BOX Ligands in Biomimetic Copper‐Mediated Dioxygen Activation: A Hemocyanin Model

Abstract

Abstract The μ‐η 2 :η 2 ‐peroxodicopper(II) core found in the oxy forms of the active sites of type III dicopper proteins have been a key target for bioinorganic model studies. Here, it is shown that simple bis(oxazoline)s (BOXs), which are classified among the so‐called “privileged ligands”, provide a suitable scaffold for supporting such biomimetic copper/dioxygen chemistry. Three derivatives R,H BOX‐Me 2 (R = H, Me, t Bu) with different backbone substituents have been used. Their bis(oxazoline)‐copper(I) complexes bind dioxygen to yield biomimetic μ‐η 2 :η 2 ‐peroxodicopper(II) species. O 2 can be reversibly released upon an increase in temperature. Their formation kinetics have been studied under cryo‐stopped‐flow conditions for the t Bu derivative, giving activation parameters Δ H ‡ on = (2.27 ± 0.18) kcal mol –1 , Δ S ‡ on = (–46.3 ± 0.8) cal K –1 mol –1 for the binding event and Δ H ‡ off = (11.7 ± 1.9) kcal mol –1 , Δ S ‡ off = (–16.1 ± 8.2) cal K –1 mol –1 for the release of O 2 , as well as thermodynamic parameters Δ H ° = (–10.0 ± 1.7) kcal mol –1 and Δ S ° = (–32.7 ± 7.4) cal K –1 mol –1 for this equilibrium. The μ‐η 2 :η 2 ‐peroxodicopper(II) complexes have been isolated as surprisingly stable solids and investigated in depth by a variety of methods, both in solution and in the solid state. Resonance Raman spectroscopy revealed a characteristic isotope‐sensitive stretch $\tilde {\nu}$ O–O = 731–742 cm –1 (Δ[ 18 O 2 ] ≈ –39 cm –1 ) and an intense feature around 280 cm –1 diagnostic for the fundamental symmetric Cu 2 O 2 core vibration. A slight butterfly‐shape of the Cu 2 O 2 core has been derived from EXAFS data and DFT calculations. SQUID magnetic data evidenced strong antiferromagnetic coupled Cu II 2 (–2 J ≥ 1000 cm –1 ). Thermal degradation in solution yields bis(hydroxo)‐bridged [( tBu,H BOX‐Me 2 )(L)Cu(OH)] 2 (PF 6 ) 2 (L = H 2 O, MeCN or THF); whereas in the case of H,H BOX‐Me 2 , ligand oxygenation has been detected. Preliminary reactivity studies with the substrate 2,4‐di‐ tert ‐butylphenol indicate the formation of the C–C coupling product 3,3′,5,5′‐tetra‐ tert ‐butyl‐2,2′‐biphenol, whereas ortho ‐hydroxylation was not observed. The copper(I) complex [( tBu,H BOX‐Me 2 )Cu(MeCN)]PF 6 as well as two dicopper(II) complexes [(L)( tBu,H BOX‐Me 2 )Cu(OH)] 2 (PF 6 ) 2 have been characterised by single‐crystal X‐ray diffraction. Considering the vast number of known BOX derivatives, a rich and versatile Cu/O 2 chemistry based on this platform is anticipated.