Symmetrical and Unsymmetrical Dicopper Complexes Based on Bis-Oxazoline Units: Synthesis, Spectroscopic Properties and Reactivity

: Copper–oxygen adducts are known for being key active species for the oxidation of C–H bonds in copper enzymes and their synthetic models. In this work, the synthesis and spectroscopic characterizations of such intermediates using dinucleating ligands based on a 1,8 naphthyridine spacer with oxazolines or mixed pyridine-oxazoline coordination moieties as binding pockets for copper ions have been explored. On the one hand, the reaction of dicopper(I) complexes with O 2 at low temperature led to the formation of a µ - η 2 : η 2 Cu 2 :O 2 peroxido species according to UV-Vis spectroscopy monitoring. The reaction of these species with 2,4-di-tert-butyl-phenolate resulted in the formation of the C–C coupling product, but no insertion of oxygen occurred. On the other hand, the synthesis of dinuclear Cu(II) bis-µ -hydroxido complexes based on pyridine–oxazoline and oxazoline ligands were carried out to further generate Cu II Cu III oxygen species. For both complexes, a reversible monoelectronic oxidation was detected via cyclic voltammetry at E 1/2 = 1.27 and 1.09 V vs. Fc + /Fc, respectively. Electron paramagnetic resonance spectroscopy (EPR) and UV-Vis spectroelectrochemical methods indicated the formation of a mixed-valent Cu II Cu III species. Although no reactivity towards exogeneous substrates (toluene) could be observed, the Cu II Cu III complexes were shown to be able to perform hydroxylation on the methyl group of the oxazoline moieties. The present study therefore indicates that the electrochemically generated Cu II Cu III species described herein are capable of intramolecular aliphatic oxidation of C–H bonds.


Introduction
An important part of the research in bio-inorganic chemistry is currently focused on the development of model complexes that mimic the catalytic center of enzymes.In the field of copper-metalloenzymes, low-temperature oxygenation of synthetic Cu I or Cu I 2 compounds has provided a variety of structurally and spectroscopically characterized Cu 2 O 2 species including high valent species [1] (Scheme 1).The combination with their respective reactivity profiles has provided useful information on dicopper-metalloenzyme structure and function [2,3].In particular, Cu 2 -containing enzymes activate O 2 to generate Cu 2 O 2 species capable of oxidizing various substrates varying from catechol to methane [4].To prepare model complexes, the nature of the supporting ligands employed, the presence of substituents to control the bulkiness and the electronic properties (donor/acceptor groups) and flexibility of the ligand control the final structure of the Cu 2 O 2 species.The majority of dinucleating ligands with tridentate arms described in the literature have been used to generate bis-µ-oxido dicopper(III) complex or equilibrium mixtures of (µ-η 2 :η 2 ) peroxido dicopper(II) and bis-µ-oxido species [5][6][7][8][9][10] (Scheme 1).By contrast, dinucleating ligands with tetradentate arms have predominantly led to cis-µ-1,2-peroxido dicopper(II) complexes [11] or trans-µ-1,2-peroxido-dicopper(II) complexes [12][13][14][15][16].
In this context, we reported the synthesis of the symmetrical Cu2Py4 complex (Py4 ligand is presented on Scheme 2) containing a naphthyridine spacer (known to be redoxinert, and to promote two well-defined coordination sites with a short metal-metal distance) associated with bis-pyridyl arms [17].With the Cu2Py4 bis(µ-hydroxido) complex, we showed that a mixed valent Cu II Cu III intermediate could be generated and activate strong sp 3 C-H bonds [18].In addition, from the corresponding dinuclear Cu I 2Py4 species, no O2 adduct was detected [19].With this background, in this study, we describe two novel naphthyridine-bridged ligands (Scheme 2) using bis-oxazoline moieties as binding site.Bis-oxazoline (BOX) ligands have found numerous applications, in particular in the field of asymmetric synthesis [20].In particular, the steric bulk of the oxazoline group provides hindrance around the copper centers, stabilizing potential intermediates formed.This concept was applied by Meyer et al. in the copper-O2 activation field showing that such an entity was able to stabilize a µ-η 2 :η 2 -peroxido-dicopper(II) complex [21].Here, we have employed Ox4 and Ox2Py2 ligands for the preparation of dinuclear copper(I) and (II) complexes.Aiming at generating mixed valent Cu II Cu III -oxygen species, we have followed two strategies.In a first approach (Strategy 1, Scheme 3), Cu I 2 complexes have been reacted with O2 in order to generate stable (µ-η 2 :η 2 ) peroxido Cu II 2 complexes that can be further reduced/protonated.The second approach (Strategy 2) is based on the electrochemical/chemical mono-oxidation of stable Cu II 2-hydroxido or Cu II 2-bis(µ-hydroxido) complexes, as previously developed by our group with the Py4 ligand [17].In this context, we reported the synthesis of the symmetrical Cu 2 Py 4 complex (Py 4 ligand is presented on Scheme 2) containing a naphthyridine spacer (known to be redoxinert, and to promote two well-defined coordination sites with a short metal-metal distance) associated with bis-pyridyl arms [17].With the Cu 2 Py 4 bis(µ-hydroxido) complex, we showed that a mixed valent Cu II Cu III intermediate could be generated and activate strong sp 3 C-H bonds [18].In addition, from the corresponding dinuclear Cu I 2 Py 4 species, no O 2 adduct was detected [19].
inert, and to promote two well-defined coordination sites with a short metal-m tance) associated with bis-pyridyl arms [17].With the Cu2Py4 bis(µ-hydroxido) c we showed that a mixed valent Cu II Cu III intermediate could be generated and strong sp 3 C-H bonds [18].In addition, from the corresponding dinuclear Cu I 2Py4 no O2 adduct was detected [19].With this background, in this study, we describe two novel naphthyridineligands (Scheme 2) using bis-oxazoline moieties as binding site.Bis-oxazoline (B ands have found numerous applications, in particular in the field of asymmetric s [20].In particular, the steric bulk of the oxazoline group provides hindrance aro copper centers, stabilizing potential intermediates formed.This concept was ap Meyer et al. in the copper-O2 activation field showing that such an entity was abl bilize a µ-η 2 :η 2 -peroxido-dicopper(II) complex [21].Here, we have employed Ox4 and Ox2Py2 ligands for the preparation of d copper(I) and (II) complexes.Aiming at generating mixed valent Cu II Cu III -oxygen we have followed two strategies.In a first approach (Strategy 1, Scheme 3), Cu I 2 co have been reacted with O2 in order to generate stable (µ-η 2 :η 2 ) peroxido Cu II 2 co that can be further reduced/protonated.The second approach (Strategy 2) is base electrochemical/chemical mono-oxidation of stable Cu II 2-hydroxido or Cu II 2-bis(µido) complexes, as previously developed by our group with the Py4 ligand [17].With this background, in this study, we describe two novel naphthyridine-bridged ligands (Scheme 2) using bis-oxazoline moieties as binding site.Bis-oxazoline (BOX) ligands have found numerous applications, in particular in the field of asymmetric synthesis [20].In particular, the steric bulk of the oxazoline group provides hindrance around the copper centers, stabilizing potential intermediates formed.This concept was applied by Meyer et al. in the copper-O 2 activation field showing that such an entity was able to stabilize a µ-η 2 :η 2 -peroxido-dicopper(II) complex [21].
Here, we have employed Ox 4 and Ox 2 Py 2 ligands for the preparation of dinuclear copper(I) and (II) complexes.Aiming at generating mixed valent Cu II Cu III -oxygen species, we have followed two strategies.In a first approach (Strategy 1, Scheme 3), Cu I  2 complexes have been reacted with O 2 in order to generate stable (µ-η 2 :η 2 ) peroxido Cu II  2 complexes that can be further reduced/protonated.The second approach (Strategy 2) is based on the electrochemical/chemical mono-oxidation of stable Cu II 2 -hydroxido or Cu II 2 -bis(µhydroxido) complexes, as previously developed by our group with the Py 4 ligand [17].Scheme 3. Possible strategies for formation of Cu II Cu III oxygen-mixed-valent species.

Synthesis and Characterizations
Complex Cu I 2Py4 was synthesized according to the procedure described by Tilley et al. [26].The two air-sensitive Cu(I) complexes based on Ox4 and Ox2Py2 ligands (named Cu I 2Ox4 and Cu I 2Ox2Py2, respectively) were prepared using a similar procedure: under argon, one equivalent of ligand (Ox4 or Ox2Py2) was reacted with 2.1 equivalents of [Cu I (CH3CN)4]OTf in tetrahydrofuran (THF).In both cases, the reaction produced an orange precipitate with 70% or 92% yield, respectively.Unfortunately, no suitable crystal for X-ray diffraction analysis could be obtained. 1H-NMR characterization of the two complexes was carried out in CD3CN (Figure S4).Peaks centered around 4.0 ppm and 1.35 ppm can be attributed to the CH2 and CH3 groups of the oxazoline entities.Two peaks Scheme 3. Possible strategies for formation of Cu II Cu III oxygen-mixed-valent species.

Synthesis and Characterizations
Complex Cu I 2Py4 was synthesized according to the procedure described by Tilley et al. [26].The two air-sensitive Cu(I) complexes based on Ox4 and Ox2Py2 ligands (named Cu I 2Ox4 and Cu I 2Ox2Py2, respectively) were prepared using a similar procedure: under argon, one equivalent of ligand (Ox4 or Ox2Py2) was reacted with 2.1 equivalents of [Cu I (CH3CN)4]OTf in tetrahydrofuran (THF).In both cases, the reaction produced an orange precipitate with 70% or 92% yield, respectively.Unfortunately, no suitable crystal for X-ray diffraction analysis could be obtained. 1H-NMR characterization of the two complexes was carried out in CD3CN (Figure S4).Peaks centered around 4.0 ppm and 1.35 ppm can be attributed to the CH2 and CH3 groups of the oxazoline entities.Two peaks  ]OTf in tetrahydrofuran (THF).In both cases, the reaction produced an orange precipitate with 70% or 92% yield, respectively.Unfortunately, no suitable crystal for X-ray diffraction analysis could be obtained. 1H-NMR characterization of the two complexes was carried out in CD 3 CN (Figure S4).Peaks centered around 4.0 ppm and 1.35 ppm can be attributed to the CH 2 and CH 3 groups of the oxazoline entities.Two peaks (doublets) were detected around 4 ppm, which did not appear on the 1 H-NMR spectrum of the ligand itself.This result is a good indicator for copper(I) coordination to the ligand, as the two diastereotopic protons of the ligand are no longer in an equivalent environment.Two singlets at around 1.35 ppm matching to the CH 3 groups of the oxazoline moieties support this result.

Reactivity
In order to generate Cu 2 /O 2 adducts, dioxygen was bubbled through solutions of Cu I 2 Ox 4 and Cu I 2 Ox 2 Py 2 complexes in acetone at low temperature (T = 193 K).The reaction was monitored via UV-Vis spectroscopy (Figures 1 and S5).For both complexes, the spectrum of the initial dicopper(I) solution under N 2 was taken as the baseline for more accurate determination of the wavelength of the arising new absorption bands.(doublets) were detected around 4 ppm, which did not appear on the 1 H-NMR spectrum of the ligand itself.This result is a good indicator for copper(I) coordination to the ligand, as the two diastereotopic protons of the ligand are no longer in an equivalent environment.Two singlets at around 1.35 ppm matching to the CH3 groups of the oxazoline moieties support this result.

Reactivity
In order to generate Cu2/O2 adducts, dioxygen was bubbled through solutions of Cu I 2Ox4 and Cu I 2Ox2Py2 complexes in acetone at low temperature (T = 193 K).The reaction was monitored via UV-Vis spectroscopy (Figures 1 and S5).For both complexes, the spectrum of the initial dicopper(I) solution under N2 was taken as the baseline for more accurate determination of the wavelength of the arising new absorption bands.
Figure 1.UV-vis monitoring of the addition of O2 on Cu I 2Ox4; parameters: optical path = 1 cm; solvent: acetone, concentration 0.094 mM, T = 193 K.The baseline was taken on the dicopper(I) complex solution before O2 addition for better monitoring of the peroxide absorption bands (justifying the use of relative absorbance (ΔAbs.)instead of absorbance (Abs.) on the graph).
For complex Cu I 2Ox4, four new bands with wavelengths ranging between 330 and 700 nm appeared rapidly upon addition of dioxygen.In particular, an intense absorption band at λmax = 338 nm (ε ≈ 6400 M −1 •cm −1 ) together with a less intense one at λmax = 409 nm (ε ≈ 1000 M −1 •cm −1 ) were observed.In addition, two low-intensity bands at 530 nm (ε ≈ 350 M −1 •cm −1 ) and 637 nm (ε ≈ 312 M −1 •cm −1 ) were detected.These absorptions correspond to low energy d-d transition, as reported in a parent dicopper complex [27].The main absorption band at 338 nm is in the typical range of µ-η 2 :η 2 -peroxido-Cu II 2 oxygen species and attributed to ligand-to-metal charge transfer (LMCT) from the peroxido to the copper centers [3].A similar behavior was obtained with Cu I 2Ox2Py2.Indeed, a new absorption band was observed at λmax = 367 nm upon addition of dioxygen (ε ≈2400 M −1 •cm −1 ) [3,28] (Figure S5).As for Cu I 2Ox4, this wavelength value suggests the formation of side-on peroxido dicopper(II) species.However, both Ox4 and Ox2Py2-based peroxides were shown to be poorly stable, hence excluding any further reduction/protonation for generating mixed-valent species such as shown in Scheme 3.For complex Cu I 2 Ox 4 , four new bands with wavelengths ranging between 330 and 700 nm appeared rapidly upon addition of dioxygen.In particular, an intense absorption band at λ max = 338 nm (ε ≈ 6400 M −1 •cm −1 ) together with a less intense one at λ max = 409 nm (ε ≈ 1000 M −1 •cm −1 ) were observed.In addition, two low-intensity bands at 530 nm (ε ≈ 350 M −1 •cm −1 ) and 637 nm (ε ≈ 312 M −1 •cm −1 ) were detected.These absorptions correspond to low energy d-d transition, as reported in a parent dicopper complex [27].The main absorption band at 338 nm is in the typical range of µ-η 2 :η 2 -peroxido-Cu II  2 oxygen species and attributed to ligand-to-metal charge transfer (LMCT) from the peroxido to the copper centers [3].A similar behavior was obtained with Cu I 2 Ox 2 Py 2 .Indeed, a new absorption band was observed at λ max = 367 nm upon addition of dioxygen (ε ≈2400 M −1 •cm −1 ) [3,28] (Figure S5).As for Cu I 2 Ox 4 , this wavelength value suggests the formation of side-on peroxido dicopper(II) species.However, both Ox 4 and Ox 2 Py 2 -based peroxides were shown to be poorly stable, hence excluding any further reduction/protonation for generating mixed-valent species such as shown in Scheme 3.

Synthesis and Characterizations
The next step consisted in exploring the redox properties of the dicopper(II) bis(µ-OH) Ox 4 and Ox 2 Py 2 complexes.For this purpose, the complexation reactions of the two ligands were carried out in a classical manner.One equivalent of the ligand was dissolved in THF, and 2.1 equivalents of triethylamine and water (10 equivalents) were added followed by 2.1 equivalents of Cu(OTf) 2 .Upon diffusion of di-isopropyl ether into a concentrated acetonitrile solution of complexes, single crystals for X-ray diffraction analysis were obtained with 71% and 75% yield, respectively.Details for X-ray analysis are in Table 1.Complex 1 (Cu II 2 Ox 4 ) crystallizes as a dinuclear complex with the Cu atoms bridged by two hydroxido groups (Figure 2a) with Cu-O-Cu angles close to 90.4 • .The Cu1 and Cu2 copper atoms are set at a short distance from each other (2.7537(5) Å).The geometries of both copper atoms are described as a square-based pyramid (τ = 0.07 for Cu1 and 0.08 for Cu2) [32] with N1 and N2 of the naphthyridine spacer occupying the axial position.Although the equatorial distances are in the range of the values obtained for parent/relevant dinuclear complexes (1.9-2.1 Å) [17,[33][34][35], the nitrogen of the naphthyridine is located at 2.43-2.46Å from the copper(II) centers.These significantly longer distances could indicate a weaker donating group and a possible unbinding of these atoms in solution.

Synthesis and Characterizations
The next step consisted in exploring the redox properties of the dicopper(II) bis(µ-OH) Ox4 and Ox2Py2 complexes.For this purpose, the complexation reactions of the two ligands were carried out in a classical manner.One equivalent of the ligand was dissolved in THF, and 2.1 equivalents of triethylamine and water (10 equivalents) were added followed by 2.1 equivalents of Cu(OTf)2.Upon diffusion of di-isopropyl ether into a concentrated acetonitrile solution of complexes, single crystals for X-ray diffraction analysis were obtained with 71% and 75% yield, respectively.Details for X-ray analysis are in Table 1.Complex 1 (Cu II 2Ox4) crystallizes as a dinuclear complex with the Cu atoms bridged by two hydroxido groups (Figure 2a) with Cu-O-Cu angles close to 90.4°.The Cu1 and Cu2 copper atoms are set at a short distance from each other (2.7537(5) Å).The geometries of both copper atoms are described as a square-based pyramid (τ = 0.07 for Cu1 and 0.08 for Cu2) [32] with N1 and N2 of the naphthyridine spacer occupying the axial position.Although the equatorial distances are in the range of the values obtained for parent/relevant dinuclear complexes (1.9-2.1 Å) [17,[33][34][35], the nitrogen of the naphthyridine is located at 2.43-2.46Å from the copper(II) centers.These significantly longer distances could indicate a weaker donating group and a possible unbinding of these atoms in solution.S1 and S2).Others view and complete representation including counterions and solvent are in ESI (Figure S7a,b).
The similarly complexation of ligand Ox2Py2 afforded compound 2 (Cu II 2Ox2Py2) as a crystalline material.The unit cell encloses two crystallographically independent [C32H44Cu2N6O6](CF3SO3)2 entities and one CH3CN as solvate.Each cationic unit displays two triflate counterions.Unit 2A is shown in Figure 2b (other views on Figure S7b) and unit 2B is shown in Figure S7c (Supporting Information); each consists of two copper  S1 and S2).Others view and complete representation including counterions and solvent are in ESI (Figure S7a,b).S1 and S2 in the Supplementary Materials and display no significant difference between 2A and 2B dimers.In 2A, the Cu1A-Cu2A distance is short (2.80) Å but rather long compared to Cu II 2 Py 4 (complex 3) [17] and to Cu II 2 Ox 4 , with a distance of 2.75 Å.Each copper atom has a square-based pyramid geometry (τ = 0.01 for Cu1A and 0.02 for Cu2A) [32] with the equatorial positions occupied by the hydroxido groups and the nitrogen atoms of either the pyridines or the BOX entities and the axial positions occupied by the N atoms of the naphthyridine spacer.Bond distances between the Cu atoms and equatorial positions are of 1.9-2.0Å.The axial bonds are longer at 2.47 Å for Cu1A-N1 (the side of the BOX units) and 2.26 Å for Cu2A-N2 (the side of the pyridine units).

The similarly complexation of ligand
UV-Vis characterization of the dicopper(II) complexes 1 and 2 was carried out in acetonitrile.The complexes exhibited intense electronic transitions in the UV region at 260, 305, 310 and 317 nm (ε ~10 000 M −1 cm −1 ).These bands are similar to those of Ox 4 and Ox 2 Py 2 free ligands and have been assigned as π-π * transitions.Large bands at 580 nm and 570 nm, respectively, with weak values of molar absorptivity (ε ~100 M −1 cm −1 ) were observed for each complex and correspond to d-d transitions.These two complexes were also analyzed via ESI-MS in acetonitrile (Figure S8).Peaks were detected at 883 and 843 m/z corresponding to [M-OTf] + for [(Cu 2 (Ox 4 ))(µ-OH) 2 ](CF 3 SO 3 ) 2 and [(Cu 2 (Ox 2 Py 2 ))(µ-OH) 2 ](CF 3 SO 3 ) 2 , respectively, where M corresponds to the complex.Theoretical isotopic profiles matched experimental ones indicating that the complexes remain dinuclear in solution.

Electrochemical Oxidation of Complexes 1 and 2
We further investigated the oxidation process for both dicopper(II) complexes 1 and 2. Attempts to generate a mixed-valent Cu II Cu III species were carried out via cyclic voltammetry (CV) in a CH 3 CN solution with tetra-n-butyl ammonium perchlorate (TBAP) as the supporting electrolyte.
As shown in Figure 3, the two complexes displayed a reversible oxidation system at E 1/2 = 1.27V and 1.09 V vs. Fc + /Fc, respectively, for 1 and 2 at v = 100 mV•s −1 rendering them all out of reach of commonly used chemical oxidants [17].Noteworthy, complex 1 showed a complete loss of reversibility at a lower scan rate (v = 20 mV•s −1 ) (Figure 3a), contrary to complex 2, for which reversibility was still observed at v = 5 mV•s −1 (Figure 3b).Plots of the normalized anodic peak current Iv −1/2 against the scan rate (v) (Figure S9) showed a particular increase of Iv −1/2 at low scan rates for 1.This result is indicative of an ECE mechanism (E = electrochemical and C = chemical) where the oxidation of the complex is followed by a chemical reaction on the experimental time scale, producing new species, which, in turn, can be oxidized.The oxidation of both complexes therefore involves, at room temperature, the formation of a transient species that has a half-life of several seconds.For the oxidation process of each complex, the number of electrons was determined by using the Randles-Sevcik equation [36,37] for scan rate values for which the system remained reversible.I P was plotted against v 1/2 for complexes 1 and 2 (Figure S10), yielding values of n = 1.3 and 1.2, respectively, thus indicating a one-electron transfer for both complexes.This behavior is reminiscent of that previously obtained with complex 3 (Cu II 2 Py 4 ), which displayed a reversible system at 1.26 V vs. Fc + /Fc in the same conditions [17].
In order to avoid decomposition at room temperature because of the occurrence of an ECE process, the mono-electronic oxidized species were generated at −40 • C via bulk electrolysis of 1 and 2 (0.7 mM) in a 0.1 M NBu 4 ClO 4 /acetonitrile solution to the potentials of 1.41 V vs. Fc + /Fc for 1 and 1.26 V vs. Fc + /Fc for 2. Bulk oxidation was accompanied by a color change from pale blue/colorless to yellow for complex 2 and colorless to brown for complex 1.During the course of the low-temperature electrolysis, the samples were taken out and immediately frozen in liquid nitrogen for EPR analysis.For control experiments, to get the EPR spectrum of the final product, the oxidized species was also warmed to room temperature and then frozen in liquid nitrogen.Before electrolysis, the two complexes were EPR-silent (CH 3 CN, 100 K).The EPR spectrum of complex 2 after oxidation via electrolysis is displayed in Figure 4, along with the spectrum of the product warmed to room temperature.Spectra were recorded at 15 K, but the same features were observed from 15 to 100 K.The oxidized complex displayed four clear lines (Figure 4) with coupling constant A of 173 G, the expected EPR spectrum for a mononuclear Cu II complex in an axial geometry (an unpaired electron coupling to the nuclear spin of one copper with I = 3/2).This is consistent with a valence-localized Cu II Cu III species (the Cu III being EPR silent), defined in the Robin Day classification system [38] as a class I (classes II and III represents slight and significant delocalization, respectively).The spectrum of the complex 1 after oxidation was less resolved but four lines were still observable (A = 177 G) (Figure S11).The loss of resolution of the signal from this oxidized complex could be due to more instability of the one-oxidized species that can also be stated by its lower reversibility of the CV (Figure 3a) at room temperature compared to complex 2 (Figure 3b).For the mono-oxidized species 1, 2 and 3, in all three cases, the EPR parameters of the spectra (see Figures 4 and S11) obtained after simulation show a Cu II in an axial geometry [17].It is therefore obvious that mono-oxidation of the complexes Cu II 2 Ox 2 Py 2 and Cu II 2 Ox 4 leads to the formation of mixed-valent Cu II Cu III species.After the oxidized samples had been warmed to room temperature, the recorded spectra of all complexes at 15K displayed broad signals, indicating a mixture of several Cu II complexes in solution.In order to avoid decomposition at room temperature because of the occurrenc an ECE process, the mono-electronic oxidized species were generated at −40 °C via b electrolysis of 1 and 2 (0.7 mM) in a 0.1 M NBu4ClO4/acetonitrile solution to the potent of 1.41 V vs. Fc + /Fc for 1 and 1.26 V vs. Fc + /Fc for 2. Bulk oxidation was accompanied b color change from pale blue/colorless to yellow for complex 2 and colorless to brown complex 1.During the course of the low-temperature electrolysis, the samples were ta out and immediately frozen in liquid nitrogen for EPR analysis.For control experime to get the EPR spectrum of the final product, the oxidized species was also warmed room temperature and then frozen in liquid nitrogen.Before electrolysis, the two co plexes were EPR-silent (CH3CN, 100 K).The EPR spectrum of complex 2 after oxidat via electrolysis is displayed in Figure 4, along with the spectrum of the product warm to room temperature.Spectra were recorded at 15 K, but the same features were obser from 15 to 100 K.The oxidized complex displayed four clear lines (Figure 4) with coupl constant  ∥ of 173 G, the expected EPR spectrum for a mononuclear Cu II complex in axial geometry (an unpaired electron coupling to the nuclear spin of one copper with 3/2).This is consistent with a valence-localized Cu II Cu III species (the Cu III being EPR sile defined in the Robin Day classification system [38] as a class I (classes II and III represe slight and significant delocalization, respectively).The spectrum of the complex 1 a oxidation was less resolved but four lines were still observable ( ∥ = 177 G) (Figure S The loss of resolution of the signal from this oxidized complex could be due to more stability of the one-oxidized species that can also be stated by its lower reversibility of CV (Figure 3a) at room temperature compared to complex 2 (Figure 3b).For the mo oxidized species 1, 2 and 3, in all three cases, the EPR parameters of the spectra (see F ures 4 and S11) obtained after simulation show a Cu II in an axial geometry [17].It is the complex, the redox process was found to be irreversible at the defined scan rate (30 mV•s −1 ), suggesting a fast evolution of the generated mixed-valent species.For Cu II Ox2Py2 (2), spectroelectrochemical measurements displayed slightly different features than for 1.New absorption bands were detected at λmax = 360 nm (3420 M −1 •cm −1 ) and 424 nm (sh, 2140 M −1 •cm −1 ) (Figures 5 and S13).In the near infrared region, a broad and weak band appeared at λmax = 1185 nm (120 M −1 •cm −1 ) (Figure S13).The process was found to be fully reversible as shown by CV and from spectroscopic data since these absorption bands disappeared upon back reduction.Aiming at better analyzing the oxidized  UV-Vis-NIR time-resolved spectroelectrochemistry experiments were carried out at room temperature to further characterize the unstable mono-oxidized species.Upon mono-oxidation of Cu II 2 Ox 4 (1), new absorption bands were detected at λ max = 380 nm, 480 nm (both ε ≈ 735 M −1 •cm −1 ) and 630 nm (weak) (Figure S12).In the NIR region, a very low-intensity and broad band centered at 1680 nm was observed (Figure S12).For this complex, the redox process was found to be irreversible at the defined scan rate (30 mV•s −1 ), suggesting a fast evolution of the generated mixed-valent species.
For Cu II Ox 2 Py 2 (2), spectroelectrochemical measurements displayed slightly different features than for 1.New absorption bands were detected at λ max = 360 nm (3420 M −1 •cm −1 ) and 424 nm (sh, 2140 M −1 •cm −1 ) (Figures 5 and S13).In the near infrared region, a broad and weak band appeared at λ max = 1185 nm (120 M −1 •cm −1 ) (Figure S13).The process was found to be fully reversible as shown by CV and from spectroscopic data since these absorption bands disappeared upon back reduction.Aiming at better analyzing the oxidized product from 2, we determined the bandwidth at half-height ( Figure 4. EPR spectra of complex 2 after oxidation after bulk electrolysis at −40 °C (red), a warming to room temperature (black) in frozen solution (0.1 M NBu4ClO4 in acetonitrile) of of 2 recorded at 15 K; frequency = 9.419 GHz.Simulation was carried out with the EasySpin p [39] assuming the following parameter: g⊥ = 2.065, g// = 2.307, A⊥ = 0 G, A// = 173 G.
For Cu II Ox2Py2 (2), spectroelectrochemical measurements displayed slightly di features than for 1.New absorption bands were detected at λmax = 360 nm (3420 M and 424 nm (sh, 2140 M −1 •cm −1 ) (Figures 5 and S13).In the near infrared region, a and weak band appeared at λmax = 1185 nm (120 M −1 •cm −1 ) (Figure S13).The proce found to be fully reversible as shown by CV and from spectroscopic data since th sorption bands disappeared upon back reduction.Aiming at better analyzing the ox product from 2, we determined the bandwidth at half-height (Δν1/2 = 2460 cm −1 ) by the NIR experimental curve (Figure S14).From this value and by assuming a Cu−C tance of 2.80 Å from the X-ray structure of 2, we determined the electronic coupling element Hab (determined from the Mulliken-Hush expression [40,41]) as well as th between the experimental and theoretical values of Δν1/2 (Γ parameter).The calcu yielded Hab = 373 cm −1 and Γ = 0.45, as typically found for a class II system in the Robi classification, i.e., low delocalization of the charge, here at room temperature.No thy, this result is close to that obtained with Cu II Py4 (3) (Hab = 322 cm −1 and Γ = 0.3 and demonstrates the strong similarities between Cu II Ox2Py2 and Cu II Py4 compl likely suggests that the oxidation occurs on the copper/pyridine moieties for comp Field / G = 2460 cm −1 ) by fitting the NIR experimental curve (Figure S14).From this value and by assuming a Cu−Cu distance of 2.80 Å from the X-ray structure of we determined the electronic coupling matrix element H ab (determined from the Mulliken-Hush expression [40,41]) as well as the ratio between the experimental and theoretical values of Figure 4. EPR spectra of complex 2 after oxidation after bulk electrolysis at −40 °C (red), and a warming to room temperature (black) in frozen solution (0.1 M NBu4ClO4 in acetonitrile) of 0.7 m of 2 recorded at 15 K; frequency = 9.419 GHz.Simulation was carried out with the EasySpin progr [39] assuming the following parameter: g⊥ = 2.065, g// = 2.307, A⊥ = 0 G, A// = 173 G.
For Cu II Ox2Py2 (2), spectroelectrochemical measurements displayed slightly differe features than for 1.New absorption bands were detected at λmax = 360 nm (3420 M −1 •cm and 424 nm (sh, 2140 M −1 •cm −1 ) (Figures 5 and S13).In the near infrared region, a bro and weak band appeared at λmax = 1185 nm (120 M −1 •cm −1 ) (Figure S13).The process w found to be fully reversible as shown by CV and from spectroscopic data since these a sorption bands disappeared upon back reduction.Aiming at better analyzing the oxidiz product from 2, we determined the bandwidth at half-height (Δν1/2 = 2460 cm −1 ) by fitti the NIR experimental curve (Figure S14).(Γ parameter).The calculations yielded H ab = 373 cm −1 and Γ = 0.45, as typically found for a class II system in the Robin−Day classification, i.e., low delocalization of the charge, here at room temperature.Noteworthy, this result is close to that obtained with Cu II Py 4 (3) (H ab = 322 cm −1 and Γ = 0.39) [17] and demonstrates the strong similarities between Cu II Ox 2 Py 2 and Cu II Py 4 complexes.It likely suggests that the oxidation occurs on the copper/pyridine moieties for complex 2. EPR spectra of complex 2 after oxidation after bulk electrolysis at −40 °C (red), and warming to room temperature (black) in frozen solution (0.1 M NBu4ClO4 in acetonitrile) of 0.7 of 2 recorded at 15 K; frequency = 9.419 GHz.Simulation was carried out with the EasySpin pro [39] assuming the following parameter: g⊥ = 2.065, g// = 2.307, A⊥ = 0 G, A// = 173 G.
For Cu II Ox2Py2 (2), spectroelectrochemical measurements displayed slightly diffe features than for 1.New absorption bands were detected at λmax = 360 nm (3420 M −1 •c and 424 nm (sh, 2140 M −1 •cm −1 ) (Figures 5 and S13).In the near infrared region, a b and weak band appeared at λmax = 1185 nm (120 M −1 •cm −1 ) (Figure S13).The process found to be fully reversible as shown by CV and from spectroscopic data since thes sorption bands disappeared upon back reduction.Aiming at better analyzing the oxid product from 2, we determined the bandwidth at half-height (Δν1/2 = 2460 cm −1 ) by fi the NIR experimental curve (Figure S14).From this value and by assuming a Cu−Cu tance of 2.80 Å from the X-ray structure of 2, we determined the electronic coupling m element Hab (determined from the Mulliken-Hush expression [40,41]) as well as the between the experimental and theoretical values of Δν1/2 (Γ parameter).The calcula yielded Hab = 373 cm −1 and Γ = 0.45, as typically found for a class II system in the Robin− classification, i.e., low delocalization of the charge, here at room temperature.Note thy, this result is close to that obtained with Cu II Py4 (3) (Hab = 322 cm −1 and Γ = 0.39) and demonstrates the strong similarities between Cu II Ox2Py2 and Cu II Py4 complex likely suggests that the oxidation occurs on the copper/pyridine moieties for comple  In regard to the observed reactivity toward toluene (bond dissociation energy (BDE) = 89.8kcal mol −1 ) [42] of Cu II Cu III species generated electrochemically from Cu II 2 Py 4 , the reactivity of the mono oxidized species from 1 and 2 were probed via CV with (over 100 equiv.)and without toluene.For both complexes, the CV remained the same when toluene was added, suggesting no reactivity between the Cu II Cu III species and toluene at this timescale.Few Cu II Cu III species are reported in the literature [17,[33][34][35] and besides our previous studies [18], only one result demonstrated a reactivity on dihydroanthracene [33], a rather weak C-H bond.
To test a possible reason of this lack of observed reactivity, the ligands were analyzed after the monoelectronic-oxidation of the complexes (0.7 mM) through exhaustive electrolysis in NBu 4 ClO 4 /CH 3 CN at −40 • C at 1.26 V vs. Fc + /Fc for complex Cu II 2 Ox 2 Py 2 and at 1.41 V vs. Fc + /Fc for complex Cu II 2 Ox 4 under air.After electrolysis, the solutions were warmed to room temperature.For identification of the oxidation products, the demetallation residue was analyzed via ESI mass spectrometry (Figures S15 and S16).In the case of Cu II 2 Ox 4 , the protonated ligand [LH + H] + (where LH represent the ligand) was observed at 575 m/z, but peaks at 591 m/z, 613 m/z and 629 m/z indicated the ligand hydroxylation as [LOH + H] + , [LOH + Na] + and [LOH + K] + , respectively, corresponding to the addition of an O atom.This behavior is consistent with change of the C(CH 3 ) 2 into C(CH 3 )(CH 2 OH) as depicted in Figure S17.The peak at 630 m/z was tentatively attributed to [LCHOHCN + H] + , which could be formed by a radical coupling of the oxazoline unit with the CH 3 CN solvent.Similar products were observed from the residue of Cu II 2 Ox 2 Py 2 : peaks at 535 m/z and 557 m/z from the ligand [LH + H] + , [LH + Na] + , respectively, and peaks at 551 m/z and 573 m/z from the hydroxylated product [LOH + H] + and [LOH + Na] + .Peaks at 590 m/z and 612 m/z could tentatively be assigned to products [LCHOHCN + H] + and [LCHOHCN + Na] + , respectively.All products are consistent with a proton coupled electron transfer as the initial step of the reaction.The oxidation of the relatively strong C-H bonds of the ligands is not surprising given the high oxidation potential of the complexes (where the oxidation potential and the pKa are the two thermodynamic driving forces for proton coupled electron transfers) [42].
From the non-electrolyzed complexes (but using the same treatment with concentrated KOH), no hydroxylated products or peaks assigned to the formation of LCHOHCN were observed on the residues, demonstrating that the changes to the ligand are linked to the generation of the Cu II Cu III species.

General
Reagents were purchased from commercial sources and were used without purification.The solvents were purified via standard methods before use.ESI mass spectra were recorded on an Esquire 3000 plus Bruker Daltonis with nanospray inlet.UV-Vis analyses were performed using a Cary 50 spectrophotometer operating in the 200-1000 nm range with quartz cells.The temperature was maintained at 25 • C with a temperature control unit.NMR solution spectra ( 1 H and 13 C) at 298 K were recorded on a unity Plus 400 MHz Varian spectrometer with the deuterated solvent as a lock.X-band EPR spectra were recorded in a range of 15-100 K with a Bruker EMX Plus spectrometer equipped with a nitrogen flow (or He flow) cryostat and operating at 9.4 GHz (X band).All spectra presented were recorded under non-saturating conditions.Simulation of EPR spectra was carried out with EasySpin program [39].All electrochemical measurements were carried out under an argon atmosphere at room temperature using a Biologic SP-300 instrument.Experiments were performed with solutions of the complexes containing 0.1 M of the supporting electrolyte (TBA•ClO 4 ).For cyclic voltammetry, a standard three-electrode configuration was used consisting of a glassy carbon (d = 3 mm) working electrode, a platinum counter electrode and an Ag wire placed in an AgNO 3 (0.01 M in CH 3 CN)/NBu 4 ClO 4 (0.1 M in CH 3 CN)) solution as a pseudo reference electrode.The system was systematically calibrated against ferrocene after each experiment and all the potentials are therefore given versus the Fc + /Fc redox potential.Low-temperature electrolysis was carried out with a home-designed 3electrode cell (WE: Carbon felt, RE: Pt wire, CE: Pt grid) dipped in an acetone/dry ice bath at −40 • C for 45 min.Samples for EPR and UV-Vis analysis of the mixed-valent complex were taken every 15 min.They were instantly frozen in liquid nitrogen for EPR measurements.

Ligands' Syntheses
Synthesis of ligand Ox 4 .According to the literature procedures [22,24], the intermediates 2,7-dichloro-1,8-naphthyridine and BOX were synthesized.A total of 1.25 g (5.56 × 10 −3 mol, 2.2 eq) of BOX dissolved in 40 mL of freshly distilled THF under argon and cooled to -60 • C was slowly added to 2.5 mL (5.56 × 10 −3 mol, 2.2 eq) of 2.4 M n-BuLi.The colorless solution was stirred for 30 min and 0.526 g of 2,7-dichloro-1,8-naphthyridine was added, leading to a beige precipitate in a red-orange solution.The solution was stirred overnight and reached room temperature, resulting in the solubilization of the precipitate.After addition of water (5 mL), THF was evaporated and a 40 mL of water was added.The solution was extracted with dichloromethane (DCM) and dried over Na 2 SO 4 .The residue was purified via column chromatography (gradient of acetone/pentane) over silica to give products Ox 2 Cl and Ox 4 (79% and 20%, respectively). 1   [23] was dissolved in 15 mL of freshly distilled THF under argon and cooled to −50 • C, followed by the slow addition of 0.26 mL (0.38 × 10 −3 mol, 1.1 eq) of 1.4 M n-BuLi and the red solution was stirred for 30 min.Then, 0.133 g of 2,7-dichloro-1,8-naphthyridine was added using a powder finger.The solution was stirred overnight and allowed to reach room temperature, resulting in the formation of a precipitate.Then, 1 mL of water (1 mL) was added, dissolving the precipitate; the THF evaporated and water (20 mL) was added, and the solution was extracted with DCM (4 × 15 mL) and dried over MgSO 4 .The residue was purified via column chromatography (gradient of acetone/pentane) over silica to give the ligand Ox 2 Py 2 (140 mg, 76%). 1

Crystallographic Studies
Crystals were mounted on a Kappa APEXII Bruker-Nonius diffractometer equipped with an Incoatec µsource with multilayer mirror mono-chromated Mo-Kα radiation (λ = 0.71073 Å) and a cryosystem Oxford cryostream cooler.Intensities were corrected for Lorentz and polarization (EVAL14) and for absorption (SADABS).Structural resolutions were carried out via direct method (SIR97) or the charge flipping method (Superflip) and refinement via full-matrix least squares on F2 (SHELX2013) [43] completed using the OLEX 2 analysis package [44].The refinement of all non-hydrogen atoms was carried out with anisotropic thermal parameters.Hydrogen atoms were generated in idealized positions (excluding the hydroxido bridges, which were located on the difference Fourier map), riding on the carrier atoms, with isotropic thermal parameters.CCDC 2266887 and 2266888 contain the full data collection parameters and structural data for 2 and 1, respectively.

Spectroelectrochemistry
Thin layer room-temperature UV-Vis-NIR spectroelectrochemistry was carried out with a specific home-designed cell in a reflectance mode (WE: platinum, RE: Pt wire, CE: Pt wire).The UV-Vis and Vis-NIR optic fiber probes were purchased from Ocean Optics.Timeresolved UV-Vis-NIR detection was performed with QEPro and NIRQuest spectrometers (Ocean Insight, Orlando, FL, USA).Spectroscopic data were acquired using the Oceanview software.A DH-2000-BAL light source (Ocean Optics) was used for these experiments.The potential of the spectroelectrochemical cell was monitored using an AUTOLAB PGSTAT 100 (Metrohm, The Netherlands) potentiostat controlled by the NOVA 1.11 software.

Conclusions
Two new bridged ligands bearing a naphthyridine spacer and symmetrical or unsymmetrical coordination environment including a bis-oxazoline arm were successfully synthetized.The related Cu I 2 complex with four pyridine arms (Py 4 ) [26] displayed no dioxygen activation, whereas the corresponding Cu 2 I complexes from Ox 2 Py 2 and Ox 4 ligands were shown to bind dioxygen at −40 • C yielding µ-η 2 :η 2 -peroxido-Cu II 2 species as clearly observed by using UV-Vis spectroscopy.For both, preliminary reactivity studies with sodium 2,4-di-tert-butylphenolate were performed.The resulting product (3,3 ,5,5tetra-tert-butyl-2,2 -biphenol) indicated C-C coupling, whereas no ortho-hydroxylation was observed.The corresponding Cu II  2 complexes 1 (Cu II 2 Ox 4 ) and 2 (Cu II 2 Ox 2 Py 2 ) have been prepared and characterized via single-crystal X-ray diffraction.Electrochemical mono-oxidation provided access to mixed-valent Cu 2 II,III µ-hydroxido species with charge localization on one of the two copper ions.ESI-MS of the solution after electrolysis and demetallation show unequivocal evidence of intramolecular oxidation of the ligand through the bis-oxazoline moieties, contrary to complex 3 (Cu II 2 Py 4 ), which is active in electrocatalysis at room temperature of exogenous substrate [18].The present study therefore emphasizes that the electrochemically produced Cu II Cu III species are competent for aliphatic oxidation of C-H bonds (intramolecular or external substrate).In order to further advances towards generating a catalytic system (or oxidation of an external substrate), efforts on the synthesis of more robust ligands are currently being pursued.

Scheme 2 .
Scheme 2. Ligands used in this work.

Scheme 2 .
Scheme 2. Ligands used in this work.

Scheme 2 .
Scheme 2. Ligands used in this work.

Figure 1 .
Figure 1.UV-vis monitoring of the addition of O 2 on Cu I 2 Ox 4 ; parameters: optical path = 1 cm; solvent: acetone, concentration 0.094 mM, T = 193 K.The baseline was taken on the dicopper(I) complex solution before O 2 addition for better monitoring of the peroxide absorption bands (justifying the use of relative absorbance (∆Abs.)instead of absorbance (Abs.) on the graph).
Ox 2 Py 2 afforded compound 2 (Cu II 2 Ox 2 Py 2 ) as a crystalline material.The unit cell encloses two crystallographically independent [C 32 H 44 Cu 2 N 6 O 6 ](CF 3 SO 3 ) 2 entities and one CH 3 CN as solvate.Each cationic unit displays two triflate counterions.Unit 2A is shown in Figure 2b (other views on Figure S7b) and unit 2B is shown in Figure S7c (Supporting Information); each consists of two copper atoms bridged by two hydroxido groups.Selected bond lengths and angles are reported in Tables

Figure 5 .
Figure 5. UV-Vis−NIR monitoring of the oxidation of complex 2 via spectroelectrochemistry ing the reversibility of the redox process.Right: current intensity variation with time taken f CV at  = 30 mV•s −1 .Conditions: 7 mM in 0.1 M NBu4ClO4 in acetonitrile, optical path = 0 working electrode: Pt, room temperature.

2 Figure 5 .
Figure 5. UV-Vis−NIR monitoring of the oxidation of complex 2 via spectroelectrochemistry sho ing the reversibility of the redox process.Right: current intensity variation with time taken from CV at  = 30 mV•s −1 .Conditions: 7 mM in 0.1 M NBu4ClO4 in acetonitrile, optical path = 0.2 m working electrode: Pt, room temperature.

Figure 5 .
Figure 5. UV-Vis−NIR monitoring of the oxidation of complex 2 via spectroelectrochemistry s ing the reversibility of the redox process.Right: current intensity variation with time taken from CV at  = 30 mV•s −1 .Conditions: 7 mM in 0.1 M NBu4ClO4 in acetonitrile, optical path = 0.2 working electrode: Pt, room temperature.

Figure 5 .
Figure 5. UV-Vis−NIR monitoring of the oxidation of complex 2 via spectroelectrochemistry showing the reversibility of the redox process.Right: current intensity variation with time taken from the CV at v = 30 mV•s −1 .Conditions: 7 mM in 0.1 M NBu 4 ClO 4 in acetonitrile, optical path = 0.2 mm, working electrode: Pt, room temperature.

Synthesis and Characterizations Complex Cu I 2 Py 4 was
[26]hesized according to the procedure described by Tilley et al.[26].The two air-sensitive Cu(I) complexes based on

Ox 4 and Ox 2 Py 2 ligands (named Cu I 2 Ox 4 and Cu I 2 Ox 2 Py 2 , respectively
) were prepared using a similar procedure: under argon, one equivalent of ligand (