Surfactant-type asymmetric organocatalyst: Organocatalytic asymmetric Michael addition to nitrostyrenes in water

Article abstract of DOI:10.1039/b607846j

A surfactant-type asymmetric organocatalyst (STAO) catalyzed highly efficient Michael addition to nitroalkenes with high stereoselectivities in water without using any organic solvents or additional additives. The Royal Society of Chemistry 2006.

Full text of DOI:10.1039/b607846j

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Surfactant-type asymmetric organocatalyst: organocatalytic
asymmetric Michael addition to nitrostyrenes in water{
Sanzhong Luo,*a Xueling Mi,b Song Liu,b Hui Xua and Jin-Pei Cheng*ab
Received (in Cambridge, UK) 2nd June 2006, Accepted 3rd July 2006
First published as an Advance Article on the web 28th July 2006
DOI: 10.1039/b607846j
Lewis acid–surfactant combined catalysts (LASCs) developed by
A surfactant-type asymmetric organocatalyst (STAO) catalyzed
highly efficient Michael addition to nitroalkenes with high
stereoselectivities in water without using any organic solvents or
additional additives.
Kobayashi et al.8 and independently by Engberts and co-workers,9
have been successfully applied to a range of organic reactions in
water. Recently, LASCs in combination with chiral ligands have
been used as asymmetric catalysts in water.10 These studies
encouraged us to anticipate that a surfactant appended with a
catalytic head-group (in most cases, a catalytic counterion) would
suffice for smooth catalysis in pure water and that an extension to
asymmetric catalysis would be achieved by changing achiral
catalytic groups for chiral ones such as those in surfactant-type
asymmetric organocatalysts (STAOs). In fact, asymmetric catalysis
in water has previously been attempted using surfactants with
chiral head-groups, albeit with low enantioselectivity.4,11 To the
best of our knowledge, no highly efficient catalyst of the chiral
surfactant type has been reported up to now. To test our
hypothesis, Michael addition of cyclohexanone to nitrostyrene was
carried out in water using a series of surfactant-type asymmetric
organocatalysts.12
Catalytic asymmetric reactions in water have been the subject of
considerable research efforts in the past decade because water is an
inexpensive, safe and environmentally benign reaction medium and
it often exerts a synergistic effect on the reactivity and selectivity.1
Asymmetric organocatalysts have been recognized as the ‘‘simplest
enzyme’’ mimic.2 However, unlike enzymatic reactions in
nature, organocatalytic processes have typically been carried out
in organic solvents and, if using bulk water as the reaction medium,
low yields or low selectivity are usually observed.2a,3
Surfactants are frequently employed in order to perform
reactions in water1,4 and this strategy has also been attempted in
organocatalysis, but met with only limited success.5 Based on our
previous work on chiral ionic-liquid-type organocatalysts,6 we
envisaged that surfactant type asymmetric organocatalysts
(STAOs) that were obtained by replacing the anions with
surfactant sulfate or sulfonate (Scheme 1) might act as efficient
asymmetric catalysts in water. This kind of catalyst would
simultaneously function as an asymmetric catalyst to promote
the reactions and at the same time as a surfactant to assist in
solubilizing the organic substrates. This hypothesis should be
conceivable because (1) according to recent studies, ionic liquids
with long-chain alkyl sulfate anions still maintain the properties of
surfactants and could efficiently solubilize organic substrates in
water;7 and (2) surfactants with catalytic head groups such as
Previously, we have reported chiral ionic-liquid-type catalysts
(for example, 1a) as highly efficient organocatalysts for Michael
addition to nitroolefins under neat conditions.6 Although this type
of organocatalyst is well soluble in water, our initial efforts on an
aqueous version of the reaction using chiral ionic liquids such as
4–6 were unsuccessful (Table 1, entries 1–4 and 12). The reactions
in water resulted in poor yields or even no desired product but
insoluble material. For example, the reaction catalyzed by chiral
ionic liquids such as 1a and 3a afforded no desired product or poor
yield (Table 1, entries 1 and 11), due to the polymerization of
b-nitrostyrene in water.13 Increasing the side-chain length of the
imidazolium cation improved the product yields, but the
polymerization pathway still dominated (Table 1, entries 3–4).
Surfactant effect was also examined in our study. Chiral ionic
liquid 1a in combination with SDS (20 mol%) gave 27% yield of
Michael addition product along with polymerized by-product
(Table 1, entry 5). Further increase of the SDS loading amount
showed no improvement in the reaction and only traces of product
were observed (Table 1, entry 6).
Scheme 1 Synthesis of surfactant-type asymmetric organocatalysts
(STAOs) by (a) anion metathesis and (b) neutralization.
aBeijing National Laboratory for Molecular Sciences (BNLMS),
Centre for Molecular Science, Institute of Chemistry, Chinese Academy
of Science, Beijing, 100080, China. E-mail: luosz@iccas.ac.cn;
Fax: +86-10-62554449; Tel: +86-1062554446
Inspired by the success of LASCs, we then synthesized
surfactant-type asymmetric organocatalysts (Fig. 1) simply by
anion metathesis of chiral imidazolium bromides with surfactant
sodium salts or by neutralization of chiral imidazolium hydroxides
with surfactant Brønsted acid (Scheme 1). To our delight, the
reactions catalyzed by these catalysts provided much better yields
bDepartment of Chemistry and State-key Laboratory of Elemento-
organic Chemistry, Nankai University, Tianjin, 300071, China.
{ Electronic supplementary information (ESI) available: Experimental
procedures. See DOI: 10.1039/b607846j
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Chem. Commun., 2006, 3687–3689 | 3687

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97% ee. Further screening (Fig. 1) identified 3c as our current
optimal catalyst. In the presence of 20 mol% of 3c, the Michael
addition of cyclohexanone to nitrostyrene afforded 93% yield and
97% ee in 12 h (Table 1, entry 14). In sharp contrast, simple
combination of 2 with sodium dodecylbenzenesulfonate in water
resulted in almost complete polymerization (Table 1, entry 12).
These results along with the inefficiency of 3c under neat
conditions (Table 1, entry 15) indicated the unique properties of
3c as a highly efficient asymmetric organocatalyst in water. The
loading of 3c could be reduced to 15 mol% without comprising the
stereoselectivity (Table 1, entry 16).
Table 1 Screening of surfactant-type asymmetric organocatalysts
(STAOs) for Michael addition of cyclohexanone (5.0 equiv.) to
b-nitrostyrene in water
Entry
Catalyst
t/h
Yield (%)a
syn : antib
ee (%)c
1
2
3
1a
4
5
24
12
24
24
12
12
12
12
24
22
12
12
12
12
12
23
12
npd,e
npd,e
14e
—
—
—
nd
nd
88
—
The catalysis by surfactant-type asymmetric organocatalysts was
generally carried out in pure water without any co-catalyst. Acidic
additives such as trifluoroacetic acid (TFA), previously reported as
essential co-catalysts in chiral ionic-liquid catalysis,6 was no longer
necessary in the aqueous reaction (Table 1, entry 8 vs. 9). The
reaction was initialized simply by mixing substrates with 3c in
water, and the reaction mixture immediately turned to a white
colloid type solution upon stirring (see ESI{). During the reaction,
vigorous stirring should be maintained. When stirring was stopped
after the initial 30 min, the reaction became sluggish and afforded
only 48% yield after 12 h (Table 1, entry 17). These results suggest
that the reaction should occur through interfacial catalysis.8 When
stirring is maintained, it enhances the interfacial collisions in a
colloid-type solution and, as a consequence, leads to fast reaction
and vice versa.8,14 At this stage, the high activity of 3c in
inhomogeneous aqueous solution is not fully understood and may
be rationalized by considering the hydrophobic effect in an
aqueous micellar system.4,15
ndf
nd
4
6
25e
5g
6h
7
1a
1a
1b
1c
1c
2
3a
3a
3b
3c
3c
3c
3c
27e
95 : 5
Tracee
56
56
97 : 3
96 : 4
96 : 4
94 : 6
nd
93
92
93
90
nd
8
9i
50
40
10
11
12j
13
14
15k
16l
17n
a
20e
Tracee
56
93
96 : 4
97 : 3
99 : 1
97 : 3
96 : 4
97
97
96
97
96
37
77 (94)m
48
Yield of isolated product. Determined by 1H NMR spectroscopy.
b
c
d
Determined by HPLC analysis (Chiralcel AD-H). Conversion .
e
99%, np = no products. Polymerization of the starting material was
f
observed. nd
g
not determined. 20 mol% of SDS (sodium
=
dodecylsulfate) was added. one equivalent of SDS was used.
h
i
j
7 mol% of trifluoroacetic acid was added. 20 mol% of sodium
k
dodecylbenzenesulfonate was added. Reaction under solvent-free
l
conditions. 15 mol% of 3c was used. Yields based on recovery of
m
The Michael addition product 7 obtained from the aqueous
reaction had the (19R, 2S) absolute stereochemistry, which is the
same as that of the product obtained from chiral ionic-liquid
catalysis under neat conditions. Therefore, this stereoselectivity
could also be explained by the Seebach–Golinski model as
previously proposed.6,12,16
n
nitrostyrene. Stirring was ceased after 30 min.
of the desired Michael addition products and the polymerization
pathway became less prominent in these cases (Table 1, entries
7–10 and 13–17). For example, although chiral ionic liquid-type
catalysts such as 1a and 3a were ineffective in water, a simple
switch of the bromide with dodecyl sulfate (2b and 3b, respectively)
led to remarkably improved performance and the Michael
addition products were isolated in moderate yields with up to
We next probed the substrate scope of 3c (Table 2). Both
electron-rich and electron-deficient nitrostyrenes were shown to be
excellent Michael acceptors for cyclohexanone and the reactions all
occurred smoothly in pure water. The desired Michael products
Table 2 STAO 3c catalyzed asymmetric Michael addition in water
Entry R
Product Time/h Yield (%)a syn : antib ee (%)c
1
2
3
4
5
6
7
8
Ph
4-ClPh
2-ClPh
2-BrPh
3-NO2Ph
4-MePh
4-MeOPh
2,4-(MeO)2Ph 14
2-Naphthyl
Ph
7
8
9
10
11
12
13
12
12
12
12
36
12
15
23
15
24
93
64
.99
99
83
90
84
98
97 : 3
97 : 3
99 : 1
99 : 1
97 : 3
97 : 3
99 : 1
94 : 6
97 : 3
97 : 3
97
97
98
98
97
95
94
91
96
61
9
15
16
84
80
10d
a
Yield of isolated product. Determined by 1H NMR spectroscopy.
b
c
d
Determined by HPLC analysis (Chiralcel AD-H). The Michael
donor is isovaleraldehyde.
Fig. 1 Synthetic catalysts for screening.
3688 | Chem. Commun., 2006, 3687–3689
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were obtained in good yields (64–99%) and showed excellent
diastereoselectivity (syn : anti ¢94 : 6) and enantioselectivity
(¢91% ee) (Table 2, entries 1–9). The stereoselectivities are
comparable with those of the reactions catalyzed by Kotsuki’s
pyrrolidine-pyridines in organic solvent12c and our previous results
with chiral ionic-liquid catalysis under neat conditions.6 Most
recently, Takabe and co-workers reported a diamine–TFA
catalytic system for asymmetric Michael reaction in brine.3d In
comparison, our surfactant-type catalyst 3c demonstrated clearly
better stereoselectivity than Takabe’s catalyst in most of the cases
examined. For example, Takabe reported optimized 89% ee and
syn : anti 95 : 5 for the reaction of cyclohexanone and
b-nitrostyrene, while in our case the reaction catalyzed by 3c gave
97% ee and syn : anti 97 : 3 (Table 2, entry 1).
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under the optimized conditions but with little success. The reaction
of acetone with b-nitrostyrene resulted in trace product with most
of the starting material decomposed.17 Preliminary studies
indicated that the reaction worked with aldehyde donors such as
isovaleraldehyde (Table 2, entry 10). The Michael addition of
isovaleraldehyde to nitrostyrene gave the desired product in good
yield, high diastereoselectivity (syn : anti= 97 : 3) and moderate
enantioselectivity (61% ee).
Generally, the desired products were gradually precipitated or
separated from the water solution. In cases where phase separation
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17 The reason for the failure of the reaction involving acetone is presently
unclear. One of the referees suggested it might relate to interfacial
catalysis as acetone is water-miscible.
18 During the preparation of this manuscript, Takabe and co-workers
reported asymmetric organocatalytic Michael addition in brine using
chiral diamine–TFA catalysis: see ref. 3d.
To conclude, we have developed surfactant-type asymmetric
organocatalysts (STAOs) that were demonstrated to be efficient
asymmetric organocatalysts in pure water with no need of any
organic solvents or additional additives. The catalysts (e.g. 3c)
could catalyze Michael addition to nitroalkenes with high
reactivity and excellent diastereoselectivity and enantioselectivity
in water.18 Further studies on broadening the scope of surfactant-
type asymmetric organocatalysts in water and on developing
reusable STAOs are currently under way in our laboratory and
will be reported in due course.
This work was supported by the Natural Science Foundation of
China (NSFC 20452001, 20421202 and 20542007), the Ministry of
Science and Technology (MoST) and the Institute of Chemistry,
Chinese Academy of Sciences (ICCAS). We thank Prof. Mei-xiang
Wang for the access to HPLC.
Notes and references
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2005, 105, 3095 and references therein.
2 For selected reviews of organocatalysis, see: (a) P. I. Dalko and
L. Moisan, Angew. Chem., Int. Ed., 2004, 43, 5138; (b) A. Berkessel and
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(c) J. Seayad and B. List, Org. Biomol. Chem., 2005, 3, 719–724; (d)
M. Movassaghi and E. N. Jacobsen, Science, 2002, 298, 1904–1905.
3 For recent successful examples of asymmetric organocatalysis in water,
see: (a) Z. Jiang, Z. Liang, X. Wu and Y. Lu, Chem. Commun., 2006,
2801–2803; (b) Y. Hayashi, T. Sumiya, J. Takahashi, H. Gotoh,
T. Urushima and M. Shoji, Angew. Chem., Int. Ed., 2006, 45, 958–961;
(c) N. Mase, Y. Nakai, N. Ohara, H. Yoda, K. Takabe, F. Tanaka and
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Chem. Commun., 2006, 3687–3689 | 3689