Highly active ruthenium(II) complex catalysts bearing an unsymmetrical NNN ligand in the (asymmetric) transfer hydrogenation of ketones

Article abstract of DOI:10.1002/chem.201002039

Exceptionally active ruthenium(II) complexes without an ancillary N-H functionality, but bearing a (chiral) unsymmetrical pyridyl-benzimidazolyl-based NNN ligand, exhibited very high catalytic activity in the (asymmetric) transfer hydrogenation ((A)TH) of ketones. The corresponding Ru-H complex, which is presumably the catalytically active species, was successfully isolated and structurally characterized by X-ray crystallography. Copyright

Full text of DOI:10.1002/chem.201002039

COMMUNICATION
DOI: 10.1002/chem.201002039
Highly Active Ruthenium(II) Complex Catalysts Bearing an Unsymmetrical
NNN Ligand in the (Asymmetric) Transfer Hydrogenation of Ketones
Wenjing Ye,[a] Miao Zhao,[a] Wangming Du,[a] Quanbin Jiang,[a] Kaikai Wu,[a]
Ping Wu,[a] and Zhengkun Yu*[a, b]
N-Heterocylic ligands have recently become more and
more attractive in homogeneous catalysis and organic syn-
thesis because their organometallic complexes usually exhib-
it higher reactivity and better stability than those with phos-
phine ligands.[1] Tridentate NNN ligands such as Pybox,[2]
2,6-bisACHTUNGTRENNUNG
(imino)pyridines,[3] terpyridines,[4] and other symmet-
rical NNN ligands[5] have demonstrated their potential appli-
cations. However, examples of unsymmetrical tridentate
NNN ligands and their transition-metal complexes are
scarce.[6,7] Transition-metal complexes bearing an unsymmet-
rical polydentate ligand are usually bestowed with good cat-
alytic activity.[7–10] Thus, unsymmetrical pyridyl-based NNN
ligands are strongly desired for the construction of highly
active transition-metal complex catalysts. Functional metal
complexes[11] were obtained with symmetrical bis(benzimi-
dazol-2-yl)pyridines and bis(N-alkylbenzimidazol-2-yl)pyri-
dines, and the electronic properties of the respective ruthe-
nium complexes have been described.[12] However, only a
few of them have been applied as catalysts.[13] We recently
synthesized very efficient RuII pyridyl–pyrazolyl-based NNN
complex catalysts for transfer hydrogenation of ketones.[7]
RuII-catalyzed transfer hydrogenation reactions with 2-prop-
anol as the hydrogen source have been extensively studied
by Noyori et al.[14,15] Baratta’s group recently reported highly
active RuII 2-(aminomethyl)pyridinylphosphane complex
catalysts for the transfer hydrogenation of ketones.[10] A few
Scheme 1. The strategy for constructing highly active transition-metal
complex catalysts bearing a unsymmetrical NNN ligand.
yl)pyridine (3)[11b] were obtained by reacting 1 with 1-bro-
mopropane in the presence of NaH (Scheme 2). Reactions
of ligands 1–3 with one equivalent of [RuACHTUNTGRNEUNG(PPh)3Cl2] in re-
fluxing methanol afforded RuII complexes 4–6 in 76–91%
yields. Treatment of 5 with K2CO3 base in CH2Cl2 formed
RuII complex catalysts featuring no N H functionality have
À
also been documented for the same purpose.[16] Herein, we
report the construction of unsymmetrical (chiral) pyridyl–
benzimidazolyl-based NNN ligands and their RuII complex
catalysts for the (asymmetric) transfer hydrogenation of ke-
tones by following the strategy shown in Scheme 1.
The mono-N-alkyl derivative of bis(benzimidazol-2-yl)-
pyridine (1),[17] that is, 2, and bis(N-propylbenzimidazol-2-
[a] W. J. Ye,+ M. Zhao,+ W. M. Du, Q. B. Jiang, K. K. Wu, P. Wu,
Prof. Dr. Z. K. Yu
Dalian Institute of Chemical Physics
Chinese Academy of Sciences
457 Zhongshan Road, Dalian, Liaoning 116023 (China)
Fax : (+86) 411-8437-9227
E-mail: zkyu@dicp.ac.cn
Scheme 2. Synthesis of NNN ligands and their RuII complexes 4–8. i)
NaH, 1.0 equiv nPrBr, DMF, 808C, 3 h, 38%; ii) NaH, 2.0 equiv nPrBr,
[b] Prof. Dr. Z. K. Yu
State Key Laboratory of Organometallic Chemistry
Shanghai Institute of Organic Chemistry
CAS, 354 Fenglin Road, Shanghai 200032 (China)
DMF, 808C, 3 h, 47%; iii) [Ru
ACHTUNGTRENNUNG
[Ru(PPh3)3Cl2], MeOH, 658C, 3 h, 76%; v) [RuCAHTUNGTRENNNUG
G
658C, 3 h, 91%; vi) K2CO3, CH2Cl2, reflux, 48 h, 92%; vii) iPrOK/iPrOH,
toluene, 608C, 24 h, 50%.
[+] These authors equally contributed to this paper.
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neutral RuII complex 7. Heating a mixture of 5 or 7 with
iPrOK/iPrOH in toluene generated RuII hydride 8 (50%).
Starting from compound 9, chiral pyridyl-based benzimida-
zolyl–oxazolyl NNN ligands 12 were prepared in 64–74%
yields (Scheme 3). Treatment of 12 with one equivalent of
Figure 2. The molecular structure of complex 8.
Scheme 3. Synthesis of chiral NNN ligands 12. i) MeOH, H2SO4, reflux,
12 h. ii) 1,2-amino alcohol, 708C, 2 h for 11a; 908C, 4 h for 11b. iii)
a) SOCl2, ClCH2CH2Cl, 708C, 4 h; b) NaOH, EtOH, reflux, 12 h. iv)
BF3·Et2O, 1208C, 6 h.
1
Its H and 31P{1H} NMR spectra in CDCl3 revealed a triplet
À
at d=À5.79 ppm for Ru H and a doublet at d=49.6 ppm
(PPh3)3Cl2] in toluene at 908C produced the chiral RuII
for its trans-PPh3 ligands. The Ru H bond length is 1.53 ꢁ,
À
[Ru
[20]
À
À
complexes 13 in 86–89% yields [Eq. (1)], respectively.The
molecular structures of complexes 5 and 8 were confirmed
by X-ray crystallographic studies (Figure 1 and 2).
Complexes 4–7 were treated with a solution containing
EtONa/EtOH, iPrOK/iPrOH, or iPrOK/iPrOH in toluene
under heating. Only in the cases of 5 and 7, was the RuII hy-
dride 8 successfully isolated and structurally characterized.
indicative of an isolated Ru H bond (Figure 2). The Ru
P bond lengths are 2.3419 and 2.3190 ꢁ, and Ru N1, Ru
N3, and Ru N4 bond lengths are 2.079, 2.046, and 2.085 ꢁ,
À
À
À
respectively, demonstrating a RuII core surrounded by two
nonequivalent PPh3 ligands and three nonequivalent nitro-
gen donor atoms in a distorted bipyrimidal environment.
Then, complexes 4–7 were tested as the catalysts for the
transfer hydrogenation of acetophenone and 4’-chloroaceto-
phenone in the presence of iPrOK in refluxing 2-propanol
under a nitrogen atmosphere [Eq. (2)]. With 0.1 mol% load-
ing, their catalytic activities were exhibited as 5=7 ꢀ 4 >
6. Complex 4 showed a catalytic activity comparable to
those of 5 and 7 in the transfer hydrogenation reactions of
relatively active ketones (see the Supporting Information),
presumably due to the interconversion of the symmetrical
ligand 1 in complex 4 to unsymmetrical ligand 1ꢀ in the neu-
tral complex 4ꢀ through a g-H effect [Eq. (3)]. Under the re-
action conditions given, complex 5 can be instantly convert-
ed to 7; TLC monitoring indicated that both 5 and 7 exhibit-
ed the same catalytic activity. Introduction of an n-propyl
group to one of the 2,6-benzimidazolyl moieties broke the
symmetry of the ligands in 5 and 7, enhancing the electron-
donating ability of the ligand.
Figure 1. The molecular structure of complex 5. The chloride anion was
omitted for clarity.
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Chem. Eur. J. 2011, 17, 4737 – 4741

Ru-Catalyzed Transfer Hydrogenation of Ketones
COMMUNICATION
In a similar fashion, transfer hydrogenation reactions of a
variety of ketones were explored by using 0.1 mol% 5 as
the catalyst (Table 1). Alcohols were produced as the only
products, and the reactions reached up to 100% conversion
for the ketone substrates and final TOFs up to 180000 hÀ1
(Table 1, entry 8). In most cases, the reactions ended within
20 s, forming the corresponding alcohol products in ꢀ96%
yields. As compared with RuII complexes bearing symmetri-
cal unconvertible ligands such as 2,6-bis(3,5-dimethylpyra-
zol-1-yl)pyridine[8c] and 3, the remarkable enhancement of
the catalytic activities of complexes 5 and 7 for the transfer
hydrogenation of ketones is presumably attributed to the es-
tablishment of an unsymmetrical environment around the
RuII metal center by means of two different coordinating
donor arms at 2,6-positions of the pyridyl backbone.
Table 1. Transfer hydrogenation of ketones catalyzed by complex 5.[a]
Entry
Ketone
Time
Yield[b]
[%]
final TOF
[hÀ1
N
]
1
2
20 s
98
176400
20 s
10 min
80
98
144000
5880
Next, the asymmetric transfer hydrogenation of acetophe-
none was investigated (Table 2). At ambient temperature
(ca. 288C), acetophenone was converted to form the alcohol
in 96% yield and 56% ee by using 0.1 mol% 13a as the cat-
3
4
20 s
99
178200
30 min
60 min
95
97
1900
970
Table 2. Asymmetric transfer hydrogenation of acetophenone catalyzed
by complexes 13.[a]
5
6
20 s
>99
178200
Entry
Cat.
Temp.
[oC]
Time
[min]
Yield[b]
[%]
ee[b]
[%]
Final TOF
G
A
]
20 s
87
95
156600
11400
1
2
3
4
5
6
7
13a
13b
13b
rt
rt
rt
40
40
60
82
3
4
96
96
95
96
96
95
96
56 (S)
79 (R)
79 (R)
79 (R)
79 (R)
79 (R)
72 (R)
19200
14400
9500
57600
11520
5 min
6[c]
1
13b
7
8
9
20 s
20 s
20 s
99
100
96
178200
180000
172800
13b[d]
13b[d]
13b[e]
10
1
1
114000
288000
[a] Conditions: ketone, 2.0 mmol (0.1m in 20 mL iPrOH); catalyst 13, 0.1
mol%, ketone/iPrOK/13=1000:10:1; 0.1 MPa, about 288C. [b] Deter-
mined by GC analysis (column: HP-Chiral B233). The absolute configu-
ration of the alcohol product was obtained by comparing its optical rota-
tion with the literature data. [c] iPrOK/cat.=5:1. [d] 0.05 mol% cat.
[e] 0.02 mol% cat.
10
20 s
98
176400
alyst (Table 2, entry 1), whereas 13b gave a much better
enantioselectivity (79% ee) of the target product (Table 2,
entry 2). These results suggest that the steric effect of the
substituent on the chiral oxazolyl moiety clearly affected the
enantioselectivity of the product. Complex 13b was thus em-
ployed as the catalyst to screen the asymmetric transfer hy-
drogenation conditions. Using 0.05–0.1 mol% catalyst at 40–
608C, the asymmetric transfer hydrogenation reaction also
took place efficiently without loss of the enantioselectivity
of the product (Table 2, entries 4–6), whereas the reaction
proceeded rapidly in refluxing 2-propanol to produce the
product with a lower enantioselectivity (72% ee; Table 2,
entry 7).
11
12
13
20 s
97
174600
57600
58200
1 min
1 min
96
97[c]
14
15
20 s
20 s
98
176400
178200
>99
Under the optimized conditions, asymmetric transfer hy-
drogenation reactions of various aromatic ketones were ex-
plored with 0.1 mol% 13b as the catalyst at ambient tem-
[a] Conditions: ketone, 2.0 mmol (0.1m in 20 mL iPrOH); catalyst 5,
0.1 mol%, ketone/iPrOK/5=1000:20:1; 0.1 MPa, 828C. [b] By GC analy-
sis. [c] By H NMR analysis.
1
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4739

Z. K. Yu et al.
Table 3. Asymmetric transfer hydrogenation of ketones catalyzed by
metric transfer hydrogenation reactions proceeded rapidly
to afford less enantioselective alcohols (86–89% ee, Table 3,
entries 11 and 12). All the major alcohol products had an R
configuration, the highest final TOF value was 14850 hÀ1
(Table 3, entry 7). Notably, RuII complexes bearing a Ph-
Pybox[18] or a chiral bis(2-imidazolyl)pyridine ligand[19] ex-
hibited much lower catalytic efficiency than 13b in the
asymmetric transfer hydrogenation of aromatic ketones.
The 1:1 molar ratio reaction of 8 with benzophenone in
CDCl3 was monitored by NMR measurements, which re-
vealed a slow reaction at room temperature; after heating
complex 13b.[a]
Entry
Ketone
Time
[min]
Yield[b]
[%]
ee[b]
[%]
Final TOF
[hÀ1
G
N
]
1
2
4
96
95
79
90
97
14400
633
45[c]
45
for 5 h the Ru H triplet of 8 disappeared. The 1H NMR
À
3
>99
1320
spectrum showed a singlet at d=5.84 ppm for Ph2CHOH
(24%), the 13C NMR spectrum showed a signal at d=
77.37 ppm for CHCl3, and the 31P NMR spectrum showed a
signal at d=22.39 ppm for the PPh3 ligands of complex 7
4
5
6
7
30
30
20[c]
4
>99
94
97
89
94
95
1980
1960
À
À
(49% isolated yield) [Eq. (4)], demonstrating H D/H Cl
exchanges between 8 and CDCl3. Within 2.5 h the same re-
action in refluxing iPrOH afforded Ph2CHOH in 89% iso-
lated yield. Addition of the PPh3 ligand ([PPh3]/5=1–5) to
the reaction system decreased the conversion of acetophe-
none to 56–20% under the same conditions (Table 1). Com-
plex 8 exhibited the same catalytic activity as 5 and 7 did in
the transfer hydrogenation reaction of acetophenone, sug-
gesting that 8 may be the catalytically active species.[10c,f,21]
In conclusion, we have developed a strategy to construct
highly active RuII NNN complex catalysts for the (asymmet-
ric) transfer hydrogenation of ketones. Novel RuII com-
plexes bearing a (chiral) unsymmetrical pyridyl–benzimida-
zolyl-based NNN ligand were synthesized and found to ex-
hibit high catalytic activity in transfer hydrogenation and
asymmetric transfer hydrogenation of ketones. These com-
plexes are thus rare examples of exceptionally active RuII
98
1470
99
14850
8
5
10
5[c]
99
93
95
96
92
92
11880
5580
5700
9
10
À
NNN complex catalysts that do not feature an ancillary N
H functionality.
11
12
5
5
98
98
86
89
11760
11760
Experimental Section
[a] Conditions: ketone, 2.0 mmol ( 0.1m in 20 mL iPrOH); 0.1 mol%
13b, ketone/iPrOK/13b=1000:10:1; 0.1 MPa, about 288C. [b] Deter-
mined by GC analysis (column: HP-Chiral B233). All the major alcohol
products had an R configuration by comparing their optical rotations
with the literature data. [c] 0.2 mol% catalyst.
A general procedure for the catalytic transfer hydrogenation of ketones:
Under a N2 atmosphere, the mixture of a ketone (2 mmol), iPrOH
(9.8 mL), and a catalyst solution (10 mL) containing the RuII complex
(2 mmmol) in iPrOH was stirred at the stated temperature for 5 min.
perature (Table 3). The target
alcohol products from the reac-
tions of acetophenone, propio-
phenone,
2’-chloroacetophe-
none, and 2’-bromoacetophe-
none were obtained in 90–
97% ee (Table 3, entries 2–4).
Other ortho- and meta-substi-
Then 0.2 mL of a 0.1m iPrOK solution in iPrOH was added to initiate
the reaction. Thereafter, 0.1 mL of the reaction mixture was sampled and
immediately diluted with 0.5–1.0 mL iPrOH precooled at 08C for GC
analysis. After the reaction was complete, the reaction mixture was con-
tuted aromatic ketones reached 93–99% conversion within
4–30 min, forming the products in 89–96% ee (Table 3, en-
tries 5–10). For para-substituted acetophenones, their asym-
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Ru-Catalyzed Transfer Hydrogenation of Ketones
COMMUNICATION
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1
Acknowledgements
We are grateful to the 973 Program (2009CB825300), the National Natu-
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Received: July 19, 2010
Published online: March 14, 2011
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4741