New Ruthenium Complexes Based on Tetradentate Bipyridine Ligands for Catalytic Hydrogenation of Esters

Article abstract of DOI:10.1002/asia.201600506

New bipyridinemethanamine-containing tetradentate ligands and their corresponding ruthenium complexes have been synthesized. The synthesized complexes performed well in the hydrogenation of a variety of esters with high efficiency (TON up to 9700) giving alcohols in good yields.

Full text of DOI:10.1002/asia.201600506

DOI: 10.1002/asia.201600506
Communication
Hydrogenation
New Ruthenium Complexes Based on Tetradentate Bipyridine
Ligands for Catalytic Hydrogenation of Esters
Fangyuan Wang,[a] Xuefeng Tan,[a] Hui Lv,*[a, b] and Xumu Zhang*[a, c]
and a series of efficient catalysts for ester reduction have been
Abstract: New bipyridinemethanamine-containing tetra-
developed by Saudan,[5] Ikariya,[6] Kuriyamma,[7] Morris,[8]
dentate ligands and their corresponding ruthenium com-
Gusev,[9] Pidko,[10] and others.[11] Very recently, Zhou[12] and our
plexes have been synthesized. The synthesized complexes
group[13] reported the bipyridyl-containing tetradentate ligands
performed well in the hydrogenation of a variety of esters
and a pyridin-2-ylmethanamine-containing tetradentate ligand,
with high efficiency (TON up to 9700) giving alcohols in
respectively, both of the ligands exhibited high catalytic activi-
good yields.
ties in ester reduction under mild conditions and gave excel-
lent results (Figure 1, TON up to 80000 and TOF up to
Ester reduction is one of the most important reactions and
widely used in organic synthesis; however, this fundamental
transformation is still a challenge both in the laboratory and
industry. Generally, the ester reduction heavily relies on metal–
hydride reagents (e.g., LiAlH4 or NaBH4),[1] which suffer from in-
herent drawbacks, such as use of stoichiometric amounts of
the reagents, hazardous operations, tedious workup proce-
dures, and high level of residual wastes.[2] In addition, the re-
duction of esters in industry mainly proceeds by heterogene-
ous catalysis under harsh conditions (200–3008C, 200–
300 atm).[3] Therefore, the development of efficient and envi-
ronmentally friendly approaches is highly desirable.
Figure 1. Efficient catalysts for ester hydrogenation.
In the past decades, homogenous catalytic hydrogenation of
esters has been widely investigated, but significant progresses
have only been made recently. In 2006, Milstein and co-work-
ers reported their pioneer work in catalytic hydrogenation of
esters with a PNN pincer-type ruthenium complex, in which an
aromatization/dearomatization process was involved and ex-
hibited good activities under relatively mild conditions (5 atm
H2, 1158C).[4] Since then, catalytic hydrogenation of esters with
homogenous catalysts have undergone a rapid development,
10000 hÀ1 for catalyst I, and TON up to 91000 and TOF up to
1896 hÀ1 for catalyst II). Although great progresses have been
made in the reduction of ester, developing more practical and
efficient ligands in terms of ease of preparation and high turn-
over number (TON) is significant. Herein, we report a new type
of bipyridinemethanamine-containing tetradentate ligands and
their applications in catalytic hydrogenation of esters.
Intrigued by the great success of catalyst I and catalyst II in
ester reduction, we reasoned that the bipyridine fragment of
catalyst I is critical to keep high activity due to the coordina-
tion capability and stability. For catalyst II, the pyridinemethan-
amine unit is very important to keep high acidity of the NÀH
group,[14] which is essential to activate the carbonyl group of
esters. We envisioned that combination of the two key frag-
ments in one molecule may exhibit high catalytic activity in
ester reduction. With these thoughts in mind, we designed
two bipyridinemethanamine-containing tetradentate ligands,
which could be prepared by a concise synthetic route de-
scribed in Scheme 1. Subsequently, their Ru complexes were
prepared by the following procedure: [RuCl2(PPh3)3] was react-
ed with the ligands in toluene at 1108C, and then the precipi-
tation was washed by anhydrous ether. Ruthenium complexe-
s A and B were obtained as air-stable (stable in air for at least
[a] F. Wang, X. Tan, Prof. H. Lv, Prof. X. Zhang
Key Laboratory of Biomedical Polymers of Ministry of Education & College
of Chemistry and Molecular Sciences
Wuhan University, Wuhan, Hubei 430072 (China)
E-mail: huilv@whu.edu.cn
xumu@whu.edu.cn
[b] Prof. H. Lv
Beijing National Laboratory for Molecular Sciences
CAS Key Laboratory of Molecular Recognition and Function
Institute of Chemistry, Chinese Academy of Sciences
100190 Beijing (China)
[c] Prof. X. Zhang
Department of Chemistry
South University of Science and Technology of China
Shenzhen, Guangdong, 518055 (China)
Supporting information for this article can be found under http://
dx.doi.org/10.1002/asia.201600506.
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Table 1. Hydrogenation of methyl benzoate with ruthenium complexes A
and B.[a]
Entry
Cat (mol%)
Base (mol%)
Solvent
Yield [%][b]
1
2
3
4
5
6
7
8
A (0.02)
B (0.02)
B (0.01)
B (0.01)
B (0.01)
B (0.01)
B (0.01)
B (0.01)
B (0.01)
B (0.01)
B (0.01)
B (0.01)
B (0.01)
NaOMe (10)
NaOMe (10)
NaOMe (10)
NaOMe (5)
NaOEt (5)
KOtBu (5)
NaOEt (5)
NaOEt (5)
NaOEt (5)
NaOEt (5)
NaOEt (5)
NaOEt (5)
NaOEt (5)
toluene
toluene
toluene
toluene
toluene
toluene
MeOH
EtOH
iPrOH
THF
dioxane
neat
DCM
40
99
65
94
98
8
8
31
26
16
14
5
9
Scheme 1. The preparation of tetradentate bipyridine ligands and their cor-
responding ruthenium complexes. Reaction conditions: (1) nBuLi, ZnCl2·2THF,
THF, À788C, 2 h. (2) [Pd(PPh3)4], 6-bromopyridine-2-carbaldehyde, THF, rt–
508C, 36 h. (3) 37% HCl (aq), THF, 608C, 4 h. (4) 2-(diphenylphosphino)ethan-
amine, NaBH4, MeOH, rt, 8 h. (5) NaBH4, MeOH, rt, 8 h, 2-(diphenylphosphi-
no)benzenemethanamine.
10
12
11
13
0
[a] Reaction conditions: methyl benzoate (5 mmol), solvent (3 mL), H2
(50 atm), 1008C, 16 h. [b] Yield was determined by GC using n-tridecane
as internal standard.
3 months) deep red–violet solids in excellent yields. The
31P NMR spectra of complexes A and B exhibited singlets at
d=47.77 and 49.68 ppm, respectively, demonstrating that the
phosphorus atoms of the ligands were coordinated to the
ruthenium atom. The geometry structure of complex B was es-
tablished by X-ray diffraction analysis, which revealed that the
catalyst was a hexacoordinate complex (Figure 2).
further optimization. On decreasing the catalyst loading to
0.01 mol%, the reaction proceeded smoothly and generated
benzyl alcohol with 6500 TON (Table 1, entry 3). Subsequently,
the screening of bases and solvents revealed that NaOEt and
toluene were the best choice and afforded desired product
with up to 9800 TON (Table 1, entries 4–13)
In order to evaluate the efficiency of complexes A and B in
the reduction of esters, we chose methyl benzoate as a model
substrate to optimize the reaction conditions. As shown in
Table 1, when the reaction was carried out in toluene at 1008C
under 50 atm of H2, complex B exhibited excellent activity in
the presence of NaOMe (10 mol%), and methyl benzoate was
reduced to alcohol with full conversion, whereas complex A
just gave moderate yield under the same conditions (Table 1,
entries 1–2). Thus, complex B was chosen as the catalyst for
Also, the effects of temperature and pressure of hydrogen
were investigated. The pressure of H2 is critical to the reaction
(Table 2, entries 1–4). Generally, a lower pressure gives inferior
results for the reaction. The best turnover number was ob-
tained, when the reaction was carried out at 50 atm of H2. Fur-
ther increasing the hydrogen pressure to 70 atm had no posi-
tive effects on the yield. The temperature also has a great in-
fluence on the reaction. Generally, increasing the temperature
was beneficial for the turnover numbers, but when the tem-
perature was higher than 808C, there was no further improve-
ment of the yield (Table 2, entry 3 and entries 5-7)
Table 2. Optimization of the reaction temperature and pressure of H2.[a]
Entry
P [atm][b]
T [8C][c]
Yield [%][d]
1
2
3
4
5
6
7
10
30
50
70
50
50
50
100
100
100
100
40
8
31
98
98
14
90
99
Figure 2. X-ray structure of complex B. Thermal ellipsoids set at 30% proba-
bility. H atoms and disorders were omitted for clarity. Selected bond lengths
[ꢁ] and angles [8]: Ru1–N1 2.077(3), Ru1–N2 2.007(3), Ru1–N3 2.101(3), Ru1–
P1 2.2895(9), Ru1–Cl1 2.4167(9), Ru1–Cl2 2.4172(8), N2–Ru1–N1 78.59(12),
N2–Ru1–N3 80.60(12), N1–Ru1–N3 158.81(12), N2–Ru1–P1 174.07(8), N1–
Ru1–P1 107.34(9), N3–Ru1–P1 93.51(8), N2–Ru1–Cl1 85.29(8), N1–Ru1–Cl1
93.15(8), N3–Ru1–Cl1 89.05(8), P1–Ru1–Cl1 94.04(3), N2–Ru1–Cl2 86.42(8),
N1–Ru1–Cl2 90.38(7), N3–Ru1–Cl2 84.38(8), P1–Ru1–Cl2 93.67(3), Cl1–Ru1–
Cl2 170.17(3).
60
80
[a] Reaction conditions: methyl benzoate (5 mmol), NaOEt (0.25 mmol),
toluene (3 mL), 16 h. [b] Pressure of H2. [c] Temperature of the reaction.
[d] Yield was determined by GC using n-tridecane as internal standard.
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Consequently, the substrate scope of the hydrogenation of
carboxylic esters was examined under optimal conditions
(808C, 50 atm H2, toluene). As shown in Table 3, all esters ex-
amined here can be reduced to the corresponding alcohols, al-
though there were great differences in turnover numbers. Gen-
erally, unfunctionalized esters, such as simple aromatic esters
and aliphatic esters, can be reduced with higher turnover num-
bers than functionalized esters. For aromatic esters, the steric
and electronic effects have great influences on the results. Aro-
matic esters with high steric hindrance, such as isopropyl ben-
zoate, gave the corresponding alcohols with a substantial re-
duction in TONs compared with methyl and benzyl benzoate
(Table 3, entries 1–3). Substituent groups on the benzene ring,
regardless of their electron-donating or -withdrawing nature,
are inferior to the reaction, and the TON dropped dramatically.
(Table 3, entries 4–5). Aliphatic esters performed well for this
reaction and long chain aliphatic esters were converted to al-
cohols with relative low turnover numbers (Table 3, Entries 6–
8). Cyclic aliphatic ester was also converted to 1, 6-Hexanediol
smoothly with more than 1000 TONs (Table 3, Entry 9). Func-
tionalized esters, such as dimethyl succinate typically challeng-
ing substrate for ester reduction were also tolerated for this re-
action and generated corresponding alcohols with moderate
TONs (Table 3, Entry 10). Unsaturated carboxylic esters were
also evaluated, but they didn’t exhibited chemoselectivity in
the reaction, both alkene group and ester group were convert-
ed with moderate to high TONs (Table 3, Entries 11–12).
In conclusion, we have synthesized new bipyridinemethana-
mine-containing tetradentate ligands and their corresponding
ruthenium complexes, which exhibited good catalytic activities
in the reduction of esters (up to 9700 TON). The reaction dis-
played a wide substrate scope, giving alcohols in good to ex-
cellent yields. Development of new strategies and novel cata-
lysts for the ester hydrogenation is ongoing in our group.
Experimental Section
Table 3. Catalytic hydrogenation of esters in the presence of Complex
B.[a]
General procedure for the reduction of esters
In an argon glovebox, a 5 mL glass vial equipped with a magnetic
stirring bar was added the required amount of complex B (0.01–
0.5 mol%, or toluene solution of complex B, 1 mgmLÀ1) and NaOEt
(5 mol%) successively. In the mixture was added substrate
(5 mmol) and toluene (3 mL in all), then the glass vial was placed
in a 150 mL stainless-steel reactor (5 glass vials were used each
time). The autoclave was carefully pressurized/depressurized with
hydrogen (20 atm) gas three times before the reaction pressure of
50 atm was adjusted. The hydrogenation was performed at 808C
for 16 h. The autoclave was depressurized carefully and the crude
mixture was filtered through a plug of silica, and then was purified
by column chromatography to obtain the desired product.
Entry
1
Substrate
Product
S/C
Yield [%][b]
99 (97)
10000
2
3
10000
2500
97 (95)
98 (93)
4
2500
91 (89)
Acknowledgements
5
6
2000
5000
82 (80)
71 (70)
We are grateful for the financial support by a grant from
Wuhan University (203273463), the Youth Chen-Guang Science
and Technology Project of Wuhan City (2015071704011640),
Natural Science Foundation of Hubei Province (2014CFB181),
“111” Project of the Ministry of Education of China, and the Na-
tional Natural Science Foundation of China (Grant No.
21372179, 21432007, 21402145).
7c
8
5000
2500
95
99 (95)
9
2500
200
48
Keywords: alcohols · esters · pyridine ligands · ruthenium ·
synthetic methods
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11
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Revised: May 9, 2016
Final Article published: && &&, 0000
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Communication
COMMUNICATION
Hydrogenation
Fangyuan Wang, Xuefeng Tan, Hui Lv,*
Xumu Zhang*
&& – &&
New Ruthenium Complexes Based on
Tetradentate Bipyridine Ligands for
Catalytic Hydrogenation of Esters
A straightforward way to alcohols!
New bipyridinemethanamine-containing
tetradentate ligands and their corre-
sponding ruthenium complexes have
been synthesized. The synthesized com-
plexes performed well in the hydroge-
nation of a variety of esters with high
efficiency (TON up to 9700) giving alco-
hols in good yields (see scheme).
Chem. Asian J. 2016, 00, 0 – 0
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These are not the final page numbers! ÞÞ