-atom transfer to a tertiary amine on the cryptand, forming an N-oxide, unlike other models of copper mononuclear monooxygenase enzymes.

Three copper complexes with an N-methylated cryptand, LTEA, bearing a tris(2aminoethylamine moiety have been synthesized and compared. Two copper(II)-chloride complexes, [LTEACuCl](SbF 6 )(MeOH) and [LTEACuCl 2 ](MeCN) were characterized in solution and solid state by UV/Vis and X-ray crystallography. Both had square-based geometries with C 1 -symmetry and no encapsulation of the chloride ion. A Cu(II)-fluoride complex, in which the ligand is protonated, [LTEAHCuF](BF 4 ) 2 (MeCN) 0.5 , adopted C 3 -symmetry with complete encapsulation of the coordination sphere as characterized by UV/Vis, EPR and X-ray crystallography. Reactivity of the complexes with H 2 O 2 /Et 3 N was explored using UV/Vis and CSI-MS. Only the fluoride complex was found to form a Cu(II)hydroperoxo intermediate.

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