An efficient proline-based homogeneous organocatalyst with recyclability

Article abstract of DOI:10.1039/c7nj03912c

In this work, a homogeneous organocatalyst was developed for the asymmetric reduction of imines. This catalyst could be separated by cyclodextrin-modified Fe₃O₄@SiO₂ magnetic nanoparticles and then released back into a fre

Full text of DOI:10.1039/c7nj03912c

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PAPER
Jason B. Benedict et al.
The role of atropisomers on the photo-reactivity and fatigue of
diarylethene-based metal–organic frameworks
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DOI: 10.1039/C7NJ03912C
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COMMUNICATION
An efficient proline-based homogeneous organocatalyst with
recyclability
a
b
a
a
a
a
Qiang Li, Yuan Li, Jingdong Wang, Yingjie Lin, Zhonglin Wei, Haifeng Duan, Qingbiao Yang,
Received 00th January 20xx,
Accepted 00th January 20xx
*
a
Fuquan Bai, and Yaoxian Li a
*b
DOI: 10.1039/x0xx00000x
www.rsc.org/
In this work, a homogeneous organocatalyst was developed for the many groups and has emerged as a class for broad employment,
which gained excellent isolated yield. In 2008, S. Luo et al. firstly
constructed a magnetic nanoparticle (MNP)-supported chiral amine
catalyst. In recent years, increased attention has been paid on the
development and application of supported catalysts in industries to
asymmetric reduction of imines, which can be separated by
cyclodextrin-modified Fe3O4@SiO magnetic nanoparticles and
then released back into a fresh reaction for more than seven times.
Furthermore, a new catalytic mechanism is proposed and
investigated through theoretical calculations.
2
8, 9
broaden the practical range of chiral organocatalysts. Gradually,
other methods for the immobilization of organocatalysts have been
attempted and achieved satisfactory results, such as dendrimer-
Asymmetric catalytic reduction of imines is one of the most
important and efficient methods in the preparation of chiral amines
in industrial and academic circles; chiral amines are a ubiquitous
1
0
11
supported,
supported
metal nanoparticles-supported,
and cyclodextrin-supported
ionic liquid-
1
2
13
catalytic methods.
However, most immobilized catalysts are facing the same severe
problem, that is, most of them will have a negative effect on the high
activity of organocatalysts, leading to lower efficiency performance
compared with their homogeneous counterparts. Most of them are
jointed on bulk carriers and used as heterogeneous catalysts, which
hamper the spatial configuration of catalysts. Thus, immobilized
catalysts, such as MNP-supported catalyst, suffer from decreased
1
structure motif in enzymes, DNA and other natural products . Several
synthetic methodologies have been developed for the synthesis of
2
chiral amines . For instance, in 2004 Bruce H. Lipshutz et al. have
reported an asymmetric reduction of imines using Cu-based catalysts
3
with regard to both chemical yields and enantioselectivities. In 2013
Yuan qin Chang and co-workers reported a Fe-based catalyst material
4
with high activity and is similar to a commercial Pt/C catalyst.
14-16
activity and poor control in the process.
Moreover, organocatalysts have been recently considered
remarkable alternatives for asymmetric hydrogenation to gain chiral In this work, we reported an efficient catalyst based on L-proline
amines, considering their low toxicity, operational simplicity, and to promote the asymmetric reduction of imines, which can be
5
17
high efficiency. Among the reported strategies, L-proline and its recycled for seven times through self-assembly method based
derivatives have shown considerable catalytic efficiency in different
organic transformations. Nowadays, widespread interest has been
devoted on the development of new organocatalysts based on L-
proline, especially its derivatives that can be utilized as chiral
catalysts for reduction of imines to attain enantiomerically enriched
amines with moderate optical yields.7
18
on host–guest molecular recognition using cyclodextrin-
6
19
modified Fe
3
O
4
@SiO
2
magnetic nanoparticles (MNPs) . The
cycle is shown in Figure. 1. Particularly, a different catalytic
mechanism model is proposed. The trace of H O in the reaction
system is critical as a bridge of hydrogen bond between the
catalyst and substrate. Furthermore, to investigate the
mechanism, a theoretical calculation was conducted, which
2
2
0
Organocatalysts have some superiority to metal catalysts, but many
of them still suffered from some difficulties and disadvantages. For
instance, the proline and its derivatives are difficult to be reused and
recycled even though they are frequently consumed, thereby
restricting these catalysts from practical applications. Therefore the
immobilization of proline and its derivatives have been the focus of
2
confirmed that H O can be beneficial in reducing the total
energy of the catalytic system and can easily form л–л stacking.
a.College of Chemistry, Jilin University, E-mail: yangqb@jlu.edu.cn; Changchun
1
30021, P.R. China;
b.
Institute of Theoretical Chemistry, Laboratory of Theoretical and Computational
Chemistry, Jilin University, Changchun 130023, P. R. China;
†
Footnotes relating to the title and/or authors should appear here.
Electronic Supplementary Information (ESI) available: [details of any supplementary
information available should be included here]. See DOI: 10.1039/x0xx00000x
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 1
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Journal Name
However, the reduction of 1a, as catalyzed by cataVlyieswt Abrt,iclgeaOvnelinae
racemic product.
Table 1. Optimization studied on the reduction of 1a
DOI: 10.1039/C7NJ03912C
b
c
Temp[℃]
Yield [%]
ee [%]
Entrya
solvent
Time[h]
Figure.1. Recyclability of L-proline derivative.
1
2
3
4
5
6
7
8
9
DMSO
DMF
96
48
48
48
48
48
48
48
48
48
48
48
48
72
72
72
72
72
12
24
48
rt
0
0
0
0
0
0
0
0
0
0
0
-10
-20
-30
-40
-30
-30
-30
-30
-30
NRd
55
--
1
0
--
3
0
3
5
71
60
42
89
90
90
92
92
81
0
FTIR was carried out to investigate the bonding information of the
Et
CH
2
O
36
NR
catalyst/Fe
3
O
4
@SiO
@SiO
2
-β-CD (D). The broad band centered at 467 cm and the
2
-β-CD MNPs. Figure. 2 shows the FTIR spectra of
d
3
OH
Fe
3
O
4
(A), Fe
@SiO
3
O
4
2
(B), Fe @SiO -β-CD (C), and catalyst a
3
O
4
2
THF
92
72
75
64
92
67
95
94
96
96
98
87
77
94
81
89
98
−
1
/Fe
3
O
4
Toluene
Benzene
Ethyl acetate
−
1
band at 1091 cm were ascribed to the Fe–O and Si–O stretching
vibrations. Therefore, SiO was successfully deposited on the surface
of the Fe MNPs. Bands at 2923 and 1654 cm were attributed to
the alkane C–H stretching vibration and O–H bending vibration of
cyclodextrin, which revealed the linkage of β-CD and Fe @SiO
2
2
−
1
3
CH CN
3 4
O
1
1
1
0
1
2
CHCl
ClCH
3
2
CH
2
Cl
3
O
4
CH
2
CH
2
CH
2
CH
2
CH
2
CH
2
CH
2
CH
2
CH
2
CH
2
Cl
2
Cl
2
Cl
2
Cl
2
Cl
2
Cl
2
Cl
2
Cl
2
Cl
2
Cl
2
−
1
MNPs. In addition, bands at 1400 and 1627 cm (C–C stretching of
benzene skeleton) are found in Figure. 2 (D), which are exclusive and
ascribed to the catalyst. Therefore, based on the data from FTIR, the
13
1
1
1
1
1
19
2
2
4
5
6
7
8
resulting product of the catalyst/Fe
3
O
4
@SiO
2
-β-CD inclusion complex
e
f
magnetic nanoparticles was doubtlessly prepared via host–guest
self-assembly interactions
85
90
92
0
1
a
The reactions were performed using 0.25mmol of imine and 0.75mmol of
trichlorosilane with 0.025mmol of catalyst.
b
Isolated yields.
Determined by chiral HPLC.
No reaction
C
d
e
The reactions were performed using 0.25mmol of imine and 0.75mmol of
trichlorosilane with 0.0125mmol of catalyst.
F
The reactions were performed using 0.25mmol of imine and 0.75mmol of
trichlorosilane with 0.025mmol of catalyst b.
Variation of the ordinary imines 1a–r was examined to obtain the
substrate scope of the reaction and investigate the generality of
catalyst a under the optimal reaction condition (Table 1). The results
are summarized in Table 2. In the case of all amines, a dramatic
difference in selectivity was observed, in that using electron-
withdrawing groups obtained slightly low selectivity, which
suggested that electronic interaction was supposed to be the key
factor. Furthermore, imines with the same p-substituent group with
Figure. 2. The FTIR spectra of Fe
3 4 2 3 4
O (A), SiO @Fe O (B), β-
CD/SiO @Fe (C), and catalyst a MNPs (D).
2
3 4
O
Initially, solvents including polar and non-polar solvents were tested. either electron-withdrawing or electron-donating R2 exhibited
Among the different solvents, which we have tried, CH Cl showed enantioselectivity that is marginally lower than that with R , which
2
2
1
good results and has a short reaction time and high yield (89% ee). indicated that the difference of the p-substituent position may be
Table 1 shows the time when the reaction was carried out at −30 ℃ crucial to the advantages of the steric configuration between the
within 48 h and when the reaction exhibited high yield 2a with good catalyst and the imines due to the steric hindrance effect. Apparently,
enantioselectivity. When the amount of catalyst a decreased to 5 the electron-rich amines, such as 2e–2l, exhibited enantioselectivity
mol% (Table 1, entry 17), the yield and enantioselectivity decreased. especially 2j, which is higher than that in electron-withdrawing
2
| J. Name., 2012, 00, 1-3
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amines, like 2b–2d and 2m–2p, when the p-substituent groups are group and a hydrogen bond between the imine nitrogVeienwaAnrtdiclaenOinlilninee
placed in R or R . In the case of amines 2e–2h, a significantly reduced hydrogen. In addition, the results presenteDdOinI: 1T0a.1b0l3e9/1C7(eNnJt0r3y91128C)
1
2
yield and enantioselectivity were observed, which were fairly lower showed that catalyst b can obtain high yield but without
than those in 2i–2l, demonstrating that a steric repulsion occurred enantioselectivity. Arene–arene interactions between the catalyst
between the imines and catalyst. Thus, the p-substituents in R are and the substrates appear to be crucial in the formation of a steric
2
crucial in the steric properties, and the mechanism can account for transition state. However, as shown in Table 2, the catalyst obtained
the observed stereochemistry. The bulky adamantane group of the highly excellent yield and enantioselectivity when the p-substituent
catalyst and the p-substituents of imines b–h stayed away from one groups are placed in R
another, given the steric repulsion, which was compared with the the stability of steric configuration between catalyst and imines with
high level of enantioselectivity obtained from that with the p- bulky group on N-phenyl moiety of R was disturbed by the
substituents in R , such as imines i–l. Compared with 2e, another adamantane moiety on catalyst a, as shown in Figure 3.
electron-rich group was placed in the phenyl moiety of R for 2q; then,
1 2
rather than in R . This finding revealed that
2
1
1
the yield and enantioselectivity were increased as expected. Furthermore, to investigate the effect of hydrogen bonding between
However, further investigation with broad substrates to present catalyst and imines, anhydrous system was considered. Nevertheless,
more detailed comparison is required. When the methyl of imine was the reaction gave corresponding products that were rarely and
replaced with n-propyl as imine 1r, the yield and enantioselectivity toughly processed. However, when trace amounts of D
of 2r were lower than that of 2a. We speculate that when the catalyst added to the anhydrous solvent, the reaction returned to normal.
and HSiCl
get closer to the imines, the n-propyl moiety will afford Moreover, the increase of the product molecular mass was observed
more obstruction than methyl moiety due to the steric effect.
2
O were
3
and measured by HRMS (Figure S5). Therefore, the hydrogen
bonding was formed between O of water and H of catalyst. Then, the
Table 2. Reduction of imines 1a-r with trichlorosilane catalyzed by H of water and N of substrate moved to each other to form another
catalyst a
hydrogen bond. This finding suggested that water plays an important
role as a bridge in the hydrogen bonding formation. Therefore, these
results are consistent with the proposed mechanism model.
Consequently, the proposed interactions could result in the attack
from the Re face of the imine 1a to obtain the optically active amine
(
S)-2.
Entrya
R1
R2
X
product Yieldb
%]
eec
[%]
[
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
C
C
C
C
C
C
C
C
6
6
6
6
6
6
6
6
H
H
H
H
H
H
H
H
5
5
5
5
5
5
5
5
C
6
H
5
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
2a
2b
2c
2d
2e
2f
2g
2h
2i
96
92
80
68
73
88
83
78
73
87
95
90
93
85
88
87
51
93
64
4-FC
4-BrC
4-IC
4-CH
4-CH
4-CH
6
H
4
92
81
70
80
92
91
87
96
97
92
91
6
H
4
4
6
H
3
3
3
6 4
OC H
C
CH
6
H
2
4
C
4
6
H
4
4-t-BuC
6
H
Figure. 3. Proposed transition state of catalyst a
4-CH
4-CH
4-CH
4-t-BuC
4-FC
4-BrC
4-IC
4-NO
4-CH
3
3
3
C
CH
OC
6
H
4
C
C
C
C
C
C
C
C
H
6 5
H
6 5
H
6 5
H
6 5
H
6 5
H
6 5
H
6 5
H
6 5
0
1
2
3
4
5
6
7
8
2
C
6
H
4
4
2j
2k
2l
As shown in Figures S6, S7, and S8, blue fragments represent strong
electrostatic interactions, such as hydrogen bond interaction, in the
corresponding region. Red fragments imply intensive steric effects.
Green region suggests low electron density, which corresponds to
Van der Waals (VDW) interaction. In Figure S6, a blue portion near
6
H
4
6
H
6
H
4
2m 88
6
H
4
4
2n
2o
2p
2q
2r
91
90
56
95
70
6
H
2
C
6
H
4
the H
in the model A. Thus, strong hydrogen bonds were formed. In Figure
S8, the colors are light blue and green blue near the H –N group
and the H –O portion are presented separately in model C.
2 2 1
–N group and a blue-green one are shown near the H –O part
3
OC
6
H
4
4-CH
C
3
OC
6
H
4
C
H
6 5
H
6 5
n-propyl
a
2
2
The reactions were performed using 0.25mmol of imine and 0.75mmol of
trichlorosilane with 0.025mmol of catalyst a. -30℃, 48h, CH
Isolated yields.
Determined by chiral HPLC.
2
Cl
2
.
1
b
Meanwhile, the corresponding scatter graph shows that the absolute
values of the electrostatic interaction of model A, which range from
C
−
0.05 to −0.02, are higher than those of model C. The grass-green
isosurface near H –N in B exhibited the weakest hydrogen bond
effect. Moreover, the green portion implies that VDW interaction
exists between the phenyl of catalyst and N-phenyl of R on imines
in model A. However, the isosurface between the phenyl of catalyst
and R on imines shown as model C suggests little VDW interaction.
To provide an explanation on the mechanism of catalytic behavior, a
new plausible transition state model was proposed on the basis of
the available experimental data. Many researchers, such as Takuya
Kanemitsu and Andrei V. Malkov, have independently shown the
transition state for the reduction of imines with chiral
1
2
2
1
20, 21
organocatalysts.
A different transition state model was proposed
Thus, model A is more stable than models B and C shown as Figure.
S9.
for catalyst a in a similar method. The catalyst could coordinate with
trichlorosilane and activate the reducing agent in a synergistic
manner. The reaction was accelerated presumably through the
22
coordination between the silicon atom and oxygen of the amide
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To classify the catalyst performance in
a
homogeneous
Acknowledgements
This study was funded by the National Natural Science Foundation
of China (No. 21174052) and the Natural Science Foundation of Jilin
View Article Online
DOI: 10.1039/C7NJ03912C
catalysis/heterogeneous separation, the recyclability and optimal
conditions of catalyst a should be examined. A series of eight
consecutive runs were carried out, and the results are shown in Table
3 4 2
s3. The magnetic cyclodextrin-modified Fe O @SiO
with large Province of China (No. 20160101311JC).
23
24
surface area and outstanding stability can be reused more than
seven times. In addition, a little drop in activity was observed after
five runs, which caused
a slight decrease in yield and
Notes and references
enantioselectivity (Table s3, entries 1–6). After each run, the
recycled amount of catalyst a was detected by RP-HPLC (Figure S3).
However, a 7.4 % loss was observed in each run, presumably
including 2.7% loss in the process of extraction, 3% loss for the
1.
2.
3.
4.
5.
6.
7.
T. Kanemitsu, A. Umehara, R. Haneji, K. Nagata and T. Itoh,
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inclusion interaction of SiO
2 3
formed in the hydrolysis of HSiCl , and
1
.7% loss in the process of self-assembly. With more than six runs,
some catalysts were supplemented into the continual reaction,
making the amount of catalyst approach an initial amount of 10
mol%, as shown in Figure 4. Moreover, significant increases in yield
and enantioselectivity occurred, and the catalyst retrieved a high
activity as that in the first run. Therefore, although a slight loss of
catalyst occurred in the recyclable process, this self-assembly
method can efficiently recycle almost all catalysts to support the high
activity and catalyze the reaction for each run without any obvious
loss of activity.
2
527.
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2.
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2
Figure. 4. Recyclability of catalyst
a
for the reduction of imine
a. The reactions were performed using 0.25mmol of imine and
.75mmol of trichlorosilane with 0.025mmol (10mol%, 10.9mg)
1
0
2
D. Zhang, C. Zhou, Z. Sun, L.-Z. Wu, C.-H. Tung and T. Zhang,
Nanoscale, 2012, 4, 6244-6255.
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Conclusions
We developed a homogeneous catalyst for the reduction of imines
with recyclability. This method has several advantages, including
homogeneous catalysis, heterogeneous efficient isolation of catalyst,
and easy workup. The catalyst also has good activity performance
2
015, 141, 33-40.
B. S. Takale, S. Tao, X. Yu, X. Feng, T. Jin, M. Bao and Y.
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(
95% ee) and could be recycled up to eight runs with only a slight
drop in activity. Once we supplemented some catalysts, the activity
performed like a fresh catalyst. Moreover, a new mechanism model
was proposed by investigating the л–л stacking for the catalyst and
N-phenyl of imines and presenting water as a bridge, which was
23.
4.
confirmed by theoretical calculations
.
2
W. Wang, Y. Li, M. Sun, C. Zhou, Y. Zhang, Y. Li and Q. Yang,
Chemical Communications, 2012, 48, 6040-6042.
Conflicts of interest
“There are no conflicts to declare”.
4
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New Journal of Chemistry
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A homogeneous organocatalyst for asymmetric reduction of imine can be reused for many cycles
through self-assembly method using MNPs.