Highly enantioselective Michael addition reactions in water catalyzed by an insoluble MPS-supported 4-sulfonamidyl prolinol tert-butyldiphenylsilyl ether

Article abstract of DOI:10.1016/j.tetlet.2009.04.011

The development of a highly efficient, insoluble, and non-swelling MPS-supported organocatalyst for the direct asymmetric Michael reaction of ketones and aldehydes to nitrostyrenes at room temperature in water is described. Excellent yields (up to 100%) a

Full text of DOI:10.1016/j.tetlet.2009.04.011

Tetrahedron Letters 50 (2009) 3054–3058
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Highly enantioselective Michael addition reactions in water catalyzed by an
insoluble MPS-supported 4-sulfonamidyl prolinol tert-butyldiphenylsilyl ether
*
Yongming Chuan, Guihua Chen, Yungui Peng
Key Laboratory on Luminescence and Real-Time Analysis, Ministry of Education, School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
The development of a highly efficient, insoluble, and non-swelling MPS-supported organocatalyst for the
direct asymmetric Michael reaction of ketones and aldehydes to nitrostyrenes at room temperature in
water is described. Excellent yields (up to 100%) and high stereoselectivities (up to 94% dr and 93% ee)
were achieved with 10 mol % of the catalyst. The resin-bound catalyst was simply separated and recov-
ered by filtration, and reused for six consecutive trials without significant loss of activity and
enantioselectivity.
Received 20 January 2009
Revised 31 March 2009
Accepted 3 April 2009
Available online 9 April 2009
Ó 2009 Elsevier Ltd. All rights reserved.
Environmental concerns associated with chemical processes
have encouraged the development of more environmentally
friendly methodologies for organic reactions. Recently, organic
reactions that took place in water have attracted a great deal of
attention because water is safe, economical, and environmentally
benign, and is considered to be a substitute for conventional organ-
ic solvents.1 The synthesis of enantiopure molecules is another
important issue.2 In this field, asymmetric organocatalytic reac-
tions have been proven to be very effective for achieving this goal
and have witnessed a tremendous growth in recent years.3 Organ-
ocatalysts are environmentally benign due to avoidance of use of
heavy metals, inexpensiveness, and good stability to moisture
and air.4b Thus, the development of organocatalysts that catalyze
asymmetric reactions in water is currently a highly sought-after
goal for green chemistry.4
However, organocatalysts still suffer drawbacks such as the
requirement of high catalyst loading, sophisticated, and time-con-
suming process in final separation.5l To solve these difficulties, the
development of easily recoverable and reusable polymer-sup-
ported catalysts appears attractive.5 Recently, recyclable chiral
organocatalysts have attracted considerable interest among organ-
ic chemists and have been developed to catalyze asymmetric
organic reactions.5 Amongst them, some recoverable organocata-
lyst (both non-supported and supported) have been developed
for the asymmetric Michael addition of ketones or aldehydes to
nitrostyrenes, such as fluorous pyrrolidine sulfonamide,6 ionic
liquid-supported pyrrolidine-based catalyst,7 polymer-supported
pyrrolidine,8 and thiourea catalyst.9 Although many good results
have been achieved using supported organocatalysts, the catalysis
is mainly performed under homogeneous conditions. Heteroge-
neous catalysis by polymer-supported organocatalysts has rarely
been documented.8a Moreover, compared with soluble polymer-
supported organocatalysts, insoluble polymer-supported ones
have shown advantages such as product purification and catalyst
recovery. Hence, development of highly effective insoluble poly-
mer-supported organocatalysts is highly desirable.
On the other hand, Michael addition of carbonyl compounds to
nitroalkenes affording versatile bifunctional products in an atom-
economical manner has been extensively studied and considerable
efforts have been directed toward the development of an organo-
catalytic asymmetric version over recent years.10,11 With an inter-
est in developing an efficient chiral organocatalytic system to
achieve high yield and enantioselectivity in Michael addition, we
have developed prolinol tert-butyldiphenylsilyl ether as organo-
catalysts for direct Michael reaction of ketones to nitroalkenes.
Although high levels of enantioselectivity (73–95% ee) and diaste-
reoselectivity (P20:1 dr) were achieved, the catalytic efficiency
was low (up to 20 mol % catalyst loading).12 It is therefore of
importance to recover and reuse this kind of organocatalyst, which
will make the reactions more economical and environmentally
friendly.
For optimal performance, we have designed and introduced
trans-4-amino substituent on the pyrrolidine ring of the prolinol
tert-butyldiphenylsilyl ether, which could play a double role. On
the one hand, the formation of thiourea or sulfonamide bond pro-
vides a convenient way to graft the chiral pyrrolidine monomer
onto the polystyrene backbone. On the other hand, the thiourea
or sulfonamide proton could activate the nitrostyrene by hydrogen
bond effectively. In this Letter, we report that those novel insoluble
and non-swelling MPS-supported organocatalysts catalyzed
Michael addition of ketones to nitrostyrene in water in excellent
yields and high enantioselectivities.
Four of the MPS-supported organocatalysts 1a–d (Fig. 1) were
synthesized and screened in asymmetric Michael addition of cyclo-
hexanone to nitrostyrene under various conditions (Table 1). Initial
* Corresponding author. Tel.: +86 23 68254290; fax: +86 23 68254000.
E-mail addresses: pengyungui@hotmail.com, pyg@swu.edu.cn (Y. Peng).
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.04.011

Y. Chuan et al. / Tetrahedron Letters 50 (2009) 3054–3058
3055
cated that the dibenzylamide was not as effective as the bulky
group CH2OTBDPS in shielding the si-face of enamine double bond.
In order to achieve high reactivity and enantioselectivity, vari-
ous reaction conditions were examined; a series of solvents includ-
ing hexane, pentane, toluene, DCM, CHCl3, Et2O, THF, DMF, i-PrOH,
and H2O were screened using 1c as catalyst in the presence of
10 mol % benzoic acid as additive (Table 1, entries 3, 5–14). Good
enantioselectivities were obtained in hexane, pentane, and H2O
(Table 1, entries 3, 5, and 14). To our delight, the reactivity was in-
creased when the reaction proceeded in water in comparison with
that in hexane. The yields increased from 71% to 78% and the reac-
tion time was shortened from 5 d to 4 d. The enantioselectivity
slightly decreased from 92% ee to 90% ee (Table 1, entries 3 and
14). We also studied the influence of acid additive and reactive
temperature on the reaction. When the additive was changed from
benzoic acid into p-nitrobenzoic acid, the yield and the enantiose-
lectivity increased from 78% to 89% and from 90% ee to 93% ee,
respectively (Table 1, entries 14 and 15). When the reaction ran
at rt, the reaction time was shortened from 4 d to 2 d. The yield in-
creased from 89% to 94% and the enantioselectivity decreased
slightly from 93% ee to 91% ee (Table 1, entries 15 and 19). Control
experiment has shown that the influence of insoluble polystyrene
part of catalyst 1c was only on the reactivity, not on selectivity or
diastereoselectivity. Under the same reaction conditions, when the
reaction catalyzed by the non-supported catalyst 1f, the same
selectivity and diastereoselectivity were obtained, the reaction
time was shortened from 2 d to 0.5 d (Table 1, entries 19 and 20).
With the optimal conditions in hand, a variety of nitrostyrenes
with different substitutions were investigated and the results are
summarized in Table 2.14 Generally, nitrostyrenes bearing both
electron-withdrawing (Table 2, entries 2–11, 17) and electron-
donating (Table 2, entries 12–16, 20) aryl groups and heterocyclic
groups (Table 2, entries 18 and 19) gave the desired products with
high selectivities (dr up to 97/3 and ee up to 93%) in excellent
yields. The substitution position of b-nitrostyrenes in some
S
OTBDPS
NH
N
H
N
H
O
a
1
Bn
N
S
Bn
NH
N
H
N
H
1b
OTBDPS
O
NH
O
S N
H
O
1c
O
Bn
N
NH
Bn
S N
H
O
1d
O
OTBDPS
NH
O
Bn
Bn
N
S N
NH
1e
H
1f
O
HO
Figure 1. Chiral organocatalysts tested.
tests showed that the performance of catalysts 1a and 1c13 was
superior to that of 1b and 1d especially the enantioselectivities
of the products. (trans-4-hydroxyprolylamide 1e, which is the sim-
ilar monomer of 1b and 1d, has also shown good results when it
was used to catalyze the asymmetric Michael addition of alde-
hydes to nitroalkene).11c Good yield (89%) was achieved when
the reaction was catalyzed by 1a in the presence of PhCOOH as
an additive in hexane at 10 °C after 3 d (Table 1, entry 1). When
1c was used as the catalyst, the reactivity decreased; leading to
71% yield after 5 d (Table 1, entry 3). However, the enantioselectiv-
ity increased slightly from 89% ee to 92% ee. The reaction pro-
ceeded smoothly to give the product in 83% and 50% yields,
respectively, in the presence of 1b or 1d. However, the enantiose-
lectivity decreased dramatically and only 30% ee and 19% ee were
obtained, respectively (Table 1, entries 2 and 4). These results indi-
Table 1
Optimization of the reaction conditions
O
Ph
O
NO2
Catalyst 1(10 mol%)
Solvent, Additive
NO2
+
Ph
2a
3a
4a
Entry
Catalyst
Solvent
Additive
Temperature (°C)
Time (d)
Yield (%)c
ee (%)d syn
dre (syn/ anti)
1a
1a
1b
1c
1d
1c
1c
1c
1c
1c
1c
1c
1c
1c
1c
1c
1c
1c
1c
1c
1f
Hexane
Hexane
Hexane
Hexane
Pentane
Cyclohexane
Toluene
DCM
CHCl3
Et2O
THF
DMF
i-PrOH
H2O
H2O
H2O
H2O
H2O
H2O
H2O
PhCOOH
PhCOOH
PhCOOH
PhCOOH
PhCOOH
PhCOOH
PhCOOH
PhCOOH
PhCOOH
PhCOOH
PhCOOH
PhCOOH
PhCOOH
PhCOOH
p-NO2–PhCOOH
p-NO2–PhCOOH
PhCOOH
CH3COOH
p-NO2–PhCOOH
p-NO2–PhCOOH
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
rt
3
3
5
4
89
83
71
50
91
68
86
87
44
70
68
Trace
Trace
78
89
84
89
30
92
19
88
90
86
87
82
78
86
—
97/3
95/5
94/6
94/6
93/7
94/6
93/7
92/8
91/9
93/7
93/7
—
2a
3a
4a
5a
4
6a
6.5
5.5
6
6
5
7
4
4
4
4
1
1
1
2
0.5
7a
8a
9a
10a
11a
12a
13a
14b
15b
16a
17a
18a
19b
20b
—
—
90
93
90
88
87
91
91
94/6
95/5
93/7
93/7
92/8
93/7
93/7
rt
rt
rt
rt
91
55
94
100
a
All reactions performed with 10 equiv cyclohexanone, 20 mol % additive, and 0.25 mmol nitrostyrene in the presence of 10 mol % 1 in 1 mL solvent.
Using 10 mol % additive, 0.5 mL H2O.
Isolated yield.
b
c
d
e
Determined by chiral HPLC analysis.
Determined by 1H NMR of the crude products

3056
Y. Chuan et al. / Tetrahedron Letters 50 (2009) 3054–3058
Table 2
Catalytic asymmetric Michael addition of ketones or aldehydes to nitrostyrene under optimized conditionsa
O
R3
*
O
Catalyst 1c (10 mol%)
p-NO2-PhCO2H
H2O, rt
NO2
NO2
*
R2
4
R1
R1
+
R3
R2
2
3
Entry
R1
R2
R3
Note
Time (h)
Yield (%)b
dr (syn/anti)c
ee (%)d
1
2
3
4
5
6
7
8
–(CH2)4–
–(CH2)4–
–(CH2)4–
–(CH2)4–
–(CH2)4–
–(CH2)4–
–(CH2)4–
–(CH2)4–
–(CH2)4–
–(CH2)4–
–(CH2)4–
–(CH2)4–
–(CH2)4–
–(CH2)4–
–(CH2)4–
–(CH2)4–
–(CH2)4–
–(CH2)4–
–(CH2)4–
Ph
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
4o
4p
4q
4r
4s
48
24
48
47
57
71
28
71
42
72
48
55
71
72
72
72
29
48
72
94
95
94
96
93
98
97
92
100
95
100
95
97
87
96
86
90
91
98
93/7
95/5
94/6
95/5
94/6
95/5
97/3
93/7
96/4
93/7
94/6
94/6
95/5
88/12
95/5
94/6
96/4
89/11
89/11
91
90
85
93
92
91
93
91
90
92
90
92
90
87
91
93
93
88
86
2-ClPh
4-ClPh
2-BrPh
3-BrPh
4-BrPh
2-FPh
4-FPh
9
2-NO2Ph
3-NO2Ph
4-NO2Ph
4-CH3Ph
2-CH3OPh
4-CH3OPh
1-Naphthyl
2-Naphthyl
2,4-Cl2Ph
2-Furyl
10
11
12
13
14
15
16
17
18
19
2-Thienyl
O
O
20
21
–(CH2)4–
4t
72
72
84
57
93/7
91
84
R1
R2
O
O
Ph
4u
90/10
22
CH3
H
H
H
H
H
Ph
Ph
Ph
Ph
Ph
n-Bu
4v
4w
4x
4y
4w
4z
72
12
19
19
72
86
39
99
95
94
76
42
—
90
77
74
74
81
89
23e
24e
25e
26e,f
27g
C2H5
C3H7
C6H13
C2H5
97/3
97/3
88/12
97/3
5/95
–(CH2)4–
a
All reactions performed with 10 equiv cyclohexanone, 10 mol % additive, and 0.25 mmol nitrostyrenes in the presence of 10 mol % 1c in 0.5 mL H2O at room temperature.
b
c
d
e
f
Isolated yield.
Determined by 1H NMR of the crude products.
Determined by chiral HPLC analysis.
20 equiv aldehyde.
0 °C.
g
20 mol % catalyst 1c and 20 mol % additive.
substrates had a slight influence on the diastereoselectivities and
The high stereoselectivity may be tentatively explained by
acyclic synclinal transition state model originally proposed by See-
bach and Golinski.15 As shown in Figure 2, for cyclohexanone, the
bulky group (–CH2OTBDPS) should effectively shield the si-face
enantioselectivities as well as on the yields. For example, when
the methoxyl group position of nitrostyrene was changed from
ortho to para, the yield decreased from 97% to 87% and the
enantioselectivity decreased from 90% ee to 87% ee (Table 2, en-
tries 13 and 14). However, the influence of bromo and nitro
substituents on the aryl ring was on the diastereoselectivities
and enantioselectivities (Table 2, entries 4–6, and 9–11). Other
ketone and aldehyde substrates were investigated as well. Acetone
gave the desired product in high enantioselectivities (90% ee)
with poor yield (39%) (Table 2, entry 22). Good enantioselectivity
(74–81% ee) and diastereoselectivity (76–94% dr) were obtained
when aldehydes were used as donors (Table 2, entries 23–26).
These results are better than those of the reactions catalyzed by
the insoluble PS-supported pyrrolidine catalyst reported
previously.8a
In addition, the recyclability of the MPS-supported sulfonam-
idyl prolinol tert-butyldiphenylsilyl ether was investigated. When
the reaction was complete, the catalyst was filtered using a sin-
tered glass funnel and washed with ethyl acetate followed by
dichloromethane. After being dried in vacuo, 1c was reused
directly without further purification, and it was recovered and
reused for six consecutive trials without significant loss of activity
and enantioselectivity (Table 3, entries 1–6).
Table 3
Recycling and reuse of catalyst in Michael addition of cyclohexanone to nitrostyrenea
O
Ph
O
NO2
Catalyst 1c
p-NO2-PhCO2H
H2O, rt
NO2
+
Ph
2a
3a
4a
Entry
Time (d)
Yieldb (%)
eec syn (%)
drd syn:anti
1
2
3
4
5
6
1.4
2.5
2
3
3
92
94
91
92
89
82
92
92
92
91
92
91
93/7
93/7
93/7
93/7
92/8
92/8
4
a
All reactions performed with 10 equiv cyclohexanone, 20 mol % additive, and
0.25 mmol nitrostyrenes in the presence of 20 mol % 1c in 0.5 mL H2O at room
temperature.
b
Isolated yield.
c
Determined by chiral HPLC analysis.
d
Determined by 1H NMR of the crude products.

Y. Chuan et al. / Tetrahedron Letters 50 (2009) 3054–3058
3057
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acceptors approach from the non-shielded side to give the
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effectively.
In conclusion, we have developed a novel MP-sulfonyl chloride
resin-supported sulfonamidyl prolinol tert-butyldiphenylsilyl
ether catalytic system. Only 10 mol % catalyst loading was needed
for good yields (up to 100%) and high stereoselectivities (up to 97/3
dr and 93% ee). When used in the Michael reaction at room tem-
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in subsequent reactions. Further investigations of the applications
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Acknowledgments
We are grateful for financial support from the Natural Science
Foundation of China (NSFC 20572087 and 20872120), the Ministry
of Education, PR China (No. 106141), and the Program for New
Century Excellent Talents (NCET-06-0772) in University.
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2009.04.011.
References and notes
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Angew. Chem., Int. Ed. 2008, 47, 4719; (b) Hayashi, Y.; Itoh, T.; Ohkubo, M.;
Ishikawa, H. Angew. Chem., Int. Ed. 2008, 47, 4722; (c) Palomo, C.; Vera, S.;
Mielgo, A.; Gómez-Bengoa, E. Angew. Chem., Int. Ed. 2006, 45, 5984; (d) Clarke,
M. L.; Fuentes, J. A. Angew. Chem., Int. Ed. 2007, 46, 930; (e) Barros, M. T.;
Phillips, A. M. F. Eur. J. Org. Chem. 2007, 178; (f) Li, P. H.; Wang, L.; Wang, M.;
Zhang, Y. C. Eur. J. Org. Chem. 2008, 1157.
1. For reviews on organic synthesis in water, see: (a) Lindstrom, U. M. Chem. Rev.
2002, 102, 2751; (b) Li, C. J. Chem. Rev. 2005, 105, 3095; (c) Kobayashi, S.;
Manabe, K. Acc. Chem. Res. 2002, 35, 209; (d) Grieco, P. A. Organic Synthesis in
Water; Blackie Academic & Professional: New York, 1998; (e) Li, C. J.; Chan, T. H.
Organic Reactions in Aqueous Media; Wiley: New York, 1997.
2. Reviews see: (a) Tomioka, K.; Nagaoka, Y.; Yamaguchi, M. In Comprehensive
Asymmetric Catalysis; Jacobsen, E. N., Pfaltz, A., Yamamoto, H., Eds.; Springer:
New York, 1999; (b) Berner, O. M.; Tedeschi, L.; Enders, D. Eur. J. Org. Chem.
2002, 1877; (c) Krause, N.; Hoffmann-Röder, A. Synthesis 2001, 2, 171; (d)
Christoffers, J.; Koripelly, G.; Rosiak, A.; Rössle, M. Synthesis 2007, 9, 1279; (e)
Tsukamoto, M.; Kagan, H. B. Adv. Synth. Catal. 2002, 344, 453; (f) Satyanarayana,
T.; Kagan, H. B. Adv. Synth. Catal. 2005, 347, 737.
3. Reviews see: (a) Dalko, P. I.; Moisan, L. Angew. Chem., Int. Ed. 2004, 43, 5138; (b)
Seayad, J.; List, B. Org. Biomol. Chem. 2005, 3, 719; (c) Berkessel, A.; Groger, H.
Asymmetric Organocatalysis: From Biomimetic Concepts to Applications in
12. Liu, F. Y.; Wang, S. W.; Wang, N.; Peng, Y. G. Synlett 2007, 2415.
13. Synthesis of catalyst 1c:
O
H2N
S NH
O
SO2Cl
Pyridine, DMAP
CH2Cl2
OTBDPS
+
OTBDPS
N
N
Boc
Boc
a
b
c
O
S NH
TFA
CH2Cl2
O
OTBDPS
Asymmetric Synthesis; Wiley-VCH Verlag GmbH
& Co. KGaA: Weinheim,
N
1c
H
Germany, 2005; (d) Tsogoeva, S. B. Eur. J. Org. Chem. 2007, 11, 1701; (e)
Connon, S. J. Chem. Commun. 2008, 2499; (f) Vicario, J. L.; Badía, D.; Carrillo, L.
Synthesis 2007, 14, 2065; (g) Almasßi, D.; Alonso, D. A.; Nájera, C. Tetrahedron:
Asymmetry 2007, 18, 299; (h) Pellissier, H. Tetrahedron 2007, 63, 9267; (i) Notz,
W.; Tanaka, F.; Barbas, C. F., III Acc. Chem. Res. 2004, 37, 580; (j) List, B. Acc.
Chem. Res. 2004, 37, 548.
Pyridine (2 mL) and a (1.1 g) in CH2Cl2 (2 mL) were added to a suspension solution
of MP-sulfonyl resin b (0.5 g, f = 1.2 mmol/g) and DMAP 37 mg in CH2Cl2 (3 mL) at
0 °C. The resulting mixture was gently stirred for 24 h at room temperature. The
mixture was filtered and the resin was washed successively with CH2Cl2, CH3OH,
and CH2Cl2 (three times) and then dried under vacuum to afford resin c (0.659 g,
f = 0.58 mmol/g). IR (KBr): 3418, 3218, 3062, 3025, 2924, 2854, 2364, 2342,
2137, 1798, 1776, 1700, 1603, 1490, 1171, 1123, 1034, 1007, 756, 700,
506 cmÀ1.Elemental Anal. N, 2.02; C, 72.58; H, 6.63. Trifluoroacetic acid (2 mL)
was added to a suspension of resin c (0.659 g) in CH2Cl2 (5 mL) at 0 °C and then
the mixture was warmed to room temperature and gently stirred overnight. The
mixture was filtered and washed successively with 20% Et3N/THF, CH2Cl2, CH3OH,
THF, and CH2Cl2 (three times). The solid was dried under vacuum to afford catalyst
1c (0.58 g, f = 0.43 mmol/g). IR (KBr): 3418, 3218, 3062, 3025, 2924, 2854, 2364,
2342, 2137, 1798, 1776, 1700, 1603, 1490, 1171, 1123, 1034, 1007, 756, 700,
506 cmÀ1. Elemental Anal. N, 2.2; C, 72.29; H, 6.68.
4. For selected examples of organocatalyzed reactions in pure water; see: (a)
Mase, N.; Nakai, Y.; Ohara, N.; Yoda, H.; Takabe, K.; Tanaka, F.; Barbas, C. F., III J.
Am. Chem. Soc. 2006, 128, 734; (b) Hayashi, Y.; Sumiya, T.; Takahashi, J.; Gotoh,
H.; Urushima, T.; Shoji, M. Angew. Chem., Int. Ed. 2006, 45, 958; (c) Tang, Z.;
Yang, Z. H.; Cun, L. F.; Gong, L. Z.; Mi, A. Q.; Jiang, Y. Z. Org. Lett. 2004, 6, 2285;
(d) Dickerson, T. J.; Janda, K. D. J. Am. Chem. Soc. 2002, 124, 3220; (e) Mase, N.;
Watanabe, K.; Yoda, H.; Takabe, K.; Tanaka, F.; Barbas, C. F., III J. Am. Chem. Soc.
2006, 128, 4966; (f) Vishnumaya Singh, V. K. Org. Lett. 2007, 9, 1117; (g) Zhu, S.
L.; Yu, S. Y.; Ma, D. W. Angew. Chem., Int. Ed. 2008, 47, 545; (h) Yan, Z. Y.; Niu, Y.
N.; Wei, H. L.; Wu, L. Y.; Zhao, Y. B.; Liang, Y. M. Tetrahedron: Asymmetry 2006,
17, 3288; (i) Luo, S. Z.; Mi, X. L.; Liu, S.; Xu, H.; Cheng, J. P. Chem. Commun. 2006,
3687.
14. General procedure for asymmetric Michael addition of ketones or aldehydes to
nitroolefins catalyzed by 1c: The catalyst 1c (f = 0.45 mmol/g, 56 mg, 10 mol %),

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Y. Chuan et al. / Tetrahedron Letters 50 (2009) 3054–3058
p-nitrobenzoic acid (4.2 mg, 10 mmol %), and cyclohexanone (10 equiv,
anhydrous Na2SO4, and concentrated under reduced pressure. The residue was
purified by flash chromatography on silica gel (ethyl acetate/petroleum ether
as eluent) to afford the Michael addition product (58 mg, 94%) as a white solid.
The enantiomeric excess was determined by HPLC on a chiral phase chiralpak
AD-H/AS-H column (91% ee).
0.26 mL) were mixed in 0.5 mL water at room temperature. After stirring for
10 min, the nitroolefin (37.3 mg, 0.25 mmol) was added. The resulting
suspension was gently stirred at room temperature for 1–3 d and then
directly filtered. The solid resin was washed with ethyl acetate and the organic
filtrate was washed with saturated NaHCO3 and NaCl solution, dried over
15. Seebach, D.; Golinski, J. Helv. Chim. Acta 1981, 64, 1413.