Chiral ionic liquid containing L-proline unit as a highly efficient and recyclable asymmetric organocatalyst for Aldol reaction

Article abstract of DOI:10.1246/cl.2007.628

A functionalized chiral ionic liquid (CIL) containing L-proline unit exhibits as a highly efficient and recyclable asymmetric organocatalyst for aldol condensation of aldehydes and ketones in [Bmim][BF₄] at room temperature, which afford the co

Full text of DOI:10.1246/cl.2007.628

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Chemistry Letters Vol.36, No.5 (2007)
Chiral Ionic Liquid Containing L-Proline Unit as a Highly Efficient
and Recyclable Asymmetric Organocatalyst for Aldol Reaction
1
Ã1;2
Li Zhou and Lei Wang
Department of Chemistry, Huaibei Coal Teachers College, Huaibei, Anhui 235000, P. R. China
Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, P. R. China
1
2
(Received February 9, 2007; CL-070155; E-mail: leiwang@hbcnc.edu.cn)
A functionalized chiral ionic liquid (CIL) containing L-pro-
media for inducing asymmetric synthesis.15 However, there are
few reports on chiral ILs for inducing asymmetric reaction, but
efficient one with high enantiomeric excess (ee) is still rare.16
Here, we wish to explore a functionalized chiral ionic liquid
(CIL) containing L-proline unit as a highly efficient and recycla-
ble asymmetric organocatalyst for aldol reactions. In the pres-
ence of the CIL (approximately 10 mol % of L-proline unit),
the aldol reactions between acetone and a variety of aldehydes
occurred smoothly in 1-n-butyl-3-methylimidazolium tetrafluor-
line unit exhibits as a highly efficient and recyclable asymmetric
organocatalyst for aldol condensation of aldehydes and ketones
in [Bmim][BF4] at room temperature, which afford the corre-
sponding products with satisfactory isolated yields and enantio-
meric excesses.
ꢀ
-Hydroxy carbonyl and 1,3-diol units are frequently
found in the skeleton of natural products. The aldol reaction is
a powerful and concise method for preparing these units from
two carbonyl compounds such as a ketone and an aldehyde, or
an aldehyde and an aldehyde. Over the last three decade, the
catalytic enantioselective aldol reaction has received a great deal
oborate [Bmim][BF ] to afford the corresponding products with
4
satisfactory isolated yields (53–94%) and ee (64–93%). It is
noteworthy that both of the CIL and [Bmim][BF ] are recycled
4
up to six times with only minor decreases in product yields, but
always maintenances in ee.
1
of attention from synthetic organic chemists. Mukaiyama et al.
2
The synthesis of the chiral ionic liquid containing L-proline
unit was carried out following the route described in Scheme 1.
It was readily prepared through a straightforward three-step
procedure from commercially available starting materials and
reagents in good yield and high purity.
established the chiral Lewis acid-catalyzed aldol reactions,
Denmark et al. developed chiral Lewis base-catalyzed aldol re-
3
4
actions, and Barbas et al. demonstrated antibodies and aldolase
5
enzymes catalyzed aldol reactions, as the principal chemical
reactions for the stereoselective construction of complex polyol
architecture. In comparison with the above-mentioned processes
using the pregeneration of enolates or enolate equivalents as the
aldol donor, the direct aldol reaction is highly economic. In
For the evaluation of the catalytic properties of chiral ionic
liquid catalyst and optimization of aldol reaction conditions, the
reaction between p-nitrobenzaldehyde and acetone served as a
model reaction. The aldol reaction took place smoothly at room
temperature in the presence of chiral ionic liquid (10 mol %) in
1
997, Shibasaki et al. reported the first example of a direct asym-
6
metric aldol reaction catalyzed by heterobimetallic complexes.
Three years later, Trost and Ito designed a zinc complex for the
direct catalytic asymmetric aldol reaction with high enantiose-
lectivities. Meanwhile, List, Barbas, and their co-workers found
that L-proline could work as a catalyst in the direct asymmetric
aldol reaction between a ketone and an aldehyde. Since then,
L-proline and its structural analogues have been widely used in
asymmetric catalytic direct aldol reactions. However, highly
[Bmim][BF ] to generate the product in 94% yield and 82%
4
ee. It is better than the results from the use of acetone, DMSO
or [Bmim][PF ] as the solvent. The anion of the ionic liquids
6
7
affects on the reaction. A slightly lower yield and ee were
observed using [Bmim][PF ] as solvent instead of [Bmim][BF ].
6
4
8
The reaction temperature plays an important role in the reaction.
ꢀ
At the room temperature (25 C), the reaction took place
smoothly with both good isolated yield and enantioselectivity.
A slightly higher yield was obtained along with sacrificing ee
9
enantioselective for a comparably narrow range of substrates
and requirement of 30 mol % catalyst loading are usually
observed in some cases. So, it is desirable to develop highly
enantioselective and efficient chiral organocatalysts with broad
substrate applicability and low catalyst loading or their recycla-
bility in this field.
ꢀ
when the reaction was performed at 40 C. Meanwhile, a slightly
higher ee was observed along with decreasing yield when the
HO
Br
N
N
CO2Bn
N
BrCH2CH2Br
Cbz
Br
In the last decade, room temperature ionic liquids (ILs) have
attracted much attention as environmentally benign reaction
media because of their many fascinating and intriguing proper-
ties such as high thermal and chemical stability, no measurable
N
N
NaH/THF
CH3
CH3
O
N
O
1
0
N
vapor pressure, no flammability, and high loading capacity.
Br
H2/Pd/C
CH3OH
1
1
N
Br
They have been widely used in many areas of organic, organo-
metallic,12 and enzymatic syntheses as well as in analytical
applications.14 In most cases, ILs can be recycled easily. Chiral
ILs are particularly attractive owing to their potential for chiral
discrimination, as in asymmetric synthesis and optical resolution
of racemates. Recent publications have documented the prepara-
tion of various chiral ILs and their potential utility as reaction
CO2H
N
N
CO2Bn
H
N
13
CH3
Chiral IL
CH3
Cbz
O
O
OH
O
Chiral IL
+
H
[Bmim]BF4
R
R
Scheme 1.
Copyright Ó 2007 The Chemical Society of Japan

Chemistry Letters Vol.36, No.5 (2007)
629
Table 1. Chiral ionic liquid catalyzed asymmetric aldol reac-
a
and ee. It is noteworthy that both of CIL and [Bmim][BF4] are
recycled up to six times with only minor decreases in product
yields, but always maintenances in ee.
tion
b
c
Entry
Aldehyde
Ketone
Yield /% ee /%
1
2
3
4
5
6
7
8
9
p-NO2C6H4CHO
p-BrC6H4CHO
p-ClC6H4CHO
p-CNC6H4CHO
p-CF3C6H4CHO
o-NO2C6H4CHO
o-ClC6H4CHO
o-BrC6H4CHO
2-Cl-6-ClC6H3CHO CH3COCH3
2-Cl-4-ClC6H3CHO CH3COCH3
2-Cl-5-NO2C6H3CHO CH3COCH3
m-NO2C6H4CHO
4-Cl-3-NO2C6H3CHO CH3COCH3
p-CH3C6H4CHO CH3COCH3
CH3COCH3
CH3COCH3
CH3COCH3
CH3COCH3
CH3COCH3
CH3COCH3
CH3COCH3
CH3COCH3
94
72
76
84
82
90
70
75
93
82
92
94
84
53
82
83
84
83
86
92
93
82
84
64
76
84
65
77
We gratefully acknowledge financial support by the Nation-
al Natural Science Foundation of China.
References and Notes
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1
1
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0
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2
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4
6, 7503.
CH3COCH3
4
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aAldehyde (0.5 mmol), acetone (1.0 mL), [Bmim][BF4] (1.0
mL), and chiral ionic liquid (contains 0.05 mmol of L-proline
b
unit) was stirred at room temperature for 24 h. Isolated yields.
c
Determined by chiral HPLC analysis.
5
6
ꢀ
reaction was performed at 0 to À10 C. It is interesting to note
that both of isolated yields and ee were maintained when more
than 10 mol % of chiral ionic liquid loading was added to the
reaction. A lower yield of aldol product was isolated when less
than 10 mol % of chiral ionic liquid was used in the reaction. It
was found that the reaction was accomplished as the reaction
was carried out for more than 24 h.
7
8
B. M. Trost, H. Ito, J. Am. Chem. Soc. 2000, 122, 12003.
B. List, R. A. Lerner, C. F. Barbas, III, J. Am. Chem. Soc. 2000,
1
22, 2395.
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24, 6798. b) Z. Tang, F. Jiang, L.-T. Yu, X. Cui, L.-Z. Gong,
9
To examine the versatility of this method, we extended our
studies to a variety of aldehydes and acetone. As the results
shown in Table 1, aromatic aldehydes bearing electron-with-
drawing groups, such as chloro, bromo, cyano, trifluoromethyl,
and nitro groups, were able to undergo smoothly aldol condensa-
tion with acetone in the presence of chiral ionic liquid (10
mol %) in [Bmim][BF4] at room temperature. The reactions
generated the corresponding aldol products in good yields (53–
1
A.-Q. Mi, Y.-Z. Jiang, Y.-D. Wu, J. Am. Chem. Soc. 2003,
125, 5262. c) A. Bassan, W. Zou, E. Reyes, F. Himo, Angew.
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1
1
1
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3
9
4%) and good enantioselectivities (64–93% ee). However,
aromatic aldehydes bearing electron-donating group, such as
methyl, was also able to undergo aldol condensation with
acetone under the standard reaction conditions in lower yields
53%) and good enantioselectivity (77% ee).
To screen the recyclability of chiral ionic liquid (CIL) and
Bmim][BF4], a more practical method was applied to the
3
(
4
2
851. b) J. Ding, T. Welton, D. W. Armstrong, Anal. Chem.
004, 76, 6819.
[
reaction between p-nitrobenzaldehyde and acetone under present
reaction conditions. When p-nitrobenzaldehyde was treated with
acetone with a catalyst loading of 10 mol % L-proline unit at
room temperature for 24 h, the desired aldol condensation prod-
uct was obtained in 94% yield with 82% ee. After carrying out a
reaction, isolating the product from the reaction mixture, wash-
ing with solvents, drying, and recovering CIL and [Bmim][BF4],
fresh starting materials were charged into the reaction system.
The reactions still proceeded well. The CIL and [Bmim][BF4]
are recycled six repetitive cycles with only minor decreases in
product yields, but always maintenances ee.
In conclusion, we have developed a chiral ionic liquid
containing L-proline unit for asymmetric inducing direct aldol
reaction between aldehyde and ketone. The reaction was carried
out in the presence of the CIL (10 mol % of L-proline unit) in
[Bmim][BF4] at room temperature. The reactions generated
the corresponding products with satisfactory isolated yields
15 a) M. L. Patil, C. V. L. Rao, K. Yonezawa, S. Takizawa, K.
Onitsuka, H. Sasai, Org. Lett. 2006, 8, 227. b) K. Fukumoto,
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1
2
0600. d) G. H. Tao, L. He, N. Sun, Y. Kou, Chem. Commun.
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6 Only 3 to 12% ee for the photochemical di-ꢁ-methane
rearrangement (J. Ding, V. Desikan, X. Han, T. L. Xiao, R.
Ding, W. S. Jenks, D. W. Armstrong, Org. Lett. 2005, 7, 335),
1
1
0 to 25% ee for the Michael addition of diethyl malonate chal-
cone (Z. Wang, Q. Wang, Y. Zhang, W. Bao, Tetrahedron Lett.
005, 46, 4657), up to 44% ee for the Baylis–Hillman coupling
B. P e´ got, G. Vo-Thanh, D. Gori, A. Loupy, Tetrahedron Lett.
004, 45, 6425), and up to 99% ee for the Michael addition to
2
(
2
nitroolefins (S. Luo, X. Mi, L. Zhang, S. Liu, H. Xu, J.-P. Cheng,
Angew. Chem., Int. Ed. 2006, 45, 3093), were obtained using
Chiral ILs inducing respectively.
Published on the web (Advance View) April 7, 2007; doi:10.1246/cl.2007.628