An efficient Morita-Baylis-Hillman reaction for the synthesis of multifunctional 2-hydroxy-3-nitrobut-3-enoate derivatives

Article abstract of DOI:10.1016/j.tet.2010.10.061

An efficient thiourea promoted MBH reaction of various conjugated nitroalkenes with ethyl glyoxylate was developed. The desired multifunctional products, 2-hydroxy-3-nitro-4-aryl/alkylbut-3-enoate derivatives were obtained in good to high chemical yields

Full text of DOI:10.1016/j.tet.2010.10.061

Tetrahedron 66 (2010) 9875e9879
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Tetrahedron
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An efficient MoritaeBayliseHillman reaction for the synthesis of multifunctional
2-hydroxy-3-nitrobut-3-enoate derivatives
y
y
*
Hsuan-Hao Kuan , Raju Jannapu Reddy , Kwunmin Chen
Department of Chemistry, National Taiwan Normal University, Taipei 116, Taiwan, ROC
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 2 August 2010
Received in revised form 13 October 2010
Accepted 22 October 2010
Available online 28 October 2010
An efficient thiourea promoted MBH reaction of various conjugated nitroalkenes with ethyl glyoxylate
was developed. The desired multifunctional products, 2-hydroxy-3-nitro-4-aryl/alkylbut-3-enoate de-
rivatives were obtained in good to high chemical yields (56e92%) with DMAP (20 mol %) under solvent-
free conditions or imidazole (100 mol %) in the presence of water.
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
MoritaeBayliseHillman reaction
Nitroalkenes
Organocatalysis
Thiourea
Aqueous media
1. Introduction
compounds with DMAP (40 mol %) in CH3CN or imidazole
(100 mol %) in CHCl3 or THF to give the desired MBH adducts with
MoritaeBayliseHillman (MBH),1 a tertiary amine catalyzed
reaction, has emerged as one of the important CeC bond forming
methods in organic synthesis to give densely functionalized prod-
ucts. Various activated alkenes, such as enals,2 enones,3 acrylates,4
and acrylamides5 have been successfully employed in MBH and
related reactions, where reaction products have been extensively
used for further applications.6 One of the major drawbacks of this
reaction is the poor reaction rates, which limits the range of sub-
strates tolerated.7 Several attempts for substantial rate acceleration
of the MBH reaction that involved the addition of a co-catalyst and
optimization of reaction conditions have been reported.8 In addi-
tion, it is only recently that nitroalkenes were found to be useful
Michael acceptors for MBH reactions.9 The potential use of the
adducts, includes chemical transformations, biological evaluations,
and the complexity of the reaction sequence make this approach an
interesting chemical process.6b,10,11 On the other hand, environ-
mental concerns have stimulated a new concept of chemical re-
actions under solvent-free conditions or in aqueous media. Organic
processes in aqueous medium have attracted a great deal of at-
tention and have become one of the most exciting research areas.12
Namboothiri and co-workers reported the reaction of a variety
of conjugated nitroalkenes with activated non-enolizable carbonyl
decent to good chemical yields.13
In continuation to our research interest in organocatalysis,14 the
thiourea promoted an efficient MBH reaction of a variety of nitro-
alkenes with ethyl glyoxylate was developed. The multifunctional
2-hydroxy-3-nitrobut-3-enoate derivatives were obtained with
good to high chemical yields (56e92%) under the optimum con-
ditions. Furthermore, we were able to successfully carry out the
MBH reactions in an aqueous solvent system.3f,12b
2. Results and discussion
The ethyl glyoxylate 1 (in 50% toluene) and b-nitrostyrene 2a
were chosen as model substrates. We suspected the presence of
a thiourea componentcould synergisticallyactivatethe nitroalkenes
and ethyl glyoxylate, subsequently enhancing the reactivity.15 Var-
ious thiourea promoters were studied. An initial screening using
various solvents with thiourea catalysts I was carried out. The
reaction proceeded smoothly in CHCl3 to afford the desired product
with 70% yield when imidazole and thiourea I (20 mol %) was used
(Table 1, entry 1). The chemical yield improved slightly when the
reaction was carried out in THF over 3 h (Table 1, entry 2). However,
the reactivitydecreased under neatconditions, in brine, and inwater
(Table 1, entries 3e5). It is shown here that the use of a mixed solvent
system failed to improve the chemical outcome (Table 1, entry 6).
Next, weexamined thereactions ofvarious thiourea catalysts IIeVin
water (Table 1, entries 7e10). Fortunately, the desired product 3a
* Corresponding author. E-mail address: kchen@cc.ntnu.edu.tw (K. Chen).
y
Equal contributions made to this work.
0040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.10.061

9876
H.-H. Kuan et al. / Tetrahedron 66 (2010) 9875e9879
Table 2
was obtained with 88% chemical yield within a 1 h reaction in the
presence of thiourea III (Table 1, entry 8). It is interesting to note that
thiourea III exhibited better activity than that of I (with four 3,
5-trifluoromethyl substituents on the phenyl rings). The hydroxy
group in the phenyl group may contribute to this result.
Optimization of the MBH reaction
OH
III
Thiourea
Base
O
NO2
NO2
EtO2C
Ph
3a
Ph
EtO2C
H
water, rt
2a
1
Table 1
Thiourea catalysts screening for MBH reaction of ethyl glyoxylate 1 with
b-nitro-
styrene 2a in the presence of imidazolea
Entry
Base (mol %)
III (mol %)
Time (h)
% Yielda
1
2
3
4
5
6
Imidazole (100 mol %)
Imidazole (100 mol %)
Imidazole (50 mol %)
Imidazole (20 mol %)
DMAP (20 mol %)
DMAP (20 mol %)
DMAP (20 mol %)
DMAP (10 mol %)
DABCO (20 mol %)
DABCO (20 mol %)
20
10
20
20
20
20
20
20
20
20
1
4
8
12
1
0.5
0.5
0.5
5
88
80
70
68
75
70
92
80
d
OH
I-V
Thiourea
O
NO2
Imidazole
solvent, rt
NO2
EtO2C
Ph
H
EtO2C
R1
Ph
2a
1
3a
7b
8b
9
R6
CF3
R2
S
S
10b
10
d
R3
N
N
H
R5
N
N
N
H
CF3
a
Isolated yield.
No other solvent was added.
H
H
R4
b
V
R1 = R3 = R5 = R6 = CF3; R2 = R4 = H
I
:
: R1 = R3 = R4 = H; R2 = OMe; R5 = R6 = CF3
II
the other hand, for electron-donating group of nitroalkenes, the
reactions also proceeded smoothly to afford the MBH adducts with
good to high chemical yields (Table 3, entries 9e12). However, the
presence of a methoxy substituent at ortho and para position,
resulted in a decrease in reactivity in the presence of imidazole
(Table 3, entries 10 and 12). Hetero-aromatic nitroalkenes were also
suitable substrates for the MBH reaction, where high chemical
yields were obtained (Table 3, entries 13 and 14). The reactivity
decreased when aliphatic nitroalkenes were used, giving moderate
chemical yields (Table 3, entries 15 and 16). The structures of
2-hydroxy-3-nitrobut-3-enoate derivatives 3aep were fully char-
acterized using IR, 1H, 13C NMR spectral data, and HRMS analyses
and product 3a was further confirmed by single crystal X-ray data
analysis (Fig. 1).17
: R1 = R2
=
R3 =H R4 = OH, R5 = R6 = CF3
III
IV: R1 = R2 = R3 = R5 = R6 = H; R4 = OH
Entry
Thiourea (20 mol %)
Solvent
Time (h)
% Yieldb
1
2
3
4
5
6
7
8
9
I
I
I
I
I
I
II
III
IV
V
CH3Cl3
THF
Neat
Brine
H2O
THF/H2O
H2O
H2O
1
3
0.5
2
2
3
4
1
2
70
80
65
60
72
70
dc
88
80
60
H2O
H2O
10
4
a
Unless otherwise specified, the reaction was carried out with ethyl glyoxylate 1
-nitrostyrene 2a (0.2 mmol), imidazole (0.2 mmol), and
(in 50% toluene, 0.6 mmol),
b
thiourea catalysts IeV (20 mol %) in 0.2 mL of solvent indicated at ambient
Table 3
temperature.
Substrate scope for MBH reactiona
b
Isolated yield.
Unseparable mixtures were observed.
c
OH
O
Thiourea III (20 mol%)
NO2
NO2
+
EtO2C
R
EtO2C
H
DMAP (20 mol%)/neat OR
Imidazole (100 mol%)/H2O
To further optimize the reaction conditions, screening of bases
(imidazole, DMAP and DABCO) was carried out. As expected, the
reactivity decreased, when low amounts of either imidazole or
thiourea III were used in water (Table 2, entries 1e4). We then
studied the effect of DMAP in the MBH reaction. The desired product
was obtained with comparable chemical yields when DMAP
(20 mol %) was used under similar reaction conditions (Table 2,
entries 5 and 6). The chemical yield was significantly improved to
a satisfactory 92% when the reaction was carried out using ethyl
2a-p
1
R
3a-p
entry
R (2)
3aep
DMAPb
Imidazolec
Time (h)
Time (h)
Yieldd
Yieldd
1
2
3
4
5
6
7
8
C6H5 (2a)
3a
0.5
0.5
0.5
0.5
0.5
0.5
1.5
1.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
92
57
73
88
85
88
75
70
88
75
85
84
87
86
56
83
1.0
1.5
1.0
1.5
1.5
1.5
1.5
2.0
3.0
12.0
4.0
12.0
1.5
1.5
8.0
8.0
88
86
80
75
82
74
75
75
81
78
75
77
84
82
35
47
2-CF3C6H4 (2b)
3-CF3C6H4 (2c)
3-ClC6H4 (2d)
4-ClC6H4 (2e)
3b
3c
3d
3e
3f
glyoxylate and b-nitrostyrene under solvent-free condition (Table 2,
2-BrC6H4 (2f)
entry 7). By contrast, the reactions failed to proceed when DABCO
was employed as the nucleophile (Table 2, entries 9 and 10). After
optimizing conditions, the best reaction condition was realized
using ethyl glyoxylate 1 (3.0 equiv), nitroalkenes (1.0 equiv), and
thiourea catalyst III (20 mol %) in the presence of DMAP (20 mol %)
under solvent-free condition or imidazole (100 mol %) in water at
ambient temperature.
To test the general utility of the optimized reaction conditions,
we examined the reaction with a variety of nitroalkenes and ethyl
glyoxylate.16 The results are tabulated in Table 3. The use of electron
withdrawing substituted nitroalkenes gave the desired adducts
with good to high chemical yields (Table 3, entries 2e8). For all the
substrates studied, no significant differences in reactivity were
observed when the nucleophilic species DMAP and imidazole were
used for the reaction. Most of the reactions were completed in 2 h
at ambient temperature under optimized reaction conditions. On
3-BrC6H4 (2g)
4-BrC6H4 (2h)
4-MeC6H4 (2i)
2-MeOC6H4 (2j)
3-MeOC6H4 (2k)
4-MeOC6H4 (2l)
2-Thienyl (2m)
2-Furyl (2n)
3g
3h
3i
3j
3k
3l
3m
3n
3o
3p
9
10
11
12
13
14
15
16
C6H5CH2CH2 (2o)
(CH3)2CHCH2 (2p)
a
All the reactions were carried out with ethyl glyoxylate 1 (in 50% toluene,
0.6e1.0 mmol) and nitroolefins 2aep (0.2 mmol) in the presence of catalyst III
(20 mol %).
b
DMAP (20 mol %) used with ethyl glyoxylate (5 equiv) under solvent-free con-
dition at ambient temperature.
c
Ethyl glyoxylate (3 equiv) used with imidazole (100 mol %) in water at ambient
temperature.
d
Isolated yields.

H.-H. Kuan et al. / Tetrahedron 66 (2010) 9875e9879
9877
Imidazole mediated MBH reaction: Imidazole (13.7 mg,
0.20 mmol) was added to a stirred solution of ethyl glyoxylate 1
(50% in toluene, 0.12 mL, 0.6 mmol), corresponding nitroolefins
2aep (0.20 mmol), and thiourea III (15.3 mg, 0.04 mmol) in water
(0.2 mL) at ambient temperature. The reaction mixture was stirred
until the starting material disappeared completely by inspection of
TLC by UV lamp (254 nm). The mixture was extracted with ethyl
acetate (10 mLꢁ2). The layers were separated and the organic layer
was washed with brine and dried over MgSO4. The solvent was
removed under reduced pressure and the residue was purified by
flash column chromatography on silica gel (eluting with hexanes/
ethyl acetate¼4:1) to give the desired pure products 3aep.
4.2.1. Ethyl 2-hydroxy-3-nitro-4-phenylbut-3(E)-enoate (3a). IR (
cmꢀ1): 3491, 3070, 2982, 1749, 1650, 1532, 1447, 1336, 1296, 1255,
1222, 1104, 1012; 1H NMR (400 MHz, CDCl3):
8.33 (s, 1H), 7.60e7.54
n/
d
(m, 2H), 7.53e7.47 (m, 3H), 5.24 (d, J¼5.5 Hz,1H), 4.39e4.21 (m, 2H),
Fig. 1. ORTEP diagram of 3a at 50% probability level.
3.70 (d, J¼5.9 Hz, 1H), 1.27 (t, J¼7.1 Hz, 3H); 13C NMR (100 MHz,
CDCl3):
d 170.5, 147.9, 139.2, 131.0, 130.9, 129.8, 129.2, 65.9, 63.0,
13.9 ppm; LRMS (EI) m/z 252 (Mþþ1, 11%), 234 (15), 187 (17), 178
(100), 160 (20), 131 (9), 116 (38), 107 (27), 79 (6); HRMS (ESI) m/z:
[MþNa]þ calcd for C12H13NO5Na 274.0691, found 274.0685. Crystal
data for 3a at 296 K: C12H13NO5, M 251.23, monoclinic, P21/n,
3. Conclusions
In summary, an efficient thiourea promoted MoritaeBayliseHill-
man reaction was developed for the synthesis of multifunctional 2-
hydroxy-3-nitrobut-3-enoate derivatives. Treatment of a variety of
nitroalkenes (aromatic, hetero-aromatic, and aliphatic) and ethyl
glyoxylate (in 50% toluene) with DMAP or imidazole to give the de-
sired adducts with good to high chemical yields. The reaction pro-
ceeded smoothly, when DMAP (20 mol %) under solvent-free
condition or imidazole (100 mol %) in the presence of water with
thiourea III (20 mol %) as a co-catalyst. The synthetic applications of
the MBH adducts were studied in our laboratory.
3
ꢀ
ꢀ
ꢀ
ꢀ
a¼10.7256(3) A, b¼7.6027(2) A, c¼15.2187(5) A, V¼1240.39(6) A ,
ꢀ
Z¼4,
l
¼0.71073 A, Dc¼1.345 g/cm3,
m
¼0.0446 mmꢀ1
, 2181 re-
flections, 163 parameters, R¼0.0619, Rw¼0.0916 for all data.
4.2.2. Ethyl 2-hydroxy-3-nitro-4-(2-trifluoromethylphenyl) but-3(E)-
enoate (3b). IR (
1535, 1451, 1347, 1318, 1263, 1226, 1171, 1119, 1060, 1034, 1019; 1H
NMR (400 MHz, CDCl3):
n
/cmꢀ1): 3491, 3070, 2989, 2915, 1753, 1665, 1580,
d
8.49 (d, J¼2.0 Hz, 1H), 7.83e7.79 (m, 1H),
7.72e7.65 (m, 1H), 7.65e7.58 (m, 2H), 4.95 (s, 1H), 4.35e4.19 (m,
2H), 3.65 (s, 1H), 1.26 (t, J¼7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3):
4. Experimental
d
170.1, 149.6, 135.8, 132.4, 130.4, 129.5 (q, J¼31 Hz), 129.4, 129.2,
126.6 (q, J¼5 Hz), 123.5 (q, J¼272 Hz), 65.9, 63.1, 13.8 ppm; LRMS
(EI) m/z 319 (Mþ, 27%), 302 (11), 256 (6), 246 (54), 212 (55), 184
(100), 132 (15); HRMS (ESI) m/z: [MþNa]þ calcd for C13H12F3NO5Na
342.0565, found 342.0573.
4.1. General information
Infrared spectra were obtained using a Perkin Elmer Spectrum
RX spectrometer with thin films of products coated on NaCl plates.
Only absorption frequencies higher than 1000 cmꢀ1 were reported.
1H and 13C NMR spectra were measured on the Bruker Avance
400 MHz instruments, and spectral data are reported in parts per
4.2.3. Ethyl 2-hydroxy-3-nitro-4-(3-trifluoromethylphenyl) but-3(E)-
enoate (3c). IR (
1535, 1443, 1329, 1207, 1167, 1126, 1078, 1016; 1H NMR (400 MHz,
CDCl3): 8.31 (s, 1H), 7.87e7.82 (m, 1H), 7.80e7.73 (m, 2H),
n
/cmꢀ1): 3483, 3077, 2989, 2915, 1749, 1657, 1613,
million relative to tetramethylsilane (TMS,
d
¼0.0) using CDCl3 as
d
solvent for 1H NMR and relative to the central CDCl3 resonance
7.69e7.61 (m, 1H), 5.13 (d, J¼5.6 Hz, 1H), 4.39e4.26 (m, 2H), 3.73 (d,
(d
¼77.0) for 13C NMR. HRMS analysis was accomplished at the
J¼5.8 Hz, 1H), 1.29 (t, J¼7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3):
Academia Sinica, Scientific Instrument Center (EI and ESI). All re-
actions under standard conditions were monitored by thin-layer
chromatography (TLC) on Merck precoated TLC plates (silica gel 60
F254). The products were purified by flash column chromatography
silica gel 60 (Merck, 230e400 mesh) using the indicated eluent.
d
170.0, 149.1, 137.1, 132.7, 131.8 (q, J¼32 Hz), 131.7, 129.9, 127.5 (q,
J¼3 Hz), 126.4 (q, J¼4 Hz), 123.5 (q, J¼271 Hz), 65.7, 63.2, 13.9 ppm;
LRMS (EI) m/z 319 (Mþ, 25%), 301 (7), 256 (13), 246 (60), 230 (8),184
(100), 175 (15), 131 (7); HRMS (ESI) m/z: [MþNa]þ calcd for
C13H12F3NO5Na 342.0565, found 342.0560.
4.2. General experimental procedure
4.2.4. Ethyl 4-(3-chlorophenyl)-2-hydroxy-3-nitrobut-3(E)-enoate
(3d). IR (
n
/cmꢀ1): 3469, 2989, 2915, 2856, 1749, 1653, 1565, 1528,
DMAP catalyzed MBH reaction: DMAP (4.9 mg, 0.04 mmol) was
added to a stirred solution of ethyl glyoxylate 1 (50% in toluene,
0.2 mL, 1.0 mmol), corresponding nitroolefins 2aep (0.20 mmol),
and thiourea III (15.3 mg, 0.04 mmol) under neat conditions at
ambient temperature. The mixture was stirred until the starting
material disappeared completely by inspection of TLC by UV lamp
(254 nm). To the mixture were added ethyl acetate (10 mL) and
water (0.5 mL). The layers were separated and the organic layer was
washed with brine and dried over MgSO4. The solvent was removed
under reduced pressure and the residue was purified by flash col-
umn chromatography on silica gel (eluting with hexanes/ethyl
acetate¼4:1) to give the desired pure adducts, 2-hydroxy-3-nitro-
but-3-enoates 3aep.
1473, 1340, 1259, 1108, 1016; 1H NMR (400 MHz, CDCl3):
d 8.24 (s,
1H), 7.58e7.54 (m, 1H), 7.50e7.40 (m, 3H), 5.17 (d, J¼4.4 Hz, 1H),
4.38e4.24 (m, 2H), 3.72 (d, J¼5.2 Hz, 1H), 1.28 (t, J¼7.2 Hz, 3H); 13C
NMR (100 MHz, CDCl3):
d 170.2, 148.7, 137.4, 135.3, 132.5, 130.9,
130.5, 129.5, 127.7, 65.7, 63.1, 13.9 ppm; LRMS (EI) m/z 285 (Mþ,
42%), 267 (59), 222 (25), 214 (32), 212 (100), 194 (39), 150 (76), 141
(22), 84 (13); HRMS (ESI) m/z: [MþNa]þ calcd for C12H12ClNO5Na
308.0302, found 308.0305.
4.2.5. Ethyl 4-(3-chlorophenyl)-2-hydroxy-3-nitrobut-3(E)-enoate
(3e). IR (
1491, 1340, 1255, 1229, 1093, 1012; 1H NMR (400 MHz, CDCl3):
8.27 (s, 1H), 7.57e7.43 (m, 4H), 5.16 (d, J¼4.0 Hz, 1H), 4.39e4.20
n
/cmꢀ1): 3454, 2989, 2923, 2841, 1749, 1653, 1591, 1528,
d

9878
H.-H. Kuan et al. / Tetrahedron 66 (2010) 9875e9879
(m, 2H), 3.72 (d, J¼5.2 Hz, 1H), 1.27 (t, J¼7.2 Hz, 3H); 13C NMR
1432, 1340, 1300, 1266, 1163, 1108; 1H NMR (400 MHz, CDCl3):
d 8.29
(100 MHz, CDCl3):
d
170.2, 148.1, 137.9, 137.5, 131.1, 129.6, 129.2,
(s, 1H), 7.43e7.36 (m, 1H), 7.17e7.12 (m, 1H), 7.12e7.08 (m, 1H),
7.07e7.01 (m, 1H), 5.27 (d, J¼5.7 Hz, 1H), 4.37e4.21 (m, 2H), 3.85 (s,
3H), 3.70 (d, J¼6.0 Hz, 1H), 1.27 (t, J¼7.1 Hz, 3H); 13C NMR (100 MHz,
65.8, 63.1, 13.9 ppm; LRMS (EI) m/z 286 (Mþþ1, 16%), 268 (26), 222
(16), 214 (31), 212 (100), 194 (6), 152 (13), 150 (57), 141 (32), 131
(11); HRMS (EI) m/z: [M]þ calcd for C12H12ClNO5 285.0404, found
285.0410.
CDCl3):
d 170.5, 160.0, 148.0, 139.2, 132.1, 130.3, 122.1, 116.9, 114.8,
65.9, 63.0, 55.4,14.0 ppm; LRMS (EI) m/z 281 (Mþ, 36%), 263 (43), 218
(9), 208 (100), 190 (68), 162 (38), 146 (30), 137 (11), 109 (17); HRMS
(EI) m/z: [M]þ calcd for C13H15NO6 281.0899, found 281.0893.
4.2.6. Ethyl 4-(2-bromophenyl)-2-hydroxy-3-nitrobut-3(E)-enoate
(3f). IR (
1436, 1347, 1263, 1229, 1104, 1027; 1H NMR (400 MHz, CDCl3):
8.37 (s, 1H), 7.75e7.67 (m, 1H), 7.62e7.55 (m, 1H), 7.48e7.39 (m,
n
/cmꢀ1): 3469, 2989, 2915, 2849, 1749, 1653, 1532, 1465,
4.2.12. Ethyl 2-hydroxy-4-(4-methoxyphenyl)-3-nitrobut-3(E)-enoate
d
(3l). IR (
1510, 1462, 1329, 1307, 1263, 1178, 1104, 1071, 1023; 1H NMR
(400 MHz, CDCl3): 8.30 (s, 1H), 7.61e7.52 (m, 2H), 7.05e6.97 (m,
n
/cmꢀ1): 3461, 2982, 2915, 2841, 1749, 1646, 1606, 1524,
1H), 7.39e7.31 (m, 1H), 5.07 (d, J¼6.0 Hz, 1H), 4.39e4.20 (m, 2H),
3.67 (d, J¼6.0 Hz, 1H), 1.28 (t, J¼7.2 Hz, 3H); 13C NMR (100 MHz,
d
CDCl3):
d
170.2, 148.7, 138.2, 133.3, 132.0, 131.8, 130.5, 127.9, 124.8,
2H), 5.26 (d, J¼5.7 Hz, 1H), 4.37e4.19 (m, 2H), 3.87 (s, 3H), 3.73 (d,
65.9, 63.1, 13.9 ppm; LRMS (EI) m/z 329 (Mþþ1, 2%), 311 (17), 256
(69), 250 (84), 238 (10), 194 (27), 177 (80), 159 (100), 132 (29), 102
(10); HRMS (ESI) m/z: [MþNa]þ calcd for C12H12BrNO5Na 351.9797,
found 351.9794.
J¼6.0 Hz, 1H), 1.25 (t, J¼7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3):
d
170.6, 162.2, 145.9, 139.5, 132.2, 123.1, 114.8, 66.0, 62.9, 55.5,
13.9 ppm; LRMS (EI) m/z 281 (Mþ, 23%), 208 (100), 146 (5), 137 (18);
HRMS (EI) m/z: [M]þ calcd for C13H15NO6 281.0899, found 281.0898.
4.2.7. Ethyl
(3g). IR (
/cmꢀ1): 3454, 2989, 2915, 2849, 1749, 1650, 1561, 1528,
1473, 1340, 1259, 1229, 1108, 1071, 1016; 1H NMR (400 MHz, CDCl3):
8.23 (s, 1H), 7.76e7.70 (m, 1H), 7.66e7.60 (m, 1H), 7.54e7.47 (m,
4-(3-bromophenyl)-2-hydroxy-3-nitrobut-3(E)-enoate
4.2.13. Ethyl
(3m). IR (
/cmꢀ1): 3432, 2989, 2915, 2841, 1749, 1635, 1521, 1418,
1307, 1252, 1218, 1159, 1100, 1053, 1016; 1H NMR (400 MHz, CDCl3):
8.39 (s, 1H), 7.74e7.70 (m, 1H), 7.60e7.56 (m, 1H), 7.24e7.20 (m,
2-hydroxy-3-nitro-4-(thiophen-2-yl)but-3(E)-enoate
n
n
d
d
1H), 7.41e7.33 (m, 1H), 5.16 (d, J¼5.6 Hz,1H), 4.39e4.24 (m, 2H), 3.72
1H), 5.57 (d, J¼5.3 Hz,1H), 4.38e4.22 (m, 2H), 3.72 (d, J¼5.9 Hz,1H),
(d, J¼5.6 Hz, 1H), 1.29 (t, J¼7.0 Hz, 3H); 13C NMR (100 MHz, CDCl3):
1.26 (t, J¼7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3):
d 170.3, 144.7,
d
170.1, 148.7, 137.2, 133.8, 132.8, 132.4, 130.7, 128.1, 123.2, 65.7, 63.1,
136.0, 133.4, 132.9, 131.8, 128.7, 66.2, 63.0, 13.9 ppm; LRMS (EI) m/z
257 (Mþ, 12%), 240 (24), 194 (11), 184 (100), 168 (7), 138 (16), 122
(19), 113 (31); HRMS (EI) m/z: [M]þ calcd for C10H11NO5S 257.0358,
found 257.0362.
14.0 ppm; LRMS (EI) m/z 329 (Mþþ1, 14%), 311 (36), 266 (19), 256
(100), 238 (37), 196 (43), 194 (47), 160 (64), 132 (30), 84 (11); HRMS
(EI) m/z: [M]þ calcd for C12H12BrNO5 328.9899, found 328.9908.
4.2.8. Ethyl 4-(4-bromophenyl)-2-hydroxy-3-nitrobut-3(E)-enoate
4.2.14. Ethyl 4-(furan-2-yl)-2-hydroxy-3-nitrobut-3(E)-enoate (3n). IR
(3h). IR (
1488, 1403, 1336, 1303, 1259, 1233, 1100, 1071, 1012; 1H NMR
(400 MHz, CDCl3): 8.24 (s, 1H), 7.67e7.60 (m, 2H), 7.48e7.40 (m,
n
/cmꢀ1): 3476, 2989, 2915, 2849, 1749, 1650, 1587, 1532,
(n
/cmꢀ1): 3476, 3063, 2989, 2915, 2849, 1746, 1650, 1517, 1469, 1322,
1303, 1229, 1097, 1060, 1023; 1H NMR (400 MHz, CDCl3):
d 7.96 (s, 1H),
d
7.70 (m, 1H), 7.05e7.02 (m, 1H), 6.66e6.62 (m, 1H), 6.00 (s, 1H),
2H), 5.15 (d, J¼5.6 Hz,1H), 4.39e4.20 (m, 2H), 3.73 (d, J¼5.6 Hz,1H),
4.37e4.20 (m, 2H), 3.66 (s, 1H), 1.25 (t, J¼7.2 Hz, 3H); 13C NMR
1.27 (t, J¼7.0 Hz, 3H); 13C NMR (100 MHz, CDCl3):
d
170.2, 148.1,
(100 MHz, CDCl3): d 170.8, 147.9, 146.4, 143.8, 124.2, 122.9, 113.4, 66.3,
137.9, 132.5, 131.2, 129.7, 125.9, 65.8, 63.1, 13.9 ppm; LRMS (EI) m/z
329 (Mþþ1, 8%), 267 (5), 258 (100), 232 (32), 194 (33), 187 (23), 131
(8); HRMS (EI) m/z: [M]þ calcd for C12H12BrNO5 328.9899, found
328.9896.
62.7, 14.0 ppm; LRMS (EI) m/z 241 (Mþ, 11%), 178 (6), 168 (100), 105
(20), 97 (14), 83 (6); HRMS (EI) m/z: [M]þ calcd for C10H11NO6
241.0586, found 241.0582.
4.2.15. Ethyl 2-hydroxy-3-nitro-6-phenylhex-3(E)-enoate (3o). IR (
cmꢀ1): 3410, 2923, 2849, 1735, 1646, 1554, 1454, 1370, 1159, 1108,
1056, 1023; 1H NMR (400 MHz, CDCl3):
7.39e7.16 (m, 6H), 5.07 (d,
n/
4.2.9. Ethyl 2-hydroxy-4-(4-methylphenyl)-3-nitrobut-3(E)-enoate
(3i). IR (
1329, 1292, 1259, 1229, 1185, 1104, 1071, 1019; 1H NMR (400 MHz,
CDCl3): 8.30 (s, 1H), 7.51e7.44 (m, 2H), 7.33e7.27 (m, 2H), 5.25 (d,
n
/cmꢀ1): 3491, 2982, 2915, 2849, 1749, 1650, 1609, 1524,
d
J¼4.4 Hz, 1H), 4.34e4.17 (m, 2H), 3.47 (d, J¼5.2 Hz, 1H), 2.89 (t,
d
J¼7.4 Hz, 2H), 2.77e2.68 (m, 2H), 1.25 (t, J¼7.0 Hz, 3H); 13C NMR
J¼6.0 Hz, 1H), 4.37e4.20 (m, 2H), 3.70 (d, J¼6.0 Hz, 1H), 2.42 (s, 3H),
(100 MHz, CDCl3): d 170.4, 148.8, 140.7, 139.4, 128.8, 128.3, 126.7,
1.26 (t, J¼7.0 Hz, 3H); 13C NMR (100 MHz, CDCl3):
d
170.6, 147.1,
65.2, 62.9, 34.4, 29.6, 14.0 ppm; LRMS (EI) m/z 280 (Mþþ1, 2%), 244
(6), 188 (16), 155 (44), 125 (55), 91 (100), 55 (5); HRMS (ESI) m/z:
[MþNa]þ calcd for C14H17NO5Na 302.1004, found 302.0999.
141.9, 139.5, 130.0, 128.0, 66.0, 62.9, 29.7, 21.5, 13.9 ppm; LRMS (EI)
m/z 265 (Mþ, 6%), 247 (8), 230 (4), 202 (7), 201 (32), 192 (100), 174
(5), 131 (6), 130 (19), 121 (35), 93 (6); HRMS (EI) m/z: [M]þ calcd for
C13H15NO5 265.0950, found 265.0955.
4.2.16. Ethyl 2-hydroxy-6-methyl-3-nitrohept-3(E)-enoate (3p). IR
(n
/cmꢀ1): 3432, 2967, 2915, 2856,1746, 1642, 1561, 1528, 1465, 1370,
4.2.10. Ethyl 2-hydroxy-4-(2-methoxyphenyl)-3-nitrobut-3(E)-enoate
1347,1270,1222,1104,1064,1019; 1H NMR (400 MHz, CDCl3):
d 7.38
(3j). IR (
1491, 1462, 1440, 1336, 1296, 1255, 1163, 1108, 1019; 1H NMR
(400 MHz, CDCl3): 8.54 (s, 1H), 7.57e7.52 (m, 1H), 7.51e7.44 (m,
n
/cmꢀ1): 3454, 2982, 2915, 2841, 1746, 1650, 1598, 1524,
(t, J¼8.2 Hz, 1H), 5.09 (d, J¼6.0 Hz, 1H), 4.36e4.21 (m, 2H), 3.52 (d,
J¼6.3 Hz, 1H), 2.33e2.27 (m, 2H), 1.92 (septet, J¼6.6 Hz, 1H), 1.26 (t,
J¼7.1 Hz, 3H); 1.02 (d, J¼3.0 Hz, 3H); 1.00 (d, J¼3.1 Hz, 3H); 13C NMR
d
1H), 7.07e7.01 (m, 1H), 7.00e6.95 (m, 1H), 5.23 (d, J¼4.8 Hz, 1H),
(100 MHz, CDCl3): d 170.6, 148.9, 141.2, 65.2, 62.9, 36.8, 28.4, 22.4,
4.37e4.21 (m, 2H), 3.91 (s, 3H), 3.69 (d, J¼5.7 Hz, 1H), 1.27 (t,
22.3, 14.0 ppm; LRMS (EI) m/z 232 (Mþþ1, 17%), 168 (10), 167 (12),
158 (99), 140 (51), 129 (42), 112 (27), 98 (45), 96 (60), 71 (36), 70
(100), 67 (75); HRMS (ESI) m/z: [MþNa]þ calcd for C10H17NO5Na
254.1004, found 254.1010.
J¼7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3):
d 170.7, 158.6, 147.2, 135.9,
133.0, 130.2, 120.9, 120.0, 110.9, 66.2, 62.8, 55.7, 13.9 ppm; LRMS (EI)
m/z 281 (Mþ, 38%), 264 (6), 209 (14), 208 (100), 190 (7), 146 (10), 137
(21), 133 (7); HRMS (EI) m/z: [M]þ calcd for C13H15NO6 281.0899,
found 281.0893.
Acknowledgements
4.2.11. Ethyl 2-hydroxy-4-(3-methoxyphenyl)-3-nitrobut-3(E)-enoate
We thank the National Science Council of the Republic of China
(NSC 99-2113-M-003-002-MY3 and NSC 99-2119-M-003-001-
(3k). IR (n
/cmꢀ1): 3439, 2915, 2841, 1749, 1646, 1528, 1491, 1465,

H.-H. Kuan et al. / Tetrahedron 66 (2010) 9875e9879
9879
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16. The reaction of nitroalkenes with some activated carbonyl compounds, such as
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