Polymer-immobilized pyrrolidine-based chiral ionic liquids as recyclable organocatalysts for asymmetric Michael additions to nitrostyrenes under solvent-free reaction conditions

Article abstract of DOI:10.1002/ejoc.200701037

A polymer immobilized pyrrolidine-based chiral ionic liquid 5a was synthesized and was found to be a highly efficient catalyst for the Michael additions of ketones and aldehydes to nitrostyrenes, which afforded the corresponding adducts in good yields (up

Full text of DOI:10.1002/ejoc.200701037

SHORT COMMUNICATION
DOI: 10.1002/ejoc.200701037
Polymer-Immobilized Pyrrolidine-Based Chiral Ionic Liquids as Recyclable
Organocatalysts for Asymmetric Michael Additions to Nitrostyrenes under
Solvent-Free Reaction Conditions
[a]
[a,b]
[a]
[a]
Pinhua Li, Lei Wang,*
Min Wang, and Yicheng Zhang
Keywords: Immobilized chiral ionic liquids / Asymmetric Michael additions / Organocatalysis / Nitrostyrenes / Solvent-
free reactions
A polymer immobilized pyrrolidine-based chiral ionic liquid
a was synthesized and was found to be a highly efficient
catalyst for the Michael additions of ketones and aldehydes
to nitrostyrenes, which afforded the corresponding adducts
in good yields (up to 97%), excellent enantioselectivities (up
to Ͼ99% ee) and high diastereoselectivities (up to Ͼ99:1 dr)
under solvent-free reaction conditions. In addition, the cata-
lyst 5a could be reused at least eight times without a signifi-
cant loss of its catalytic activity and stereoselectivity.
5
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2008)
Introduction
organic reactions. In recent years, immobilization of chiral
organocatalysts on supports has received considerable inter-
est. Much effort has been spent to develop asymmetric or-
ganic reactions catalyzed by supported organocatalysts. -
Asymmetric carbon–carbon bond and carbon–hetero-
atom bond-forming reactions are among the most challeng-
ing endeavors in organic synthesis, and much attention has
been paid to design and application of organocatalysts for
asymmetric reactions in recent years.[ The asymmetric
Michael addition reactions of nucleophiles to nitroalkenes
have attracted much attention from a large number of or-
ganic chemists working in the area of an easy transforma-
tion of the versatile nitro functionality into an amine, nitrile
Proline supported on silical gel, polymers, and ionic liquids
[12]
has been successfully used in aldol reactions.
Recently,
1]
some recyclable organocatalysts, such as fluorous pyrrolidine
[13]
sulfonamides,
catalysts,
ionic liquid supported pyrrolidine-based
[14]
[15]
and polymer-supported thiourea catalysts
for the asymmetric Michael addition of ketones and alde-
hydes with nitroolefins have also been developed. We were
pleased to find that the novel designed polymer-supported
pyrrolidine-based organocatalysts 5a, 5b and 5c, which were
easily prepared from (S)-Boc--proline as shown in
Scheme 1, catalyzed the reactions of ketones and aldehydes
with aryl-substituted nitroolefins smoothly at room tem-
perature in high yields with excellent diastereoselectivities
and enantioselectivities under solvent-free reaction condi-
tions (Scheme 1).
[
2]
oxide, ketone, carboxylic acid, hydrogen atom, etc. In the
past decade, various enantioselective processes have been
[
3]
developed by using chiral ligand–metal complexes and
metal-free chiral organocatalysts[
1c–1f]
as catalysts. The or-
ganocatalytic asymmetric Michael addition of ketones with
nitroolefins was pioneered by List[ and Barbas, indepen-
dently. Since then, interest in the field of asymmetric
Michael addition has increased intensively, and various ef-
fective organocatalysts have been developed, such as modi-
4]
[5]
[
6]
[7]
fied -prolines, pyrrolidine-based diamines, chiral di-
[
8]
[9]
amines, chiral guanidines, cinchona alkaloid based bi-
Results and Discussion
[
10]
functional organocatalysts,
urea(thiourea)-based bifunc-
tional organocatalysts,[ etc. Environmental concerns as-
11]
Initially, various solvents and additives were examined at
sociated with chemical processes have encouraged the devel- room temperature using 5a as a catalyst and (E)-β-nitrosty-
opment of environmentally more friendly methodologies for rene as a substrate. The Michael addition of cyclohexanone
to nitrostyrene was chosen as a model reaction. As shown
in Table 1, the Michael addition reactions proceeded
[
a] Department of Chemistry, Huaibei Coal Teachers College,
Huaibei, Anhui 235000, P. R. China
Fax: +86-561-3090-518
smoothly in polar solvents, such as CH CN, EtOH, DMF
3
and H O, to generate the products in moderate to excellent
2
E-mail: leiwang@hbcnc.edu.cn
[
b] State Key Laboratory of Organometallic Chemistry, Shanghai yields with excellent enantioselectivities and diastereoselec-
Institute of Organic Chemistry, Chinese Academy of Sciences,
tivities (Entries 1–4, Table 1), whereas using Et O, CH Cl
2
2
2
Shanghai 200032, P. R. China
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
and THF as solvents resulted in poor yields and similar
enantioselectivities and diastereoselectivities (Entries 5–7,
Eur. J. Org. Chem. 2008, 1157–1160
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1157

P. Li, L. Wang, M. Wang, Y. Zhang
SHORT COMMUNICATION
Scheme 1. Synthesis of polymer-immobilized pyrrolidine-based chiral ionic liquids 5a, 5b and 5c and their applications in the Michael
additions.
Table 1). The Michael additions also proceeded smoothly Table 1. Optimization of the reaction conditions.[a]
in nonpolar solvents, such as toluene and hexane, to give
the products in excellent yields with excellent enantio-
selectivities and diastereoselectivities (Entries 8–9, Table 1).
However, a slightly higher yield with similar enantio-
selectivity and diastereoselectivity were observed under sol-
Entry
Catalyst
Solvent
CH CN
EtOH
DMF
Yield[b] (%)
ee[c] (%)
dr[d]
vent-free reaction conditions (Entry 10, Table 1). Moreover,
a slightly higher enantioselectivity and almost the same dia-
stereoselectivity were achieved when the reaction tempera-
ture was lowered to 0 °C, without a significant decrease of
the reaction rate (Entry 14, Table 1). Interestingly, the ad-
dition of a catalytic amount of an organic acid, such as
TFA, could reduce dramatically the reaction rate along with
a loss of enantiomeric excess (Entry 11, Table 1). It was also
found that the reaction was accomplished as it was carried
out for more than 24 h (Entry 12, Table 1). It should be
noted that good isolated yield, ee and dr were obtained
when up to 10 mol-% of 5a active units was added to the
reaction mixture. A lower yield of the Michael addition
product was isolated when less than 10 mol-% of 5a loading
was used in the reaction (Entry 13, Table 1). Under stan-
dard reaction conditions, but use of catalysts 5b and 5c in-
1
2
3
4
5
6
7
8
9
5a
5a
5a
5a
5a
5a
5a
5a
5a
5a
5a
5a
5a
5a
5b
5c
3
86
90
75
80
25
40
36
94
95
97
90
82
78
95
91
94
98
98
99
99
98
98
98
98
99
99
91
98
98
Ͼ99
98
99
98:2
99:1
98:2
99:1
98:2
98:2
98:2
98:2
98:2
99:1
97:3
99:1
99:1
99:1
99:1
99:1
2
H O
Et O
2
2 2
CH Cl
THF
hexane
toluene
neat
neat
neat
neat
neat
neat
neat
1
0
11[
e]
[f]
12
[g]
13
[h]
14
15
16
[
a] Nitrostyrene (1.0 mmol), cyclohexanone (2.0 mmol), catalyst 5
(
contains 0.10 mmol of active loading), in solvent (2 mL) at room
stead of 5a, the Michael adducts were also obtained, and temperature for 24 h. [b] Isolated yields. [c] Determined by HPLC
–
–
–
using chiralpak AD-H column. [d] Diasteromeric ratio, dr
the exchange of Br for BF and PF , respectively, has
4
6
1
(
syn/anti), determined by H NMR spectroscopy. [e] 5 mol-% TFA
no obvious effects on both the activities and selectivities
Entries 15 and 16, Table 1).
was added at room temperature, and the reaction time was 48 h. [f]
(
The reaction time was 12 h. [g] 5 mol-% of catalyst 5a was added.
Under the optimized reaction conditions for Michael [h] The reaction temperature was 10 °C.
additions of nitroolefins with ketones, which involve the use
of 5 mol-% of 5a as catalyst in the absence of solvent at
room temperature for 24 h, the reactions of a variety of diastereoselectivities and enantioselectivities (Entries 1–16,
nitroolefins with different substituents and ketones and Table 2). Generally, substituents on aryl groups slightly in-
aldehydes were investigated, and the results are summarized fluenced the diastereoselectivities and enantioselectivities,
in Table 2. Various styrene-type nitroolefins reacted as well as the yields. For example, phenyl rings in nitro-
smoothly with cyclohexanone in high yields with excellent olefins with both electron-withdrawing and -donating
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© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 1157–1160

Polymer-Immobilized Pyrrolidine-Based Chiral Ionic Liquids
Table 2. Michael additions of ketones and an aldehyde to (E)-β-nitrostyrenes catalyzed by 5a.[a]
[
a] Nitroolefin (1.0 mmol), ketone or aldehyde (2.0 mmol), 5a (contains 0.10 mmol of active loading), under solvent-free reaction condi-
tions at room temperature for 24 h. [b] Isolated yields. [c] Determined by HPLC using chiralpak AD-H column. [d] Diasteromeric ratio,
dr (syn/anti), determined by H NMR spectroscopy. [e] At 0 °C for 48 h.
1
groups gave the desired products with high selectivities (up product was obtained when an aliphatic substituted nitro-
to Ͼ99:1 dr and up to Ͼ99% ee) in excellent yields. Unfor- olefin was used as substrate (Entry 17, Table 2). Moreover,
tunately, a medium yield but good enantioselectivity of the Michael reactions were evaluated with other ketones,
Eur. J. Org. Chem. 2008, 1157–1160
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
1159

P. Li, L. Wang, M. Wang, Y. Zhang
SHORT COMMUNICATION
and it was found that tetrahydrothiopyran-4-one and tetra- Acknowledgments
hydro-4H-pyran-4-one were also suitable substrates as
Michael donors (Entries 18 and 19, Table 2). However,
We gratefully acknowledge financial support by the National
Natural Science Foundation of China (No. 20772043,
acetone, cyclopentanone and isobutyraldehyde served as 20572031).
efficient Michael donors to generate the desired adducts
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[
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Supporting Information (see footnote on the first page of this arti-
cle): Experimental details, preparation of polymer-immobilized
pyrrolidine-based chiral ionic liquids, experimental procedure for
Michael addition reactions, spectral and HPLC data.
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Received: November 5, 2007
Published Online: January 29, 2008
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Eur. J. Org. Chem. 2008, 1157–1160