- Email: [email protected]
Cinchona-derived prolinamide in Brønsted acidic ionic liquids: A novel and recyclable catalytic system for asymmetric aldol reaction
G Model
ARTICLE IN PRESS
CATTOD-9817; No. of Pages 6
Catalysis Today xxx (2015) xxx–xxx
Contents lists available at ScienceDirect
Catalysis Today journal homepage: www.elsevier.com/locate/cattod
Cinchona-derived prolinamide in Brønsted acidic ionic liquids: A novel and recyclable catalytic system for asymmetric aldol reaction Lan-Lan Lou a,b , Jiong Zhang a,b , Huanling Du a,b , Bo Zhao a,b , Shanshan Li a,b , Wenjun Yu a,b , Kai Yu c , Shuangxi Liu a,b,d,∗ a Institute of New Catalytic Materials Science and Key Laboratory of Advanced Energy Materials Chemistry (Ministry of Education), School of Materials Science and Engineering, Nankai University, Tianjin 300071, China b National Institute for Advanced Materials, Nankai University, Tianjin 300071, China c College of Environmental Science and Engineering, Nankai University, Tianjin 300071, China d Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300072, China
a r t i c l e
i n f o
Article history: Received 15 May 2015 Received in revised form 11 September 2015 Accepted 10 October 2015 Available online xxx Keywords: Asymmetric aldol reaction Brønsted acidic ionic liquid Organocatalysis Prolinamide
a b s t r a c t Cinchonine-derived prolinamide in Brønsted acidic ionic liquids was utilized for the first time as a novel and recyclable catalytic system for the asymmetric direct aldol reaction of acetone with aromatic aldehydes. The effects of the Brønsted acidity and amount of ionic liquid, co-solvents, catalyst amount, and reaction temperature on the catalytic activity and enantioselectivity were studied in detail. Good to high yields and ee values were achieved for the aldol reaction of various aromatic aldehydes with neat acetone in 1-methylimidazolium tetrafluoroborate ([Hmim]+ BF4 − ) in the presence of 10 mol% of catalyst at room temperature. [Hmim]+ BF4 − was also identified as a Brønsted acid additive for the reaction and beneficial to the enhancement of catalytic performance. Moreover, the enhanced interaction between prolinamide and acidic ionic liquid facilitated the recoverability and reusability of organocatalyst. The catalyst recycling experiments indicated that there was only a slight loss in activity and enantioselectivity after four runs. © 2015 Elsevier B.V. All rights reserved.
1. Introduction Organocatalysis, the third pillar in the field of asymmetric catalysis, has recently received extensive attention due to the low cost and toxicity of organocatalysts, as well as their easy handling and utilization as compared with enantioselective transition-metal catalysts [1–3]. The asymmetric direct aldol reaction is one of the most powerful carbon-carbon bond forming processes for the synthesis of enantiomerically pure -hydroxy ketones, which are highly valuable building blocks and intermediates in organic synthesis and pharmaceutical industry [4–8]. Since the prolinecatalyzed direct aldol reaction was firstly reported by List and Barbas III [9,10], organocatalyzed aldol reaction has remained an active research area in the field of asymmetric catalysis. Over the past few years, a wide variety of organocatalysts, especially proline derivatives, have been developed for asymmetric aldol reactions
∗ Corresponding author at: Institute of New Catalytic Materials Science and Key Laboratory of Advanced Energy Materials Chemistry (Ministry of Education), School of Materials Science and Engineering, Nankai University, Tianjin 300071, China. E-mail address: [email protected] (S. Liu).
in an attempt to improve the catalytic activity and enantioselectivity [11–17]. For example, Xiao et al. [18] reported a new kind of organocatalysts for the asymmetric direct aldol reactions by the combination of proline with cinchona alkaloids, and high isolated yields and enantioselectivities were obtained in the presence of the Brønsted acid additives. However, the difficulties in catalyst recycling and product separation under homogeneous catalytic system often hinder the practical applications of these organocatalysts. Consequently, the development of practical, efficient and easily recoverable organocatalysts is highly desirable. Considerable efforts have been spent in the last decade on the immobilization of proline and its derivatives by using various supports, such as inorganic materials [19–25], organic polymers [26–31] and ionic liquids [32–37], to achieve a simplified separation of the catalyst from the product. More recently, ionic liquids have attracted considerable interest as environmentally benign media in the synthesis and catalysis owing to their unique properties such as unusual dissolution ability, enormous diversity, high thermal stability and recyclability [38–42]. They have also been employed as green and recoverable solvents for direct asymmetric aldol reactions. Since Loh et al. [43] and Toma et al. [44] independently reported the use of ionic liquid
http://dx.doi.org/10.1016/j.cattod.2015.10.004 0920-5861/© 2015 Elsevier B.V. All rights reserved.
Please cite this article in press as: L.-L. Lou, et al., Cinchona-derived prolinamide in Brønsted acidic ionic liquids: A novel and recyclable catalytic system for asymmetric aldol reaction, Catal. Today (2015), http://dx.doi.org/10.1016/j.cattod.2015.10.004
G Model
ARTICLE IN PRESS
CATTOD-9817; No. of Pages 6
L.-L. Lou et al. / Catalysis Today xxx (2015) xxx–xxx
2
N
N H2N
HO
N
1. N-Boc-Proline, DCC 2. TFA/CH2Cl2
N cinchonine
N
H
NH
O
N
N 1
9-amino epi-cinchonine Scheme 1. Synthesis of cinchonine-derived prolinamide catalyst 1.
[Bmim]+ PF6 − (Bmim = 1-butyl-3-methylimidazolium) as solvent in the proline-catalyzed aldol reactions in 2002, some research about aldol reactions in ionic liquid phases catalyzed by proline and its derivatives have been documented [45–51]. These organocatalysts indeed can be recycled and reused for several times, while moderate isolated yields and enantiomer excess (ee) values were usually achieved. Herein we wish to explore the use of Brønsted acidic ionic liquids in catalytic asymmetric aldol reaction by cinchonine-derived prolinamide catalyst. The ionic liquids here not only provided a recyclable solvent system, but also acted as Brønsted acid additives, which were known to be of great importance for the activation of the aldol acceptor in the enamine-based organocatalytic asymmetric aldol reaction [5,9,14,15,18]. Moreover, the catalyst was expected to be well confined in ionic liquids in view of the acid–base interaction between ionic liquid and prolinamide. To the best of our knowledge, this is the first report on the utilization of chiral prolinamide catalyst dissolved in Brønsted acidic ionic liquids for aldol reaction. In the absence of any other acid additives, this catalytic system was found to be highly efficient and enantioselective for the asymmetric aldol reaction of acetone with various aromatic aldehydes. Furthermore, the catalyst in ionic liquid was very stable and could be reused four times with only a slight loss in activity and enantioselectivity. 2. Experimental 2.1. General N-t-Butyloxycarbonyl-d-proline (AR), N,N dicyclohexylcarbodiimide (DCC, AR), aromatic aldehydes (AR), trifluoroacetic acid (TFA, AR), 1-methylimidazole (AR) and tetrafluoroboric acid (AR, 40%) were purchased from Aladdin Chemistry Co., Ltd. Cinchonine was provided by Shanghai Ruji Biotechnology Co., Ltd. Dichloromethane and chloroform were distilled from calcium hydride. Tetrahydrofuran (THF) was dried over sodium/benzophenone. All other materials were purchased from common commercial sources and used without further purification. 1 H NMR spectrum was recorded on a Varian Mercury Vx-300 (300 MHz) spectrometer using tetramethylsilane as an internal reference. The UV–vis absorption spectra were recorded on a Shimadzu UV-2550 UV–vis spectrophotometer. ee values were determined by HPLC with a chiral AS-H column, using an Agilent1200 chromatograph equipped with a VWD detector. 2.2. Synthesis of cinchonine-derived prolinamide catalyst 1 Firstly, as shown in Scheme 1, 9-amino epi-cinchonine was synthesized from cinchonine according to the literature [52]. 1 H NMR (CDCl3 , 300 MHz): ı (ppm) 0.85–0.99 (m, 1H), 1.08–1.15 (m, 1H), 1.48–1.60 (m, 3H), 2.05 (s, 2H), 2.24–2.26 (m, 1H), 2.90–3.10
H N + HL
N
0-5 oC
L
N
N
CH3
CH3
L-: BF4-, CH3COO-, CH3CH(OH)COO-, HSO4-, ClScheme 2. Synthesis of Brønsted acidic ionic liquids.
(m, 5H), 4.79 (d, J = 8.1 Hz, 1H), 5.01–5.04 (m, 2H), 5.87 (m, 1H), 7.54–8.36 (m, 5H), 8.91 (d, J = 4.5 Hz, 1H). A typical procedure for the synthesis of cinchonine-derived prolinamide organocatalyst was carried out as follows [18]. To a stirred solution of N-t-butyloxycarbonyl-d-proline (1.1 g, 5.1 mmol) in dry dichloromethane (40 mL) at 0 ◦ C, DCC (1.05 g, 5.1 mmol) was added. The reaction mixture was left stirring for 30 min and then, a solution of 9-amino epi-cinchonine (1.0 g, 3.4 mmol) in dry dichloromethane (10 mL) was added dropwise. The reaction mixture was warmed to room temperature and left stirring for 12 h. After filtration, the solvent was evaporated under reduced pressure and the crude product was purified using column chromatography on silica gel eluting with ethyl acetate/methanol (4:1) to afford the product as a white solid. Then, this solid was dissolved in a mixture of TFA/dichloromethane (1:4, 15 mL) with stirring at 0 ◦ C and the reaction solution was allowed to come to room temperature. After 2 h, concentrated aqueous ammonia was added to quench the reaction and the resulting solution was extracted with dichloromethane (20 mL 3×). The organic fractions were combined, dried over anhydrous sodium sulfate, filtered, and the solvent was evaporated under reduced pressure. The crude product was purified using column chromatography on silica gel eluting with ethyl acetate/methanol (2:1). The purified 1 was isolated as a white solid (1.04 g, 78% yield over two steps). 1 H NMR (CDCl3 , 300 MHz) ı (ppm) 0.98–1.04 (m, 1H), 1.25–1.30 (m, 1H), 1.53–1.67 (m, 6H), 1.98–2.05 (m, 1H), 2.25–2.38 (m, 1H), 2.84–2.90 (m, 1H), 2.98–3.06 (m, 5H), 3.17–3.22 (m, 1H), 3.74–3.77 (m, 1H), 5.13–5.18 (m, 2H), 5.46–5.49 (m, 1H), 5.86–5.95 (m, 1H), 7.38 (d, J = 3.6 Hz, 1H), 7.61 (t, J = 5.4 Hz, 1H), 7.74 (t, J = 5.4 Hz, 1H), 8.13 (d, J = 6.3 Hz, 1H), 8.36–8.43 (m, 2H), 8.88 (d, J = 3.6 Hz, 1H). 2.3. Synthesis of Brønsted acidic ionic liquids [Hmim]+ L− The Brønsted acidic ionic liquids were synthesized as shown in Scheme 2. In a typical process [53,54], a 100 mL three necked, round-bottom flask was charged with 1-methylimidazole (6.15 g, 75 mmol), which was allowed to cool to 0 ◦ C in an ice bath with stirring. Then 40% aqueous tetrafluoroboric acid (75 mmol) was added at a rate sufficient to maintain the reaction temperature at 0–5 ◦ C. After continuous stirring for another 2 h, water was evaporated under reduced pressure to afford the desired product 1-methylimidazolium tetrafluoroborate ([Hmim]+ BF4 − ) as a
Please cite this article in press as: L.-L. Lou, et al., Cinchona-derived prolinamide in Brønsted acidic ionic liquids: A novel and recyclable catalytic system for asymmetric aldol reaction, Catal. Today (2015), http://dx.doi.org/10.1016/j.cattod.2015.10.004
G Model
ARTICLE IN PRESS
CATTOD-9817; No. of Pages 6
L.-L. Lou et al. / Catalysis Today xxx (2015) xxx–xxx Table 1 Calculation of H0 of different Brønsted acidic ionic liquids.
0.6
a b c
a: blank + b: [Hmim] CH3CH(OH)COO
0.4
d
c: [Hmim] CH3COO
0.3
e
0.5
Absorbance
3
+
-
+
-
d: [Hmim] BF4 +
-
e: [Hmim] Cl + f: [Hmim] HSO4
f 0.2
Ionic liquid
ABSmax
[I] (%)
[HI+ ] (%)
H0
Blank [Hmim]+ CH3 CH(OH)COO− [Hmim]+ CH3 COO− [Hmim]+ BF4 − [Hmim]+ Cl− [Hmim]+ HSO4 −
0.541 0.502 0.473 0.411 0.318 0.252
100 92.8 87.4 76.0 58.8 46.6
0 7.2 12.6 24.0 41.2 53.4
− 2.10 1.83 1.49 1.14 0.93
Table 2 Asymmetric aldol reaction of 4-nitrobenzaldehyde with acetone in different ionic liquids.a
0.1
O
0.0
OH O
H 300
400
500
600
700
+
800
Wavelength (nm) Fig. 1. UV–vis absorption spectra of 4-nitroaniline in different Brønsted acidic ionic liquids.
colorless liquid. 1 H NMR (DMSO, 300 MHz) ı (ppm) 3.82 (s, 3 H), 7.51 (t, 1H), 7.57 (t, 1H), 8.78 (s, 1H). Other four ionic liquids including [Hmim]+ CH3 COO− , [Hmim]+ CH3 CH(OH)COO− , [Hmim]+ HSO4 − and [Hmim]+ Cl− were synthesized by following the same procedure as above except that acetic acid, lactic acid, sulfuric acid and hydrochloric acid were utilized, respectively, instead of tetrafluoroboric acid. 2.4. Asymmetric aldol reaction of acetone with aromatic aldehydes A typical procedure for the asymmetric aldol reaction was as follows. To a stirred solution of catalyst 1 (0.03 mmol) in ionic liquid (2.0 mL), acetone (0.5 mL) was added. The reaction mixture was stirred at room temperature for 30 min. The aldehyde (0.3 mmol) was then added and the reaction continued at room temperature. As the reaction was complete as determined by TLC, the reaction mixture was extracted by diethyl ether (5 mL 3×), and the combined organic layer was concentrated in vacuo and purified using column chromatography on silica gel eluting with the appropriate mixture of ethyl acetate/petroleum ether to afford the pure aldol product. The remaining ionic liquid phase containing catalyst 1 was dried in vacuo and subjected to the next run. 3. Results and discussion 3.1. Brønsted acidities of ionic liquids The Brønsted acidities of ionic liquids were evaluated by determining the Hammett acidity functions (H0 ) using UV–vis spectroscopy [55,56]. The Hammett function (H0 ) is defined as H0 = pK(I)aq + log([I]s /[IH+ ]s ) where pK(I)aq is the pKa value of the indicator referred to an aqueous solution, [I]s and [IH+ ]s are the molar concentrations of unprotonated and protonated forms of the indicator in the solvent, respectively. The Brønsted acidities of different ionic liquids were determined with 4-nitroaniline (pK(I)aq = 0.99) as indicator and ethanol as solvent. As shown in Fig. 1, the maximum absorbance of the unprotonated form of the indicator can be observed at 372 nm in ethanol, which decreased with the addition of ionic liquids, indicating that the indicator was partially in the form as [IH+ ]. Thus the [I]/[IH+ ] ratio could be determined from the measured absorbances, and then the Hammett function H0 of different ionic
1/ionic liquid r.t.
O2N Entry 1 2 3 4 5
O
* O 2N
Ionic liquid +
−
[Hmim] BF4 [Hmim]+ CH3 CH(OH)COO− [Hmim]+ CH3 COO− [Hmim]+ Cl− [Hmim]+ HSO4 −
t (h)
Yield (%)b
Conv. (%)
ee (%)c
36 24 6 48 48
65 74 – <5 <5
>99 >99 >99 – –
51 44 65 – –
a Reactions were performed with 0.3 mmol of 4-nitrobenzaldehyde and 0.5 mL of acetone and 2.0 mL of ionic liquid in the presence of 10 mol% of 1 at room temperature. b Isolated yield. c ee % were determined by HPLC. The absolute configuration was S.
liquids was calculated. As listed in Table 1, the type of anions has great effect on the acidities of ionic liquids. [Hmim]+ HSO4 − exhibits a stronger Brønsted acidity than the other four ionic liquids, and the Brønsted acidity of [Hmim]+ CH3 CH(OH)COO− is relatively weak. The Brønsted acidity order of the ionic liquids is as follows: [Hmim]+ HSO4 − > [Hmim]+ Cl− > [Hmim]+ BF4 − > [Hmim]+ CH3 COO− > [Hmim]+ CH3 CH(OH)COO− . 3.2. Asymmetric aldol reaction with different acidic ionic liquids The direct aldol reaction of 4-nitrobenzaldehyde with acetone catalyzed by 1 in different acidic ionic liquids was carried out and the results are listed in Table 2. When [Hmim]+ BF4 − was used, the reaction proceeded to completion in 36 h to afford the product in 65% yield and 51% ee. As compared with [Hmim]+ BF4 − , higher catalytic activity while lower enantioselectivity were achieved for the aldol reaction with ionic liquid [Hmim]+ CH3 CH(OH)COO− (Table 2, entry 2). Among the ionic liquids investigated, the utilization of [Hmim]+ CH3 COO− led to the best catalytic performance. In [Hmim]+ CH3 COO− , the reaction completed within 6 h to give the product in 65% ee. Very low catalytic activity was produced when the other two ionic liquids, [Hmim]+ HSO4 − and [Hmim]+ Cl− , were used. These results indicate that the catalytic performance is closely related to the ionic liquid acidity, and that a suitable Brønsted acidity level has a beneficial effect on the catalytic performance. Higher activity and enantioselectivity can be achieved when [Hmim]+ CH3 COO− was employed. And the reactions both in stronger and weaker acidic ionic liquids gave inferior catalytic performance. However, it should be noted that when [Hmim]+ CH3 COO− was employed, the separation of the reaction products from this ionic liquid phase was unsuccessful by extraction with various organic solvents. While for other four ionic liquids, the reaction products could be readily separated by solvent extraction from the ionic liquid phase and the catalyst 1 retained in ionic liquids could be reused. With regard to both the catalytic performance and catalyst reusability, [Hmim]+ BF4 − was identified as
Please cite this article in press as: L.-L. Lou, et al., Cinchona-derived prolinamide in Brønsted acidic ionic liquids: A novel and recyclable catalytic system for asymmetric aldol reaction, Catal. Today (2015), http://dx.doi.org/10.1016/j.cattod.2015.10.004
G Model
ARTICLE IN PRESS
CATTOD-9817; No. of Pages 6
L.-L. Lou et al. / Catalysis Today xxx (2015) xxx–xxx
4
Table 3 Asymmetric aldol reaction of 4-nitrobenzaldehyde with acetone under different conditions.a Entry
Amount of [Hmim]+ BF4 − (mL)
T (◦ C)
Amount of 1 (mol%)
t (h)
Yield (%)
ee (%)
1 2 3 4 5 6 7
1.0 2.0 3.0 1.0 1.0 1.0 1.0
Rt Rt Rt 0 40 Rt Rt
10 10 10 10 10 5 15
24 36 48 24 24 24 24
66 65 59 22 65 15 68
60 51 51 57 51 54 62
a
Reactions were performed with 0.3 mmol of 4-nitrobenzaldehyde and 0.5 mL of acetone.
Table 4 Asymmetric aldol reaction of acetone to 4-nitrobenzaldehyde with various cosolvents.a Entry 1 2 3 4 5 6 7 8 9 10
Co-solvent Acetone CH2 Cl2 CHCl3 THF Et2 O DMF DMSO CH3 CN MeOH H2 O
Yield (%) 80 67 75 80 78 56 49 65 36 70
ee (%) 67 67 59 64 55 62 56 46 62 57
a Reactions were performed with 0.3 mmol of aromatic aldehyde, 0.5 mL of acetone and 0.5 mL of co-solvent in 1.0 mL of [Hmim]+ BF4 − in the presence of 10 mol% of 1 at room temperature for 24 h.
the suitable acidic ionic liquid and was selected for further studies to optimize the reaction conditions. 3.3. Effects of reaction conditions on the asymmetric aldol reaction The effect of ionic liquid amount on the catalytic activity and enantioselectivity for direct aldol reaction was investigated. As shown in Table 3, with the increase of the amount of [Hmim]+ BF4 − , the reaction proceeded more slowly, meanwhile, the yield and ee value decreased gradually, which may be explained by the relatively higher diffusional resistance in the reaction system. An optimum result with 66% yield and 60% ee was achieved in 24 h as the reaction was operated using 1.0 mL of ionic liquid. The effects of reaction temperature and catalyst amount on the catalytic performance are also displayed in Table 3. It could be found that the catalytic activity increased remarkably with the increasing of reaction temperature. A much lower yield of 22% was obtained as the reaction was carried out at 0 ◦ C for 24 h with an ee value of 57%. The reaction at room temperature furnished the aldol product in 66% yield and 60% ee. A further increase in reaction temperature to 40 ◦ C led to a lower ee of 51%. Thus the following reactions in the present work were all conducted at room temperature. The data listed in Table 3 also revealed that the catalyst amount had a significant effect on the catalytic activity for the asymmetric aldol reaction. A pronounced increase in yield from 15% to 66% could be observed when the catalyst amount was increased from 5 mol% to 10 mol%, while the enantioselectivity was found not to depend markedly on the catalyst amount. Further increasing the catalyst amount caused no obvious enhancement in yield as well as in ee value (Table 3, entry 7). It should be noted that the catalyst amount of 10 mol% was three times lower with respect to the use of proline in the previous reports [9,35,36,43,44]. In attempt to further improve the catalytic activity and enantioselectivity, co-solvents were employed. As shown in Table 4, a variety of co-solvents were screened in the model reaction between 4-nitrobenzaldehyde and acetone. It could be found that the
Table 5 Asymmetric aldol reaction of 4-nitrobenzaldehyde with acetone in different conditions.a Entry 1 2 3 4 5 6
Ionic liquid +
−
[Hmim] BF4 – [Bmim]+ BF4 − [Hmim]+ BF4 − [Hmim]+ BF4 − [Hmim]+ BF4 −
Acid additiveb
Yield (%)
ee (%)
– – – Benzoic acid Catechol Acetic acid
80 78 39 77 81 75
67 44 45 62 65 65
a Reactions were performed with 0.3 mmol of aromatic aldehyde and 1.0 mL of acetone in 1.0 mL of ionic liquid in the presence of 10 mol% of 1 at room temperature for 24 h. b The amount of acid additive was 10 mol%.
utilization of the co-solvents with relatively low polarity, such as THF, acetone, Et2 O, CHCl3 , and CH2 Cl2 , generally led to the enhancement of isolated yields. For example, an increase in yield from 66% to 80% was achieved when THF or acetone was used as co-solvent. Improved ee values were produced with the addition of acetone, CH2 Cl2 and THF, while inferior enantioselectivities were presented by using Et2 O and CHCl3 as co-solvents. The utilization of highly polar organic solvents showed a negative effect on the catalytic activities (Table 4, entries 6–9). Among all the co-solvents studied, polar protic solvent MeOH gave the lowest activity, which may be due to the detrimental effect of alcoholic solvents on the hydrogen bonding interaction between the catalyst and the substrate. It could be also observed that a lower ee of 46% was obtained when CH3 CN was selected. Besides the organic solvents, water as a green solvent was also applied in the reaction, and a good yield of 70% with an ee of 57% was achieved. Thus acetone was considered as the most suitable one among the co-solvents examined with regard to both the yield and enantioselectivity, and the corresponding reaction afforded the product in 80% yield and 67% ee. The Brønsted acid additive was considered to be important to facilitate the enamine-based organocatalytic asymmetric aldol reaction [5,9,14,15,18]. The ionic liquid [Hmim]+ BF4 − , as a strong Brønsted acid, acts here not only as a solvent, but also as a Brønsted acid additive for the reaction. In order to investigate the effect of Brønsted acidic ionic liquids on the catalytic performance, the reaction without any ionic liquids was performed under otherwise identical conditions. As shown in Table 5, a high yield of 78% and a low ee of 44% were achieved. This indicates that the asymmetric aldol reaction between 4-nitrobenzaldehyde and acetone can occur with relatively low enantioselectivity in the presence of prolinamide catalyst 1 without any acid additive, which is in accordance with that reported in the literature [18]. For the purpose of comparison, a neutral iminazolium-based ionic liquid [Bmim]+ BF4 − was also synthesized according to the method we previously reported [57] and applied in the asymmetric aldol reaction of 4-nitrobenzaldehyde with acetone. It could be found that the reaction in [Bmim]+ BF4 − proceeded very slowly, and a low yield of 39% along with a relatively low ee of 45% was obtained after 24 h (Table 5, entry 3). This documented that the introduction of common ionic liquids had no positive effect on the enantioselectivity
Please cite this article in press as: L.-L. Lou, et al., Cinchona-derived prolinamide in Brønsted acidic ionic liquids: A novel and recyclable catalytic system for asymmetric aldol reaction, Catal. Today (2015), http://dx.doi.org/10.1016/j.cattod.2015.10.004
G Model
ARTICLE IN PRESS
CATTOD-9817; No. of Pages 6
L.-L. Lou et al. / Catalysis Today xxx (2015) xxx–xxx Table 6 Asymmetric aldol reaction of acetone to various aromatic aldehydes.a
O
80
OH O +
1/[Hmim]+BF4r.t.
Yield ee
O
* R
60
Entry
R
Yield (%)
ee (%)c
1 2 3 4 5 6 7 8 9
4-NO2 2-NO2 4-Cl 2-Cl 2,4-Cl2 4-Br 4-F 4-CF3 4-CN
80 73 78 77 86 61 69 74 72
67 70 71 74 78 76 75 82 84
%
H
R
5
40
20
0 1
a
Reactions were performed with 0.3 mmol of aromatic aldehyde and 1.0 mL of acetone and 1.0 mL of [Hmim]+ BF4 − in the presence of 10 mol% of 1 at room temperature for 24–120 h.
and led to a notable decrease in the catalytic efficiency due mainly to the mass transfer limitation in ionic liquid system. Comparing these results with those achieved in [Hmim]+ BF4 − , it can be concluded that the utilization of Brønsted acidic ionic liquids can not only increase the product enantioselectivity but also accelerate the catalytic reaction. In an attempt to get further insight into the role of [Hmim]+ BF4 − , the control experiments were carried out by the use of additional acid additives including benzoic acid, catechol and acetic acid. The results, given in Table 5, showed that the employment of these three acid additives had no obviously positive effects on the enhancement of catalytic performance. The superior activity and enantioselectivity were achieved when the reaction was performed in [Hmim]+ BF4 − without any other acid additive. 3.4. Asymmetric aldol reaction of various aromatic aldehydes With the optimized reaction conditions in hand, the substrate scope of the catalytic asymmetric aldol reaction was then explored. As shown in Table 6, all the aromatic aldehydes examined underwent reaction with acetone to furnish the corresponding aldol product in moderate to high yields and ee values with the presence of 10 mol% of catalyst at room temperature. In general, reactions of the aromatic aldehydes with ortho substituents afforded products in lower yields but slightly higher ee values than those with para substituents, which may be due to the greater steric hindrance of ortho substituents (Table 6, entries 1 and 3 vs. 2 and 4). 4-Nitrobenzaldehyde gave a better yield and lower ee than 4-halogen aromatic aldehydes. The dichlorine-substituted benzaldehyde was found to be more reactive and enantioselective than mono-substituted aldehydes (Table 6, entries 3 and 4 vs. 5). 4-(Trifluoromethyl)benzaldehyde was converted to the corresponding -hydroxy ketone in a moderate yield of 74% and a high ee of 82%. Moreover, the reaction of 4-cyanobenzaldehyde with acetone provided the best ee value of 84% with a yield of 72%. 3.5. Catalyst recycling and stability The recyclability of catalyst system 1/[Hmim]+ BF4 − was investigated in the model reaction of 4-nitrobenzaldehyde and acetone. On completion of each reaction, the reaction mixture was extracted by diethyl ether, and the ionic liquid phase containing catalyst 1 was subjected to the next run with a fresh batch of acetone and aldehyde. As shown in Fig. 2, the catalytic activity and enantioselectivity remained basically unchanged in the first three runs. A yield of 78% along with an ee value of 64% was achieved in the third
2
3
4
Run Fig. 2. Recycle studies of 1/[Hmim]+ BF4 − in the asymmetric aldol reaction of 4nitrobenzaldehyde with acetone.
run. While a decrease in yield and ee value was observed in the subsequent fourth run. This may be probably due to the catalyst system 1/[Hmim]+ BF4 − being partially extracted into the organic phase during the recycling procedures. Indeed, about 10% of mass loss was found for the ionic liquid phase containing catalyst 1 after four cycles. For the purpose of comparison, the catalyst 1 supported in neutral ionic liquid [Bmim]+ BF4 − was also studied in the recycling experiments. It was found that the catalytic activity and enantioselectivity decreased significantly with each recycle. During the first three recycling runs, the yield declined from 30% to 18% then to 8%, and no reaction was observed after recycling three times. This indicated the chiral prolinamide catalyst in [Bmim]+ BF4 − has a greater tendency to be extracted into the organic phase than that in [Hmim]+ BF4 − . Thus it could be concluded that the introduction of acidic ionic liquid can significantly enhance the stability of the catalyst system due probably to the stronger interaction between the catalyst and ionic liquid.
4. Conclusion Brønsted acidic ionic liquids [Hmim]+ L− were applied in the asymmetric direct aldol reaction of acetone with aromatic aldehydes catalyzed by the prolinamide organocatalyst 1 derived from 9-amino epi-cinchonine. [Hmim]+ BF4 − was found to be the most suitable ionic liquid for the catalytic system, and the superior activity and enantioselectivity were achieved in 1.0 mL of [Hmim]+ BF4 − with neat acetone in the presence of 10 mol% of 1 at room temperature. The ionic liquid, as a Brønsted acid additive, was demonstrated to play a positive effect on the enhancement of catalytic performance. Moreover, the catalyst recycling experiments showed that the application of acidic ionic liquid could effectively improve the affinity of catalyst 1 to ionic liquid, thus increasing the catalyst stability. The catalyst 1 in [Hmim]+ BF4 − could be reused four times with only a slight loss of activity and enantioselectivity.
Acknowledgements We gratefully acknowledge the support of this research by the National Natural Science Foundation of China (Grant No. 21203102), the Tianjin Municipal Natural Science Foundation (Grant Nos. 14JCQNJC06000 and 14JCZDJC32000), MOE (IRT13R30) and 111 Project (B12015).
Please cite this article in press as: L.-L. Lou, et al., Cinchona-derived prolinamide in Brønsted acidic ionic liquids: A novel and recyclable catalytic system for asymmetric aldol reaction, Catal. Today (2015), http://dx.doi.org/10.1016/j.cattod.2015.10.004
G Model CATTOD-9817; No. of Pages 6
ARTICLE IN PRESS L.-L. Lou et al. / Catalysis Today xxx (2015) xxx–xxx
6
References [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] [22] [23] [24] [25] [26]
P.I. Dalko, L. Moisan, Angew. Chem. Int. Ed. 43 (2004) 5138–5175. A. Dondoni, A. Massi, Angew. Chem. Int. Ed. 47 (2008) 4638–4660. J.G. Hernandez, E. Juaristi, Chem. Commun. 48 (2012) 5396–5409. R. Mahrwald (Ed.), Modern Methods in Stereoselective Aldol Reactions, Wiley-VCH, Weinheim, Germany, 2013. S. Mukherjee, J.W. Yang, S. Hoffmann, B. List, Chem. Rev. 107 (2007) 5471–5569. J. Guillena, C. Najera, D.J. Ramon, Tetrahedron: Asymmetry 18 (2007) 2249–2293. B.M. Trost, C.S. Brindle, Chem. Soc. Rev. 39 (2010) 1600–1632. V. Bisai, A. Bisai, V.K. Singh, Tetrahedron 68 (2012) 4541–4580. B. List, R.A. Lerner, C.F. Barbas III, J. Am. Chem. Soc. 122 (2000) 2395–2396. K. Sakthivel, W. Notz, T. Bui, C.F. Barbas III, J. Am. Chem. Soc. 123 (2001) 5260–5267. S.K. Panday, Tetrahedron: Asymmetry 22 (2011) 1817–1847. Z. Tang, Z.-H. Yang, X.-H. Chen, L.-F. Cun, A.-Q. Mi, Y.-Z. Jiang, L.-Z. Gong, J. Am. Chem. Soc. 127 (2005) 9285–9289. Y. Hayashi, T. Sumiya, J. Takahashi, H. Gotoh, T. Urushima, M. Shoji, Angew. Chem. Int. Ed. 45 (2006) 958–961. N. Mase, Y. Nakai, N. Ohara, H. Yoda, K. Takabe, F. Tanaka, C.F. Barbas III, J. Am. Chem. Soc. 128 (2006) 734–735. S. Luo, H. Xu, J. Li, L. Zhang, J.-P. Cheng, J. Am. Chem. Soc. 129 (2007) 3074–3075. J. Huang, X. Zhang, D.W. Armstrong, Angew. Chem. Int. Ed. 46 (2007) 9073–9077. M. Vasiloiu, D. Rainera, P. Gaertner, C. Reichel, C. Schröder, K. Bica, Catal. Today 200 (2013) 80–86. J.-R. Chen, X.-L. An, X.-Y. Zhu, X.-F. Wang, W.-J. Xiao, J. Org. Chem. 73 (2008) 6006–6009. E.G. Doyagüez, F. Calderón, F. Sánchez, A. Fernández-Mayoralas, J. Org. Chem. 72 (2007) 9353–9356. J.S. Gao, J. Liu, J.T. Tang, D.M. Jiang, B. Li, Q.H. Yang, Chem. Eur. J. 16 (2010) 7852–7858. N. Hara, S. Nakamura, N. Shibata, T. Toru, Adv. Synth. Catal. 352 (2010) 1621–1624. S. Calogero, D. Lanari, M. Orrù, O. Piermatti, F. Pizzo, L. Vaccaro, J. Catal. 282 (2011) 112–119. H. Yang, S. Li, X. Wang, F. Zhang, X. Zhong, Z. Dong, J. Ma, J. Mol. Catal. A: Chem. 363–364 (2012) 404–410. R. Tan, C. Li, J. Luo, Y. Kong, W. Zheng, D. Yin, J. Catal. 298 (2013) 138–147. Z. An, Y. Guo, L. Zhao, Z. Li, J. He, ACS Catal. 4 (2014) 2566–2576. M. Gruttadauria, F. Giacalone, A.M. Marculescu, R. Notoa, Adv. Synth. Catal. 350 (2008) 1397–1405.
[27] S. Luo, J. Li, L. Zhang, H. Xu, J.-P. Cheng, Chem. Eur. J. 14 (2008) 1273–1281. [28] A. Lu, T.P. Smart, T.H. Epps, D.A. Longbottom, R.K. ÓReilly, Macromolecules 44 (2011) 7233–7241. [29] C. Ayats, A.H. Henseler, M.A. Pericàs, ChemSusChem 5 (2012) 320–325. [30] X. Zhang, W. Zhao, L. Yang, Y. Cui, J. Appl. Polym. Sci. 118 (2013) 3537–3542. [31] G. Sz"oll"osia, A. Csámpai, C. Somlai, M. Fekete, M. Bartók, J. Mol. Catal. A: Chem. 382 (2014) 86–92. [32] K. Bica, P. Gaertner, Eur. J. Org. Chem. (2008) 3235–3250. [33] Y. Qiao, A.D. Headley, Catalysts 3 (2013) 709–725. [34] S. Luo, X. Mi, L. Zhang, S. Liu, H. Xu, J.-P. Cheng, Angew. Chem. Int. Ed. 45 (2006) 3093–3097. [35] W. Miao, T.H. Chan, Adv. Synth. Catal. 348 (2006) 1711–1718. [36] M. Gruttadauria, S. Riela, C. Aprile, P. Lo Meo, F. D’Anna, R. Noto, Adv. Synth. Catal. 348 (2006) 82–92. [37] V. Gauchot, A.R. Schmitzer, J. Org. Chem. 77 (2012) 4917–4923. [38] T. Welton, Chem. Rev. 99 (1999) 2071–2083. [39] P. Wasserscheid, W. Keim, Angew. Chem. Int. Ed. 39 (2000) 3772–3789. [40] V.I. Pârvulescu, C. Hardacre, Chem. Rev. 107 (2007) 2615–2665. [41] M. Petkovic, K.R. Seddon, L.P.N. Rebelo, C.S. Pereira, Chem. Soc. Rev. 40 (2011) 1383–1403. [42] J.P. Hallett, T. Welton, Chem. Rev. 111 (2011) 3508–3576. [43] T.-P. Loh, L.-C. Feng, H.-Y. Yang, J.-Y. Yang, Tetrahedron Lett. 43 (2002) 8741–8743. ˇ Toma, E. Solˇcániová, Chem. Commun. [44] P. Kotrusz, I. Kmentová, B. Gotov, S. (2002) 2510–2511. [45] A. Córdova, Tetrahedron Lett. 45 (2004) 3949–3952. [46] H.-M. Guo, L.-F. Cun, L.-Z. Gong, A.-Q. Mi, Y.-Z. Jiang, Chem. Commun. (2005) 1450–1452. [47] M. Lombardo, F. Pasi, S. Easwar, C. Trombini, Adv. Synth. Catal. 349 (2007) 2061–2065. [48] J. Shah, H. Blumenthal, Z. Yacob, J. Liebscher, Adv. Synth. Catal. 350 (2008) 1267–1270. [49] M. Lombardo, S. Easwar, F. Pasi, C. Trombinia, D.D. Dhavale, Tetrahedron 64 (2008) 9203–9207. [50] Y. Qian, X. Zheng, Y. Wang, Eur. J. Org. Chem. (2010) 3672–3677. [51] X. Zhang, W. Zhao, C. Qu, L. Yang, Y. Cui, Tetrahedron: Asymmetry 23 (2012) 468–473. [52] B. Vakulya, S. Varga, A. Csámpai, T. Soós, Org. Lett. 7 (2005) 1967–1969. [53] J.D. Holbrey, K.R. Seddon, J. Chem. Soc. Dalton Trans. (1999) 2133–2139. [54] H.-P. Zhu, F. Yang, J. Tang, M.-Y. He, Green Chem. 5 (2003) 38–39. [55] C. Thomazeau, H. Olivier-Bourbigou, L. Magna, S. Luts, B. Gilbert, J. Am. Chem. Soc. 125 (2003) 5264–5265. [56] H. Xing, T. Wang, Z. Zhou, Y. Dai, J. Mol. Catal. A: Chem. 264 (2007) 53–59. [57] L.-L. Lou, Y. Dong, K. Yu, S. Jiang, Y. Song, S. Cao, S. Liu, J. Mol. Catal. A: Chem. 333 (2010) 20–27.
Please cite this article in press as: L.-L. Lou, et al., Cinchona-derived prolinamide in Brønsted acidic ionic liquids: A novel and recyclable catalytic system for asymmetric aldol reaction, Catal. Today (2015), http://dx.doi.org/10.1016/j.cattod.2015.10.004
ARTICLE IN PRESS
CATTOD-9817; No. of Pages 6
Catalysis Today xxx (2015) xxx–xxx
Contents lists available at ScienceDirect
Catalysis Today journal homepage: www.elsevier.com/locate/cattod
Cinchona-derived prolinamide in Brønsted acidic ionic liquids: A novel and recyclable catalytic system for asymmetric aldol reaction Lan-Lan Lou a,b , Jiong Zhang a,b , Huanling Du a,b , Bo Zhao a,b , Shanshan Li a,b , Wenjun Yu a,b , Kai Yu c , Shuangxi Liu a,b,d,∗ a Institute of New Catalytic Materials Science and Key Laboratory of Advanced Energy Materials Chemistry (Ministry of Education), School of Materials Science and Engineering, Nankai University, Tianjin 300071, China b National Institute for Advanced Materials, Nankai University, Tianjin 300071, China c College of Environmental Science and Engineering, Nankai University, Tianjin 300071, China d Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300072, China
a r t i c l e
i n f o
Article history: Received 15 May 2015 Received in revised form 11 September 2015 Accepted 10 October 2015 Available online xxx Keywords: Asymmetric aldol reaction Brønsted acidic ionic liquid Organocatalysis Prolinamide
a b s t r a c t Cinchonine-derived prolinamide in Brønsted acidic ionic liquids was utilized for the first time as a novel and recyclable catalytic system for the asymmetric direct aldol reaction of acetone with aromatic aldehydes. The effects of the Brønsted acidity and amount of ionic liquid, co-solvents, catalyst amount, and reaction temperature on the catalytic activity and enantioselectivity were studied in detail. Good to high yields and ee values were achieved for the aldol reaction of various aromatic aldehydes with neat acetone in 1-methylimidazolium tetrafluoroborate ([Hmim]+ BF4 − ) in the presence of 10 mol% of catalyst at room temperature. [Hmim]+ BF4 − was also identified as a Brønsted acid additive for the reaction and beneficial to the enhancement of catalytic performance. Moreover, the enhanced interaction between prolinamide and acidic ionic liquid facilitated the recoverability and reusability of organocatalyst. The catalyst recycling experiments indicated that there was only a slight loss in activity and enantioselectivity after four runs. © 2015 Elsevier B.V. All rights reserved.
1. Introduction Organocatalysis, the third pillar in the field of asymmetric catalysis, has recently received extensive attention due to the low cost and toxicity of organocatalysts, as well as their easy handling and utilization as compared with enantioselective transition-metal catalysts [1–3]. The asymmetric direct aldol reaction is one of the most powerful carbon-carbon bond forming processes for the synthesis of enantiomerically pure -hydroxy ketones, which are highly valuable building blocks and intermediates in organic synthesis and pharmaceutical industry [4–8]. Since the prolinecatalyzed direct aldol reaction was firstly reported by List and Barbas III [9,10], organocatalyzed aldol reaction has remained an active research area in the field of asymmetric catalysis. Over the past few years, a wide variety of organocatalysts, especially proline derivatives, have been developed for asymmetric aldol reactions
∗ Corresponding author at: Institute of New Catalytic Materials Science and Key Laboratory of Advanced Energy Materials Chemistry (Ministry of Education), School of Materials Science and Engineering, Nankai University, Tianjin 300071, China. E-mail address: [email protected] (S. Liu).
in an attempt to improve the catalytic activity and enantioselectivity [11–17]. For example, Xiao et al. [18] reported a new kind of organocatalysts for the asymmetric direct aldol reactions by the combination of proline with cinchona alkaloids, and high isolated yields and enantioselectivities were obtained in the presence of the Brønsted acid additives. However, the difficulties in catalyst recycling and product separation under homogeneous catalytic system often hinder the practical applications of these organocatalysts. Consequently, the development of practical, efficient and easily recoverable organocatalysts is highly desirable. Considerable efforts have been spent in the last decade on the immobilization of proline and its derivatives by using various supports, such as inorganic materials [19–25], organic polymers [26–31] and ionic liquids [32–37], to achieve a simplified separation of the catalyst from the product. More recently, ionic liquids have attracted considerable interest as environmentally benign media in the synthesis and catalysis owing to their unique properties such as unusual dissolution ability, enormous diversity, high thermal stability and recyclability [38–42]. They have also been employed as green and recoverable solvents for direct asymmetric aldol reactions. Since Loh et al. [43] and Toma et al. [44] independently reported the use of ionic liquid
http://dx.doi.org/10.1016/j.cattod.2015.10.004 0920-5861/© 2015 Elsevier B.V. All rights reserved.
Please cite this article in press as: L.-L. Lou, et al., Cinchona-derived prolinamide in Brønsted acidic ionic liquids: A novel and recyclable catalytic system for asymmetric aldol reaction, Catal. Today (2015), http://dx.doi.org/10.1016/j.cattod.2015.10.004
G Model
ARTICLE IN PRESS
CATTOD-9817; No. of Pages 6
L.-L. Lou et al. / Catalysis Today xxx (2015) xxx–xxx
2
N
N H2N
HO
N
1. N-Boc-Proline, DCC 2. TFA/CH2Cl2
N cinchonine
N
H
NH
O
N
N 1
9-amino epi-cinchonine Scheme 1. Synthesis of cinchonine-derived prolinamide catalyst 1.
[Bmim]+ PF6 − (Bmim = 1-butyl-3-methylimidazolium) as solvent in the proline-catalyzed aldol reactions in 2002, some research about aldol reactions in ionic liquid phases catalyzed by proline and its derivatives have been documented [45–51]. These organocatalysts indeed can be recycled and reused for several times, while moderate isolated yields and enantiomer excess (ee) values were usually achieved. Herein we wish to explore the use of Brønsted acidic ionic liquids in catalytic asymmetric aldol reaction by cinchonine-derived prolinamide catalyst. The ionic liquids here not only provided a recyclable solvent system, but also acted as Brønsted acid additives, which were known to be of great importance for the activation of the aldol acceptor in the enamine-based organocatalytic asymmetric aldol reaction [5,9,14,15,18]. Moreover, the catalyst was expected to be well confined in ionic liquids in view of the acid–base interaction between ionic liquid and prolinamide. To the best of our knowledge, this is the first report on the utilization of chiral prolinamide catalyst dissolved in Brønsted acidic ionic liquids for aldol reaction. In the absence of any other acid additives, this catalytic system was found to be highly efficient and enantioselective for the asymmetric aldol reaction of acetone with various aromatic aldehydes. Furthermore, the catalyst in ionic liquid was very stable and could be reused four times with only a slight loss in activity and enantioselectivity. 2. Experimental 2.1. General N-t-Butyloxycarbonyl-d-proline (AR), N,N dicyclohexylcarbodiimide (DCC, AR), aromatic aldehydes (AR), trifluoroacetic acid (TFA, AR), 1-methylimidazole (AR) and tetrafluoroboric acid (AR, 40%) were purchased from Aladdin Chemistry Co., Ltd. Cinchonine was provided by Shanghai Ruji Biotechnology Co., Ltd. Dichloromethane and chloroform were distilled from calcium hydride. Tetrahydrofuran (THF) was dried over sodium/benzophenone. All other materials were purchased from common commercial sources and used without further purification. 1 H NMR spectrum was recorded on a Varian Mercury Vx-300 (300 MHz) spectrometer using tetramethylsilane as an internal reference. The UV–vis absorption spectra were recorded on a Shimadzu UV-2550 UV–vis spectrophotometer. ee values were determined by HPLC with a chiral AS-H column, using an Agilent1200 chromatograph equipped with a VWD detector. 2.2. Synthesis of cinchonine-derived prolinamide catalyst 1 Firstly, as shown in Scheme 1, 9-amino epi-cinchonine was synthesized from cinchonine according to the literature [52]. 1 H NMR (CDCl3 , 300 MHz): ı (ppm) 0.85–0.99 (m, 1H), 1.08–1.15 (m, 1H), 1.48–1.60 (m, 3H), 2.05 (s, 2H), 2.24–2.26 (m, 1H), 2.90–3.10
H N + HL
N
0-5 oC
L
N
N
CH3
CH3
L-: BF4-, CH3COO-, CH3CH(OH)COO-, HSO4-, ClScheme 2. Synthesis of Brønsted acidic ionic liquids.
(m, 5H), 4.79 (d, J = 8.1 Hz, 1H), 5.01–5.04 (m, 2H), 5.87 (m, 1H), 7.54–8.36 (m, 5H), 8.91 (d, J = 4.5 Hz, 1H). A typical procedure for the synthesis of cinchonine-derived prolinamide organocatalyst was carried out as follows [18]. To a stirred solution of N-t-butyloxycarbonyl-d-proline (1.1 g, 5.1 mmol) in dry dichloromethane (40 mL) at 0 ◦ C, DCC (1.05 g, 5.1 mmol) was added. The reaction mixture was left stirring for 30 min and then, a solution of 9-amino epi-cinchonine (1.0 g, 3.4 mmol) in dry dichloromethane (10 mL) was added dropwise. The reaction mixture was warmed to room temperature and left stirring for 12 h. After filtration, the solvent was evaporated under reduced pressure and the crude product was purified using column chromatography on silica gel eluting with ethyl acetate/methanol (4:1) to afford the product as a white solid. Then, this solid was dissolved in a mixture of TFA/dichloromethane (1:4, 15 mL) with stirring at 0 ◦ C and the reaction solution was allowed to come to room temperature. After 2 h, concentrated aqueous ammonia was added to quench the reaction and the resulting solution was extracted with dichloromethane (20 mL 3×). The organic fractions were combined, dried over anhydrous sodium sulfate, filtered, and the solvent was evaporated under reduced pressure. The crude product was purified using column chromatography on silica gel eluting with ethyl acetate/methanol (2:1). The purified 1 was isolated as a white solid (1.04 g, 78% yield over two steps). 1 H NMR (CDCl3 , 300 MHz) ı (ppm) 0.98–1.04 (m, 1H), 1.25–1.30 (m, 1H), 1.53–1.67 (m, 6H), 1.98–2.05 (m, 1H), 2.25–2.38 (m, 1H), 2.84–2.90 (m, 1H), 2.98–3.06 (m, 5H), 3.17–3.22 (m, 1H), 3.74–3.77 (m, 1H), 5.13–5.18 (m, 2H), 5.46–5.49 (m, 1H), 5.86–5.95 (m, 1H), 7.38 (d, J = 3.6 Hz, 1H), 7.61 (t, J = 5.4 Hz, 1H), 7.74 (t, J = 5.4 Hz, 1H), 8.13 (d, J = 6.3 Hz, 1H), 8.36–8.43 (m, 2H), 8.88 (d, J = 3.6 Hz, 1H). 2.3. Synthesis of Brønsted acidic ionic liquids [Hmim]+ L− The Brønsted acidic ionic liquids were synthesized as shown in Scheme 2. In a typical process [53,54], a 100 mL three necked, round-bottom flask was charged with 1-methylimidazole (6.15 g, 75 mmol), which was allowed to cool to 0 ◦ C in an ice bath with stirring. Then 40% aqueous tetrafluoroboric acid (75 mmol) was added at a rate sufficient to maintain the reaction temperature at 0–5 ◦ C. After continuous stirring for another 2 h, water was evaporated under reduced pressure to afford the desired product 1-methylimidazolium tetrafluoroborate ([Hmim]+ BF4 − ) as a
Please cite this article in press as: L.-L. Lou, et al., Cinchona-derived prolinamide in Brønsted acidic ionic liquids: A novel and recyclable catalytic system for asymmetric aldol reaction, Catal. Today (2015), http://dx.doi.org/10.1016/j.cattod.2015.10.004
G Model
ARTICLE IN PRESS
CATTOD-9817; No. of Pages 6
L.-L. Lou et al. / Catalysis Today xxx (2015) xxx–xxx Table 1 Calculation of H0 of different Brønsted acidic ionic liquids.
0.6
a b c
a: blank + b: [Hmim] CH3CH(OH)COO
0.4
d
c: [Hmim] CH3COO
0.3
e
0.5
Absorbance
3
+
-
+
-
d: [Hmim] BF4 +
-
e: [Hmim] Cl + f: [Hmim] HSO4
f 0.2
Ionic liquid
ABSmax
[I] (%)
[HI+ ] (%)
H0
Blank [Hmim]+ CH3 CH(OH)COO− [Hmim]+ CH3 COO− [Hmim]+ BF4 − [Hmim]+ Cl− [Hmim]+ HSO4 −
0.541 0.502 0.473 0.411 0.318 0.252
100 92.8 87.4 76.0 58.8 46.6
0 7.2 12.6 24.0 41.2 53.4
− 2.10 1.83 1.49 1.14 0.93
Table 2 Asymmetric aldol reaction of 4-nitrobenzaldehyde with acetone in different ionic liquids.a
0.1
O
0.0
OH O
H 300
400
500
600
700
+
800
Wavelength (nm) Fig. 1. UV–vis absorption spectra of 4-nitroaniline in different Brønsted acidic ionic liquids.
colorless liquid. 1 H NMR (DMSO, 300 MHz) ı (ppm) 3.82 (s, 3 H), 7.51 (t, 1H), 7.57 (t, 1H), 8.78 (s, 1H). Other four ionic liquids including [Hmim]+ CH3 COO− , [Hmim]+ CH3 CH(OH)COO− , [Hmim]+ HSO4 − and [Hmim]+ Cl− were synthesized by following the same procedure as above except that acetic acid, lactic acid, sulfuric acid and hydrochloric acid were utilized, respectively, instead of tetrafluoroboric acid. 2.4. Asymmetric aldol reaction of acetone with aromatic aldehydes A typical procedure for the asymmetric aldol reaction was as follows. To a stirred solution of catalyst 1 (0.03 mmol) in ionic liquid (2.0 mL), acetone (0.5 mL) was added. The reaction mixture was stirred at room temperature for 30 min. The aldehyde (0.3 mmol) was then added and the reaction continued at room temperature. As the reaction was complete as determined by TLC, the reaction mixture was extracted by diethyl ether (5 mL 3×), and the combined organic layer was concentrated in vacuo and purified using column chromatography on silica gel eluting with the appropriate mixture of ethyl acetate/petroleum ether to afford the pure aldol product. The remaining ionic liquid phase containing catalyst 1 was dried in vacuo and subjected to the next run. 3. Results and discussion 3.1. Brønsted acidities of ionic liquids The Brønsted acidities of ionic liquids were evaluated by determining the Hammett acidity functions (H0 ) using UV–vis spectroscopy [55,56]. The Hammett function (H0 ) is defined as H0 = pK(I)aq + log([I]s /[IH+ ]s ) where pK(I)aq is the pKa value of the indicator referred to an aqueous solution, [I]s and [IH+ ]s are the molar concentrations of unprotonated and protonated forms of the indicator in the solvent, respectively. The Brønsted acidities of different ionic liquids were determined with 4-nitroaniline (pK(I)aq = 0.99) as indicator and ethanol as solvent. As shown in Fig. 1, the maximum absorbance of the unprotonated form of the indicator can be observed at 372 nm in ethanol, which decreased with the addition of ionic liquids, indicating that the indicator was partially in the form as [IH+ ]. Thus the [I]/[IH+ ] ratio could be determined from the measured absorbances, and then the Hammett function H0 of different ionic
1/ionic liquid r.t.
O2N Entry 1 2 3 4 5
O
* O 2N
Ionic liquid +
−
[Hmim] BF4 [Hmim]+ CH3 CH(OH)COO− [Hmim]+ CH3 COO− [Hmim]+ Cl− [Hmim]+ HSO4 −
t (h)
Yield (%)b
Conv. (%)
ee (%)c
36 24 6 48 48
65 74 – <5 <5
>99 >99 >99 – –
51 44 65 – –
a Reactions were performed with 0.3 mmol of 4-nitrobenzaldehyde and 0.5 mL of acetone and 2.0 mL of ionic liquid in the presence of 10 mol% of 1 at room temperature. b Isolated yield. c ee % were determined by HPLC. The absolute configuration was S.
liquids was calculated. As listed in Table 1, the type of anions has great effect on the acidities of ionic liquids. [Hmim]+ HSO4 − exhibits a stronger Brønsted acidity than the other four ionic liquids, and the Brønsted acidity of [Hmim]+ CH3 CH(OH)COO− is relatively weak. The Brønsted acidity order of the ionic liquids is as follows: [Hmim]+ HSO4 − > [Hmim]+ Cl− > [Hmim]+ BF4 − > [Hmim]+ CH3 COO− > [Hmim]+ CH3 CH(OH)COO− . 3.2. Asymmetric aldol reaction with different acidic ionic liquids The direct aldol reaction of 4-nitrobenzaldehyde with acetone catalyzed by 1 in different acidic ionic liquids was carried out and the results are listed in Table 2. When [Hmim]+ BF4 − was used, the reaction proceeded to completion in 36 h to afford the product in 65% yield and 51% ee. As compared with [Hmim]+ BF4 − , higher catalytic activity while lower enantioselectivity were achieved for the aldol reaction with ionic liquid [Hmim]+ CH3 CH(OH)COO− (Table 2, entry 2). Among the ionic liquids investigated, the utilization of [Hmim]+ CH3 COO− led to the best catalytic performance. In [Hmim]+ CH3 COO− , the reaction completed within 6 h to give the product in 65% ee. Very low catalytic activity was produced when the other two ionic liquids, [Hmim]+ HSO4 − and [Hmim]+ Cl− , were used. These results indicate that the catalytic performance is closely related to the ionic liquid acidity, and that a suitable Brønsted acidity level has a beneficial effect on the catalytic performance. Higher activity and enantioselectivity can be achieved when [Hmim]+ CH3 COO− was employed. And the reactions both in stronger and weaker acidic ionic liquids gave inferior catalytic performance. However, it should be noted that when [Hmim]+ CH3 COO− was employed, the separation of the reaction products from this ionic liquid phase was unsuccessful by extraction with various organic solvents. While for other four ionic liquids, the reaction products could be readily separated by solvent extraction from the ionic liquid phase and the catalyst 1 retained in ionic liquids could be reused. With regard to both the catalytic performance and catalyst reusability, [Hmim]+ BF4 − was identified as
Please cite this article in press as: L.-L. Lou, et al., Cinchona-derived prolinamide in Brønsted acidic ionic liquids: A novel and recyclable catalytic system for asymmetric aldol reaction, Catal. Today (2015), http://dx.doi.org/10.1016/j.cattod.2015.10.004
G Model
ARTICLE IN PRESS
CATTOD-9817; No. of Pages 6
L.-L. Lou et al. / Catalysis Today xxx (2015) xxx–xxx
4
Table 3 Asymmetric aldol reaction of 4-nitrobenzaldehyde with acetone under different conditions.a Entry
Amount of [Hmim]+ BF4 − (mL)
T (◦ C)
Amount of 1 (mol%)
t (h)
Yield (%)
ee (%)
1 2 3 4 5 6 7
1.0 2.0 3.0 1.0 1.0 1.0 1.0
Rt Rt Rt 0 40 Rt Rt
10 10 10 10 10 5 15
24 36 48 24 24 24 24
66 65 59 22 65 15 68
60 51 51 57 51 54 62
a
Reactions were performed with 0.3 mmol of 4-nitrobenzaldehyde and 0.5 mL of acetone.
Table 4 Asymmetric aldol reaction of acetone to 4-nitrobenzaldehyde with various cosolvents.a Entry 1 2 3 4 5 6 7 8 9 10
Co-solvent Acetone CH2 Cl2 CHCl3 THF Et2 O DMF DMSO CH3 CN MeOH H2 O
Yield (%) 80 67 75 80 78 56 49 65 36 70
ee (%) 67 67 59 64 55 62 56 46 62 57
a Reactions were performed with 0.3 mmol of aromatic aldehyde, 0.5 mL of acetone and 0.5 mL of co-solvent in 1.0 mL of [Hmim]+ BF4 − in the presence of 10 mol% of 1 at room temperature for 24 h.
the suitable acidic ionic liquid and was selected for further studies to optimize the reaction conditions. 3.3. Effects of reaction conditions on the asymmetric aldol reaction The effect of ionic liquid amount on the catalytic activity and enantioselectivity for direct aldol reaction was investigated. As shown in Table 3, with the increase of the amount of [Hmim]+ BF4 − , the reaction proceeded more slowly, meanwhile, the yield and ee value decreased gradually, which may be explained by the relatively higher diffusional resistance in the reaction system. An optimum result with 66% yield and 60% ee was achieved in 24 h as the reaction was operated using 1.0 mL of ionic liquid. The effects of reaction temperature and catalyst amount on the catalytic performance are also displayed in Table 3. It could be found that the catalytic activity increased remarkably with the increasing of reaction temperature. A much lower yield of 22% was obtained as the reaction was carried out at 0 ◦ C for 24 h with an ee value of 57%. The reaction at room temperature furnished the aldol product in 66% yield and 60% ee. A further increase in reaction temperature to 40 ◦ C led to a lower ee of 51%. Thus the following reactions in the present work were all conducted at room temperature. The data listed in Table 3 also revealed that the catalyst amount had a significant effect on the catalytic activity for the asymmetric aldol reaction. A pronounced increase in yield from 15% to 66% could be observed when the catalyst amount was increased from 5 mol% to 10 mol%, while the enantioselectivity was found not to depend markedly on the catalyst amount. Further increasing the catalyst amount caused no obvious enhancement in yield as well as in ee value (Table 3, entry 7). It should be noted that the catalyst amount of 10 mol% was three times lower with respect to the use of proline in the previous reports [9,35,36,43,44]. In attempt to further improve the catalytic activity and enantioselectivity, co-solvents were employed. As shown in Table 4, a variety of co-solvents were screened in the model reaction between 4-nitrobenzaldehyde and acetone. It could be found that the
Table 5 Asymmetric aldol reaction of 4-nitrobenzaldehyde with acetone in different conditions.a Entry 1 2 3 4 5 6
Ionic liquid +
−
[Hmim] BF4 – [Bmim]+ BF4 − [Hmim]+ BF4 − [Hmim]+ BF4 − [Hmim]+ BF4 −
Acid additiveb
Yield (%)
ee (%)
– – – Benzoic acid Catechol Acetic acid
80 78 39 77 81 75
67 44 45 62 65 65
a Reactions were performed with 0.3 mmol of aromatic aldehyde and 1.0 mL of acetone in 1.0 mL of ionic liquid in the presence of 10 mol% of 1 at room temperature for 24 h. b The amount of acid additive was 10 mol%.
utilization of the co-solvents with relatively low polarity, such as THF, acetone, Et2 O, CHCl3 , and CH2 Cl2 , generally led to the enhancement of isolated yields. For example, an increase in yield from 66% to 80% was achieved when THF or acetone was used as co-solvent. Improved ee values were produced with the addition of acetone, CH2 Cl2 and THF, while inferior enantioselectivities were presented by using Et2 O and CHCl3 as co-solvents. The utilization of highly polar organic solvents showed a negative effect on the catalytic activities (Table 4, entries 6–9). Among all the co-solvents studied, polar protic solvent MeOH gave the lowest activity, which may be due to the detrimental effect of alcoholic solvents on the hydrogen bonding interaction between the catalyst and the substrate. It could be also observed that a lower ee of 46% was obtained when CH3 CN was selected. Besides the organic solvents, water as a green solvent was also applied in the reaction, and a good yield of 70% with an ee of 57% was achieved. Thus acetone was considered as the most suitable one among the co-solvents examined with regard to both the yield and enantioselectivity, and the corresponding reaction afforded the product in 80% yield and 67% ee. The Brønsted acid additive was considered to be important to facilitate the enamine-based organocatalytic asymmetric aldol reaction [5,9,14,15,18]. The ionic liquid [Hmim]+ BF4 − , as a strong Brønsted acid, acts here not only as a solvent, but also as a Brønsted acid additive for the reaction. In order to investigate the effect of Brønsted acidic ionic liquids on the catalytic performance, the reaction without any ionic liquids was performed under otherwise identical conditions. As shown in Table 5, a high yield of 78% and a low ee of 44% were achieved. This indicates that the asymmetric aldol reaction between 4-nitrobenzaldehyde and acetone can occur with relatively low enantioselectivity in the presence of prolinamide catalyst 1 without any acid additive, which is in accordance with that reported in the literature [18]. For the purpose of comparison, a neutral iminazolium-based ionic liquid [Bmim]+ BF4 − was also synthesized according to the method we previously reported [57] and applied in the asymmetric aldol reaction of 4-nitrobenzaldehyde with acetone. It could be found that the reaction in [Bmim]+ BF4 − proceeded very slowly, and a low yield of 39% along with a relatively low ee of 45% was obtained after 24 h (Table 5, entry 3). This documented that the introduction of common ionic liquids had no positive effect on the enantioselectivity
Please cite this article in press as: L.-L. Lou, et al., Cinchona-derived prolinamide in Brønsted acidic ionic liquids: A novel and recyclable catalytic system for asymmetric aldol reaction, Catal. Today (2015), http://dx.doi.org/10.1016/j.cattod.2015.10.004
G Model
ARTICLE IN PRESS
CATTOD-9817; No. of Pages 6
L.-L. Lou et al. / Catalysis Today xxx (2015) xxx–xxx Table 6 Asymmetric aldol reaction of acetone to various aromatic aldehydes.a
O
80
OH O +
1/[Hmim]+BF4r.t.
Yield ee
O
* R
60
Entry
R
Yield (%)
ee (%)c
1 2 3 4 5 6 7 8 9
4-NO2 2-NO2 4-Cl 2-Cl 2,4-Cl2 4-Br 4-F 4-CF3 4-CN
80 73 78 77 86 61 69 74 72
67 70 71 74 78 76 75 82 84
%
H
R
5
40
20
0 1
a
Reactions were performed with 0.3 mmol of aromatic aldehyde and 1.0 mL of acetone and 1.0 mL of [Hmim]+ BF4 − in the presence of 10 mol% of 1 at room temperature for 24–120 h.
and led to a notable decrease in the catalytic efficiency due mainly to the mass transfer limitation in ionic liquid system. Comparing these results with those achieved in [Hmim]+ BF4 − , it can be concluded that the utilization of Brønsted acidic ionic liquids can not only increase the product enantioselectivity but also accelerate the catalytic reaction. In an attempt to get further insight into the role of [Hmim]+ BF4 − , the control experiments were carried out by the use of additional acid additives including benzoic acid, catechol and acetic acid. The results, given in Table 5, showed that the employment of these three acid additives had no obviously positive effects on the enhancement of catalytic performance. The superior activity and enantioselectivity were achieved when the reaction was performed in [Hmim]+ BF4 − without any other acid additive. 3.4. Asymmetric aldol reaction of various aromatic aldehydes With the optimized reaction conditions in hand, the substrate scope of the catalytic asymmetric aldol reaction was then explored. As shown in Table 6, all the aromatic aldehydes examined underwent reaction with acetone to furnish the corresponding aldol product in moderate to high yields and ee values with the presence of 10 mol% of catalyst at room temperature. In general, reactions of the aromatic aldehydes with ortho substituents afforded products in lower yields but slightly higher ee values than those with para substituents, which may be due to the greater steric hindrance of ortho substituents (Table 6, entries 1 and 3 vs. 2 and 4). 4-Nitrobenzaldehyde gave a better yield and lower ee than 4-halogen aromatic aldehydes. The dichlorine-substituted benzaldehyde was found to be more reactive and enantioselective than mono-substituted aldehydes (Table 6, entries 3 and 4 vs. 5). 4-(Trifluoromethyl)benzaldehyde was converted to the corresponding -hydroxy ketone in a moderate yield of 74% and a high ee of 82%. Moreover, the reaction of 4-cyanobenzaldehyde with acetone provided the best ee value of 84% with a yield of 72%. 3.5. Catalyst recycling and stability The recyclability of catalyst system 1/[Hmim]+ BF4 − was investigated in the model reaction of 4-nitrobenzaldehyde and acetone. On completion of each reaction, the reaction mixture was extracted by diethyl ether, and the ionic liquid phase containing catalyst 1 was subjected to the next run with a fresh batch of acetone and aldehyde. As shown in Fig. 2, the catalytic activity and enantioselectivity remained basically unchanged in the first three runs. A yield of 78% along with an ee value of 64% was achieved in the third
2
3
4
Run Fig. 2. Recycle studies of 1/[Hmim]+ BF4 − in the asymmetric aldol reaction of 4nitrobenzaldehyde with acetone.
run. While a decrease in yield and ee value was observed in the subsequent fourth run. This may be probably due to the catalyst system 1/[Hmim]+ BF4 − being partially extracted into the organic phase during the recycling procedures. Indeed, about 10% of mass loss was found for the ionic liquid phase containing catalyst 1 after four cycles. For the purpose of comparison, the catalyst 1 supported in neutral ionic liquid [Bmim]+ BF4 − was also studied in the recycling experiments. It was found that the catalytic activity and enantioselectivity decreased significantly with each recycle. During the first three recycling runs, the yield declined from 30% to 18% then to 8%, and no reaction was observed after recycling three times. This indicated the chiral prolinamide catalyst in [Bmim]+ BF4 − has a greater tendency to be extracted into the organic phase than that in [Hmim]+ BF4 − . Thus it could be concluded that the introduction of acidic ionic liquid can significantly enhance the stability of the catalyst system due probably to the stronger interaction between the catalyst and ionic liquid.
4. Conclusion Brønsted acidic ionic liquids [Hmim]+ L− were applied in the asymmetric direct aldol reaction of acetone with aromatic aldehydes catalyzed by the prolinamide organocatalyst 1 derived from 9-amino epi-cinchonine. [Hmim]+ BF4 − was found to be the most suitable ionic liquid for the catalytic system, and the superior activity and enantioselectivity were achieved in 1.0 mL of [Hmim]+ BF4 − with neat acetone in the presence of 10 mol% of 1 at room temperature. The ionic liquid, as a Brønsted acid additive, was demonstrated to play a positive effect on the enhancement of catalytic performance. Moreover, the catalyst recycling experiments showed that the application of acidic ionic liquid could effectively improve the affinity of catalyst 1 to ionic liquid, thus increasing the catalyst stability. The catalyst 1 in [Hmim]+ BF4 − could be reused four times with only a slight loss of activity and enantioselectivity.
Acknowledgements We gratefully acknowledge the support of this research by the National Natural Science Foundation of China (Grant No. 21203102), the Tianjin Municipal Natural Science Foundation (Grant Nos. 14JCQNJC06000 and 14JCZDJC32000), MOE (IRT13R30) and 111 Project (B12015).
Please cite this article in press as: L.-L. Lou, et al., Cinchona-derived prolinamide in Brønsted acidic ionic liquids: A novel and recyclable catalytic system for asymmetric aldol reaction, Catal. Today (2015), http://dx.doi.org/10.1016/j.cattod.2015.10.004
G Model CATTOD-9817; No. of Pages 6
ARTICLE IN PRESS L.-L. Lou et al. / Catalysis Today xxx (2015) xxx–xxx
6
References [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] [22] [23] [24] [25] [26]
P.I. Dalko, L. Moisan, Angew. Chem. Int. Ed. 43 (2004) 5138–5175. A. Dondoni, A. Massi, Angew. Chem. Int. Ed. 47 (2008) 4638–4660. J.G. Hernandez, E. Juaristi, Chem. Commun. 48 (2012) 5396–5409. R. Mahrwald (Ed.), Modern Methods in Stereoselective Aldol Reactions, Wiley-VCH, Weinheim, Germany, 2013. S. Mukherjee, J.W. Yang, S. Hoffmann, B. List, Chem. Rev. 107 (2007) 5471–5569. J. Guillena, C. Najera, D.J. Ramon, Tetrahedron: Asymmetry 18 (2007) 2249–2293. B.M. Trost, C.S. Brindle, Chem. Soc. Rev. 39 (2010) 1600–1632. V. Bisai, A. Bisai, V.K. Singh, Tetrahedron 68 (2012) 4541–4580. B. List, R.A. Lerner, C.F. Barbas III, J. Am. Chem. Soc. 122 (2000) 2395–2396. K. Sakthivel, W. Notz, T. Bui, C.F. Barbas III, J. Am. Chem. Soc. 123 (2001) 5260–5267. S.K. Panday, Tetrahedron: Asymmetry 22 (2011) 1817–1847. Z. Tang, Z.-H. Yang, X.-H. Chen, L.-F. Cun, A.-Q. Mi, Y.-Z. Jiang, L.-Z. Gong, J. Am. Chem. Soc. 127 (2005) 9285–9289. Y. Hayashi, T. Sumiya, J. Takahashi, H. Gotoh, T. Urushima, M. Shoji, Angew. Chem. Int. Ed. 45 (2006) 958–961. N. Mase, Y. Nakai, N. Ohara, H. Yoda, K. Takabe, F. Tanaka, C.F. Barbas III, J. Am. Chem. Soc. 128 (2006) 734–735. S. Luo, H. Xu, J. Li, L. Zhang, J.-P. Cheng, J. Am. Chem. Soc. 129 (2007) 3074–3075. J. Huang, X. Zhang, D.W. Armstrong, Angew. Chem. Int. Ed. 46 (2007) 9073–9077. M. Vasiloiu, D. Rainera, P. Gaertner, C. Reichel, C. Schröder, K. Bica, Catal. Today 200 (2013) 80–86. J.-R. Chen, X.-L. An, X.-Y. Zhu, X.-F. Wang, W.-J. Xiao, J. Org. Chem. 73 (2008) 6006–6009. E.G. Doyagüez, F. Calderón, F. Sánchez, A. Fernández-Mayoralas, J. Org. Chem. 72 (2007) 9353–9356. J.S. Gao, J. Liu, J.T. Tang, D.M. Jiang, B. Li, Q.H. Yang, Chem. Eur. J. 16 (2010) 7852–7858. N. Hara, S. Nakamura, N. Shibata, T. Toru, Adv. Synth. Catal. 352 (2010) 1621–1624. S. Calogero, D. Lanari, M. Orrù, O. Piermatti, F. Pizzo, L. Vaccaro, J. Catal. 282 (2011) 112–119. H. Yang, S. Li, X. Wang, F. Zhang, X. Zhong, Z. Dong, J. Ma, J. Mol. Catal. A: Chem. 363–364 (2012) 404–410. R. Tan, C. Li, J. Luo, Y. Kong, W. Zheng, D. Yin, J. Catal. 298 (2013) 138–147. Z. An, Y. Guo, L. Zhao, Z. Li, J. He, ACS Catal. 4 (2014) 2566–2576. M. Gruttadauria, F. Giacalone, A.M. Marculescu, R. Notoa, Adv. Synth. Catal. 350 (2008) 1397–1405.
[27] S. Luo, J. Li, L. Zhang, H. Xu, J.-P. Cheng, Chem. Eur. J. 14 (2008) 1273–1281. [28] A. Lu, T.P. Smart, T.H. Epps, D.A. Longbottom, R.K. ÓReilly, Macromolecules 44 (2011) 7233–7241. [29] C. Ayats, A.H. Henseler, M.A. Pericàs, ChemSusChem 5 (2012) 320–325. [30] X. Zhang, W. Zhao, L. Yang, Y. Cui, J. Appl. Polym. Sci. 118 (2013) 3537–3542. [31] G. Sz"oll"osia, A. Csámpai, C. Somlai, M. Fekete, M. Bartók, J. Mol. Catal. A: Chem. 382 (2014) 86–92. [32] K. Bica, P. Gaertner, Eur. J. Org. Chem. (2008) 3235–3250. [33] Y. Qiao, A.D. Headley, Catalysts 3 (2013) 709–725. [34] S. Luo, X. Mi, L. Zhang, S. Liu, H. Xu, J.-P. Cheng, Angew. Chem. Int. Ed. 45 (2006) 3093–3097. [35] W. Miao, T.H. Chan, Adv. Synth. Catal. 348 (2006) 1711–1718. [36] M. Gruttadauria, S. Riela, C. Aprile, P. Lo Meo, F. D’Anna, R. Noto, Adv. Synth. Catal. 348 (2006) 82–92. [37] V. Gauchot, A.R. Schmitzer, J. Org. Chem. 77 (2012) 4917–4923. [38] T. Welton, Chem. Rev. 99 (1999) 2071–2083. [39] P. Wasserscheid, W. Keim, Angew. Chem. Int. Ed. 39 (2000) 3772–3789. [40] V.I. Pârvulescu, C. Hardacre, Chem. Rev. 107 (2007) 2615–2665. [41] M. Petkovic, K.R. Seddon, L.P.N. Rebelo, C.S. Pereira, Chem. Soc. Rev. 40 (2011) 1383–1403. [42] J.P. Hallett, T. Welton, Chem. Rev. 111 (2011) 3508–3576. [43] T.-P. Loh, L.-C. Feng, H.-Y. Yang, J.-Y. Yang, Tetrahedron Lett. 43 (2002) 8741–8743. ˇ Toma, E. Solˇcániová, Chem. Commun. [44] P. Kotrusz, I. Kmentová, B. Gotov, S. (2002) 2510–2511. [45] A. Córdova, Tetrahedron Lett. 45 (2004) 3949–3952. [46] H.-M. Guo, L.-F. Cun, L.-Z. Gong, A.-Q. Mi, Y.-Z. Jiang, Chem. Commun. (2005) 1450–1452. [47] M. Lombardo, F. Pasi, S. Easwar, C. Trombini, Adv. Synth. Catal. 349 (2007) 2061–2065. [48] J. Shah, H. Blumenthal, Z. Yacob, J. Liebscher, Adv. Synth. Catal. 350 (2008) 1267–1270. [49] M. Lombardo, S. Easwar, F. Pasi, C. Trombinia, D.D. Dhavale, Tetrahedron 64 (2008) 9203–9207. [50] Y. Qian, X. Zheng, Y. Wang, Eur. J. Org. Chem. (2010) 3672–3677. [51] X. Zhang, W. Zhao, C. Qu, L. Yang, Y. Cui, Tetrahedron: Asymmetry 23 (2012) 468–473. [52] B. Vakulya, S. Varga, A. Csámpai, T. Soós, Org. Lett. 7 (2005) 1967–1969. [53] J.D. Holbrey, K.R. Seddon, J. Chem. Soc. Dalton Trans. (1999) 2133–2139. [54] H.-P. Zhu, F. Yang, J. Tang, M.-Y. He, Green Chem. 5 (2003) 38–39. [55] C. Thomazeau, H. Olivier-Bourbigou, L. Magna, S. Luts, B. Gilbert, J. Am. Chem. Soc. 125 (2003) 5264–5265. [56] H. Xing, T. Wang, Z. Zhou, Y. Dai, J. Mol. Catal. A: Chem. 264 (2007) 53–59. [57] L.-L. Lou, Y. Dong, K. Yu, S. Jiang, Y. Song, S. Cao, S. Liu, J. Mol. Catal. A: Chem. 333 (2010) 20–27.
Please cite this article in press as: L.-L. Lou, et al., Cinchona-derived prolinamide in Brønsted acidic ionic liquids: A novel and recyclable catalytic system for asymmetric aldol reaction, Catal. Today (2015), http://dx.doi.org/10.1016/j.cattod.2015.10.004