Synthesis and structures of ruthenium–NHC complexes and their catalysis in hydrogen transfer reaction

Summary Ruthenium complexes [Ru(L1)2(CH3CN)2](PF6)2 (1), [RuL1(CH3CN)4](PF6)2 (2) and [RuL2(CH3CN)3](PF6)2 (3) (L1= 3-methyl-1-(pyrimidine-2-yl)imidazolylidene, L2 = 1,3-bis(pyridin-2-ylmethyl)benzimidazolylidene) were obtained through a transmetallation reaction of the corresponding nickel–NHC complexes with [Ru(p-cymene)2Cl2]2 in refluxing acetonitrile solution. The crystal structures of three complexes determined by X-ray analyses show that the central Ru(II) atoms are coordinated by pyrimidine- or pyridine-functionalized N-heterocyclic carbene and acetonitrile ligands displaying the typical octahedral geometry. The reaction of [RuL1(CH3CN)4](PF6)2 with triphenylphosphine and 1,10-phenanthroline resulted in the substitution of one and two coordinated acetonitrile ligands and afforded [RuL1(PPh3)(CH3CN)3](PF6)2 (4) and [RuL1(phen)(CH3CN)2](PF6)2 (5), respectively. The molecular structures of the complexes 4 and 5 were also studied by X-ray diffraction analysis. These ruthenium complexes have proven to be efficient catalysts for transfer hydrogenation of various ketones.

In the family of metal complexes supported by functionalized NHCs, ruthenium complexes have long been a research focus on various applications such as catalysis and photochemistry [17][18][19][20][21][22][23][24][25][26]. However, the majority of such ruthenium complexes often contain coordinated aromatic carbocycles [27][28][29]. In contrast, only a few examples Ru(II) complexes of functionalized NHCs containing easily dissociating acetonitrile ligands have been studied [30][31][32]. We have reported the synthesis of some pyridine-and phenanthrolin-functionalized Ru(II)-NHC complexes containing acetonitrile ligands [33,34]. The most notable example is the acetonitrile-coordinated dinuclear Ru(II)-NHC complex derived from 3,6-bis(N-(pyridylmethyl)imidazolylidenyl)pyridazine, which is a very efficient catalyst for the oxidation of alkenes [35]. In continuation of our studies on functionalized Ru(II)-NHC complexes containing acetonitrile ligands, we herein report the synthesis and characterization of three pyrimidine-and pyridine-functionalized NHC-ruthenium complexes containing two, four, and three acetonitrile ligands, respectively. These complexes show good catalytic activity in the transfer hydrogenation of ketones. The reaction of acetonitrile-coordinated Ru-NHC complex 2 with other donors such as triphenylphosphine and 1,10-phenanthroline was also studied.

Results and Discussion
Synthesis and characterization of [Ru(L1) 2 (CH 3 CN) 2 ](PF 6 ) 2 (1), [RuL1(CH 3 CN) 4 ](PF 6 ) 2 (2) and [RuL2(CH 3 CN) 3 ](PF 6 ) 2 (3) The ruthenium-NHC complexes 1 and 2 were synthesized by using the corresponding nickel-NHC complexes as the carbene transfer agent [36]. The reaction of imidazolium salt HL1(PF 6 ) (L1 = 3-methyl-1-(pyrimidine-2-yl)imidazolylidene) with Raney nickel afforded the nickel-NHC complexes which were not isolated [30]. The subsequent reaction of the generated nickel-NHC complexes with a quarter equivalent of [Ru(pcymene)Cl 2 ] 2 in refluxing acetonitrile solution afforded bis-NHC complex [Ru(L1) 2 (CH 3 CN) 2 ](PF 6 ) 2 (1) in a yield of 76% (Scheme 1). When a half equivalent of [Ru(p-cymene)Cl 2 ] 2 and an excess of NH 4 PF 6 were employed under the same conditions, the reaction afforded the mono-NHC complex [RuL1(CH 3 CN) 4 ](PF 6 ) 2 (2) in 53% yield. It is worth noting that most of the structurally characterized acetonitrile complexes are obtained through the reaction of halides with silver complexes (AgPF 6 or AgBF 4 ) in acetonitrile solution [20]. The reaction in refluxing acetonitrile is more convenient than the above mentioned procedure. The formulations of complexes 1 and 2 were first characterized by NMR measurements and further confirmed by elemental analysis and X-ray diffraction. In the 1 H NMR spectra of complexes 1 and 2, disappearance of the resonances assigned to the imidazolium acidic CH and p-cymene protons were observed. The acetonitrile protons of complex 1 were found at 2.41 ppm as a singlet. However, the protons of acetonitrile ligands of complex 2 were found at 2.52, 2.12, and 1.96 ppm as three singlets. This illustrates that the three acetonitrile ligands in complex 2 are magnetic unequivalent. The 13 C NMR spectra of 1 and 2 exhibit resonance signals at 193.1 and 193.0 ppm ascribed to the carbenic carbons.
The ruthenium-NHC complexes 1 and 2 are stable in air and under light irradiation. Single crystals suitable for X-ray diffraction could be obtained by slow diffusion of Et 2 O into CH 3 CN solutions and the detailed structure of 1 is depicted in Figure 1. In complex 1, the central ruthenium ion is hexacoordinated by two bidentate NHC ligands and two acetonitrile ligands in an Scheme 2: Synthesis of 3. octahedral geometry. One NHC ligand, one acetonitrile ligand and one carbon atom of the other NHC ligand occupy the equatorial plane in which two carbon atoms of two NHC ligands are mutually trans-arranged. The remaining acetonitrile ligand and one nitrogen atom of the NHC ligand lie on the axial positions. The angles (N-Ru-N) of adjacent nitrogen atoms and Ru(II) ion are in the range of 83.9 to 94.0°. The Ru-C distance (2.066 Å) is consistent with the reported values in known Ru-NHC complexes [17][18][19][20][21][22][23][24][25][26][27][28][29]. The Ru-N pyrimidine distance (2.081 Å) is slightly longer than Ru-N acetonitrile (2.033 Å). The cationic structure of 2 is shown in Figure 2. The central Ru(II) ion is surrounded by one pyrimidine-functionalized NHC ligand and four acetonitrile ligands also in a typical octahedral geometry. The Ru ion lies on a twofold axis. The bidentate NHC ligand and two cis-arranged acetonitrile molecules form a Ru(L1)(CH 3 CN) 2 plane, whereas the other two acetonitrile molecules occupy the axial positions. The bond length of Ru-C NHC is 1.989 Å, which is slightly shorter than those found in Ru-NHC complexes [12][13][14][15][16][17][18] and in complex 1. The bond distance of Ru-N acetonitrile (2.113 Å) at the trans-position of the carbene ligand is longer than the other three Ru-N acetonitrile bonds (2.023-2.033 Å) and the Ru-N pyrimidine (2.064 Å). Similarly, the reaction of the in situ generated nickel-NHC complex from imidazolium salt HL2(PF 6 ) (L2 = 1,3bis(pyridin-2-ylmethyl)benzimidazolylidene) with a half equivalent of [Ru(p-cymene)Cl 2 ] 2 and an excess of NH 4 PF 6 in a refluxing acetonitrile solution afforded the tri-acetonitrile coordinated Ru(II)-NHC complex [RuL2(CH 3 CN) 3 ](PF 6 ) 2 (3) in a yield of 61% (Scheme 2). The formation of 3 was also confirmed by the 1 H NMR and 13 C NMR spectra. The 1 H NMR spectrum of 3 shows characteristic resonance signals due to the pyridyl, methylene, benzimidazolylidene and acetonitrile groups. The absence of a benzimidazole acidic C2-H proton illustrates the formation of the Ru-C bond. The acetonitrile protons appear at 2.35 and 2.08 ppm as two singlets. The 13 C NMR spectrum of 3 exhibits a resonance peak at 190 ppm, which is ascribed to the carbenic carbon atom. Complex 3 has been further identified by X-ray crystallography and the cationic structure of molecular 3 is depicted in Figure 3. The ruthenium ion is coordinated by a tridentate pincer NHC ligand and three acetonitrile ligands also in an octahedral geometry. The symmetrical pincer-type NCN ligand and an acetonitrile ligand occupy the equatorial plane and the remaining two acetonitrile ligands are located at the axial positions. The N-Ru-N angles of the three acetonitrile ligands and the Ru(II) ion are 86.03, 89.12 and 174.99°, respectively. Similar to complex 2, the bond distance of Ru-N acetonitrile (2.130 Å) at the trans-position of the carbene ligand is slightly longer than the other bond distances of Ru-N acetonitrile (2.030 and 2.028 Å) and the Ru-C (1.947 Å) is shorter than that of many known Ru-C carbene distances [17][18][19][20][21][22][23][24][25][26][27][28][29].

Catalytic transfer hydrogenation reaction
Ruthenium-NHC complexes are known to be efficient catalysts for transfer hydrogenation reactions [23,[37][38][39]. The ruthenium-NHC complexes presented above are stabilized by strong Ru-carbene bonds and contain 2-4 easily dissociating acetonitrile molecules, and are thus ideal catalysts. We tested their catalytic activities for transfer hydrogenation of ketones. Firstly, acetophenone was selected as the model substrate to evaluate the catalytic activities of complexes 1-3. The standard experiment was carried out at 80 °C with varied Ru loadings from 1 to 0.01 mol % and the results are summarized in Table 1. The reaction profiles show that acetophenone could be reduced to 1-phenylethanol in 89-99% yield within 0.5 h using 1 mol % of the Ru catalysts (Table 1, entries 1, 5 and 9). When the amount of catalysts is decreased to 0.1 mol %, the corresponding conversion still reached 79-89% (Table 1, entries 2, 6 and 10). 1-Phenylethanol could also be obtained in excellent yields using 0.1 mol % and 0.01 mol % Ru catalysts when the reaction time was extended to 1 and 3 h, respectively (Table 1, entries 3, 7, 11 and 4, 8, 12). At catalyst loadings of 0.01 mol %, TOF of 1-3 are 3000, 3233, and 3200 h −1 for transfer hydrogenation of acetophenone which are nearly identical to that of [Ru( Me CC meth ) 2 is so far one of the most efficient catalyst for transfer hydrogenation of acetophenone which gave 1-phenylethanol in a conversion of 93% with a catalyst loading of 0.1 mol % [20,41]. When the same amount of complexes 1-3 was used, the reaction gave 1-phenylethanol in 89%, 99% and 99% yields, respectively. These data illustrate that complexes 1-3 are all quite active catalysts for transfer hydrogenation reactions. It seems that complexes 2 and 3 are a bit better than 1 for this transformation. The trans-effect of carbene ligand may promote the substitution of trans-positioned acetonitrile ligand by other substrates in the catalytic reaction.
Since complexes 2 and 3 are found to be the efficient catalysts for transfer hydrogenation of acetophenone, we further explored their catalytic potential in the reduction of other aromatic and aliphatic ketones. The reaction conditions are similar as those described in the transfer hydrogenation of acetophenone and 0.1 mol % of Ru catalyst is utilized. The obtained results are given in Table 2. Complexes 2 and 3 are found to be very active in transfer hydrogenation of cyclohexanone, and cyclohexanol are almost quantitatively yielded within 0.5 h ( Table 2, entries 1 and 2). The catalyst systems are also found to be good for the reduction of aromatic ketones bearing electron-withdrawing substituents ( Table 2, entries 3-8) and electron-donating groups ( Table 2, entries 9 and 10), and the target product could be obtained in excellent yields (90-99%). Bulkier aromatic ketone benzophenone is also tested in this reaction with 92% and 94% conversion after 3 h (Table 2, entries 11 and 12). In addition, it is worth mentioning that the two ruthenium complexes exhibited a high tolerance towards sulfur species, 2-acetylthiophene is efficiently hydrogenated ( Reactions of tetra-acetonitrile Ru(II)-NHC complex 2 with triphenylphosphine and 1,10-phenanthroline The coordinated acetonitrile ligands could be easily replaced by various Nand P-donors [22]. The reactions of the acetonitrile-  still in the normal range as compared with the similar reaction [33]. In the 1 H NMR of 4, singlets at 2.14 and 2.07 ppm are ascribed to three CH 3 CN ligands, and the rest peaks are belonged to NHC and triphenylphosphine ligand. 1

Conclusion
In summary, Ru-NHC complexes bearing pyrimidine-and pyridine-functionalized NHC ligands have been prepared through a carbene transfer reaction using nickel-NHC as the carbene source. Their structures have been definitely determined by X-ray crystallography. The catalytic behavior of di-, tetra-and tri-acetonitrile-coordinated ruthenium complexes in transfer hydrogenation reactions was studied. These ruthenium complexes were found to be highly efficient catalysts for transfer hydrogenation of ketones. The catalytic properties of the ruthenium complexes in other organic transformation will be further studied.

Experimental
All chemicals were obtained from commercial suppliers in reagent grade quality and were used as received. HL1PF 6 and HL2PF 6 were synthesized according to the reported method [42,43]. 1 H and 13 C NMR spectra were recorded on a Bruker Avance-400 (400 MHz) spectrometer operating at 400 MHz for 1 H and at 100 MHz for 13 C. Chemical shifts (δ) were expressed in ppm downfield to TMS at δ = 0 ppm and coupling constants (J) were expressed in Hz. Elemental analyses were performed by a Flash EA 1112 ThermoFinnigan analyzer.

Synthesis of [RuL1(CH 3 CN) 4 ](PF 6 ) 2 (2).
A mixture of HL1(PF 6 ) (153 mg, 0.5 mmol), excess Raney nickel (300 mg) in 10 mL MeCN was stirred at 80 °C for 24 h. After it was cooled to room temperature, the solution was filtered through Celite. Then [Ru(p-cymene)Cl 2 ] 2 (153 mg, 0.25 mmol) and NH 4 PF 6 (163 mg, 1.0 mmol) was added to the filtrate and stirred at reflux for 12 h. The mixture was filtered through Celite to remove precipitated NiCl 2 and all volatiles were evaporated under reduced pressure. The residue was washed with water and dried in vacuo. The yellow residue was dissolved in MeCN and concentrated to about 2 mL. The addition of Et 2 O induced precipitation of the product as a yellow solid. Yield: 190 mg, 53%. Anal. calcd for C 16

Synthesis of [RuL1(PPh 3 )(CH 3 CN) 3 ](PF 6 ) 2 (4).
A mixture of 2 (142 mg, 0.2 mmol) and triphenylphosphine (262 mg, 1.0 mmol) in 5 mL CH 3 CN was stirred at 80 °C for 6 h. Then the mixture was filtered through Celite and all volatiles were Typical procedure for catalytic transfer hydrogenation reaction The ketone (1.0 mmol), KOH (0.2 mmol) and 2 mL of iPrOH were placed in a Schlenk tube. Anisole (0.25 mmol) was added as an internal GC standard. The mixture was heated at 80 °C and then catalyst solution (0.01 mmol, 0.001 mmol, or 0.0001 mol of ruthenium complexes in iPrOH (1 mL) was injected. Aliquots (0.2 mL) were taken at fixed time intervals, quenched with 1 mL of H 2 O and extracted with 3 mL of Et 2 O. The product yields were determined by GC analysis.

X-ray diffraction analysis
Single-crystal X-ray diffraction data were collected at 298(2) K on a Siemens Smart-CCD area-detector diffractometer with a MoKα radiation (λ = 0.71073 Å) by using a ω-2θ scan mode. Unit-cell dimensions were obtained with least-squares refinement. Data collection and reduction were performed using the Oxford Diffraction CrysAlisPro software [44]. All structures were solved by direct methods, and the non-hydrogen atoms were subjected to anisotropic refinement by full-matrix least squares on F 2 using the SHELXTXL package [45]. Hydrogen atom positions for all of the structures were calculated and allowed to ride on their respective C atoms with C-H distances of 0.93-0.97 Å and U iso (H) = −1.2-1.5U eq (C). Details of the X-ray experiments and crystals data are summarized in Table 3.

Supporting Information
Supporting Information File: Supporting Information File 1 X-ray crystallographic data CCDC 1407422-1407426.