A family of ligand and anion dependent structurally diverse Cu(II) Schiff-base complexes and their catalytic efficacy in an O-arylation reaction in ethanolic media

Abstract

Two nitrato bridged dinuclear systems [Cu₂(L1)₂(NO₃)₃]NO₃·H₂O (1) and [Cu₂(L2)₂(NO₃)₃]NO₃·MeOH (2), five monomeric complexes viz. [Cu(L3)(NO₃)]NO₃ (3), [Cu(L4)(NO₃)]NO₃ (4), [Cu(L5)(NO₃)]NO₃ (5), [Cu(L6)(NO₃)NO₃] (7), [Cu(L7)(NO₃)]NO₃ (8) and one hetero bi-bridged (phenoxido and water) dinuclear complex [Cu₂(L2)₂(H₂O)₂](ClO₄)₄·4H₂O (6) have been synthesized and characterized using several physicochemical methods (L1 = 1-(N-3-methoxysalicylideneimino)-ethane-2-piperazine, L2 = 1-(N-3-ethoxysalicylideneimino)-ethane-2-piperazine, L3 = 1-(N-4′-ethoxy-α-methylasalicylideneimino)-ethane-2-piperazine, L4 = 1-(N-5′-chloro-α-methylasalicylideneimino)-ethane-2-piperazine, L5 = 1-(N-5-chlorosalicylideneimino)-ethane-2-piperazine, L6 = 1-(N-4-methoxysalicylideneimino)-ethane-2-piperazine and L7 = 1-(N-4′-methoxy-α-methylasalicylideneimino)-ethane-2-piperazine). X-ray structural analysis showed that complexes 1 and 2 are discrete dinuclear species where the pentacoordinated metal centers are bridged through a nitrate ion. In 3, 4, 5 and 8 the monomeric copper center displays a square pyramidal geometry with a weak axial Cu–O bond. In 7, the monomeric copper center shows a distorted octahedral geometry with two coordinated nitrate anions. However, in 6 the two copper centers coordinate in different manners (one is square-pyramidal and the other is distorted octahedral) and are bridged through a phenoxido group and a water molecule. All complexes efficiently catalyze the C–O coupling reaction under homogeneous conditions at 80 °C to afford unsymmetrical diaryl ethers using nitroarenes to act as an excellent electrophile. Notably, the reaction is carried out in ethanol media which facilitates the avoidance of toxic wastes. Structurally diverse copper(II) Schiff-base complexes have rarely been used systematically in catalytic C–O coupling reactions.

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1. Introduction

Diaryl ethers are ubiquitous structural motifs that represent a large number of natural biologically active compounds (K13, perrottetin, teicoplanin and vancomycin) (Scheme 1) and they are also important in polymer industries.^1–8 Classically, these compounds have been synthesized via copper-catalyzed Ullmann type cross-coupling reactions of aryl halides and phenols at very high temperatures (125–220 °C) that require stoichiometric amounts of catalyst.^9–11 Low to moderate yields are often obtained following these classic methods. Recently attempts have been made to develop a new synthesis route for diaryl ethers under milder reaction conditions.^6,10–22 Buchwald, Hartwig and Beller developed palladium catalyzed processes for C–O cross-coupling reactions under mild conditions.^23–28 In spite of palladium catalyzed methods being highly active the prospect of their application in large scale reactions for industrial production is limited due to the high expense of palladium and its toxicity as well as the need to use phosphorated ligands in the process.^29,30 In 1998, Chen, Lam and Evans developed a new route to build carbon–heteroatom bonds, using arylboronic acid instead of aryl halides which produces undesirable by-products.^31–33 This problem is difficult to mitigate as phenylboronic acids release water through triphenylboroxime formation and enhance phenol formation from phenylboronic acid that leads to competition between phenol and phenolic derivatives for O-arylation.^34–38 Copper-based catalysts have been developed for O-arylation reactions of nitroarenes to achieve diaryl ethers.^2,7 In this study we demonstrated that cheap nitroarenes resolve the problem of unwanted by-product formation.

Scheme 1 Selected bioactive compounds featuring an aryl ether moiety.

The selection of suitable metal salts and multidentate ligands is very important as they play dominant roles in the control and adjustment of the architecture of coordination complexes.^39–42 The coordination chemistry of Schiff-base ligands is particularly interesting as the selection of suitable amines and aldehydes/ketones, which can afford steric and electronic influence originating from different substituent groups, may create structural and functional variations.^43–46 These types of structural diversity have a significant impact in the fields of catalysis,^47,48 magnetism,^49,50 and DNA cleavage studies.⁵¹ Ramadan et al. studied the oxidase catalytic activity of mononuclear and dinuclear Cu(II) complexes towards the aerobic oxidation of vitamin C.⁴⁷ The enantioselective cyclopropanation of styrene is efficiently catalyzed by monomeric and dimeric Cu(II) chiral Schiff-base complexes.⁴⁸ Lin et al. used structurally diverse copper complexes as the catalyst for the copolymerization of carbon dioxide and cyclohexene oxide.⁵² Copper(II) Schiff-base complexes containing the Cu₂O₂ moiety have also been investigated exhaustively with reference to their catecholase activity.^53–58 We have employed copper(II) Schiff-base complexes in the catalytic olefin epoxidation reaction in homogeneous and heterogeneous conditions.^59–62 Nevertheless, the catalytic efficacy of Cu(II) Schiff-base complexes vis-à-vis their structural diversities has rarely been explored. We are particularly interested to explore the catalytic efficacy of structurally diverse Schiff-base copper complexes in coupling reactions.

We report here the syntheses and crystal structures of a family of structurally diverse copper(II) Schiff-base complexes and their application in catalytic O-arylation reactions. All the complexes efficiently catalyze O-arylation reactions of phenolic derivatives with nitroarenes in ethanol media under milder conditions. For practical applications, copper(II)-based catalysts are promising alternatives by virtue of their low cost and insensitivity to air as well as their ability to cut down undesirable by-products in O-arylation reactions. To our knowledge, there have been only very few reports in which copper(II) Schiff-base complexes have been used to catalyze C–O coupling reactions.^63,64

2. Experimental section

2.1. Materials

N-(2-Ethylamino)piperazine, o-vanilline, 3-ethoxysalicylaldehyde, 5-chlorosalicylaldehyde, 4′-ethoxy-2′-hydroxyacetophenone, 5′-chloro-2′-hydroxyacetophenone, 4-methoxysalicylaldehyde and 4′-methoxy-2′-hydroxyacetophenone were purchased from Aldrich. Solvents (analytical grade), cesium carbonate, copper(II) nitrate trihydrate, copper(II) perchlorate hexahydrate, substituted phenols and other chemicals were purchased from Merck (India) Pvt. Ltd. Solvents were dried before use.

2.2. Physical measurements

Elemental analysis was performed using a Perkin-Elmer 240C elemental analyzer. Fourier transform-infrared spectra of KBr pellets were measured using a Perkin-Elmer SPECTRUM II FTIR spectrometer. The UV-Vis spectral measurements were carried out using a Shimadzu UV-Vis 1700 spectrophotometer. Thermogravimetric differential thermal analysis (TG-DTA) measurements were performed using a Perkin-Elmer (Singapore) Pyris Diamond TG/DTA unit. The heating rate was programmed at 4 °C min⁻¹ with a protecting stream of N₂ flowing at a rate of 150 mL min⁻¹. The powder X-ray diffraction (XRD) patterns of samples were recorded using a Bruker D8 Advance diffractometer using Cu Kα radiation (λ = 1.54 Å). ¹H and ¹³C NMR spectra were measured using a Bruker Avance DPX 300 NMR (300 MHz) and 600 MHz spectrometer. Mass spectra were measured using a Waters XEVO-G2QTOF#YCA351 high resolution mass spectrometer.

Caution! Perchlorate salts of metal complexes coordinated with organic ligands are potentially explosive. They should be handled with care and only a small amount of material should be prepared.

2.3. Synthesis of the Schiff-base ligands L1, L2, L3, L4, L5, L6 and L7

The Schiff-base L1 was prepared by mixing 20 mL of ethanolic solution of N-(2-ethylamino)piperazine (0.491 g, 4 mmol) and o-vaniline (0.608 g, 4 mmol) together in a flat bottom flask. The mixture was then refluxed for 30 min. The resulting yellow colored solution was then cooled to room temperature. Ethanol was then separated almost completely from the mixture using a rotary evaporator. The amine N-(2-ethylamino)piperazine was mixed with 3-ethoxysalicylaldehyde, 4′-ethoxy-2′-hydroxyacetophenone, 5′-chloro-2′-hydroxyacetophenone, 5-chlorosalicylaldehyde, 4-methoxysalicylaldehyde and 4′-methoxy-2′-hydroxyacetophenone to synthesize ligands L2, L3, L4, L5, L6 and L7 respectively. All ligands were characterized using ¹H and ¹³C NMR, HRMS and elemental analysis (see ESI†).

2.4. Synthesis of complex 1

A 10 mL ethanolic solution of Cu(NO₃)₂·3H₂O (0.24 g, 1 mmol) was added dropwise to a 10 mL ethanolic solution of L1 (1 mmol). The resulting deep green mixture was kept undisturbed without stirring at room temperature. On slow evaporation of the filtrate, dark green cube shaped crystals appeared in a day. They were collected by filtration and washed first with the mother liquor then with a few drops of diethylether. The yield was ca. 81% based on the metal. The phase purity of bulk 1 was confirmed using powder XRD (Fig. S14, ESI†) and elemental analysis. Elemental analysis calcd C 35.94, H 4.74, N 14.97; found C 35.9, H 4.7, N 14.9.

2.5. Synthesis of complexes 2–8

All complexes were synthesized following a similar procedure to that of 1, using L2, L3, L4, L5, L6 and L7, respectively, for complexes 2, 3, 4, 5, 7 and 8 instead of L1. The crystals which separated were deep green in color. Complex 6 was prepared by the same procedure only selecting L2 as the ligand and Cu(ClO₄)₂·6H₂O instead of Cu(NO₃)₂·3H₂O. The single crystals of 6 were light green in color. The yields of these complexes were ca. 86, 73, 76, 57, 79 and 83% respectively based on the metal. The phase purities of the complexes were confirmed using powder XRD (Fig. S15–S21, ESI†) and elemental analysis. Elemental analysis for 2 calcd C 38.71, H 5.24, N 14.56; found C 38.7, H 5.2, N 14.5; for 3 calcd C 40.21, H 5.26, N 14.62; found C 40.2, H 5.2, N 14.6; for 4 calcd C 35.83, H 4.30, N 14.92; found C 35.8, H 4.2, N, 14.9; for 5 calcd C 34.29, H 3.98, N 15.38; found C 34.3, H 3.9, N 15.4; for 6 calcd C 30.80, H 4.83, N 7.18; found C 30.8, H 4.8, N 7.1; for 7 calcd C 37.31, H 5.22, N 14.50; found C 37.3, H 5.2, N 14.4.

2.6. X-ray crystallography

X-ray diffraction data for all compounds were collected using a Bruker Smart Apex CCD X-ray diffractometer using graphite-monochromated Mo Kα radiation (λ = 0.71073 Å). Integrated intensities and cell refinements were determined with the SAINT⁶⁵ software package using a narrow-frame integration algorithm. An empirical absorption correction⁶⁶ (SADABS) was applied. The structure was solved using direct methods and refined using a full-matrix least-squares technique against F² with the anisotropic displacement parameters for non-hydrogen atoms, with the programs SHELXS97 and SHELXL97.⁶⁷ Hydrogen atoms were placed at the calculated positions using suitable riding models with isotropic displacement parameters derived from their carrier atoms. In the final difference Fourier maps there were no noteworthy peaks other than the ghost peaks surrounding the metal centers. A summary of the crystal data and relevant refinement parameters is given in Table 1.

Table 1 Crystal data and refinement details of compounds 1–7

Complex	1	2	3	4	5	6	7
Formula	C28H42Cu2N10O18	C31H47Cu2N10O16.50	C16H25CuN5O8	C14H20ClCuN5O7	C13H18ClCuN5O7	C30H56Cl4Cu2N6O25	C15H25CuN5O9
Formula weight	933.82	950.86	478.95	469.34	455.31	1169.68	482.95
Crystal system	Monoclinic	Monoclinic	Monoclinic	Monoclinic	Monoclinic	Triclinic	Monoclinic
Space group	C2/c	C2/c	P21/c	P21/c	P21/c	P1̄	P21/n
a (Å)	15.3483(9)	15.2074(4)	23.3712(6)	22.6374(13)	22.0294(6)	9.1817(4)	12.0035(5)
b (Å)	12.7358(8)	12.6983(3)	6.5538(2)	6.6010(4)	6.6638(2)	11.7822(5)	9.5610(4)
c (Å)	19.0760(11)	20.2333(5)	12.8896(3)	12.4456(7)	12.1691(3)	22.0042(10)	18.1151(8)
α (°)	90	90	90	90	90	86.723(2)	90
β (°)	92.446(4)	91.6930(10)	90.7490(10)	97.759(2)	98.658(2)	89.312(2)	105.715(3)
γ (°)	90	90	90	90	90	83.934(2)	90
V (Å^3)	3725.4(4)	3905.51(17)	1974.13(9)	1842.71(19)	1766.06(8)	2363.19(18)	2001.28(15)
Z	4	4	4	4	4	2	4
D calc (g cm^−3)	1.665	1.617	1.611	1.692	1.712	1.644	1.603
μ (mm^−1)	1.234	1.176	1.163	1.380	1.437	1.217	1.151
R int	0.0811	0.0322	0.039	0.049	0.025	0.032	0.059
Unique data	4116	4348	5305	3871	5396	12 608	4521
Data with I > 2(I)	2247	3525	4114	3487	4483	8436	2859
R 1 (I > 2(I))	0.0756	0.0620	0.0346	0.0397	0.0329	0.0492	0.0480
wR2 (I > 2(I))	0.2470	0.1570	0.0877	0.0839	0.0843	0.1329	0.1307
(GOF) on F^2	1.032	1.056	1.037	1.202	1.038	1.028	0.965

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2.7. Catalytic reactions

A fixed amount of Cu(II) complex (1 mol%) was added to a round-bottom flask that contained a solution of 4-nitrobenzaldehyde (0.151 g, 1 mmol), phenol (0.094 g, 1 mmol) and K₂CO₃ (0.326 g, 1 mmol) in ethanol (4 mL). The reaction mixture was refluxed at 80 °C for 8 h. The reaction conversion was monitored using the TLC (thin layer chromatography) method. After 8 h the reaction mixture was cooled to room temperature and the mixture was extracted with water and diethyl ether (2 × 15 mL). The organic layers thus collected were combined and washed with brine, dried over anhydrous Na₂SO₄, and concentrated in vacuo. The residue was purified using column chromatography on silica gel (mesh 60–120) using an n-hexane/ethyl acetate mixture as the eluent to give the desired product. The product was characterized using ¹H, ¹³C-NMR, HRMS and elemental analysis and then compared with literature data. To study the progress of the reaction, mixtures were collected at the desired intervals and the products were isolated following the above procedure (Fig. 3 and 4).

3. Results and discussion

3.1. Synthesis

The Schiff-base ligands L1 and L2 were prepared by the 1 : 1 condensation of 3-methoxysalicylaldehyde and 3-ethoxysalicylaldehyde with N-(2-ethylamino)piperazine in ethanol solution respectively. The ethanolic solution of the ligand was allowed to react with a copper(II) nitrate salt to prepare the bis-complexes, [Cu₂(L1)₂(NO₃)₃]NO₃·MeOH (1) and [Cu₂(L2)₂(NO₃)₃]NO₃·MeOH (2). The absence of any electron donating functional group at the 3-position of salicylaldehyde and/or 2-hydroxyacetophenone produced monomer complexes, e.g. [Cu(L3)(NO₃)]NO₃ (3), [Cu(L4)(NO₃)]NO₃ (4), [Cu(L5)(NO₃)]NO₃ (5), [Cu(L6)(NO₃)₂]MeOH (7) and [Cu(L7)(NO₃)]NO₃ (8). Here the nitrate anions also have some contribution to the structure direction. They show three different modes in 1 and 2, as a bridging agent, terminal cap and also as a charge balancing ion. In 3–5, 7 and 8 they only act as capping and charge balancing agents. In all the above seven complexes Schiff-base ligands showed tridentate (NNO donor) coordination. When a copper(II) perchlorate salt was used instead of a copper(II) nitrate L2 afforded a hetero-bridged dinuclear complex, [Cu₂(L2)₂(H₂O)₂](ClO₄)₄·4H₂O (6), where L2 acts as both a tri- and tetra-dentate (NNO and N₂O₂ donor, respectively) chelating ligand. Besides, the phenoxide and water oxygen bridged two different copper centers. In 6 the water molecules are in three different environments, as bridging or simple coordinating ligands and as water of crystallization. In all Schiff-base ligands proton liberated from the phenolic OH group bonded to the nitrogen atom of the piperazine ring to form zwitterionic neutral molecules. Synthetic routes for complexes (1–8) are given in Scheme 2.

Scheme 2 Synthetic routes for complexes 1–8.

3.2. Thermal analysis

Thermogravimetric analysis confirmed that complexes 1–5 and 7 were thermally stable up to ∼185 °C as shown in Fig. S1 and S2 (see ESI†). The TG curve indicated that 1 and 2 start to lose water molecules from the beginning and a mass loss of approximately 2.02 and 1.91% are shown up to a temperature of 140 °C. This mass loss was in good agreement with the theoretical values of 1.93 and 1.87% for 1 and 2 respectively, corresponding to the loss of one molecule of crystalline water. The corresponding DTA (differential thermal analysis) curves showed an endothermic peak for both compounds at ∼75 °C. Compounds 3–5 and 7 experienced no such loss for deaquation, however, after 180 °C (230 °C for 7) all the compounds showed a continuous mass loss up to 800 °C due to the decomposition, showing two exothermic peaks at ∼230 °C and ∼410 °C in the DTA curves. Thermogravimetric analysis of complex 6 was performed up to a temperature of 200 °C; further heating was avoided as complex 6 contains explosive perchlorate anions (Fig. S2, see ESI†). The TG curve of 6 showed mass loss from room temperature which continued up to 200 °C. This mass loss corresponds to the liberation of water of crystallization and afterwards coordinated water molecules. The corresponding DTA curve showed two broad endothermic peaks at ∼62 and 148 °C.

3.3. Spectroscopic analysis

In the IR spectra of complexes 1–8 the characteristic vibration band of the azomethine ν(C=N) group was observed at around 1600 cm⁻¹ (Fig. S3 and S4†). Peaks observed in the range 3060–2610 cm⁻¹ were due to the stretching vibration of methyl (–CH₃), methylene (–CH₂–) and aromatic C–H bonds. The appearance of a strong band for the phenolic C–O group near 1210 cm⁻¹ in IR spectra of the compounds indicates the presence of the phenolic oxygen atom. The presence of a broad band at ca. 3450 cm⁻¹ for 1 and 2 and 3500 cm⁻¹ for 6 indicates the presence of water molecules. In complexes 1–5, 7 and 8 the characteristic, strong peaks for the stretching vibrations of nitrate molecules appeared at ∼1440 cm⁻¹ (ν₅), 1380 cm⁻¹ (ν₁) and 1020 cm⁻¹ (ν₂). Two strong peaks appearing at 1100 cm⁻¹ (ν₃) and 915 cm⁻¹ (ν₄) for 6 were ascribed to the characteristic vibration bands of uncoordinated perchlorate anions.

Electronic absorption spectra of all the complexes and ligands were recorded in ethanol media (Fig. S5–S7, see ESI†). The free ligand L1 showed three intra-ligand charge transfer bands at 416, 292 and 220 nm, which were significantly shifted to lower wavelengths in complex 1 (Fig. S6, see ESI†). Ligand L2 showed intra-ligand charge transfer bands at 370, 293 and 218 nm, amongst them the first band was shifted to a lower wavelength and the other bands to higher wavelengths upon complexation, both in the case of 2 and 6 (Fig. S6, see ESI†). The rest of the ligands L3–L7 also showed three intra-ligand charge transfer bands; amongst them the first two bands were shifted to lower wavelengths and the other bands remained in the same position in complexes 3, 4, 5, 7 and 8. The spectra showed a single absorption band at 639, 638, 620, 624, 641, 632, 641 and 622 nm for complexes 1–8, respectively. The position of these bands was typical of d–d transitions for Cu(II) complexes.⁶⁸ For all the complexes bands appearing in the region 290–310 nm were attributed to a π–π* transition within the ligand⁶⁹ and the other bands appearing around 390 nm were due to L → M charge transfer transitions.

3.4. Crystal structure of complexes (1–7)

Complexes 1 and 2 containing 3-methoxy- and 3-ethoxy-derivatives of Schiff-bases are isostructural. The crystal structures confirm the chair conformation of the piperazine ring in both complexes. The N₂O donor Schiff-base binds the Cu(II) centers in a tridentate manner (Fig. 1). Both complexes crystallize in the monoclinic space group C2/c and consist of a centrosymmetric dinuclear cationic [Cu₂(Lx)₂(NO₃)₃]⁺ (x = 1 or 2) moiety as shown in Fig. 1a and b respectively. Selected bond distances and angles are collated in Table S1 (see ESI†). The copper centers feature a 5 coordinated square pyramidal geometry in both compounds as the Addison parameter (τ = |b − a|/60° where b and a are the two largest angles around the central atom; τ = 0 and 1 for perfect square pyramidal and trigonal bipyramidal geometries, respectively) for 1 and 2 is 0.022 and 0.038 respectively.⁷⁰ The axial position is occupied by the oxygen atom (O(6)) of the bridged nitrato group with the longest distance (Table S1†). Three donor atoms (O(2), N(1) and N(2) in 1 and O(1), N(1) and N(3) in 2) from the chelating ligand occupy the three equatorial positions and the other one is occupied by the oxygen atom (O(3)) from the terminal nitrate group. Apart from that a weak interaction is found from the oxygen atom (O(4)) of the terminal nitrato group at the distances 2.734(7) and 2.651(4) for 1 and 2, respectively. Intermolecular H-bonding gives further stability to both 1 and 2 (Table S4, see ESI†). Fig. S8 and S9† show that both 1 and 2 display a 2D supramolecular network.

Fig. 1 ORTEP diagrams of complexes 1 (a) and 2 (b).

Structure determination reveals that complex 3 consists of a cationic monomer (Fig. 2a) and it crystallizes in a monoclinic space group P2₁/c. The selected bond lengths and angles are summarized in Table S2.† The copper center is five-coordinated with an elongated square-pyramidal (4 + 1) geometry. An oxygen atom (O(23)) from the nitrato group coordinates axially at a very long distance 2.5440(15) Å. The Addison parameter of the copper center is 0.069, indicating its square pyramidal geometry. A copper(II) complex with a similar structure was observed in the case of the Schiff-base derived from 4′-methoxy-2′-hydroxyacetophenone (complex 8 in our case) instead of 4′-ethoxy-2′-hydroxyacetophenone.⁷¹ Complex 3 gains further stabilization through intermolecular H-bonding and a 1D supramolecular chain has been found (Table S4, see ESI†) where the uncoordinated anionic nitrate molecule plays an important role in the formation of this zigzag chain (Fig. S10†).

Fig. 2 ORTEP diagrams of complexes 3 (a), 4 (b), 5 (c), 6 (d) and 7 (e).

Single crystal X-ray structure determination reveals that complexes 4 and 5 are also cationic monomers like 3 and crystallize in a monoclinic space group P2₁/c (Fig. 2b and c respectively). In both of them the Cu(II) ion features a pentacoordinated square pyramidal geometry where an oxygen atom (O(20), O(19) for 4 and 5 respectively) of the coordinated nitrato group occupies the axial position with a long distance of 2.550(3) and 2.5440(15) Å (Table S2†). The Addison parameters of the copper centers are 0.067 and 0.108 for 4 and 5 respectively, indicating their square pyramidal geometry. Both 4 and 5 form a 1D zigzag supramolecular structure through intermolecular H-bonding like complex 3 (Table S4, Fig. S11 and S12 respectively; see ESI†).

Complex 6 consists of a discrete dinuclear unit of copper(II) (Fig. 2d). Selected bond parameters and angles are given in Table S3.† The complex contains two different [CuL2] units, two coordinated water molecules and four uncoordinated perchlorate anions with four crystalline water molecules. The Cu(1) atom features a pentacoordinated coordination sphere with square-pyramidal geometry. The equatorial plane is formed by the two nitrogen atoms N(12) and N(15), and the bridged phenoxido oxygen atom (O(1)) of one of the Schiff-bases (tetradentate). An oxygen atom O(41) from the bridged water molecule completes the basal plane. Another terminal water molecule (O42) occupies the axial position at a distance of 2.233(3) Å (Fig. 2d). The Addison parameter of Cu(1) is 0.052, indicating its square pyramidal geometry. The basal positions of the octahedral Cu(2) atom are occupied by two nitrogen atoms N(32) and N(35), and a phenoxido oxygen atom O(21) of the neighboring Schiff-base ligand. The fourth position of the equatorial plane and one elongated apical position are occupied by the bridged phenoxido oxygen atom (O(1)) and the ethoxide oxygen atom (O(8)) of the tetradentate Schiff-base ligand. The bridged oxygen atom of the water molecule (O(41)) coordinates to the elongated side to complete the distorted octahedral geometry around Cu(2) with a bond distance of 2.493(2) Å. The Cu⋯Cu distance in 6 is much closer (3.227) than in the other two dimers 1 and 2 (6.08 and 6.18, respectively). In 1 and 2 nitrates act as μ_1,3 bridging ligands but in 6 phenoxide and water have no other option than to bind in μ_1,1 bridging modes. This probably is the cause for the two copper centers to come closer. Crystalline water and perchlorate anions give the complex further stability through inter-molecular H-bonding (Table S4, see ESI†). Numerous examples of mixed bi-bridged complexes containing phenoxido, alkoxido or hydroxido ligands featuring Cu₂O₂ or Cu₂O₃ moieties have been reported so far, however, there is no example of Cu(II) Schiff-base complexes in which two copper centers are bridged through mixed phenoxido/water bridges. In this regard complex (6) is a unique example.

The last member of the family, compound 7, crystallizes in a monoclinic space group P2₁/c. The copper center is five-coordinated with square-pyramidal geometry where three donor atoms of the Schiff-base ligand (O(4), N(2) and N(3)) occupy the basal plane. An oxygen atom (O(1)) of the coordinated nitrato group binds to the copper center to complete the equatorial plane. A second oxygen atom (O(8)) from the second coordinated nitrato group coordinates axially at a long distance of 2.484(3) Å. The structure is quite similar to those of compounds 3, 4 and 5, but the difference is in the weak interaction that originates from the oxygen atom (O(3)) of one nitrate, at a distance of 2.734(7), that coordinates axially to copper center. This minute structural change in 7 generates a 2D supramolecular structure through H-bonding (Table S4 and Fig. S13 see ESI†).

3.5. Catalytic activity study

Initially, optimization studies for C–O coupling reactions were undertaken using p-methylphenol and p-nitrobenzaldehyde as the substrates and complex 1 as the catalyst under various reaction conditions as given in Table 2. To begin with we explored the effect of solvents since solvent plays an important role in transition-metal catalyzed transformations. Among different solvents, the highest yield of product was obtained in DMF (entry 1). However, ethanol was selected (entry 14) for environmental concerns. It was generally found that the O-arylation reaction was much faster with Cs₂CO₃ than with K₂CO₃ or Na₂CO₃ due to the higher solubility of Cs₂CO₃.⁷² However, the use of K₂CO₃ will be more economic than that of Cs₂CO₃ for large scale production. Other bases such as KOH, Na₂CO₃, CH₃COONa, tert-BuOK, and DABCO showed a slower formation of 4-formayl-4′-methyldiphenylether after 8 hours (entries 8–12). Cheap K₂CO₃ showed a satisfactory yield and was chosen for the O-arylation reaction (entry 14). The isolated yield increased sharply with the increase of reaction temperature (entries 14–16). The copper concentration in the reaction mixture was another important factor to investigate. Thus, the O-arylation reaction was carried out in the presence of 0.1, 0.2, 0.5, 1 and 2 mol% of catalyst (entries 17–21). A maximum conversion was achieved with 1 mol% of catalyst in 8 hours as shown in Fig. 3 and 4. Notably isolated yields were not up to the mark with lower concentrations of catalyst. Additionally, increasing the catalyst concentration beyond 1 mol% did not enhance the reaction rate significantly. No reaction occurred in the absence of catalyst in 8 hours (entry 13) and no induction period was observed in all the reactions (Fig. 3 and 4). A mixture of copper nitrate salt and ligand L1 as well as copper nitrate salt itself was used as a catalyst which afforded a moderate to low conversion in the coupling reaction (Table 2; entries 21 and 22). Thus the optimum conditions for the catalytic reaction were as follows: K₂CO₃ (base), ethanol (solvent), 1 mol% catalyst and a reaction temperature of 80 °C.

Table 2 Optimization of the reaction conditions^a

Entry	Catalyst	Base	Solvent	Yield^b (%)
a Reaction conditions: p-nitrobenzaldehyde (1.1 mmol), p-methylphenol (1.0 mmol), base (1.2 mmol), catalyst (1 mol%), solvent (3 mL) at 80 °C for 8 h. b Isolated yield. c Temperature was 30 °C. d Temperature was 50 °C. e 0.1 mol% compound 1. f 0.2 mol% compound 1. g 0.5 mol% compound 1. h 2 mol% compound 1.
1	Compound 1	K2CO3	DMF	97
2	Compound 1	K2CO3	DMSO	87
3	Compound 1	K2CO3	Toluene	18
4	Compound 1	K2CO3	Acetonitrile	36
5	Compound 1	K2CO3	Methanol	73
6	Compound 1	K2CO3	Ethyleneglycol	70
7	Compound 1	K2CO3	Dioxane	42
8	Compound 1	KOH	Ethanol	62
9	Compound 1	Na2CO3	Ethanol	64
10	Compound 1	CH3COONa	Ethanol	0
11	Compound 1	tBuOK	Ethanol	18
12	Compound 1	DABCO	Ethanol	0
13	—	K2CO3	Ethanol	0
14	Compound 1	K2CO3	Ethanol	88
15	Compound 1	K2CO3	Ethanol	21^c
16	Compound 1	K2CO3	Ethanol	57^d
17	Compound 1	K2CO3	Ethanol	12^e
18	Compound 1	K2CO3	Ethanol	28^f
19	Compound 1	K2CO3	Ethanol	62^g
20	Compound 1	K2CO3	Ethanol	88^h
21	Cu(NO3)2·3H2O + L1	K2CO3	Ethanol	41
22	Cu(NO3)2·3H2O	K2CO3	Ethanol	8

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Fig. 3 Plot showing the progress of the O-arylation reaction for p-nitrobenzaldehyde () and p-nitrobenzonitrile () with p-methylphenol catalyzed by complex 1.

Fig. 4 Plot showing the progress of the O-arylation reaction catalyzed by 1, 3 and 6 using p-nitrobenzaldehyde and p-methylphenol as the reactants.

Under the optimized reaction conditions, the scope and applicability of the coupling reaction using p-nitrobenzaldehyde with substituted phenol to unsymmetrical diaryl ethers were investigated (Table 3). At first, the impact of the electronic properties of the aryl moiety of the phenols on the yield of the catalytic reactions was evaluated using various substitutions on the phenol moiety. The results obtained in test reactions demonstrate that the electronic properties of the phenols affect the product yield (Table 3, entries 1–5). Substituted phenols possessing electron donating methyl groups accelerate the reaction to yield products in a greater amount in comparison to simple phenols. However, p-methylphenol showed a higher yield than o-methylphenol indicating that the yield is also affected by the steric effects of substitution (Table 3, entries 2 and 3). Additionally, catalysts were capable of activating less nucleophilic phenols (2-naphthol and 1-naphthol) to react with p-nitrobenzaldehyde and afforded good yields (Table 3, entries 6 and 7 respectively). We investigated the reactions of p-nitrobenzonitrile, and o- or p-dinitrobenzene with different phenols and collected the results in Table 3. Notably they also exhibit almost the same yields with the same trends in the catalytic reactions. The progress of the O-arylation reaction for p-nitrobenzaldehyde and p-nitrobenzonitrile with p-methylphenol catalyzed by complex 1 is given in Fig. 3. The coupling reactions of electron-deficient phenols with aryl halides have been challenging as the corresponding phenolates are weak nucleophiles.⁷³ Recently, Li et al. reported the O-arylation of p-hydroxyacetophenone with p-fluorobenzonitrile in DMF media at a temperature of 90 °C under a N₂ atmosphere.⁷⁴ Buchwald and his group also studied the reactivity of some electron-deficient phenols in C–O coupling reactions at 100–110 °C.⁷³ However, in all the above reported processes aryl halides were used as electrophiles. For the first time, the results presented here demonstrate that p-nitrobenzonitrile can behave as an electrophile in the O-arylation of p-hydroxyacetophenone and can afford very good yields in ethanolic media.

Table 3 The O-arylation of p-nitrobenzaldehyde with phenols^a

Entry	Aryl alcohol	Product	Catalyst	Yield^c (wt%)	TOF^d (h^−1)
a Reaction conditions: p-nitrobenzaldehyde (1.1 mmol), aryl alcohol (1.0 mmol), K2CO3 (1.2 mmol), catalyst (1 mol%), EtOH (3 mL) at 80 °C for 8 h. b Except for catalyst 6 (3 hours). c Isolated yield. d mol diaryl ether per mol copper per h. e 10 hours.
1			1	81	5
			2	81	5
			3	88	11
			4	84	11
			5	84	11
			6 ^b	94	16
			7	78	10
			8	87	11
2			1	88	6
			2	88	6
			3	93	12
			4	91	12
			5	92	12
			6	97	16
			7	83	10
			8	89	11
3			6	92	15
4			6	94	16
5			6	95	16
6			6	84	14
7			6	89	15
8			6	98	16
9			6	90	15
10			6	96	16
11			6	98	16
12^e			6	43	5
13			6	93	15
14			6	85	14
15			6	97	16
16			6	90	15
17			6	98	16
18			1	—	—
			2
			3
			4
			5
			6
			7
			8

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All the copper(II) Schiff-base complexes (1–8) efficiently catalyzed the O-arylation reactions. The turn over frequency calculation demonstrates that the catalytic efficacy of complex 6 is better than other monomeric and dimeric complexes. The two nitrato-bridged dimers 1 and 2 were less efficient than others perhaps due to the higher coordination number. The five monomers (3, 4, 5, 7 and 8) were a little bit less efficient than 6. Amongst the monomers 7 shows the lowest efficiency which may be due to the steric-crowding around the metal center. To test the stability of the complexes in the reaction medium HRMS spectra of all compounds were recorded in ethanol media. Mass spectra confirm that both monomeric and dimeric complexes are stable in boiling ethanol (see ESI†). We compared the efficacy of our catalyst with some Cu(II) salts, Cu(II) salts with amines and a previously reported nitrato-bridged 1D Cu(II) Schiff-base complex⁶¹ under the optimized reaction conditions and the results are summarized in Table S5 (see ESI†). After even a cursory look at Table S5† it will be clear that Cu(II) salts act as poor catalysts but their activity increases in presence of amines perhaps due to the in situ formation of a metal-amine chelate. The catalytic efficiency (TOF) of the previously reported nitrato-bridged complex showed an efficiency close to that of the monomer catalysts.

A plausible mechanism has been suggested based on the previous reports.⁷⁵ According to recent studies on the mechanism of copper-catalyzed O-arylation reactions, it is assumed that the reaction proceeds with an initial nucleophilic substitution (NuH) over the copper complex (Scheme 3). The base used here abstracts the O–H proton from phenol, thereby generating a nucleophile. Then oxidative addition of the nitroarene (ArNO₂) occurs through coordination with the Cu atom followed by reductive elimination to give the desired O-arylated products (Scheme 3).

Scheme 3 Plausible mechanism of the reaction.

4. Conclusion

Seven structurally diverse copper complexes containing mono- and dimeric structures, depending on the nature of the Schiff-base ligands or copper salts, have been synthesized and fully characterized using X-ray single-crystal structural analyses. Their molecular structures differ in the solid state under the influence of the varied stereo-electronic character of the Schiff-base ligands with the copper salt used. Dinuclear complex 6 exhibits a hitherto unknown Cu(II) Schiff-base complex structure in which two copper centers are bridged through mixed phenoxido/water bridges. All complexes are highly active in the catalysis of the C–O coupling reactions of phenols with p-nitrobenzaldehyde/p-nitrobenzonitrile in an environmentally benign solvent, ethanol. The result presented here is a rare example of C–O coupling reactions catalyzed by a copper(II) Schiff-base complex. Notably, the catalysts are efficient enough to activate electron-deficient phenols towards O-arylation reactions to afford diarylethers. This catalytic procedure also resolves the problem of unwanted by-product formation by using a cheaper variety of substrate, nitroarenes. Further investigations on the synthesis of the structurally diverse Schiff-base complexes and their application as catalysts in other organic reactions are currently in progress in our laboratory.

Acknowledgements

Financial support from Council of Scientific and Industrial Research (CSIR), New Delhi by a grant (Grant No. 01(2542)/11/EMR-II) (to S. K.) is gratefully acknowledged. T. M. and D. S. thanks the CSIR, New Delhi, for awarding them fellowship. Authors also thank Department of Science and Technology, Govt. of India to fund Department of Chemistry, Jadavpur University for procuring a single-crystal X-ray diffractometer, 300 MHz NMR spectrometer, HRMS and powder XRD system. T. M. thanks Mr Debabrata Ganguly, University of Calcutta for his help in this work.

References

1. N. T. S. Phan, T. T. Nguyen, C. V. Nguyen and T. T. Nguyen, Appl. Catal., A, 2013, 457, 69–77.
2. N. T. S. Phan, T. T. Nguyen, V. T. Nguyen and K. D. Nguyen, ChemCatChem, 2013, 5, 2374–2381.
3. H. Wang, A. Yu, A. Cao, J. Chang and Y. Wu, Appl. Organomet. Chem., 2013, 27, 611–614.
4. G. Evano, N. Blanchard and M. Toumi, Chem. Rev., 2008, 108, 3054–3131.
5. R. Zhang, J. Liu, S. Wang, J. Niu, C. Xia and W. Sun, ChemCatChem, 2011, 3, 146–149.
6. D. Maiti and S. L. Buchwald, J. Org. Chem., 2010, 75, 1791–1794.
7. J. Chen, X. Wang, X. Zheng, J. Ding, M. Liu and H. Wu, Tetrahedron, 2012, 68, 8905–8907.
8. M. Mondal, S. K. Bharadwaj and U. Bora, New J. Chem., 2015, 39, 31–37.
9. F. Ullmann, Ber. Dtsch. Chem. Ges., 1904, 37, 853–854.
10. D. Ma and Q. Cai, Org. Lett., 2003, 5, 3799–3802.
11. J. W. Tye, Z. Weng, R. Giri and J. F. Hartwig, Angew. Chem., Int. Ed., 2010, 49, 2185–2189.
12. D. Ma and Q. Cai, Org. Lett., 2006, 45, 1276–1279.
13. R. K. Gujadhur, C. G. Bates and D. Venkataraman, Org. Lett., 2001, 3, 4315–4317.
14. S. M. Islam, N. Salam, P. Mondal, A. S. Roy, K. Ghosh and K. Tuhina, J. Mol. Catal. A: Chem., 2014, 387, 7–19.
15. J.-F. Marcoux, S. Doye and S. L. Buchwald, J. Am. Chem. Soc., 1997, 119, 10539–10540.
16. H. J. Cristau, P. P. Cellier, S. Hamada, J.-F. Spindler and M. Taillefer, Org. Lett., 2004, 6, 913–916.
17. H. Rao, Y. Jin, H. Fu, Y. Jiang and Y. Zhao, Chem.–Eur. J., 2006, 12, 3636–3646.
18. Y.-J. Chen and H.-H. Chen, Org. Lett., 2006, 8, 5609–5612.
19. A. Ouali, J.-F. Spindler and M. Taillefer, Adv. Synth. Catal., 2006, 348, 499–505.
20. R. A. Altman and S. L. Buchwald, Org. Lett., 2007, 9, 643–646.
21. A. Ouali, J.-F. Spindler, A. Jutand and M. Taillefer, Adv. Synth. Catal., 2007, 349, 1906–1916.
22. S. Benyahya, F. Monnier, M. W. C. Man, C. Bied, F. Ouazzani and M. Taillefer, Green Chem., 2009, 11, 1121–1123.
23. M. Platon, L. Cui, S. Mom, P. Richard, M. Saeys and J.-C. Hierso, Adv. Synth. Catal., 2011, 353, 3403–3414.
24. J. P. Wolfe, S. Wagaw, J.-F. Marcoux and S. L. Buchwald, Acc. Chem. Res., 1998, 31, 805–818.
25. L. Salvi, N. R. Davis, S. Z. Ali and S. L. Buchwald, Org. Lett., 2012, 14, 170–173.
26. A. Aranyos, D. W. Old, A. Kiyomori, J. P. Wolfe, J. P. Sadighi and S. L. Buchwald, J. Am. Chem. Soc., 1999, 121, 4369–4378.
27. S. Harkel, K. Kumar, D. Michalik, A. Zapf, R. Jackstell, F. Rataboul, T. Riemeier, A. Monsees and M. Beller, Tetrahedron Lett., 2005, 46, 3237–3240.
28. Q. Shelby, N. Kataoka, G. Mann and J. Hartwig, J. Am. Chem. Soc., 2000, 122, 10718–10719.
29. J. F. Hartwig, Acc. Chem. Res., 1998, 31, 852–860.
30. L. Yin and J. Liebscher, Chem. Rev., 2007, 107, 133–173.
31. D. M. T. Chan, K. L. Monaco, R.-P. Wang and M. P. Winters, Tetrahedron Lett., 1998, 39, 2933–2936.
32. D. A. Evans, J. L. Katz and T. R. West, Tetrahedron Lett., 1998, 39, 2937–2940.
33. P. Y. S. Lam, C. G. Clark, S. Saubern, J. Adams, M. P. Winters, D. M. T. Chan and A. Combs, Tetrahedron Lett., 1998, 39, 2941–2944.
34. H. R. Snyder, M. S. Konecky and W. J. Lennarz, J. Am. Chem. Soc., 1958, 80, 3611–3615.
35. L. Chaicharoenwimolkul, A. Munmai, S. Chairam, U. Tewasekson, S. Sapudom, Y. Lakliang and E. Somsook, Tetrahedron Lett., 2008, 49, 7299–7302.
36. H. Tsunoyama, H. Sakurai, N. Ichikuni, Y. Negishi and T. Tsukuda, Langmuir, 2004, 20, 11293–11296.
37. J. Xu, X. Wang, C. Shao, D. Su, G. Cheng and Y. Hu, Org. Lett., 2010, 12, 1964–1967.
38. H. Sakurai, H. Tsunoyama and T. Tsukuda, J. Organomet. Chem., 2007, 692, 368–374.
39. R. Carballo, B. Covelo, M. S. E. Fallah, J. Ribas and E. M. Vázquez-López, Cryst. Growth Des., 2007, 7, 1069–1077.
40. T. Maity, D. Saha and S. Koner, ChemCatChem, 2014, 6, 2373–2383.
41. J. Cao, J.-C. Liu, W.-T. Denga and N.-Z. Jin, CrystEngComm, 2013, 15, 6359–6367.
42. W.-B. Shi, A.-L. Cui and H.-Z. Kou, CrystEngComm, 2014, 16, 8027–8034.
43. M. Niu, Z. Cao, R. Xue, S. Wang, J. Dou and D. Wang, J. Mol. Struct., 2011, 996, 101–109.
44. Y.-F. Yue, E.-Q. Gao, C.-J. Fang, T. Zheng, J. Lianga and C.-H. Yan, CrystEngComm, 2008, 10, 614–622.
45. P. Bhowmik, H. P. Nayek, M. Corbella, N. A. Alcalde and S. Chattopadhyay, Dalton Trans., 2011, 40, 7916–7926.
46. D. Matoga, J. Szklarzewicz, R. Gryboś, K. Kurpiewska and W. Nitek, Inorg. Chem., 2011, 50, 3501–3510.
47. A. E. Motaleb and M. Ramadan, Transition Met. Chem., 2005, 30, 471–480.
48. A. L. Iglesias, G. Aguirre, R. Somanathan and M. Parra-Hake, Polyhedron, 2004, 23, 3051–3062.
49. C. Boskovic, A. Sieber, G. Chaboussant, H. U. Güdel, J. Ensling, W. Wernsdorfer, A. Neels, G. Labat, H. Stoeckli-Evans and S. Janssen, Inorg. Chem., 2004, 43, 5053–5068.
50. M. Yuan, F. Zhao, W. Zhang, Z.-M. Wang and S. Gao, Inorg. Chem., 2007, 46, 11235–11242.
51. S. Gama, F. Mendes, F. Marques, I. C. Santos, M. F. Carvalho, I. Correia, J. C. Pessoa, I. Santos and A. Paulo, J. Inorg. Biochem., 2011, 105, 637–644.
52. C.-Y. Tsai, B.-H. Huang, M.-W. Hsiao, C.-C. Lin and B.-T. Ko, Inorg. Chem., 2014, 53, 5109–5116.
53. B. Sreenivasulu, M. Vetrichelvan, F. Zhao, S. Gao and J. J. Vittal, Eur. J. Inorg. Chem., 2005, 4635–4645.
54. A. Neves, L. M. Rossi, A. J. Bortoluzzi, B. Szpoganicz, C. Wiezbicki, E. Schwingel, W. Haase and S. Ostrovsky, Inorg. Chem., 2002, 41, 1788–1794.
55. N. A. Rey, A. Neves, A. J. Bortoluzzi, C. T. Pich and H. Terenzi, Inorg. Chem., 2007, 46, 348–350.
56. I. A. Koval, K. Selmeczi, C. Belle, C. Philouze, E. Saint-Aman, I. Gautier-Luneau, A. M. Schuitema, M. v. Vliet, P. Gamez, O. Roubeau, M. Luken, B. Krebs, M. Lutz, A. L. Spek, J.-L. Pierre and J. Reedijk, Chem.–Eur. J., 2006, 12, 6138–6150.
57. R. E. H. M. B. Osório, R. A. Peralta, A. J. Bortoluzzi, V. R. deAlmeida, B. Szpoganicz, F. L. Fischer, H. Terenzi, A. S. Mangrich, K. M. Mantovani, D. E. C. Ferreira, W. R. Rocha, W. Haase, Z. Tomkowicz, A. dos Anjos and A. Neves, Inorg. Chem., 2012, 51, 1569–1589.
58. E. Mijangos, J. Reedijk and L. Gasque, Dalton Trans., 2008, 1857–1863.
59. S. Koner, Chem. Commun., 1998, 593–594.
60. S. Jana, S. Bhunia, B. Dutta and S. Koner, Appl. Catal., A, 2011, 392, 225–232.
61. D. Saha, T. Maity, T. Dey and S. Koner, Polyhedron, 2012, 35, 55–61.
62. D. Saha, T. Maity, R. Bera and S. Koner, Polyhedron, 2013, 56, 230–236.
63. F. Monnier and M. Taillefer, Angew. Chem., Int. Ed., 2009, 48, 6954–6971.
64. M. Islam, S. Mondal, P. Mondal, A. S. Roy, M. Mobarak and D. Hossain, J. Chem. Res., 2010, 34, 170–174.
65. Bruker, APEX 2, SAINT, XPREP, Bruker AXS Inc., Madison, Wisconsin, USA, 2007.
66. Bruker, SADABS, Bruker AXS Inc., Madison, Wisconsin, USA, 2001.
67. SHELXS97 and SHELXL97: G. M. Sheldrick, Acta Crystallogr., Sect. A: Found. Crystallogr., 2008, 64, 112–122.
68. S. Naiya, C. Biswas, M. G. B. Drew, C. J. Gomez-García, J. M. Clemente-Juan and A. Ghosh, Inorg. Chem., 2010, 49, 6616–6627.
69. A. Golcu, M. Tumer, H. Demirelli and R. A. Wheatley, Inorg. Chim. Acta, 2005, 358, 1785–1797.
70. A. W. Addison, T. N. Rao, J. Reedjik, J. V. Rijn and C. G. Verschoor, J. Chem. Soc., Dalton Trans., 1984, 1349–1356.
71. R.-B. Xu, X.-Y. Xu, M.-Y. Wang, D.-Q. Wang, T. Yin, G.-X. Xu, X.-J. Yang, L.-D. Lu, X. Wang and Y.-J. Lei, J. Coord. Chem., 2008, 61, 3306–3313.
72. B. Schlummer and U. Scholz, Adv. Synth. Catal., 2004, 346, 1599–1626.
73. C. H. Burgos, T. E. Barder, X. Huang and S. L. Buchwald, Angew. Chem., Int. Ed., 2006, 45, 4321–4326.
74. T. Ma, Y. F. Li, S. J. Zhang, F. C. Yang, C. L. Gong and J. J. Zhao, Chin. Chem. Lett., 2010, 21, 976–978.
75. E. R. Strieter, D. G. Blackmond and S. L. Buchwald, J. Am. Chem. Soc., 2005, 127, 4120–4121.

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Footnote

† Electronic supplementary information (ESI) available. CCDC 1010924–1010929 for complexes 1–6 and 1401268 for complex 7. For ESI and crystallographic data in CIF or other electronic formats see DOI: 10.1039/c5ra14758a

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