Efficient and phosphine-free bidentate N-heterocyclic carbene/ruthenium catalytic systems for the dehydrogenative amidation of alcohols and amines

Xuan-Jun Wu b, Hua-Jing Wang b, Zhao-Qi Yang c, Xiao-Sheng Tang d, Ye Yuan a, Wei Su a, Cheng Chen *a and Francis Verpoort *aef
aState Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Wuhan University of Technology, 122 Luoshi Road, Wuhan 430070, P. R. China. E-mail: chengchen@whut.edu.cn; francis.verpoort@ghent.ac.kr; Fax: (+86)-27-87879468; Tel: (+86)-27-88016035
bSchool of Chemistry, Chemical Engineering and Life Sciences, Wuhan University of Technology, 122 Luoshi Road, Wuhan 430070, P. R. China
cSchool of Pharmaceutical Sciences, Jiangnan University, Jiangsu 214122, China
dKey Laboratory of Optoelectronic Technology and Systems (Ministry of Education) College of Optoelectronic Engineering, Chongqing University, Chongqing 400044, P. R. China
eNational Research Tomsk Polytechnic University, Lenin Avenue 30, Tomsk 634050, Russian Federation
fGhent University Global Campus, 119 Songdomunhwa-Ro, Yeonsu-Gu, Incheon 21985, Korea

Received 21st August 2018 , Accepted 15th November 2018

First published on 16th November 2018


The direct amide synthesis from alcohols and amines applying various transition metal catalysts has been demonstrated as an attractive and promising process. Among various catalytic systems, N-heterocyclic carbene (NHC)-based ruthenium (Ru) ones have been testified to be active for this atom-economic transformation. Although a variety of imidazole-based NHC/Ru catalytic systems were reported to be active for this reaction, the benzimidazole-based analogs exhibited higher catalytic performance in most cases. However, these catalytic systems, which comprise a monodentate NHC ligand and a Cl or phosphine ligand as the key components, require relatively high catalyst loadings. In order to obtain more active and robust catalytic systems, we aim to bridge two monodentate ligands with one bidentate NHC ligand. Therefore, a number of CNHCC bidentate NHC precursors were designed and synthesized. Through screening of the NHC precursors and other reaction conditions, potent and phosphine-free bidentate NHC/Ru catalytic systems were discovered for the efficient amide synthesis. Interestingly, from the in situ generated catalytic system, two NHC/Ru intermediates were isolated and structurally confirmed by X-ray crystallography. Notably, these two complexes are active for the amide synthesis even at a low catalyst loading of 0.5 mol%, which could verify that they should be key intermediates during the catalysis. Probably, the current catalytic systems, featuring high efficiency and ready accessibility, could be valuable for more interesting applications.


Introduction

The amide linkage is of vital importance in various areas such as organic and biological chemistries.1–6 Although a number of synthetic methods have been reported for the amide synthesis, they usually require stoichiometric amounts of additional reagents and generate enormous amounts of waste as by-products.7–14 Consequently, it is highly desirable to develop green and sustainable strategies for the amide synthesis.15 Recently, the transition-metal-catalyzed alcohol amidation with amines has been demonstrated as an atom-economic and environmental-friendly transformation with nonpolluting dihydrogen gas as the only byproduct, showing a prosperous potential for synthetic applications.16–22 Especially, ruthenium (Ru)-based catalytic systems have been most frequently investigated.23 In 1991, the Murahashi group pioneered the Ru-catalyzed intramolecular amidation of amino alcohols.24 Later, great contributions have been made by Milstein et al. who developed a highly-active commercialized Ru catalyst, namely the Milstein catalyst, for this transformation. Notably, it is the first time to allow this amide synthesis in an intermolecular manner.25 Afterwards, the Milstein,26–28 Madsen,29–31 Williams,32,33 Hong,34–43 Crabtree,44,45 Albrecht,46 Guan,47,48 Glorius,49 Möller,50,51 Bera,52 Huynh,53 Viswanathamurthi,54–56 Mashima,57 Verpoort58–60 and Kundu61 groups reported numerous catalytic systems. Particularly, N-heterocyclic carbenes (NHCs) have been demonstrated as a class of promising ligands since their electronic and steric properties can be separately modulated to achieve the optimal structures of their respective metal complexes.62–65 Hence, a variety of Ru catalytic systems ligated by NHCs have also been developed and proven to be potent for this reaction.29–31,34–37,39,41,42,46,49–54,58

Although imidazole-based NHC/Ru catalytic systems have been extensively studied,29–31,34–37,39,41,42,49,52 their benzimidazole-derived counterparts generally exhibited better catalytic activities and attracted worldwide growing attention.50,51,53,58 Previously, Möller et al. reported an arene-Ru complex bearing a monodentate NHC ligand and two Cl ligands (as shown in Fig. 1a).50 With 3 mol% of this complex and 15 mol% of KOtBu, various amides could be efficiently synthesized. Later, Huynh et al. prepared another arene-Ru-NHC complex by introducing a phosphine ligand instead of one Cl ligand, and satisfactory results were also obtained with 5 mol% of this Ru complex and 30 mol% of NaH (Fig. 1b).53 Herein, we envisioned that bridging a monodentate NHC ligand and a Cl (or phosphine) ligand with one bidentate NHC ligand could result in more active and robust catalytic systems (Fig. 1c). With these considerations in mind, we designed and synthesized a series of CNHCC bidentate NHC precursors and constructed the corresponding NHC/Ru catalytic systems (Fig. 1d). To our delight, selective amide synthesis could be realized through extensive screening of various conditions. Notably, the catalyst loading could be as low as 0.5 mol% and a mild base (Cs2CO3) was utilized to catalyze this reaction. Moreover, it is worth noting that two bidentate NHC/Ru complexes were isolated directly from the optimized in situ catalytic system, and their structures were further confirmed by X-ray crystallography. Interestingly, these two complexes demonstrated consistent catalytic activities with the respective in situ catalytic system, which verified their significant roles as the catalytic intermediates.


image file: c8qo00902c-f1.tif
Fig. 1 The design strategy of this work.

Results and discussion

The reaction of benzyl alcohol (1a) and benzylamine (2a) was selected as a model reaction, and NHC precursor L1 was originally prepared and selected for optimization of reaction conditions. Except for amide 3a, imine 4a and unreacted alcohol 1a, ester 5a (another byproduct generated by dimerization of 1a) was also detected in most cases (as listed in Table 1). Therefore, 1.00 mol% [Ru] and 1.00 mol% L1 at refluxing toluene were applied to clearly spot the product distribution among the above compounds. Besides, 1 h of the in situ catalyst generation and 18 h of reaction time were fixed. The first and foremost, the amounts of Cs2CO3 were screened (entries 1–7, Table 1). If 1.00 mol% of Cs2CO3 was used, no amide 3a was formed (entry 1). As its amount increased to 2.00 mol%, a substantial improvement in the yield of 3a was noted (entry 2 vs. entry 1). A further increment of the base amount led to similar yields of the amide product, but lower amide selectivity against the imine and ester (entries 2–7). Thus, the ideal amount of Cs2CO3 was identified as 2.00 mol%. Afterward, other bases such as K2CO3, KOAc, KOtBu, NaH were exploited instead of Cs2CO3. However, these bases were not effective for the selective amide formation (entries 8–11). Interestingly, the volume of toluene was noticed to be crucial (entries 2, 12 and 13). A more concentrated solution prompted a higher yield of 3a and higher conversion, but much lower amide/imine selectivity (entry 12 vs. entry 2). In the case of a more diluted solution, lower conversion and yield of 3a were attained (entry 13 vs. entry 2). Therefore, an optimized condition, recognized as 1.00 mol% of [Ru], 1.00 mol% L1, 2.00 mol% of Cs2CO3 in refluxing toluene (1.5 mL), was used for further investigations.
Table 1 Optimization of reaction conditionsa

image file: c8qo00902c-u1.tif

Entry Base x Yieldsb (%)
3a 4a 5a Unreacted 1a
a Conditions: 1a (1.25 mmol), 2a (1.38 mmol), [Ru] (1.00 mol%), L1 (1.00 mol%), a base (x mol%) and toluene (1.5 mL) at refluxing temperature for 18 h. b NMR yields using 1,3,5-trimethoxybenzene as an internal standard (average of two consistent runs). c Toluene (1.0 mL). d Toluene (2.0 mL).
1 Cs2CO3 1.00 0 7 0 90
2 Cs 2 CO 3 2.00 49 4 7 35
3 Cs2CO3 3.00 48 10 6 30
4 Cs2CO3 4.00 46 12 4 33
5 Cs2CO3 5.00 46 13 4 28
6 Cs2CO3 6.00 48 9 6 31
7 Cs2CO3 7.00 47 11 3 27
8 K2CO3 2.00 0 13 0 86
9 KOAc 2.00 0 12 0 85
10 KOtBu 2.00 11 12 2 71
11 NaH 2.00 3 20 1 72
12c Cs2CO3 2.00 52 19 2 21
13d Cs2CO3 2.00 39 8 4 42


Since NHCs comprising different electronic and steric properties could affect their coordination with Ru, a series of bidentate NHC precursors with different backbone and wingtip substituents were prepared. The catalytic activities of all the precursors were thoroughly examined (as shown in Table 2). First of all, R1, R2 and R6 were fixed as H, H and Me, respectively, and distinct R3-R5 groups were utilized. When a Me group was introduced to R3, R4 or R5, the resulted precursors L2–L4 demonstrated varied catalytic activities (entries 2–4). L2, with a Me group at the R3 position, exhibited better activities than L3 and L4 (entry 2 vs. entries 3 and 4). Similarly, an F group at R3 also showed better activity than that at the R4 or R5 position, which implied that a substituent at the R3 position favors the amide formation (entries 5–7). Hence, numerous groups including Et, OMe, Cl, COOEt, NO2 were employed for R3, and Et was advantageous over other groups (entries 8–12). Next, screening of different R6 substituents was carried out, and iPr was found to be the best group (entries 8, 13 and 14). Moreover, a methyl group at both R1 and R2 positions is desirable for the reaction (entries 14–16). If the reaction was run under an argon atmosphere in a closed tube, an unsatisfactory result was attained (entry 17). Finally, the optimum NHC precursor was discovered as L15, and further increasing the reaction time from 18 h to 36 h produced 3a in 90% yield (entry 18).

Table 2 Optimization of various NHC precursorsa

image file: c8qo00902c-u2.tif

Entry NHC precursor R1 R2 R3 R4 R5 R6 Yieldsb (%)
3a 4a 5a Unreacted 1a
a 1a (1.25 mmol), 2a (1.38 mmol), [Ru] (1.00 mol%), L (1.00 mol%), Cs2CO3 (2.00 mol%) and toluene (1.5 mL) at refluxing temperature for 18 h. b NMR yields using 1,3,5-trimethoxybenzene as an internal standard (average of two consistent runs). c In an argon-filled sealed tube. d 36 h.
1 L1 H H H H H Me 49 4 7 35
2 L2 H H Me H H Me 54 4 5 26
3 L3 H H H Me H Me 40 28 3 18
4 L4 H H H H Me Me 36 12 2 42
5 L5 H H F H H Me 52 10 4 22
6 L6 H H H F H Me 41 17 2 17
7 L7 H H H H F Me 27 10 3 56
8 L8 H H Et H H Me 60 2 4 23
9 L9 H H OMe H H Me 51 6 4 24
10 L10 H H Cl H H Me 53 2 8 29
11 L11 H H COOEt H H Me 48 4 8 34
12 L12 H H NO2 H H Me 58 12 4 18
13 L13 H H Et H H Et 64 3 8 18
14 L14 H H Et H H iPr 65 5 3 22
15 L15 Me Me Et H H iPr 72 1 5 21
16 L16 Cl Cl Et H H iPr 11 9 1 75
17c L15 Me Me Et H H iPr 35 20 8 34
18 d L15 Me Me Et H H iPr 90 2 6 0


With the optimized reaction conditions in hand, the substrate scope and limitations were investigated (as depicted in Fig. 2). Sterically nonhindered amines including n-hexylamine, benzylamine and its derivatives reacted smoothly with 1a to afford the corresponding amides 3a–3e in excellent yields. Besides, heterocyclic amine 2f and secondary amine 2g could also be efficiently transformed into amides 3f and 3g. Unfortunately, our catalytic system is also sensitive to aromatic amines, and the less basic aniline (2h) yielded amide 3h in 31% yield. Moreover, 5-amino-1-pentanol could undergo intramolecular amidation to give cyclic lactam 3i in 72% yield, and treatment of 2a with various alcohols produced amides 3j–3u in moderate to high yields. Generally, amides 3j–3l could be afforded from alcohols 1j–1l in good yields. If a modestly congested alcohol (1m) was used, amide 3m could be isolated in 55% yield. Furthermore, the electronic effects were explored on the reactions of substituted benzyl alcohols with 2a. Electron-rich alcohol 1n gave amide 3n in 91% yield, while the electron-deficient alcohols (1o–1p) afforded the corresponding amides in lower yields (73–77%). It was also found that the substituent position on the phenyl ring affected the yields of the amide products. Under the standard conditions, 2-fluorobenzyl alcohol could generate amide 3r in 50% yield with 38% of the unreacted alcohol. To our delight, a catalyst loading of 2 mol% could provide 3r in 81% yield, which demonstrated superiority over the reported catalytic systems.40,58 This result inspired us to test the suitability of the current catalytic system for other ortho-substituted benzyl alcohols, and compounds 3s–3u were efficiently synthesized.


image file: c8qo00902c-f2.tif
Fig. 2 Amide synthesis from various alcohols and amines. Conditions: 1 (1.25 mmol), 2 (1.38 mmol), [Ru] (1.00 mol%), L15 (1.00 mol%), Cs2CO3 (2.00 mol%) and toluene (1.5 mL) at reflux, and isolated yields (average of two consistent runs). a36 h. b60 h. c2.00 mol% of [Ru] instead of 1.00 mol% of [Ru] for 36 h.

In order to comprehend the mechanistic insights of this reaction, we endeavored to monitor the in situ generated catalytic system by TLC. After 0.5 h, two spots with considerable intensity could be clearly seen. As the catalyst generation period was elongated, one spot was gradually transformed into the other spot until an almost constant ratio was reached. With this phenomenon in mind, we were keen on the isolation and characterization of both compounds. Interestingly, these two compounds, referred as [Ru]-1 and [Ru]-2, could be easily isolated and purified by neutral alumina column chromatography (as shown in Fig. 3), and their structures were further confirmed by X-ray crystallography (as shown in Fig. 4). When the catalyst generation time was 0.5 h, [Ru]-1 and [Ru]-2 were isolated in 29% and 22% yields, respectively. As the period for the catalyst generation increased, the yield of [Ru]-1 decreased and that of [Ru]-2 gradually increased. Further elongation of the duration led to a relatively persistent ratio of the two complexes. It was proposed that the mixture of [RuCl2(p-cymene)]2, L15, Cs2CO3 and toluene at reflux triggered the formation of [Ru]-1, which could presumably undergo an arene exchange between p-cymene and the solvent toluene to give [Ru]-2.


image file: c8qo00902c-f3.tif
Fig. 3 Identification of the generated ruthenium species from the in situ catalytic system.

image file: c8qo00902c-f4.tif
Fig. 4 Molecular structures of (a) [Ru]-1 and (b) [Ru]-2 with ellipsoids at 50% of probability. Hydrogen atoms and solvent molecules are omitted for clarity.

Furthermore, the catalytic performance of [Ru]-1 and [Ru]-2 was investigated to verify whether they are possible catalytic intermediates, and a catalyst loading of 1 mol% was firstly used (as shown in Table 3). Without Cs2CO3, no amide formation was observed (entry 1). Use of the base amount ranging from 1.00% to 3.00 mol% resulted in excellent results, and 2.00 mol% was considered as the optimal amount (entries 2–4). Expectedly, [Ru]-2 manifested comparable activity with [Ru]-1 (entry 5 vs. entry 3). In addition, evaluation of both complexes under argon in a closed vessel gave rise to moderate yields of 3a (entries 6 and 7). When the catalyst loading was reduced from 1.00 mol% to 0.50 mol%, both complexes could still provide amide 3a in more than 85% yields (entries 8 and 9). These results illustrated that the two complexes should be key intermediates during the catalysis.

Table 3 The catalytic performance of [Ru]-1 and [Ru]-2

image file: c8qo00902c-u3.tif

Entry [Ru] x y Yieldsa (%)
3a 4a 5a Unreacted 1a
a NMR yields using 1,3,5-trimethoxybenzene as an internal standard (average of two consistent runs). b 1a (1.25 mmol), 2a (1.38 mmol), [Ru]-1 or [Ru]-2 (1.00 mol%), Cs2CO3 (y mol%) and toluene (1.5 mL) at refluxing temperature for 36 h. c In a sealed tube under argon. d 1a (2.50 mmol), 2a (2.75 mmol), [Ru]-1 or [Ru]-2 (0.50 mol%), Cs2CO3 (1.00 mol%) and toluene (3.0 mL) at refluxing temperature for 36 h.
1b [Ru]-1 1.00 0.00 0 21 0 75
2b [Ru]-1 1.00 1.00 90 6 3 0
3b [Ru]-1 1.00 2.00 91 2 3 0
4b [Ru]-1 1.00 3.00 89 4 4 0
5b [Ru]-2 1.00 2.00 90 3 4 0
6b,c [Ru]-1 1.00 2.00 65 10 7 15
7b,c [Ru]-2 1.00 2.00 63 12 8 16
8d [Ru]-1 0.50 1.00 88 2 8 0
9d [Ru]-2 0.50 1.00 86 3 9 1


Since [Ru]-1 was proposed to undergo ligand exchange with the solvent toluene to generate [Ru]-2, it was necessary to further evaluate its catalytic activities in non-arene solvents (as shown in Table 4). In an open argon flow, the reaction could almost finish after 16 h, and extension of the reaction time resulted in a slightly increased yield of 3a (entries 1 and 2). If the reaction was conducted in a closed system, much lower conversion and amide selectivity were obtained (entries 3 and 4). Furthermore, non-arene solvents such as THF or cyclohexane were also attempted (entries 5–8). THF provided good amide selectivity although the reaction was incomplete even after 36 h (entries 5 and 6). In contrast, cyclohexane led to a complicated mixture of all three compounds (entries 7 and 8). These results verified that [Ru]-1 should also be an important intermediate for this catalysis.

Table 4 The catalytic activities of [Ru]-1 in non-arene solvents

image file: c8qo00902c-u4.tif

Entry Solvent Time (h) Yieldsa (%)
3a 4a 5a Unreacted 1a
a NMR yields using 1,3,5-trimethoxybenzene as an internal standard (average of two consistent runs). b In an open argon flow. c In a closed vessel under argon.
1b Toluene 16 88 3 4 3
2b Toluene 36 91 2 3 0
3c Toluene 16 51 8 6 32
4c Toluene 36 65 10 7 15
5c THF 16 72 2 2 22
6c THF 36 85 4 3 7
7c Cyclohexane 16 35 26 12 22
8c Cyclohexane 36 42 30 15 10


Based on the above experiments and the reported results,53,58 we proposed a possible pathway for the L15/Ru-catalyzed amide formation (as shown in Fig. 5). A mixture of [RuCl2(p-cymene)]2, L15 and Cs2CO3 in refluxing toluene affords two Ru complexes, namely [Ru]-1 and [Ru]-2. Besides, treatment of these two Ru species with alcohol 1 gives key Ru-alkoxide intermediate I, which could go through a similar pathway as proposed by Huynh et al.53 β-Hydride elimination of I gives rise to a hydrido complex II bound with the corresponding aldehyde, which reacts with 2 to deliver intermediate III with liberating one molecule of H2. Furthermore, III could be subsequently transformed into Ru monohydride species IVvia β-hydride elimination. Finally, ligand substitution with 1 releases amide 3 and hydrido complex V, which eliminates one H2 molecule for the regeneration of intermediate I to fulfill the catalytic cycle.


image file: c8qo00902c-f5.tif
Fig. 5 The proposed mechanism for the NHC/Ru catalyzed amidation of alcohols with amines.

Experimental

General considerations

All reactions were carried out using standard Schlenk techniques or in an argon-filled glove box unless otherwise mentioned. 1H-NMR spectra were recorded on a Bruker Avance 500 spectrometer in CDCl3 or DMSO-d6 with TMS as the internal reference, and 13C-NMR spectra were recorded in CDCl3 on a Bruker Avance 500 (126 MHz) spectrometer. The following abbreviations are used to designate multiplicities: s = singlet, brs = broad singlet, d = doublet, t = triplet, q = quartet, dd = doublet of doublets, td = triplet of doublets, m = multiplet. Singe crystal structures of [Ru]-1 and [Ru]-2 were obtained using a Bruker APEX-II CCD diffractometer. Melting points were taken on a Buchi M-560 melting point apparatus and are uncorrected. HR-MS analysis was done with a Bruker Daltonics microTOF-QII instrument or a Thermo Fisher Q Exactive Mass Spectrometer. All the substrates and solvents were obtained from commercial suppliers and used as received without further purification.

General procedure for the synthesis of L1–L16 (Scheme 1)

To a 25 ml Schlenk flask was added benzimidazole or its derivative (7.50 mmol, 1.50 equiv.), an aryl iodide (5.00 mmol, 1.00 equiv.), CuI (0.50 mmol, 10 mol%), KOH (10.0 mmol, 2.00 equiv.) and DMSO (8 mL). Then the reaction mixture was stirred at 110 °C under an argon atmosphere. After the reaction was complete (as indicated by TLC), the resulted suspension was filtered through Celite, and water (20 mL) was added to the filtrate. Then the solution was extracted with dichloromethane (3 × 20 mL), and the combined organic layers were washed with water (2 × 50 mL), brine (50 mL), dried over Na2SO4, filtrated and concentrated under reduced pressure to obtain the crude product 6, which was purified by silica gel chromatography and directly used for the next step. Furthermore, a mixture of 6 (1.00 mmol, 1.00 equiv.) and an alkyl iodide (2.0 mmol, 2.00 equiv.) and acetone (3 mL) were stirred at refluxing temperature for 12 h. The solvent was then removed under reduced pressure, and the residue was washed a few times with acetone or a mixture of petroleum ether and acetone to provide pure compounds L1–L16. The characterization data and the corresponding spectra of all the NHC precursors could be found in the ESI.
image file: c8qo00902c-s1.tif
Scheme 1 The synthetic procedure of L1–L16.

General procedure for the amide synthesis

To an oven-dried 25 mL Schlenk tube were added [Ru(p-cymene)Cl2]2 (3.9 mg, 0.00625 mmol), 1-(4-ethylphenyl)-3-isopropyl-5,6-dimethyl-1H-benzo[d]imidazol-3-ium iodide (L15, 5.3 mg, 0.0125 mmol), Cs2CO3 (8.1 mg, 0.025 mmol) and toluene (1.5 mL) inside an argon-filled glovebox. The Schlenk tube was taken out of the glovebox and heated to reflux under argon for 1 h. Afterward, the flask was cooled to room temperature before an alcohol (1.25 mmol) and an amine (1.38 mmol) were added, and the mixture was stirred at refluxing temperature under an argon atmosphere for 36 h. The procedures concerning the NMR yields and isolated yields of the required compounds could be described as follows.

For NMR yields of amide 3a, imine 4a, ester 5a and unreacted 1a, 1,3,5-trimethoxybenzene (0.50 mmol, 84.0 mg) and CHCl3 (1.0 mL) were added to the reaction mixture, and 0.1 mL of the above solution and 0.5 mL of CDCl3 were added to an NMR tube. The NMR yields were obtained based on the exact amount of 1,3,5-trimethoxybenzene. Besides, in order to obtain the isolated yields of the amides, the reaction mixture was cooled down to room temperature, and the solvent was removed under reduced pressure. Finally, the residue was purified by silica gel flash column chromatography to afford the amides. The characterization data and the corresponding spectra of all the amides could be found in the ESI.

General procedure for the isolation and purification of [Ru]-1 and [Ru]-2

Inside an argon-filled glovebox, [Ru(p-cymene)Cl2]2 (76.5 mg, 0.125 mmol), 1-(4-ethylphenyl)-3-isopropyl-5,6-dimethyl-1H-benzo[d]imidazol-3-ium iodide (L15, 105.1 mg, 0.25 mmol), Cs2CO3 (162.9 mg, 0.50 mmol) and toluene (30 mL) were added to an oven-dried two-necked round bottom flask. The reaction mixture was heated for 0.5 h before it was cooled to room temperature. Afterward, the solvent was removed and the resulted crude mixture was purified by neutral alumina column chromatography using the eluent (petroleum ether[thin space (1/6-em)]:[thin space (1/6-em)]ethyl acetate = 20[thin space (1/6-em)]:[thin space (1/6-em)]1–10[thin space (1/6-em)]:[thin space (1/6-em)]1) to give pure [Ru]-1 (47.4 mg, 29% yield) and [Ru]-2 (33.6 mg, 22% yield).

X-ray crystallography

The single crystals of the Ru complexes were grown by slow evaporation of n-pentane into a solution of [Ru]-1 or [Ru]-2 in chloroform. Diffraction data were collected with MoKa radiation (λ = 0.71073 Å), and numerical absorption corrections were applied. The structures were solved by direct methods and refined on F2 with anisotropic thermal parameters for all non-hydrogen atoms. Protons were refined at the calculated positions by using a riding model.

Conclusions

In summary, we have developed a variety of in situ Ru catalytic systems bearing phosphine-free bidentate NHC precursors. Through a systematic investigation of the ligand structures and various reaction conditions, the L15-based NHC/Ru catalytic system was found to demonstrate the optimum activity for the atom-economic alcohol amidation with amines. Particularly, this catalytic system manifested good activities for ortho-substituted benzyl alcohols. It is worth emphasizing that two bidentate NHC/Ru intermediates, which were confirmed by X-ray crystallography, could be easily isolated and purified from the in situ NHC/Ru catalytic systems. Further investigations revealed that these two complexes are effective for the amide synthesis even at a low catalyst loading of 0.5 mol%, which is indicative of their roles as key catalytic intermediates. Hopefully, the current catalytic system would be of great value for further interesting applications.

Conflicts of interest

There are no conflicts to declare.

Acknowledgements

This research was supported by the National Natural Science Foundation of China (No. 21502062). F. V. acknowledges the support from the Russian Foundation for Basic Research (No. 18-29-04047) and the Tomsk Polytechnic University Competitiveness Enhancement Program grant (VIU-195/2018).

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Footnote

Electronic supplementary information (ESI) available. CCDC 1849029 ([Ru]-1) and 1854319 ([Ru]-2). For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c8qo00902c

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