Efficient enantioselective hydrogenation of quinolines catalyzed by conjugated microporous polymers with embedded chiral BINAP ligand

Article abstract of DOI:10.1016/S1872-2067(15)60903-2

Chiral Ir complexes were successfully used in the asymmetric hydrogenation of olefins, ketones, and quinolines. However, almost all the catalytic systems could not tolerate a high catalyst loading because of the formation of an irreversible iridium dimer and trimer during the reaction. It is expected that higher catalytic activity may be achieved if the Ir-complexes were isolated in space. The development of conjugated microporous polymers (CMPs) gives the opportunity for the spatial separation of the complexes. A series of chiral CMPs based on the chiral (R)-BINAP ligand (BINAP-CMPs) with different surface areas were synthesized. The BINAP ligands were separately distributed in the framework and were three times more active than the homogeneous catalyst (TOF 340 h^-1 VS 100 h^-1) for the asymmetric hydrogenation of quinolines.

Full text of DOI:10.1016/S1872-2067(15)60903-2

Chinese Journal of Catalysis 36 (2015) 1170–1174
a v a i l a b l e a t w w w. s c i e n c e d i r e c t . c o m
j o u r n a l h o m e p a g e : w w w. e l s e v i e r. c o m / l o c a t e / c h n j c
Communication
Efficient enantioselective hydrogenation of quinolines catalyzed by
conjugated microporous polymers with embedded chiral BINAP
ligand
Xu Wang a,b, Jun Li a, Shengmei Lu a, Yan Liu a,*, Can Li a,#
a State Key Laboratory of Catalysis, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, Liaoning China
b University of Chinese Academy of Sciences, Beijing 100049, China
A R T I C L E I N F O
A B S T R A C T
Article history:
Chiral Ir complexes were successfully used in the asymmetric hydrogenation of olefins, ketones, and
quinolines. However, almost all the catalytic systems could not tolerate a high catalyst loading be-
cause of the formation of an irreversible iridium dimer and trimer during the reaction. It is expected
that higher catalytic activity may be achieved if the Ir-complexes were isolated in space. The devel-
opment of conjugated microporous polymers (CMPs) gives the opportunity for the spatial separa-
tion of the complexes. A series of chiral CMPs based on the chiral (R)-BINAP ligand (BINAP-CMPs)
with different surface areas were synthesized. The BINAP ligands were separately distributed in the
framework and were three times more active than the homogeneous catalyst (TOF 340 h–1 VS 100
h–1) for the asymmetric hydrogenation of quinolines.
Received 4 May 2015
Accepted 21 May 2015
Published 20 August 2015
Keywords:
Enantioselective hydrogenation
Quinoline
Polymer
BINAP
© 2015, Dalian Institute of Chemical Physics, Chinese Academy of Sciences.
Published by Elsevier B.V. All rights reserved.
Isolation effect
The asymmetric hydrogenation of quinolines is one of the
most convenient route to synthesize enantiomerically pure
tetrahydroquinoline derivatives which are important organic
synthetic intermediates and structural units of alkaloids and
biologically active compounds [1]. The first successful homo-
geneous asymmetric hydrogenation of quinolines was de-
scribed by Zhou and co-workers using a Ir catalytic system [2].
Quinolines with different substituents were investigated in
their following works [3–7]. Chan’s group subsequently de-
scribed that the air-stable and recyclable Ir-P-Phos and Ir- di-
phosphinite are efficient catalysts for the asymmetric hydro-
genation of quinolines [8–10]. Reetz and co-workers also found
that BINOL-derived diphosphonites with achiral P-ligands as
additive catalyzed the same reaction [11]. Despite these im-
portant advances, a problem in the reported reaction systems
was that good results were only obtained at a low sub-
strate-catalyst ratio. The problem with a high catalyst loading
was attributed to the formation of an irreversible iridium di-
mer and trimer during the reaction which would be pathways
for catalyst deactivation [12]. Therefore, developing a highly
efficient catalytic system for the asymmetric hydrogenation of
quinolines is still needed.
Several attempts to avoid iridium dimer formation were
tried (Scheme 1). One method is the introduction of bulky sub-
stituents onto the chiral ligands to inhibit the formation of inac-
tive dimmers and trimers, thus promoting the catalytic activity
(Scheme 1.1). Fan’s group synthesized a series of dendritic
dendrimer GnDenBINAP ligands by the condensation of the
dendritic wedges Gn-COOH with (S)-5,5’-diamino BINAP (S)-1
[13]. The GnDenBINAP ligands gave much higher catalytic ac-
* Corresponding author. Tel: +86-411-84379302; Fax: +86-411-84694447; E-mail: yanliu503@dicp.ac.cn
# Corresponding author. Tel: +86-411-84379097; Fax: +86-411-84694447; E-mail: canli@dicp.ac.cn
This work was supported by the National Natural Science Foundation of China (21322202).
DOI: 10.1016/S1872-2067(15)60903-2 | http://www.sciencedirect.com/science/journal/18722067 | Chin. J. Catal., Vol. 36, No. 8, August 2015

Xu Wang et al. / Chinese Journal of Catalysis 36 (2015) 1170–1174
1171
groups onto the coordination phosphorus atoms effectively
blocked the formation of inactive dimer and trimer species and
improved the activity of the Ir catalysts [14] (Scheme 1.1(b)).
Recently, we reported the synthesis of a series of CMPs by
embedding the chiral BINAP ligand into CMP networks. These
solid materials are efficient catalysts for the asymmetric hy-
drogenation of β-keto esters [15]. Because all the BINAPs are
embedded on the pore structure of the networks separately, we
envisioned that these heterogeneous catalysts [16–18] with an
inherent isolation effect can perform the asymmetric hydro-
genation of quinoline with high activity through preventing the
formation of dimers and trimers. (Scheme 1.2) Here, we re-
ported the results.
A typical strategy for synthesizing BINAP-CMP-3D-2 was as
follows: 1,3,5,7-Tetrakis(4-ethynylphenyl) adamantine, (R)-
4,4-DibromoBINAPO, tetrakis-(triphenylphosphine) palladium,
and copper iodide were dissolved in a mixture of dioxane and
Et3N. The reaction mixture was heated to 80 °C and stirred for
72 h under a nitrogen atmosphere. The precipitate was filtered
and washed with solvent. After reducing with HSiCl3,
BINAP-CMP-3D-2 was obtained.
We began by examining the hydrogenation of 2-
methylquinoline 1a with an iridium catalyst in the presence of
different BINAP-CMPs. We were pleased to find that the hy-
drogenation catalyzed by the BINAP-CMPs proceeded smoothly
and afforded the product with moderate enantioselectivity
(Table 1, entries 1–4). In sharp contrast, the homogeneous hy-
drogenation catalyzed by BINAP gave trace product under
same reaction conditions (Table 1, entry 5). Moreover, the cat-
alytic activity gradually increased with increasing surface area
and pore volume of the BINAP-CMPs. CMPs with larger surface
area and pore volume benefit the diffusion of substrate and
product, which makes it easier to access the active center and
improve the activity.
Scheme 1. Strategies for inhibiting the dimerization of the Ir-complex
in the hydrogenation of quinolone.
tivity than BINAP through the steric shielding effect of the
bulky dendritic wedges to reduce dimerization (Scheme
1.1(a)). Zhou and coworkers reported that introducing bulky
Scheme 2. Structure of BINAP-CMPs.

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Xu Wang et al. / Chinese Journal of Catalysis 36 (2015) 1170–1174
Table 1
Comparison of catalytic activity of the synthesized BINAP-CMPs.
Entry
BINAP-CMPs
BINAP-CMP-S
BINAP-CMP-M
BINAP-CMP-3D-1
BINAP-CMP-3D-2
BINAP
ABET a (m2/g)
Vtotal b (cm3/g)
Conversion c (%)
TOF d (h–1)
180
ee e (%)
48
50
54
54
1
2
3
4
5
170
318
279
398
—
0.37
0.46
0.76
0.77
—
9
10
12
17
5
200
240
340
100
70
Reaction conditions: quinaldine 0.25 mmol, CH2Cl2 3 mL, [Ir(COD)Cl]2 0.000125 mmol, I2 0.05 mmol, 1.5 MPa H2, 25 °C, 0.5 h. a Surface area calculated
from the N2 adsorption isotherm using the BET method. b Total pore volume at p/p0 = 0.99. c Determined by H NMR analysis of the crude product.
1
d Average TOF over the reaction time. e Determined by HPLC analysis with a Chiralpak OJ-H column.
Table 2
Table 3
Asymmetric hydrogenation of quinaldine (1a) catalyzed by the
Minimum amount of Ir/BINAP-CMP-3D-2 catalyst that can be used.
BINAP-CMP-3D-2 catalyst.
Entry Time (h) Substrate/Catalyst Conversion a (%) ee b (%)
Entry
1
2
3
4
5
6
7
8
9c,d
10c,e
11c
12c,f
13c,g
14c,h
Solvent
THF
CH2Cl2
MeOH
toluene
Conversion a (%)
ee b (%)
34
60
29
40
38
39
56
51
69
70
70
70
73
69
1
2
3
4d
5e
2
2
2
6
24
100:1
500:1
1000:1
2000:1
5000:1
99
99
99
99
93
70
64
60
53
42
99
99
88
99
99
99
99
99
99
99
99
93
95
99
benzene
dioxane
CH2Cl2/THF 1:2
CH2Cl2/toluene 1:2
CH2Cl2
Reaction conditions: quinaldine (1a) 0.25–5 mmol, CH2Cl2 3 mL, I2 0.05
mmol, 4 MPa H2, 25 °C. a,b See Table 1.
of the quinoline. It was interesting that with increasing length
of the side chain of R2, the enantioselectivity obtained with
BINAP-CMP-3D-2 increased from being slightly less than to be
obviously higher than the enantioselectivity of the homogene-
ous Ir/BINAP catalyst (Table 4, entries 1–5). The conversion
decreased with the increasing of steric hindrance (Table 4,
entries 4–6), which may be due to that bulky substituted quino-
lines suffer more diffusion resistance when diffusing through
the pore structure of the polymer. With 6-substituted quino-
lines as the substrate (Table 4, entries 7–9), low enantioselec-
tivity with complete conversion were observed.
The recyclability of the BINAP-CMP-3D-2 catalyst was also
investigated (Table 5). Upon completion of the reaction, the
Ir/BINAP-CMP-3D-2 catalyst was easily recovered by centrif-
ugation and a regular filter. The colorless filtrate from the
asymmetric hydrogenation of quinaldine (1a) did not afford
any additional product, showing the heterogeneous nature of
the reaction system. After washing with CH2Cl2 and heating
under vacuum, the solid catalyst was reused for the next cycle.
We did not see any significant deterioration in the activity for
the recovered catalyst even after five cycles.
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
Reaction conditions: quinaldine 0.25 mmol, CH2Cl2 3 mL, [Ir(COD)Cl]2
a,b
0.000125 mmol, I2 0.05 mmol, 4 MPa H2, 25 °C, 18 h. See Table 1.
c [Ir(COD)Cl]2 0.00125 mmol, 2 h. d 6.5 MPa H2. e 5 MPa H2. f 1.5 MPa H2.
g 0 °C. h 50 °C.
To obtain higher enantioselectivity, the effects of the sol-
vent, temperature and pressure were investigated by using
BINAP-CMP-3D-2 as the catalyst (Table 2). A series of organic
solvents were investigated. CH2Cl2 was the best in terms of
both conversion and enantioselectivity (Table 2, entries 1–8).
The enantioselectivity of the reaction was slightly increased at
low temperature with incomplete conversion (Table 2, entry
13). Also, the reaction did not reach completion under a low
pressure(Table 2 entry 12).
Using the optimized reaction conditions, the limit of catalyst
activity was also investigated. The BINAP-CMP-3D-2 catalyst
was found to be highly effective even at a high sub-
strate/catalyst ratio although the enantioselectivity decreased
with a low catalyst loading (Table 3).
In summary, we synthesized a series of BINAP-CMPs with
different surface areas, which gave high activity and modest
enantioselectivity in the Ir-catalyzed asymmetric hydrogena-
tion of quinolines. The catalytic activity was related to the
structural properties of the BINAP-CMPs. The CMP with a
higher surface area and pore volume gave better asymmetric
hydrogenation results. Through preventing the formation of
Using the optimal conditions, we demonstrated the scope of
quinoline for this heterogeneous hydrogenation (Table 4). All
substituted quinolines used here were hydrogenated with good
conversion and modest enantioselectivity. The reaction was
relatively insensitive to the length of the 2-alkylated side chain

Xu Wang et al. / Chinese Journal of Catalysis 36 (2015) 1170–1174
1173
Table 4
Catalytic asymmetric hydrogenation of quinoline derivatives.
Conversion a (%)
Ir/BINAP-CMP-3D-2
ee b (%)
Ir/BINAP-CMP-3D-2
Entry
R1/R2 (substrates)
Configurationc
Ir/BINAP
Ir/BINAP
72
1
2
3
4
5
6
7
8
9
H/Me (1a)
H/Et (1b)
H/n-Pr (1c)
H/n-Bu (1d)
H/i-Pr (1e)
H/Ph (1f)
F/Me (1g)
Me/Me (1h)
MeO/Me (1i)
99
99
99
80
83
84
99
99
97
24
23
16
18
13
34
23
16
9
70
77
78
77
79
44
63
67
70
R
R
R
R
R
R
S
78
74
75
75
50
77
76
78
R
R
Reaction conditions: quinoline 0.25 mmol, CH2Cl2 3 mL, [Ir(COD)Cl]2 0.00125 mmol, I2 0.05 mmol, 4 MPa H2, 25 °C, 2 h. a,b See Table 1. d The absolute
configuration is assigned by comparison of the HPLC retention time with those reported in the literature data.
2003, 125: 10536
Table 5
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Recycling experiment of the BINAP-CMP-3D-2 catalyst.
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Cycle
Conversiona (%)
eeb (%)
0
99
72
1
99
72
2
99
71
3
99
70
4
99
70
5
99
70
6
90
69
Reaction conditions: quinaldine 0.5 mmol, CH2Cl2 3 mL, [Ir(COD)Cl]2
0.00125 mmol, I2 0.05 mmol, 4 MPa H2, 25 °C, 2 h. a,b See Table 1.
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dimmers by the spatial isolation effect of the CMP, the
BINAP-CMPs gave much higher activity than the homogeneous
BINAP ligand.
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Graphical Abstract
Chin. J. Catal., 2015, 36: 1170–1174 doi: 10.1016/S1872-2067(15)60903-2
Efficient enantioselective hydrogenation of quinolines catalyzed by
conjugated microporous polymers with embedded chiral BINAP ligand
Xu Wang, Jun Li, Shengmei Lu, Yan Liu *, Can Li*
Dalian Institute of Chemical Physics, Chinese Academy of Sciences;
University of Chinese Academy of Sciences
A series of chiral BINAP-CMPs with different surface areas were synthesized
which were three times more active than the homogeneous BINAP catalyst
(TOF 340 h–1 VS 100 h–1) for the asymmetric hydrogenation of quinolines.

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