Acceptorless Dehydrogenation of N-Heterocycles and Secondary Alcohols by Ru(II)-NNC Complexes Bearing a Pyrazoyl-indolyl-pyridine Ligand

Article abstract of DOI:10.1021/acs.organomet.7b00902

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.

Full text of DOI:10.1021/acs.organomet.7b00902

Article
Cite This: Organometallics XXXX, XXX, XXX−XXX
Acceptorless Dehydrogenation of N‑Heterocycles and Secondary
Alcohols by Ru(II)-NNC Complexes Bearing a Pyrazoyl-indolyl-
pyridine 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 struc-
turally characterized by NMR analysis and X-ray single crystal
crystallographic determinations. These complexes efficiently cata-
lyzed acceptorless dehydrogenation of N-heterocycles and sec-
ondary 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 cata-
lysts and provides an atom-economical and environmentally benign
protocol for the synthesis of aromatic N-heterocyclic compounds
and ketones.
transition metal catalyzed acceptorless dehydrogenation of
N-heterocycles and alcohols, and diverse highly active homoge-
neous transition metal complex catalysts are strongly desired in
this area.
INTRODUCTION
■
Synthesis of nitrogen-containing heteroarenes1 and carbonyl
compounds2 is of great importance in organic synthesis and
medicinal chemistry. Traditional methods to access these com-
pounds usually require stoichiometric oxidants. Thus, accept-
orless catalytic dehydrogenation is desired because such a
process is atom-economical and environmentally benign, and
stoichiometric oxidants can be avoided.3 Acceptorless dehy-
drogenation (AD) reactions have also found potential appli-
cations 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 tetrahy-
droquinoline derivatives has recently been documented by using
a Cp*Ir complex bearing a 2-pyridonate ligand.5 Perdehydroge-
nation 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-hetero-
cycles.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
Cyclometalated complexes of unsymmetrical NNC ligands
have been documented as the catalysts for diverse organic trans-
formations.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 pyridine-
based pyrazolyl-N-heterocyclic carbene (NHC) ligand only exhib-
ited a poor catalytic activity for the same reactions14m (Chart 1).
It is obvious that the steric and electronic properties of a poly-
dentate 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 envi-
sioned that an indolyl might be employed to construct a pyridine-
based NNC ligand for the establishment of highly active tran-
sition 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
© XXXX American Chemical Society
A
DOI: 10.1021/acs.organomet.7b00902
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
Chart 1. Ruthenium(II)-NNC Pincer Complexes
a
Scheme 1. Synthesis of Ruthenium(II)-NNC Pincer Complexes
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-pyrazol-
1-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)
Figure 1. Molecular structure of complex 5b.
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, presum-
ably due to the strong electron-withdrawing property of 4-nitro
in the indolyl moiety of the ligand.
NNC ligand in situ generated from compound 3b, two PPh3
ligands, and one hydride in a distorted bipyrimidal environ-
ment. 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-1-
yl)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 symmet-
rical NNN ligand.
1
Characterization of Ru(II)-NNC Complexes 5. The H
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 crystallo-
graphic 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
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

Organometallics
Article
a
Table 1. Screening of Reaction Conditions
Table 2. Dehydrogenation of Tetrahydroquinolines
a,b
(6) Catalyzed by Complex 5b
b
entry
catalyst
base
temp (°C)
yield (%)
1
2
3
4
5
6
7
8
9
4a
tBuOK
tBuOK
tBuOK
tBuOK
tBuOK
tBuOK
140
140
140
140
140
140
140
140
120
35
65
24
17
10
12
42
4b
4c
A
B
c
Ru-DPP
5a
d
5b
82 (80)
54
5b
a
Conditions: 6a (0.5 mmol), catalyst (0.01 mmol), tBuOK (0.1 mol),
b
o-xylene (0.5 mL), 0.1 MPa N2, 140 °C, 48 h. Determined by GC
c
analysis. Ru-DPP represents the ruthenium(II) complex bearing a
2,6-bis(3,5-dimethylpyrazol-1-yl)pyridine ligand.14o Isolated yield given
d
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-1-
yl)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 base-
free 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-Methyl-
tetrahydroquinoline 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. Dehydrogen-
ation of tetrahydroisoquinolines and tetrahydroquinoxalines
smoothly underwent to produce the target products isoquino-
lines (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 suscep-
tible to dehydrogenation, forming 5-bromoisoquinoline (7m)
and 6-bromoquinoxaline (7r) in 58 and 65% yields, respec-
tively. 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),
b
0.1 MPa N2, 140 °C, 48 h. Yields refer to the isolated products.
system. In contrast to benzofused N-heterocycle substrates,
2,6-dimethyl-piperidine could not react to yield the target prod-
uct 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 con-
ditions 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 effi-
ciently underwent the dehydrogenation reactions to afford sub-
stituted indoles 9b−9d (78−91%). Electron-donating sub-
stituent-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 sub-
stituents 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 dehy-
drogenation reactions to occur under the stated conditions.
Next, the synthesis protocol was applied for a drug develop-
ment-relevant synthesis (Scheme 2). It has been known that
C
DOI: 10.1021/acs.organomet.7b00902
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
Table 3. Dehydrogenation of Indolines (8) Catalyzed by
Complex 5b
Table 4. Dehydrogenation of Alcohols (13) Catalyzed by
Complex 5b
a b
,
a b
,
a
Conditions: 8 (0.5 mmol), catalyst 5b (0.01 mmol), o-xylene (0.5 mL),
b
0.1 MPa N2, 140 °C, 48 h. Yields 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 envi-
ronmentally 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 modi-
fying 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 electron-
donating 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
b
(0.5 mL), 0.1 MPa N2, 140 °C, 48 h. Yields 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

Organometallics
Article
Scheme 3. Proposed Mechanism
13C{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 polar-
ization effects and empirical absorption. The structures were solved by
direct methods and refined by full-matrix least-squares on F2. All non-
hydrogen 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 crystallo-
graphic files, in CIF format, are available from the Cambridge Crystal-
lographic 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: deposit@ccdc.cam.ac.uk
or www: http://www.ccdc.cam.ac.uk).
liberates a molecule of dihydrogen and forms coordinately unsat-
urated 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 unfa-
vorable. 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
■
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 dehydro-
genation of N-heterocycles and secondary alcohols. The pres-
ent 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.
EXPERIMENTAL SECTION
Synthesis of 3a.
■
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

Organometallics
Article
Under a nitrogen atmosphere, a mixture of 2-bromo-6-(3,5-
dimethylpyrazol-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 col-
umn 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.
(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.
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
1
crystalline solid (420 mg, 86%). M.p.: >300 °C, dec. H 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.
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.
1H 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.
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-nitroindole (2c) (810 mg, 5.0 mmol) to
1
give 3c as a yellow solid (1.13 g, 68% yield). M.p.: 160−161 °C. H
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.
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 4a.
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
1
yellow crystalline solid (422 mg, 89%). M.p.: >300 °C, dec. H 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

Organometallics
Article
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 temper-
ature, 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 (C6D6-
d6, 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.
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_
request@ccdc.cam.ac.uk, 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: zkyu@dicp.ac.cn.
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.
■
Synthesis of 5b.
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. H NMR
1
REFERENCES
■
(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.
(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.
Typical Procedure for the Dehydrogenation of N-Hetero-
cycles. 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.
(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.; Florke, 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.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the ACS
Publications website at DOI: 10.1021/acs.organomet.7b00902.
■
(11) (a) Stubbs, J. M.; Hazlehurst, R. J.; Boyle, P. D.; Blacquiere, J.
M. Organometallics 2017, 36, 1692−1698. (b) Esteruelas, M. A.;
S
́ ́
Lezaun, A.; Martínez, A.; Olivan, M.; Onate, E. Organometallics 2017,
̃
36, 2996−3004. (c) Manas, M. G.; Sharninghausen, L. S.; Lin, E.;
G
DOI: 10.1021/acs.organomet.7b00902
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
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) Gulcemal, S.; Gulcemal, 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