Acceptorless Dehydrogenation of N-Heterocycles and Secondary

Feb 7, 2018 - The X-ray crystallographic files, in CIF format, are available from the Cambridge Crystallographic Data Centre on quoting deposition num...
1 downloads 5 Views 2MB Size
Download PDF
Article Cite This: Organometallics XXXX, XXX, XXX−XXX

Acceptorless Dehydrogenation of N‑Heterocycles and Secondary Alcohols by Ru(II)-NNC Complexes Bearing a Pyrazoyl-indolylpyridine Ligand Qingfu Wang,†,‡ Huining Chai,†,‡ and Zhengkun Yu*,†,§ †

Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023, PR China University of Chinese Academy of Sciences, Beijing 100049, PR China § State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Road, Shanghai 200032, PR China ‡

S Supporting Information *

ABSTRACT: Ruthenium(II) hydride complexes bearing a pyrazolyl-(2-indol-1-yl)-pyridine ligand were synthesized and structurally characterized by NMR analysis and X-ray single crystal crystallographic determinations. These complexes efficiently catalyzed acceptorless dehydrogenation of N-heterocycles and secondary alcohols, respectively, exhibiting highly catalytic activity with a broad substrate scope. The present work has established a strategy to construct highly active transition metal complex catalysts and provides an atom-economical and environmentally benign protocol for the synthesis of aromatic N-heterocyclic compounds and ketones.

■

INTRODUCTION Synthesis of nitrogen-containing heteroarenes1 and carbonyl compounds2 is of great importance in organic synthesis and medicinal chemistry. Traditional methods to access these compounds usually require stoichiometric oxidants. Thus, acceptorless catalytic dehydrogenation is desired because such a process is atom-economical and environmentally benign, and stoichiometric oxidants can be avoided.3 Acceptorless dehydrogenation (AD) reactions have also found potential applications in the field of organic hydrogen storage materials because dihydrogen is produced as the only byproduct.4 The first homogeneous catalytic system for dehydrogenation of tetrahydroquinoline derivatives has recently been documented by using a Cp*Ir complex bearing a 2-pyridonate ligand.5 Perdehydrogenation of fused bicyclic N-heterocycles with similar iridium complex catalysts supported by a bipridonate ligand was also reported.6 Cyclometalated imino-iridium complexes have been employed as the dehydrogenation catalysts for a wide range of N-heterocycles and for the dehydrogenative coupling of N-heterocycles with electrophiles.7 Well-defined iron and cobalt complexes supported by a bis(phosphino)amine pincer ligand efficiently catalyzed acceptorless dehydrogenation of N-heterocycles.8 B(C6F5)3-catalyzed dehydrogenation of N-heterocycles was achieved under metal-free conditions.9 A dehydrogenation process of N-heterocycles can also be realized under visible-light photoredox catalysis10 or by means of other transiton metal catalysts.11 Acceptorless catalytic dehydrogenation of alcohols is considered as an atom-economical approach to access carbonyl compounds.12 Many efforts have recently been devoted to © XXXX American Chemical Society

transition metal catalyzed acceptorless dehydrogenation of N-heterocycles and alcohols, and diverse highly active homogeneous transition metal complex catalysts are strongly desired in this area. Cyclometalated complexes of unsymmetrical NNC ligands have been documented as the catalysts for diverse organic transformations.13 During the ongoing investigation of transition metal complex catalysts,14 we reported highly active Ru(II)-NNC complex A bearing a pyrazolyl-(2-tolyl)-pyridine ligand as the catalyst for transfer hydrogenation of ketones in refluxing 2-propanol,14h while Ru(II) complex B supported by a pyridinebased pyrazolyl-N-heterocyclic carbene (NHC) ligand only exhibited a poor catalytic activity for the same reactions14m (Chart 1). It is obvious that the steric and electronic properties of a polydentate ligand should be compatible in order to construct a highly active transition metal complex catalyst. In situ generated cyclometalated transition metal complex intermediates can also be considered as the catalytically active species in some organic transformations.15 Intrigued by the electron-rich and potential coordinating properties of an indolyl functionality,16 we envisioned that an indolyl might be employed to construct a pyridinebased NNC ligand for the establishment of highly active transition metal complex catalysts (Chart 1). Herein, we disclose the synthesis of well-defined ruthenium(II) hydride complex catalysts of a pyrazolyl-(2-indolyl)-pyridine ligand and their Received: December 21, 2017

A

DOI: 10.1021/acs.organomet.7b00902 Organometallics XXXX, XXX, XXX−XXX

Article

Organometallics Chart 1. Ruthenium(II)-NNC Pincer Complexes

Scheme 1. Synthesis of Ruthenium(II)-NNC Pincer Complexesa

a

Legend: (i) 10 mol % CuI, 20 mol % 1,10-phenanthroline, 2.0 equiv of K2CO3, toluene, reflux, 0.1 MPa N2, 12 h; (ii) 1.0 equiv of RuCl2(PPh3)3, 5.0 equiv of NEt3, 2-propanol, reflux, 0.1 MPa N2, 8 h; (iii) 5.0 equiv of K2CO3, 2-propanol, reflux, 0.1 MPa N2, 8 h.

catalytic activity for the dehydrogenation of N-heterocycles and secondary alcohols.

■

RESULTS AND DISCUSSION Synthesis of Ligands and Ru(II)-NNC Complexes. The ligand precursors, that is, compounds 3 and complexes 4 and 5, were prepared as depicted in Scheme 1. Copper-catalyzed C−N cross-coupling reactions of 2-bromo-6-(3,5-dimethyl-pyrazol1-yl)pyridine (1) with indole (2a) or 5-substituted indoles (2b and 2c) afforded compounds 3 in 68−83% yields. Treatment of 3 with equimolar amount of RuCl2(PPh3)3 in refluxing 2-propanol in the presence of NEt3 base efficiently gave Ru(II) complexes 4a−4c (86−89%). Further refluxing a mixture of complex 4 with K2CO3 in 2-propanol generated Ru(II) hydride complexes 5a (62%) and 5b (54%), respectively. However, complex 4c could not be transformed to the corresponding Ru(II) hydride complex 5c under the same conditions, presumably due to the strong electron-withdrawing property of 4-nitro in the indolyl moiety of the ligand. Characterization of Ru(II)-NNC Complexes 5. The 1H NMR spectra of complexes 5a and 5b in C6D6 revealed triplets at −8.36 and −8.40 ppm, respectively, corresponding to the resonance of the Ru−H functionality in the complexes. The resonance signals of the Ru−C carbon appeared at 177.3 ppm for 5a and 178.6 ppm for 5b in the 13C{1H} NMR spectra, respectively. The 31P{1H} NMR signals were shown as doublets at 53.4 and 53.5 ppm for 5a and 5b, respectively, due to the P−H coupling interaction. The molecular structure of complex 5b was further confirmed by the X-ray single crystal crystallographic determination (Figure 1, see the Supporting Information for details). In the solid state, complex 5b exhibits a neutral molecular structure, and the metal center is coordinated by the

Figure 1. Molecular structure of complex 5b.

NNC ligand in situ generated from compound 3b, two PPh3 ligands, and one hydride in a distorted bipyrimidal environment. The N(3)−Ru−H(1) angle is 174.8(9)°, revealing that the hydride is positioned trans to the pyridyl nitrogen atom. The Ru−C bond length is 2.025 Å, which is similar to that in Ru(II) complexes A (2.034 Å)14h and longer than that in B (1.971 Å)14m previously reported from our group, implicating formation of a Ru−C σ-bond. The lengths of Ru−N(1) an Ru−N(3) bonds are 2.046 and 2.131 Å, respectively, which are longer than those (1.955 and 2.078 Å) in the ruthenium(II) complex bearing a symmetrical 2,6-bis(3,5-dimethylpyrazol-1yl)pyridine ligand,14o suggesting that the metal center is more accessible, and the complex may exhibit a higher catalytic activity than the corresponding Ru(II) counterpart bearing the symmetrical NNN ligand. Comparison of the Catalytic Activities of the Complexes. Initially, complexes 4 and 5 were tested as the catalysts for the dehydrogenation of 1,2,3,4-tetrahydroquinoline (6a) (Table 1). B

DOI: 10.1021/acs.organomet.7b00902 Organometallics XXXX, XXX, XXX−XXX

Article

Organometallics Table 1. Screening of Reaction Conditionsa

Table 2. Dehydrogenation of Tetrahydroquinolines (6) Catalyzed by Complex 5ba,b

entry

catalyst

base

temp (°C)

yield (%)b

1 2 3 4 5 6 7 8 9

4a 4b 4c A B Ru-DPPc 5a 5b 5b

tBuOK tBuOK tBuOK tBuOK tBuOK tBuOK

140 140 140 140 140 140 140 140 120

35 65 24 17 10 12 42 82 (80)d 54

a

Conditions: 6a (0.5 mmol), catalyst (0.01 mmol), tBuOK (0.1 mol), o-xylene (0.5 mL), 0.1 MPa N2, 140 °C, 48 h. bDetermined by GC analysis. cRu-DPP represents the ruthenium(II) complex bearing a 2,6-bis(3,5-dimethylpyrazol-1-yl)pyridine ligand.14o dIsolated yield given in parentheses.

With 2.0 mol % 4 as the catalyst and 20 mol % tBuOK as the base, the dehydrogenation reaction of 6a was conducted in o-xylene at 140 °C for 48 h, exclusively forming the target product, that is, quinoline (7a), in 24−65% yield (Table 1, entries 1−3). Complex 4b, which bears an electron-donating 4-methoxy substituent, exhibited a catalytic activity much higher than those of both 4a and 4c. Ru(II) complex catalysts A and B and that bearing a symmetrical 2,6-bis(3,5-dimethylpyrazol-1yl)pyridine ligand14o were also tested as the catalysts, exhibiting poor catalytic activities (Table 1, entries 4−6). To our delight, ruthenium(II) hydride complexes 5a and 5b could accomplish the dehydrogenation reaction more efficiently under the basefree conditions (Table 1, entries 4−5). Complex 5b achieved the highest catalytic activity among the screened Ru(II) complexes, affording product 7a in 80% isolated yield (Table 1, entry 5). It is noteworthy that lowering temperature to 120 °C reduced the reaction efficiency (Table 1, entry 6). Under the optimized conditions, the substrate scope of N-heterocycles tetrahydroquinoline derivatives (6) were explored (Table 2). Decent yields (83−89%) were obtained for the target products 7b−7d from tetrahydroquinolines substituted at 2- or 3-positon by a methyl or phenyl group (7b−7d). 4-Methyltetrahydroquinoline reacted to afford lepidine (7e) in 75% yield. Variation of the substituents on the aryl moiety of the substrates resulted in products 7f−7i (72−85%). Unexpectedly, tricyclic N-heterocycle, that is, benzo[h]quinoline (7j), was obtained in 93% yield from 1,2,3,4-tetrahydrobenzo[h]quinoline under the standard conditions, exhibiting no steric effect. Dehydrogenation of tetrahydroisoquinolines and tetrahydroquinoxalines smoothly underwent to produce the target products isoquinolines (7k, 7l, and 7n) and quinoxalines (7o−7q) in excellent yields (81−87%), showing no obvious substituent effect. However, bromo-substituted N-heterocycles were less susceptible to dehydrogenation, forming 5-bromoisoquinoline (7m) and 6-bromoquinoxaline (7r) in 58 and 65% yields, respectively. As compared with the dehydrogenation behaviors of N-heterocycles catalyzed by Shvo-type ruthenium hydride complex at 165 °C with a 5 mol % of ruthenium loading,11e our case features relatively mild conditions at 140 °C with a lower catalyst loading, i.e., 2 mol % ruthenium, achieved higher TONs or TOFs. These results have demonstrated the high catalytic activity and broad substrate scope of the present catalytic

a

Conditions: 6 (0.5 mmol), catalyst 5b (0.01 mmol), o-xylene (0.5 mL), 0.1 MPa N2, 140 °C, 48 h. bYields refer to the isolated products.

system. In contrast to benzofused N-heterocycle substrates, 2,6-dimethyl-piperidine could not react to yield the target product 2,6-dimethylpyridine (7s). Diverse synthesis methods have been developed to access indole derivatives because of their importance in chemical and pharmaceutical fields. To our delight, indoline derivatives (8) could be efficiently dehydrogenated to indoles (9) by using the same complex catalyst (5b) under the optimized reaction conditions as shown in Tables 1 and 3. In a similar manner, indoline (8a) reacted to form indole (9a) in 82% yield. The indoline substrates bearing a 2-Me, 2-Ph, or 3-Me substituent also efficiently underwent the dehydrogenation reactions to afford substituted indoles 9b−9d (78−91%). Electron-donating substituent-bearing indolines reacted to give 9e−9g (76−88%), and 7-methyl substituent exhibited a negative steric effect on the reaction efficiency. Fluoro, chloro, bromo, and nitro substituents on the phenyl ring of the indoline substrates reduced the reaction efficiency, affording 9h−9l in relatively low yields (54−75%). 5,6-Methylenedioxy-2-phenylindole (9m) and 5-chloro-2-methyl-1H-indole (9n) were obtained in 86 and 74% yields, respectively, from the corresponding disubstituted indolines. However, no dehydrogenation was observed for either N-methyl indoline or 2,3-dihydrobenzofuran to form N-methylindole (9o) or benzofuran (9p) under the same conditions. These results have revealed that the NH functionality as well as a fused benzo moiety in the N-heterocycle substrates is crucial for their catalytic dehydrogenation reactions to occur under the stated conditions. Next, the synthesis protocol was applied for a drug development-relevant synthesis (Scheme 2). It has been known that C

DOI: 10.1021/acs.organomet.7b00902 Organometallics XXXX, XXX, XXX−XXX

Article

Organometallics Table 3. Dehydrogenation of Indolines (8) Catalyzed by Complex 5ba,b

Table 4. Dehydrogenation of Alcohols (13) Catalyzed by Complex 5ba,b

a

Conditions: 8 (0.5 mmol), catalyst 5b (0.01 mmol), o-xylene (0.5 mL), 0.1 MPa N2, 140 °C, 48 h. bYields refer to the isolated products.

β-carboline motif plays a pivotal role in many pharmaceuticals. Thus, 1,2,3,4-tetrahydro-β-carbolines (11) were synthesized by Pictet−Spengler reaction of aldehyde and tryptamine (10).17 Compounds 11 underwent similar dehydrogenation reactions to afford the target β-carboline alkaloids (12) in good yields (75−80%). The present method provides a concise and environmentally benign strategy to access β-carboline derivatives by comparison with the known procedures.18 Encouraged by the above results, catalytic dehydrogenation of secondary alcohols (13) were conducted by simply modifying the reaction conditions (Table 4). With 0.5 mol % complex 5b as the catalyst in refluxing toluene, 1-phenylethanol (13a) was transformed to acetophenone (14a) in 92% yield within 24 h. Steric hindrance from the aryl moiety of the alcohol substrates had no obvious impact on the reaction efficiency. Thus, 1-phenylpropanol (13b), 1-(2-methylphenyl)ethanol (13c), and analogs were dehydrogenated to afford the target ketone products 14b−14h in 94−98% yields, regardless of the electrondonating or -withdrawing substituents. The reactions of both 1-(naphthalen-2-yl)ethanol (13i) and diphenylmethanol (13j) proceeded to form the corresponding ketones 14i (92%) and 14j (98%), respectively. Open-chain aliphatic secondary alcohols could also be efficiently dehydrogenated to give ketones 14k−14n in 87−99% yields by increasing the catalyst loading to 1.0 mol %, while cyclohexanol exhibited a relatively low reactivty to yield cyclohexanone (14o) (82%). Interestingly,

a

Conditions: 13 (0.5 mmol), catalyst 5b (0.0025 mmol), toluene (0.5 mL), 0.1 MPa N2, 140 °C, 48 h. bYields refer to the isolated products.

cholest-5-en-3β-ol could be dehydrogenated to α,β-unsaturated ketone cholest-4-en-3β-one(14p) in 62% yield under the same conditions. 5α-Cholestan-3β-ol and methyl glycyrrhetinate were also dehydrogenated to corresponding ketones 14q (76%) and 14r (52%), respectively, demonstrating a potential application of the synthesis protocol in specific pharmaceutical syntheses. It is noteworthy that when complex 5b was applied as the catalyst for the direct dehydrogenation of primary alcohols such as benzyl alcohol, allylic alcohol, and 3-phenylpropanol the reactions only formed trace amounts of the corresponding esters as the products. Reaction Mechanism. A plausible inner-sphere mechanism for the dehydrogenation of N-heterocycles is proposed in Scheme 3.19 Dissociation of a PPh3 ligand from precatalyst complex 5b generates a coordinately unsaturated ruthenium(II) hydride species which is then coordinated by substrate 6a, forming amine complex 5ba. Free PPh3 ligand was detected in the reaction mixture by 31P NMR analysis. Intramolecular interaction of amino hydrogen and hydride complex 5ba

Scheme 2. Synthesis of β-Carbolines

D

DOI: 10.1021/acs.organomet.7b00902 Organometallics XXXX, XXX, XXX−XXX

Article

Organometallics Scheme 3. Proposed Mechanism

13 C{1H} NMR spectra were recorded on a 400 MHz spectrometer, and all chemical shift values refer to δTMS = 0.00 ppm, CDCl3 (δ(1H), 7.26 ppm; δ(13C), 77.16 ppm), DMSO-d6 (δ(1H), 2.50 ppm; δ(13C), 39.52 ppm), and C6D6-d6 (δ(1H), 7.16 ppm; δ(13C), 128.06 ppm). Elemental and HRMS analysis were achieved by the Analysis Center, Dalian University of Technology and Dalian Institute of Chemical Physics, Chinese Academy of Sciences. All the chemical reagents were purchased from commercial sources and used as received unless otherwise indicated. X-ray Crystallographic Studies. The X-ray diffraction studies for complex 5b were carried out on a SMART APEX diffractometer with graphite-monochromated Mo Kα radiation (λ = 0.71073 Å). Cell parameters were obtained by global refinement of the positions of all collected reflections. Intensities were corrected for Lorentz and polarization effects and empirical absorption. The structures were solved by direct methods and refined by full-matrix least-squares on F2. All nonhydrogen atoms were refined anisotropically. All hydrogen atoms were placed in calculated positions. Structure solution and refinement were performed by using the SHELXL-97 package. The X-ray crystallographic files, in CIF format, are available from the Cambridge Crystallographic Data Centre on quoting deposition number CCDC 1524297 for complex 5b. Copies of this information may be obtained free of charge from the Director, CCDC, 12 Union Road, Cambridge CB2 IEZ, UK (Fax: + 44−1223−336033; e-mail: [email protected] or www: http://www.ccdc.cam.ac.uk). Synthesis of 3a.

liberates a molecule of dihydrogen and forms coordinately unsaturated complex 5bb. Species 5bb undergoes β-H elimination to yield ruthenium(II) hydride imine complex 5bc which tends to isomerize to the more stable intermediate complex 5bd since dehydrogenation from the C3−C4 bond is energetically unfavorable. A second dehydrogenation occurs to generate complex 5be which undergoes further β-H elimination with coordination of a molecule of substrate 6a, resulting in quinoline (7a) as the product and regenerating complex 5ba to finish the catalytic cycle.

■

CONCLUSIONS

■

EXPERIMENTAL SECTION

In summary, a versatile ruthenium(II) hydride complex bearing a pyrazolyl-(2-indolyl)- pyridine ligand was synthesized and has exhibited excellent catalytic activity for acceptorless dehydrogenation of N-heterocycles and secondary alcohols. The present work has established a strategy to construct highly active transition metal complex catalysts, and the high catalytic activity and broad substrate scope of the present catalytic system make the synthesis protocol a promising alternative route to N-heteroarenes and ketones.

General Considerations. All the manipulations of air and/or moisture-sensitive compounds were carried out under a nitrogen atmosphere using the standard Schlenk techniques. The solvents were dried and distilled prior to use by the literature methods. The solvents were dried and distilled prior to use by the literature methods. 1H and E

DOI: 10.1021/acs.organomet.7b00902 Organometallics XXXX, XXX, XXX−XXX

Article

Organometallics

(d, J = 7.5 Hz, 1 H, 3H), 7.08 (t, J = 7.3 Hz, 6 H, PPh3), 7.01 (d, J = 8.1 Hz, 1 H, 8″H), 6.95 (t, J = 7.5 Hz, 12 H, PPh3), 6.88 (m, 1 H, 4H), 6.75 (s, 1 H, 3″H), 6.67 (m, 2 H, 6″H and 7″H), 6.29 (d, J = 8.3 Hz, 1 H, 5″H), 5.86 (s, 1 H, 4′H), 2.65 (s, 3 H, C5′-CH3), 2.06 (s, 3 H, C3′-CH3). 13C{1H} NMR (CDCl3, 100 MHz, 23 °C) δ 156.4, 151.1, 140.7, 137.3, 137.1, 134.1, 134.0, 133.8, 132.3, 132.1, 128.3, 127.2, 120.3, 116.8, 115.8, 113.2, 108.9, 104.0, 100.0, 15.7, 13.8. 31P{1H} NMR (CDCl3, 162 MHz, 23 °C) δ 29.0. IR (KBr pellets, cm−1): ν 3141, 3050, 3002, 2957, 2920, 1961, 1901, 1818, 1607, 1588, 1561, 1485, 1463, 1434, 1422, 1393, 1378, 1362, 1314, 1263, 1180, 1150, 1127, 1091, 1035, 1001, 981, 850, 776, 743, 724, 697, 627, 619, 516, 499, 463, 432, 411. Anal. Calcd for C54H45ClN4P2Ru: C, 68.38; H, 4.78; N, 5.91. Found: C, 68.49; H, 4.75; N, 5.94. Synthesis of 4b.

Under a nitrogen atmosphere, a mixture of 2-bromo-6-(3,5dimethylpyrazol-1-yl)pyridine (1) (1.90 g, 7.5 mmol), indole (2a) (586 mg, 5.0 mmol), CuI (95 mg, 0.5 mmol), 1,10-phenanthroline (180 mg, 1.0 mmol), and K2CO3 (1.38 g, 10.0 mmol) in 15 mL of toluene was stirred at 110 °C for 12 h. After cooling to ambient temperature, the mixture was filtered through a short pad of Celite and rinsed with 50 mL of CH2Cl2. The combined filtrate was concentrated under reduced pressure, and the resulting residue was purified by column chromatography on silica gel (eluent petroleum ether (60−90 °C)/ ethyl acetate: 20:1, v/v) to afford 3a as a white solid (1.09 g, 76%). M.p.: 55−56 °C. 1H NMR (CDCl3, 400 MHz, 23 °C) δ 8.08 (d, J = 8.3 Hz, 1 H, 3H), 7.91 (t, J = 8.0 Hz, 1 H, 4H), 7.79 (m, 2 H, 5H and 5″H), 7.69 (d, J = 7.8 Hz, 1 H, 8″H), 7.38 (d, J = 7.9 Hz, 1 H, 2″H), 7.30 (m, 1 H, 7″H), 7.23 (m, 1 H, 6″H), 6.74 (m, 1 H, 3″H), 6.05 (s, 1 H, 4′H), 2.71 (s, 3 H, C5′-CH3), 2.35 (s, 3 H, C3′-CH3). 13C{1H} NMR (CDCl3, 100 MHz, 23 °C) δ 152.7, 150.1, 150.0, 141.6, 140.5, 134.8 130.5, 126.4, 123.1, 121.3, 121.2, 112.5, 111.4, 110.8, 109.5, 105.5, 15.0, 13.7. HRMS calcd for C18H16N4 [M]+: 288.1375; found: 288.1383. Synthesis of 3b.

In a fashion similar to that for the synthesis of 4a, 3b (159 mg, 0.5 mmol) reacted with RuCl2(PPh3)3 (480 mg, 0.5 mmol) to afford 4b as a yellow crystalline solid (420 mg, 86%). M.p.: >300 °C, dec. 1H NMR (CDCl3, 400 MHz, 23 °C) δ 7.24 (m, 13 H, 5H and PPh3), 7.06 (t, J = 7.3 Hz, 6 H, PPh3), 6.93 (t, J = 7.5 Hz, 11 H, PPh3), 6.83 (t, J = 8.9 Hz, 2 H, 4H and PPh3), 6.67 (s, 2 H, 3″H and 5″H), 6.61 (d, J = 8.2 Hz, 1 H, 3H), 6.25 (dd, J = 8.5, 2.2 Hz, 1 H, 8″H), 6.16 (d, J = 8.4 Hz, 1 H, 7″H), 5.83 (s, 1 H, 4′H), 3.78 (s, 3 H, C6″-OCH3), 2.62 (s, 3 H, C5′-CH3), 2.02 (s, 3 H, C3′-CH3). 13C{1H} NMR (CDCl3, 100 MHz, 23 °C) δ 172.6, 156.1, 155.2, 154.5, 151.0, 140.7, 138.1, 134.0, 133.9, 133.8, 132.3, 132.1, 128.3, 127.2, 119.8, 113.0, 109.0, 103.9, 103.4, 99.6, 55.5, 15.7, 13.8. 31P{1H} NMR (CDCl3, 162 MHz, 23 °C) δ 29.2. IR (KBr pellets, cm−1): ν 3139, 3052, 3001, 2985, 2954, 2930, 2830, 1962, 1901,1820, 1604, 1584, 1561, 1479, 1447, 1434, 1417, 1393, 1364, 1348, 1316, 1296, 1285, 1272, 1206, 1172, 1144, 1131, 1110, 1091, 1036, 1014, 980, 942, 845, 807, 743, 697, 636, 619, 578, 516, 498, 461, 428, 409. Anal. Calcd for C55H47ClN4OP2Ru: C, 67.51; H, 4.84; N, 5.73. Found: C, 67.42; H, 4.86; N, 5.69. Synthesis of 4c.

In a fashion similar to that for the synthesis of 3a, compound 1 (1.90 g, 7.5 mmol) was reacted with 5-methoxyindole (2b) (735 mg, 5.0 mmol) to give 3b as a white solid (1.32 g, 83% yield). M.p.: 136−137 °C. 1 H NMR (CDCl3, 400 MHz, 23 °C) δ 8.00 (d, J = 9.0 Hz, 1 H, 3H), 7.87 (t, J = 8.0 Hz, 1 H, 4H), 7.74 (m, 2 H, 5H and 5″H), 7.30 (d, J = 7.9 Hz, 1 H, 8″H), 7.14 (d, J = 2.4 Hz, 1 H, 2″H), 6.95 (dd, J = 9.0, 2.5 Hz, 1 H, 7″H), 6.67 (dd, J = 14.0, 3.5 Hz, 1 H, 3″H), 6.04 (s, 1 H, 4′H), 3.88 (s, 3 H, C6″-OCH3), 2.70 (s, 3 H, C5′-CH3), 2.35 (s, 3 H, C3′-CH3). 13C{1H} NMR (CDCl3, 100 MHz, 23 °C) δ 155.0, 152.6, 150.07, 150.05, 141.5, 140.4, 131.2, 129.8, 126.7, 113.5, 112.6, 111.1, 110.2, 109.4, 105.3, 103.0, 55.6, 14.9, 13.7. HRMS calcd for C19H18N4O [M]+: 318.1481; found: 318.1487. Synthesis of 3c.

In a fashion similar to that for the synthesis of 3a, compound 1 (1.90 g, 7.5 mmol) was reacted with 5-nitroindole (2c) (810 mg, 5.0 mmol) to give 3c as a yellow solid (1.13 g, 68% yield). M.p.: 160−161 °C. 1H NMR (CDCl3, 400 MHz, 23 °C) δ 8.56 (d, J = 2.0 Hz, 1 H, 5″H), 8.13 (dd, J = 9.2, 2.1 Hz, 1 H, 8″H), 8.07 (d, J = 9.2 Hz, 1 H, 7″H), 7.95 (t, J = 8.0 Hz, 1 H, 4H), 7.86 (d, J = 8.1 Hz, 1 H, 5H), 7.81 (d, J = 3.5 Hz, 1 H, 2″H), 7.31 (d, J = 7.8 Hz, 1 H, 3H), 6.85 (d, J = 3.4 Hz, 1 H, 3″H), 6.04 (s, 1 H, 4′H), 2.64 (s, 3 H, C5′-CH3), 2.31 (s, 3 H, C3′-CH3). 13C{1H} NMR (CDCl3, 100 MHz, 23 °C) δ 152.9, 150.6, 149.1, 142.6, 141.6, 141.0, 137.6, 129.7, 129.5, 118.3, 117.9, 112.9, 112.6, 111.3, 109.9, 106.9, 15.0, 13.7. HRMS calcd for C18H15N5O2 [M]+: 333.1226; found: 333.1227. Synthesis of 4a.

In a fashion similar to that for the synthesis of 4a, 3c (167 mg, 0.5 mmol) reacted with RuCl2(PPh3)3 (480 mg, 0.5 mmol) to afford 4c as a red crystalline solid (442 mg, 89%). M.p.: >300 °C, dec. 1H NMR (CDCl3, 400 MHz, 23 °C) δ 7.69 (m, 1 H, 5H), 7.54 (m, 1 H, 3H), 7.48 and 7.29 (m each, 2:10 H, PPh3), 7.11 (t, J = 7.3 Hz, 6 H, PPh3), 7.01 (t, J = 7.4 Hz, 11 H, PPh3), 6.78 (t, J = 8.2 Hz, 1 H, 4H), 6.64 (m, 2 H, 8″H and PPh3), 6.29 (s, 1 H, 3″H), 6.18 (t, J = 3.0 Hz, 1 H, 5″H), 5.86 (s, 1 H, 4′H), 5.65 (d, J = 8.1 Hz, 1 H, 7″H), 2.64 (s, 3 H, C5′-CH3), 2.05 (s, 3 H, C3′-CH3). 31P{1H} NMR (CDCl3, 162 MHz, 23 °C) δ 30.8. IR (KBr pellets, cm−1): ν 3053, 3020, 3002, 2984, 2957, 2922, 2345, 1960, 1904, 1832, 1775, 1605, 1587, 1562, 1492, 1457, 1434, 1413, 1394, 1345, 1314, 1303, 1277, 1230, 1185, 1168, 1134, 1091, 1039, 1029, 998, 982, 921, 863, 772, 743, 722, 657, 641, 619, 592, 516, 497, 463, 435, 408. Anal. Calcd for C54H44ClN5O2P2Ru: C, 65.29; H, 4.46; N, 7.05. Found: C, 65.22; H, 4.45; N, 7.09. Synthesis of complex 5a.

Under a nitrogen atmosphere, a mixture of 3a (144 mg, 0.5 mmol), RuCl2(PPh3)3 (480 mg, 0.5 mmol), and NEt3 (350 μL, 2.5 mmol) in 10 mL of 2-propanol was refluxed with stirring for 8 h. After cooling to ambient temperature, the precipitate was filtered off, washed with diethyl ether (5 × 10 mL), and dried under vacuum to afford 4a as a yellow crystalline solid (422 mg, 89%). M.p.: >300 °C, dec. 1H NMR (CDCl3, 400 MHz, 23 °C) δ 7.32 (m, 13 H, 5H and PPh3), 7.16 F

DOI: 10.1021/acs.organomet.7b00902 Organometallics XXXX, XXX, XXX−XXX

Article

Organometallics Under a nitrogen atmosphere, a mixture of complex 4a (190 mg, 0.2 mmol) and K2CO3 (138 mg, 1.0 mmol) in 10 mL of 2-propanol was refluxed with stirring for 8 h. After cooling to ambient temperature, all the volatiles were removed under reduced pressure. Then, 2 mL of toluene was added to dissolve the crude product. The solution was filtered and then layered by 5 mL of n-hexane for recrystallization to give 5a as red crystals (114 mg, 62%). M.p.: >300 °C, dec. 1H NMR (C6D6-d6, 400 MHz, 23 °C) δ 7.78 (m, 1 H, 5H), 7.59 (d, J = 7.7 Hz, 1 H, 3H), 7.41 (m, 12 H, PPh3), 7.12 (m, 6 H, PPh3), 6.91 (m, 16 H, 4H, 5″H, 7″H, 8″H, and PPh3), 6.49 (d, J = 8.1 Hz, 1 H, 6″H), 6.09 (s, 1 H, 3″H), 5.49 (s, 1 H, 4′H), 1.94 (s, 3 H, C5′-CH3), 1.16 (s, 3 H, C3′-CH3), −8.36 (t, J = 27.3 Hz, 1 H, Ru−H). 13C{1H} NMR (C6D6d6, 100 MHz, 23 °C) δ 177.3, 154.3, 151.1, 148.5, 140.0, 138.2, 137.8, 133.9, 132.5, 132.4, 132.1, 127.5, 121.0, 117.9, 117.0, 116.3, 110.7, 109.3, 104.4, 100.0, 15.7, 14.7. 31P{1H} NMR (C6D6-d6, 162 MHz, 23 °C) δ 53.4 (d, J(P, H) = 27.5 Hz). IR (KBr pellets, cm−1): ν 3139, 3052, 3000, 2955, 2917, 2613, 2345, 1871, 1601, 1587, 1559, 1482, 1468, 1433, 1419, 1389, 1356, 1312, 1262, 1217, 1177, 1148, 1124, 1090, 1071, 1025, 977, 923, 850, 799, 765, 743, 728, 697, 627, 587, 535, 518, 496, 463, 435, 416. Anal. Calcd for C54H46N4P2Ru: C, 70.96; H, 5.07; N, 6.13. Found: C, 71.06; H, 5.02; N, 6.09. Synthesis of 5b.

NMR spectra of the compounds (PDF) X-ray crystallographic data for 5b (XYZ) Accession Codes

CCDC 1524297 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by emailing data_ [email protected], or by contacting The Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44 1223 336033.

■

AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. ORCID

Qingfu Wang: 0000-0002-2293-9081 Huining Chai: 0000-0001-8087-3458 Zhengkun Yu: 0000-0002-9908-0017 Author Contributions

Q.F.W. and H.N.C. contributed equally to this work. Notes

The authors declare no competing financial interest.

■ ■

ACKNOWLEDGMENTS We are grateful to the National Natural Science Foundation of China (21672209).

In a fashion similar to that for the synthesis of 5a, complex 4b (196 mg, 0.2 mmol) reacted with K2CO3 (138 mg, 1.0 mmol) to afford 5b as a red crystalline solid (102 mg, 54%). M.p.: >300 °C, dec. 1H NMR (400 MHz, C6D6-d6, 23 °C) δ 7.40 (m, 13 H, 5H and PPh3), 7.00 (d, J = 8.3 Hz, 1 H, 3H), 6.90 (m, 19 H, 4H and PPh3), 6.83 (dd, J = 8.6, 2.4 Hz, 1 H, 8″H), 6.53 (d, J = 2.4 Hz, 1 H, 5″H), 6.47 (d, J = 8.0 Hz, 1 H, 7″H), 6.03 (s, 1 H, 3″H), 5.51 (s, 1 H, 4′H), 3.35 (s, 3 H, C6″-OCH3), 1.96 (s, 3 H, C5′-CH3), 1.14 (s, 3 H, C3′-CH3), −8.40 (t, J = 27.4 Hz, 1H). 13C{1H} NMR (C6D6-d6, 100 MHz, 23 °C) δ 178.6, 155.4, 154.0, 151.1, 148.5, 140.1, 138.7, 137.9, 133.9, 133.0, 132.4, 132.2, 127.5, 118.0, 110.7, 109.5, 105.3, 103.8, 99.60, 99.56, 54.9, 15.7, 14.7. 31P{1H} NMR (C6D6-d6, 162 MHz, 23 °C) δ 53.5 (J(P, H) = 24.6 Hz). IR (KBr pellets, cm−1): ν 3052, 2999, 2922, 2828, 2581, 1895, 1598, 1560, 1473, 1447, 1434, 1415, 1391, 1349, 1296, 1205, 1174, 1144, 1131, 1111, 1091, 1071, 1035, 997, 977, 941, 840, 745, 723, 697, 619, 575, 534, 517, 497, 459, 433, 417. Anal. Calcd for C55H48N4OP2Ru: C, 69.98; H, 5.13; N, 5.93. Found: C, 69.92; H, 5.15; N, 5.90. Typical Procedure for the Dehydrogenation of N-Heterocycles. A mixture of an N-heterocycles substrate (0.5 mmol) and complex 5b (0.01 mmol) in o-xylene (0.5 mL) was heated at 140 °C for 48 h under a gentle flow of nitrogen to facilitate removal of hydrogen. After the reaction was complete, the reaction mixture was cooled and condensed under reduced pressure and subject to purification by flash silica gel column chromatography to afford the corresponding product, which was identified by comparison with the authentic sample through NMR and GC analyses. Typical Procedure for the Dehydrogenation of Secondary Alcohols. A mixture of an alcohol substrate (0.5 mmol) and complex 5b (0.0025 mmol) in toluene (0.5 mL) was refluxed with stirring under a nitrogen atmosphere in an open system connected to a bubbler for 24 h. After the reaction was complete, the reaction mixture was cooled and condensed under reduced pressure and subject to purification by flash silica gel column chromatography to afford the corresponding ketone product, which was identified by comparison with the authentic sample through NMR and GC analyses.

■

REFERENCES

(1) (a) Giustra, Z. X.; Ishibashi, J. S. A.; Liu, S.-Y. Coord. Chem. Rev. 2016, 314, 134−181. (b) Eftekhari-Sis, B.; Zirak, M. Chem. Rev. 2015, 115, 151−264. (c) Guo, X.-X.; Gu, D.-W.; Wu, Z. X.; Zhang, W. B. Chem. Rev. 2015, 115, 1622−1651. (2) Allen, S. E.; Walvoord, R. R.; Padilla-Salinas, R.; Kozlowski, M. C. Chem. Rev. 2013, 113, 6234−6458. (3) (a) Daw, P.; Chakraborty, S.; Garg, J. A.; Ben-David, Y.; Milstein, D. Angew. Chem., Int. Ed. 2016, 55, 14373−14377. (b) Pena-Lopez, M.; Neumann, H.; Beller, M. ChemCatChem 2015, 7, 865−871. (c) Gunanathan, C.; Milstein, D. Science 2013, 341, 1229712. (4) (a) Preuster, P.; Papp, C.; Wasserscheid, P. Acc. Chem. Res. 2017, 50, 74−85. (b) Crabtree, R. H. ACS Sustainable Chem. Eng. 2017, 5, 4491−4498. (5) Yamaguchi, R.; Ikeda, C.; Takahashi, Y.; Fujita, K. J. Am. Chem. Soc. 2009, 131, 8410−8412. (6) (a) Fujita, K.; Wada, T.; Shiraishi, T. Angew. Chem., Int. Ed. 2017, 56, 10886−10889. (b) Fujita, K.; Tanaka, Y.; Kobayashi, M.; Yamaguchi, R. J. Am. Chem. Soc. 2014, 136, 4829−4832. (7) (a) Talwar, D.; Gonzalez-de-Castro, A.; Li, H. Y.; Xiao, J. Angew. Chem., Int. Ed. 2015, 54, 5223−5227. (b) Wu, J.; Talwar, D.; Johnston, S.; Yan, M.; Xiao, J. Angew. Chem., Int. Ed. 2013, 52, 6983−6987. (8) (a) Xu, R.; Chakraborty, S.; Yuan, H.; Jones, W. D. ACS Catal. 2015, 5, 6350−6354. (b) Chakraborty, S.; Brennessel, W. W.; Jones, W. D. J. Am. Chem. Soc. 2014, 136, 8564−8567. (9) (a) Maier, A. F. G.; Tussing, S.; Schneider, T.; Flörke, U.; Qu, Z. W.; Grimme, S.; Paradies, J. Angew. Chem., Int. Ed. 2016, 55, 12219− 12223. (b) Kojima, M.; Kanai, M. Angew. Chem., Int. Ed. 2016, 55, 12224−12227. (10) (a) Kato, S.; Saga, Y.; Kojima, M.; Fuse, H.; Matsunaga, S.; Fukatsu, A.; Kondo, M.; Masaoka, S.; Kanai, M. J. Am. Chem. Soc. 2017, 139, 2204−2207. (b) He, K. H.; Tan, F. F.; Zhou, C. Z.; Zhou, G. J.; Yang, X. L.; Li, Y. Angew. Chem., Int. Ed. 2017, 56, 3080−3084. (c) Sahoo, M. K.; Jaiswal, G.; Rana, J.; Balaraman, E. Chem. - Eur. J. 2017, 23, 14167−14172. (11) (a) Stubbs, J. M.; Hazlehurst, R. J.; Boyle, P. D.; Blacquiere, J. M. Organometallics 2017, 36, 1692−1698. (b) Esteruelas, M. A.; Lezáun, A.; Martínez, A.; Oliván, M.; Oñate, E. Organometallics 2017, 36, 2996−3004. (c) Manas, M. G.; Sharninghausen, L. S.; Lin, E.;

ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.organomet.7b00902. G

DOI: 10.1021/acs.organomet.7b00902 Organometallics XXXX, XXX, XXX−XXX

Article

Organometallics Crabtree, R. H. J. Organomet. Chem. 2015, 792, 184−189. (d) Luca, O. R.; Huang, D. L.; Takase, M. K.; Crabtree, R. H. New J. Chem. 2013, 37, 3402−3405. (e) Muthaiah, S.; Hong, S. H. Adv. Synth. Catal. 2012, 354, 3045−3053. (12) (a) Crabtree, R. T. Chem. Rev. 2017, 117, 9228−9246. (b) Gülcemal, S.; Gülcemal, D.; Whitehead, G. F. S.; Xiao, J. Chem. Eur. J. 2016, 22, 10513−10522. (c) Kopylovich, M. N.; Ribeiro, A. P. C.; Alegria, E. C. B. A.; Martins, N. M. R.; Martins, L. M. D. R.S.; Pombeiro, A. J. L. Adv. Organomet. Chem. 2015, 63, 91−174. (d) Song, H.; Kang, B.; Hong, S. H. ACS Catal. 2014, 4, 2889−2895. (e) Suzuki, T. Chem. Rev. 2011, 111, 1825−1845. (13) Chelucci, G.; Baldino, S.; Baratta, W. Coord. Chem. Rev. 2015, 300, 29−85. (14) (a) Liu, T. T.; Chai, H. N.; Wang, L. D.; Yu, Z. K. Organometallics 2017, 36, 2914−2921. (b) Chai, H. N.; Wang, Q. F.; Liu, T. T.; Yu, Z. K. Dalton Trans. 2016, 45, 17843−17849. (c) Wang, Q. F.; Wu, K. K.; Yu, Z. K. Organometallics 2016, 35, 1251−1256. (d) Chai, H. N.; Liu, T. T.; Wang, Q. F.; Yu, Z. K. Organometallics 2015, 34, 5278−5284. (e) Du, W. M.; Wang, Q. F.; Wang, L. D.; Yu, Z. K. Organometallics 2014, 33, 974−982. (f) Du, W. M.; Wu, P.; Wang, Q. F.; Yu, Z. K. Organometallics 2013, 32, 3083−3090. (g) Jin, W. W.; Wang, L. D.; Yu, Z. K. Organometallics 2012, 31, 5664−5667. (h) Du, W. M.; Wang, L. D.; Wu, P.; Yu, Z. K. Chem. - Eur. J. 2012, 18, 11550−11554. (i) Ye, W. J.; Zhao, M.; Yu, Z. K. Chem. - Eur. J. 2012, 18, 10843−10846. (j) Ye, W. J.; Zhao, M.; Du, W. M.; Jiang, Q. B.; Wu, K. K.; Wu, P.; Yu, Z. K. Chem. - Eur. J. 2011, 17, 4737−4741. (k) Zeng, F. L.; Yu, Z. K. Organometallics 2009, 28, 1855−1862. (l) Zeng, F. L.; Yu, Z. K. Organometallics 2008, 27, 2898−2901. (m) Zeng, F. L.; Yu, Z. K. Organometallics 2008, 27, 6025−6028. (n) Zeng, F. L.; Yu, Z. K. J. Org. Chem. 2006, 71, 5274−5281. (o) Deng, H. X.; Yu, Z. K.; Dong, J. H.; Wu, S. Z. Organometallics 2005, 24, 4110−4112. (15) (a) Soni, V.; Jagtap, R. A.; Gonnade, R. G.; Punji, B. ACS Catal. 2016, 6, 5666−5672. (b) Sollert, C.; Devaraj, K.; Orthaber, A.; Gates, P. J.; Pilarski, L. T. Chem. - Eur. J. 2015, 21, 5380−5386. (c) Sandtorv, A. H. Adv. Synth. Catal. 2015, 357, 2403−2435. (d) Qin, X.; Liu, H.; Qin, D.; Wu, Q.; You, J.; Zhao, D.; Guo, Q.; Huang, X.; Lan, J. Chem. Sci. 2013, 4, 1964−1969. (e) Ackermann, L. Chem. Rev. 2011, 111, 1315−1345. (16) Fu, W. C.; So, C. M.; Chow, W. K.; Yuen, O. Y.; Kwong, F. Y. Org. Lett. 2015, 17, 4612−4615. (b) So, C. M.; Lau, C. P.; Kwong, F. Y. Org. Lett. 2007, 9, 2795−2798. (17) Jiang, W.; Zhang, X.; Sui, Z. Org. Lett. 2003, 5, 43−46. (18) (a) Kamal, A.; Tangella, Y.; Manasa, K. L.; Sathish, M.; Srinivasulu, V.; Chetna, J.; Alarifi, A. Org. Biomol. Chem. 2015, 13, 8652−9662. (b) Eagon, S.; Anderson, M. O. Eur. J. Org. Chem. 2014, 2014, 1653−1665. (19) (a) Hale, L. V. A.; Malakar, T.; Tseng, K. T.; Zimmerman, P. M.; Paul, A.; Szymczak, N. K. ACS Catal. 2016, 6, 4799−4813. (b) Sawatlon, B.; Surawatanawong, P. Dalton Trans. 2016, 45, 14965− 14978. (c) Tseng, K. T.; Kampf, J. W.; Szymczak, N. K. ACS Catal. 2015, 5, 5468−5485. (d) Li, H.; Jiang, J.; Lu, G.; Huang, F.; Wang, Z.X. Organometallics 2011, 30, 3131−3141.

H

DOI: 10.1021/acs.organomet.7b00902 Organometallics XXXX, XXX, XXX−XXX