Enantioselective Michael addition of malonates to aromatic nitroalkenes catalyzed by monosaccharide-based chiral crown ethers

Article abstract of DOI:10.1016/j.tetasy.2013.12.007

The asymmetric Michael addition of diethyl malonate and α-substituted diethyl malonates to aromatic nitroalkenes was carried out under mild reaction conditions in a solid-liquid phase transfer reaction in the presence of α-d-glucopyranoside- and α-d-mannopyranoside-based crown ethers as the catalysts. The use of d-glucose-based lariat ether 1 gave the best results. The substituents of the β-nitrostyrene and the diethyl malonate had a significant impact on the chemical yields and enantioselectivity. The addition of diethyl-2-acetamidomalonate to aromatic nitroalkenes afforded the corresponding Michael adducts in moderate to high enantiomeric excess (ee up to 99%). The reaction of diethyl-2-methylmalonate with 2-nitro-β-nitrostyrene gave the adduct with 93% enantiomeric excess in the presence of crown catalyst 1.

Full text of DOI:10.1016/j.tetasy.2013.12.007

Tetrahedron: Asymmetry 25 (2014) 141–147
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Enantioselective Michael addition of malonates to aromatic
nitroalkenes catalyzed by monosaccharide-based chiral crown ethers
a
a
a
Zsolt Rapi , Balázs Démuth , György Keglevich , Alajos Grun a,b, László Drahos c, Péter L. Sóti a, Péter Bakó a,
⇑
}
a Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, PO Box 91, 1521 Budapest, Hungary
b Organic Chemical Technology Research Group of the Hungarian Academy of Sciences, Budapest, Hungary
c Chemical Research Institute for Chemistry, Hungarian Academy of Sciences, H-1525 Budapest, Hungary
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 8 October 2013
Accepted 12 December 2013
The asymmetric Michael addition of diethyl malonate and
a
-substituted diethyl malonates to aromatic
nitroalkenes was carried out under mild reaction conditions in a solid–liquid phase transfer reaction in
the presence of -glucopyranoside- and -mannopyranoside-based crown ethers as the catalysts.
The use of -glucose-based lariat ether 1 gave the best results. The substituents of the b-nitrostyrene
a-
D
a-D
D
and the diethyl malonate had a significant impact on the chemical yields and enantioselectivity. The
addition of diethyl-2-acetamidomalonate to aromatic nitroalkenes afforded the corresponding Michael
adducts in moderate to high enantiomeric excess (ee up to 99%). The reaction of diethyl-2-methylmalo-
nate with 2-nitro-b-nitrostyrene gave the adduct with 93% enantiomeric excess in the presence of crown
catalyst 1.
Ó 2013 Elsevier Ltd. All rights reserved.
1. Introduction
Herein we report a new, sugar-based chiral catalyst that can be
used in enantioselective transformations under mild conditions at
The asymmetric 1,4-addition reaction of 1,3-dicarbonyl com-
pounds to conjugated nitroalkenes is one of the most important
ambient temperature.
methods for the preparation of chiral c
-nitro carbonyl compounds,1
2. Results and discussion
which can be easily converted into various chiral amines and a wide
range of important nitrogen containing bioactive agrochemical and
pharmaceutical compounds, respectively.2 Although catalytic
asymmetric versions of this reaction have been developed, most of
them require metal catalysts or forcing reaction conditions. The
addition of diethyl acetamidomalonate and other 2-substituted
malonates to nitrostyrene derivatives has also been studied. In
recent years, this reaction has been developed by enhancing it by
different catalysts. Homogeneous catalytic methods have led, in
most cases, from moderate to good enantioselectivities. Such
catalysts were, for example, the complex of magnesium triflate and
bis(oxazoline) ligand,3 Ni(II)-bis[(R,R)-N,N-dibenzylcyclohexyl-1,
2-diamine],4 a bifunctional organocatalyst bearing a thiourea and
an amino group on a chiral scaffold,5 and a chiral calcium PYBOX
(pyridinebisoxazoline) complex.6 Recently, researchers developed
immobilized chiral bis(cyclohexyldiamin)-based Ni(II) complexes
within the phenyl-bridged periodic mesoporous organosilica, which
showed high catalytic activity and enantioselectivity in the
asymmetric Michael addition of malonates to nitroalkanes.7
One of the most attractive methods in catalytic asymmetric
synthesis is phase transfer catalysis, in which the enantioselectivity
is generated by a chiral crown catalyst.8 The hexopyranoside-based
monoaza-15-crown-5 lariat ethers described earlier possess a
special complexing ability due to their flexible side-arm containing
a heteroatom at the end. The overall complexing ability is influ-
enced by the steric and electronic properties of the N-substituent.9
The
a-D-glucopyranoside- and a-D-mannopyranoside-based crown
ethers 1 and 2, respectively, proved to be efficient catalysts (Fig. 1)
OCH3
OCH3
O
O
O
O
O
O
O
O
O
O
N
(CH2)3OH
N
(CH2)3OH
O
O
O
O
Ph
Ph
1
2
⇑
Corresponding author. Fax: +36 1 463 3648.
E-mail address: pbako@mail.bme.hu (P. Bakó).
Figure 1. Crown ethers
a-D-mannopyranoside unit.
1 and 2 incorporating an a-D-glucopyranoside or an
0957-4166/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetasy.2013.12.007

142
Z. Rapi et al. / Tetrahedron: Asymmetry 25 (2014) 141–147
in a few asymmetric reactions.10 For this reason, we decided to
apply these two macrocycles as catalysts in the addition of diethyl
malonate and 2-substituted diethyl malonate derivatives to nitro-
styrene derivatives under phase transfer conditions. A few preli-
minary results have been published in a communication.11
The optimization was performed on the reaction of diethyl ace-
tamidomalonate 4 and b-nitrostyrene 3a (Scheme 1).
tion, adduct 5a was formed as its (S)-enantiomer with a negative
specific rotation (Scheme 1). The -mannopyranoside-based cat-
alyst was inefficient in terms of enantioselectivity.
With regard to the optimal reaction conditions, the Michael
addition was carried out in a solid–liquid two phase system
employing 15 mol % of crown ether 1 or 2, and the starting mate-
rials in a 1:4 mixture of THF–diethyl ether as the organic phase
a
-D
Ar
O
O
O
NO2
C2H5O
C2H5O
crown cat. 1
O
C2H5O
OC2H5
O
Na2CO3
NO2
+
HN
5a
Ph
HN
THF:ether, rt
CH3
O
4
3a
CH3
Scheme 1. The addition of diethyl acetamidomalonate to b-nitrostyrene.
It is known that compounds containing an active methylene
group are those incorporating two electron withdrawing groups,
such as carbonyl groups, that make the protons relatively acidic
(e.g., the pKa for diethyl malonate is 13). While the carbonate anion
(CO23ꢀ) is not a very strong base in an aqueous medium (pKa = 8.5), it
is basic enough to be used in an organic medium to remove a proton
from the methylene group. We tried to avoid aqueous medium,
such as in the liquid–liquid two-phase systems, in order to avoid
hydrolysis of the starting materials and/or products. After using a
few anhydrous powdered alkali carbonates (Na2CO3, K2CO3,
Rb2CO3, Li2CO3), we found that the addition proceeding via carba-
nions can be carried out efficiently using sodium carbonate as the
base in a solid–liquid two-phase system. Dry alkali carbonates have
recently become popular basic reagents in solid–liquid phase
transfer systems due to certain advantages.12 It was found that
the catalytic effect of the two similar crown ethers was quite differ-
and 2 equiv of Na2CO3 as the solid phase at ambient temperature.
After reaction times of 2–24 h, products 5a–m were obtained by
preparative TLC, and the enantiomeric purity was measured by chi-
ral HPLC.
We next studied the impact of the substituents in the aromatic
ring of b-nitrostyrene on the yield and enantiomeric purity. The
results of the addition of diethyl 2-acetamidomalonate 4 to substi-
tuted nitrostyrene 3a–h and analogue derivatives 3i–m in the
presence of
in Table 2.
a-D-glucopyranoside-based catalyst 1 are summarized
It can be seen from Table 2 that the unsubstituted, the 4-chloro
and the 4-nitro substituted products 5a, 5d and 5e were obtained
with the highest (97–99%) ee, in yields of 70%, 65%, and 78%,
respectively.
The 2-Cl-, 3-Cl-, and 4-Cl products 5b–d were obtained with
enantioselectivities of 67%, 72%, and 99%, respectively (Table 2,
entries 2–4). The further the chloro-substituent was located from
the reaction center, the higher the ee. It was not possible to perform
ent. While the
slight enantiomeric excess (ee), or, as in most cases, was inefficient,
the -glucopyranoside-based catalyst was found to be an efficient
a-D-mannopyranoside lariat ether 2 induced only a
a
-D
a similar study for the nitro-substituted models, since the
catalyst. In a considerable number of cases, good or excellent ee
values were detected; because of this, the effect of the glucopyran-
oside-based catalyst was investigated herein.
2-NO2- and 3-NO2 adducts were only formed in very low yields.
However, the 4-NO2 derivative 5e was obtained with an ee value
of 97% and in a yield of 78% (Table 2, entry 5). This was similar to
models with electron-donating methoxy groups. We were unable
to prepare the 2-MeO product. The 3-MeO- and 4-MeO adducts
5g and 5h were obtained with ee values of 34% and 60%, respec-
tively, in yields of approximately 50% (Table 2, entries 7 and 8).
It can be concluded that substituents with a relatively high ste-
ric requirement, such as the NO2 and MeO groups, prevent the
addition if they are connected at the ortho position (they are not
shown in Table 2). It can also be seen that the efficiency of catalyst
1 is highly dependent on the nature of the substituent on the aro-
matic ring of the nitrostyrene. It seems probable that the enanti-
oselectivity of the Michael reaction is mainly influenced by the
steric factors of the substituents on the aromatic ring. The addition
of diethyl acetamidomalonate to the nitroalkene with piperonyl
substituent 3i in the presence of catalyst 1 took place with an ee
value of 70% (Table 2, entry 9).
The catalytic activity and enantioselectivity depended strongly
on the solvent used. The effect of solvents is summarized in Table 1
for the reaction of diethyl 2-acetamidomalonate 4 with b-nitrosty-
rene 3a using crown ether 1. From among the solvents, toluene and
THF proved to be the best, inducing an ee value of 61% and 66%,
respectively. Next, mixtures of solvents were used. To decrease
the polarity, diethyl ether was added to THF. Using a 1:4 mixture
of THF–diethyl ether as the solvent, the ee value was as high as
99% (the catalyst was soluble in THF, but insoluble in diethyl
ether). Regarding the temperature, 25 °C was optimal. In this reac-
Table 1
The effect of solvents in the reaction of diethyl 2-acetamidomalonate 4 with b-
nitrostyrene 3a in the presence of catalyst 1
Entry
Solvent
Time (h)
Yielda (%)
eeb (%)
The asymmetric induction was lower (45%) for the 2-naphthyl
model 5j (Table 2, entry 10). Substitution of the aryl ring by a
heteroaryl moiety led to a drastic decrease of the ee values, the
2-thiophenyl and 2-furyl derivatives 5k and 5l being obtained with
11% and 13% ee, respectively (Table 2, entries 11 and 12). If the
connection of the double-bond and the aryl ring was not immedi-
ate, as in 5m, no enantioselectivity was detected (Table 2, entry
1
2
3
4
5
6
7
Toluene
1,4-Dioxane
CH2Cl2
CH3CN
THF
9
0.5
6
0.5
1
1
82
65
72
56
63
68
70
61
50
44
26
66
85
99
Ether–THF = 1:1
Ether–THF = 4:1
3
a
Based on isolation by preparative TLC.
Enantioselectivities were determined by chiral HPLC analysis.
13). Next, we investigated how the
a-substituents of diethyl
b
malonate influenced the extent of the asymmetric induction. The

Z. Rapi et al. / Tetrahedron: Asymmetry 25 (2014) 141–147
143
Table 2
The Michael addition of diethyl 2-acetamidomalonate to nitroalkenes catalyzed by lariat ether 1
Ar
O
O
O
O
NO2
crown cat. 1
C2H5O
C2H5O
Na2CO3
C2H5O
OC2H5
NO2
+
HN Ac
Ar
HN
THF:ether, rt
Ac
3a-m
5a-m
4
Yielda (%)
eec (%)
½ ꢁ
a 2D2
b
Entry
Ar
Time (h)
Product
1
2
3
4
5
6
7
8
C6H5
2-Cl-C6H4
3-Cl-C6H4
4-Cl-C6H4
4-O2N-C6H4
2-H3CO-C6H4
3-H3CO-C6H4
4-H3CO-C6H4
Piperonyl
Naphthalen-2-yl
Thiofen-2-yl
Furan-2-yl
C6H5CH2CH2
3
3.5
4
4
6
24
2
4
5a
5b
5c
5d
5e
5f
5g
5h
5i
70
76
61
65
78
Trace
51
49
52
55
ꢀ42.8
ꢀ11.3
ꢀ14
99
67
72
99
97
—
34
60
72
45
11
13
0
ꢀ36
ꢀ22
—
ꢀ14.2
ꢀ10.6
ꢀ33
9
7
10
11
12
13
3.5
22
6
5j
5k
5l
ꢀ47.7
ꢀ13.8
ꢀ19.9
0
88
89
88
24
5m
a
b
c
Based on isolation by preparative TLC.
In CHCl3, c 1.
Enantioselectivities were determined by chiral HPLC analysis.
Table 3
The addition of a-substituted diethyl malonate to nitrostyrene catalyzed by lariat ether 1
Ph
R
O
O
O
O
crown cat. 1
NO2
C2H5O
C2H5O
NO2
Na2CO3
+
Ph
C2H5O
OC2H5
THF:ether, rt
R
3a
6a-d, 4
7a-d, 5a
Yield (%)a
eec (%)
½ ꢁ
a 2D2
b
Entry
R
Time (h)
Product
1
2
3
4
6
H
Me
Bu
OAc
NHAc
20
48
100
20
7a
7b
7c
7d
5a
61
67
50
81
70
ꢀ3
20
42
22
29
99
ꢀ25.8
ꢀ23.9
ꢀ13.1
ꢀ45
3
a
Based on isolation by preparative TLC.
In CHCl3, c 1.
Enantioselectivities were determined by chiral HPLC analysis.
b
c
results of the addition of a few
nitrostyrene are summarized in Table 3.
a
-substituted diethyl malonates to
spectra with literature data,12 although the enantioselectivity was
not determined.
Compared to the unsubstituted product 7a (Table 3, entry 1), the
substituted derivatives were formed with higher ee values. The
methyl-, butyl-, acetoxy-, and acetamido derivatives 7b, 7c, 7d,
and 5a were obtained with ee values of 42%, 22%, 29%, and 99%,
respectively (Table 3, entries 2–6). The ee value of 99% detected
in the reaction of acetamidomalonate is indeed considerable and
refers to the role of the NH group in the asymmetric induction. It
is worth noting that there was no reaction with the 2-NO2-,
2-Bn-, 2-Ph-, malonates. The reaction of a malonate with a leaving
Finally, the addition of diethyl-2-methylmalonate 6b to substi-
tuted nitrostyrenes 3a, 3f–h, 3n–p, 3e was studied in the presence
of catalyst 1. It is noteworthy that when compared to the reaction
with diethyl acetamidomalonate, other tendencies were experi-
enced. The results are summarized in Table 4.
With regard to the methoxy- or the nitro-substituted
derivatives 8a–c, 8e–g, the closer the substituent was located to
the reaction center, the higher the ee values obtained. The
2-MeO-, 3-MeO-, and 4-MeO substituted adducts 8a–c were
formed with ee values of 70%, 48% and 16%, respectively, while
the 2-NO2-, 3-NO2-, and 4-NO2-substituted adducts 8e–g were
obtained with ee values of 93%, 52%, and 8%, respectively (Table 4,
entries 2–4 and 5–7). It can be seen that in both series, the ortho-
substituted products 8a and 8e were obtained with the highest
group at the a-position led to a product of another type. We tried to
add diethyl bromomalonate to b-nitrostyrene, but this reaction
resulted in product 8 containing a cyclopropane ring instead of
the Michael adduct (Scheme 2). The compound exhibited the
substituents at the trans-position by comparison of its 1H NMR
C2H5OOC
COOC2H5
O
O
crown cat. 1
NO2
Na2CO3
+
C2O
OC2H5
*
*
NO2
THF:ether, rt
Br
Scheme 2. Reaction of diethyl 2-bromomalonate with b-nitrostyrene.

144
Z. Rapi et al. / Tetrahedron: Asymmetry 25 (2014) 141–147
Table 4
The Michael addition of diethyl 2-methylmalonate to nitroalkenes catalyzed by lariat ether 1
Ar
O
O
O
O
NO2
crown cat. 1
C2H5O
C2H5O
Na2CO3
NO2
C2H5O
OC2H5
Ar
+
CH3
THF - ether, rt
CH3
3a, 3f-h, 3e, 3n-p
6b
7b, 8a-g
Yielda (%)
eec (%)
½ ꢁ
a 2D2
b
Entry
Nitroalkene
Ar
Time (h)
Product
1
2
3
4
5
6
7
3a
3f
C6H5
48
120
40
60
24
7b
8a
8b
8c
8e
8f
67
74
51
52
72
62
65
ꢀ25.8
ꢀ20.4
ꢀ30.8
ꢀ21.6
17.5
42
70
48
15
93
52
8
2-H3CO-C6H4
3-H3CO-C6H4
4-H3CO-C6H4
2-O2N-C6H4
3-O2N-C6H4
4-O2N-C6H4
3g
3h
3n
3p
3e
150
2
ꢀ20
8g
ꢀ17.6
a
b
c
Based on isolation by preparative TLC.
In CHCl3, c 1.
Enantioselectivities were determined by chiral HPLC analysis.
enantioselectivity (70% and 93%, respectively). When carrying out
the latter reaction in the presence of the -mannopyranoside-
based crown ether 2, the yield was very low (15%) as was the ee
value (6%). However, the sign of the specific rotation was opposite
(positive). There was no reaction with the 2-Cl- and 3-Cl-nitrosty-
renes using catalyst 1.
with 93% enantiomeric excess. A cyclopropane derivative was
formed in the reaction of diethyl 2-bromomalonate and nitrosty-
rene under the conditions used in the other reactions.
a-D
The role of solid Na2CO3 in the solid–liquid phase transfer cata-
lytic reactions may be interpreted according to Makosza.13 The
crown catalysts were unable to transfer the carbonate anions
(CO23ꢀ) into the organic phase; thus the solid–liquid phase transfer
phenomena are probably not involved here. It is more plausible
that the first step, that is the proton abstraction takes place on
the surface of the solid carbonate. The anions thus formed, then
migrate into the organic phase as ion pairs with the crown ether
complexed sodium cations.
3. Conclusion
To the best of our knowledge, we are the first to accomplish the
asymmetric Michael addition of diethyl malonate and
a-substi-
tuted diethyl malonates to aromatic nitroalkenes under phase
transfer catalytic conditions using Na2CO3 as the solid phase and
a mixture of THF–diethyl ether as the solvent, in the presence of
We assume that a catalytic cycle is operating for this reaction
(Scheme 3). A complex forms from the sodium carbonate and the
-
NaCO3
Na2CO3
+
Na
+
crown ether
O
O
R
O
O
C2H5O
OC2H5
C2H5O
OC2H5
Ph
R
NO2
7
O
C
O
O
N
HO
Na
O
R
NO2
Ph
Na
C2H5O
OC2H5
NaHCO3
+
Ph
O
O
O
O
C2H5O
OC2H5
Na
R
9
10
Scheme 3.
chiral crown ethers derived from sugars. From the two monosac-
chiral crown ether. The sodium complex deprotonates the a-posi-
charide-base crown catalysts examined 1 and 2, the use of
tion of malonate 6 to give chiral sodium enolate 9 in situ. The chiral
sodium enolate thus formed, reacted with b-nitrostyrene 3a to af-
ford the initial 1,4-addition adduct 10. Subsequent protonation by
NaHCO3 afforded the Michael adduct 7, and regenerated the crown
ether catalyst.
The significant difference between the catalytic activity of the
a-D-glucopyranoside- and a-D-mannopyranoside-based crown
D-glucose-based lariat ether 1 gave the better results, although
the effect of the catalyst on the yield and enantioselectivity was
highly dependent on the substitution pattern of the reagents,
b-nitrostyrene and diethyl malonate. The addition of diethyl
2-acetamidomalonate to aromatic nitroalkenes afforded the
corresponding Michael adducts in moderate to high (34–99%)
enantiomeric excess. The reaction of diethyl 2-methylmalonate
with 2-nitro-b-nitrostyrene resulted in the adduct being obtained
ethers 1 and 2, respectively, is currently unclear; their ability to
form a complex and the structure of the complex with Na+ cations

Z. Rapi et al. / Tetrahedron: Asymmetry 25 (2014) 141–147
145
may be different. Comparing the stereostructure of azacrown
ethers 1 and 2, the glucopyranoside moiety making a 2,3-trans
anellation possible is ideal from the point of view of an ‘all gauche’
conformation of the crown ring; at the same time, the mannopy-
ranoside unit allows only a 2,3-cis-anellation that distorts the ideal
conformation.14
tr = 13.6 min, minor tr = 19.5 min; 1H NMR (CDCl3, 300 MHz), d
(ppm): 7.32–7.21 (m, 2H), 7.19–7.16 (m, 1H), 7.13–7.08 (m, 1H),
6.69 (br s, NH), 5.56–5.46 (m, 1H), 4.71–4.60 (m, 2H), 4.34–4.06
(m, 4H), 2.13 (s, 3H), 1.27 (t, J = 7.2 Hz, 6H). HRMS calcd for C17H21-
ClN2O7 400.1037. Found 400.1039.
4.2.4. Diethyl 2-acetamido-2-(1-(4-chlorophenyl)-2-nitroethyl)
malonate 5d
Yield: 65%; ½a 2D2
¼ ꢀ36 (c 1, CHCl3) 99% ee; mp 117–119 °C;
ꢁ
4. Experimental
4.1. General
HPLC: Chiralpack AD, eluent hexane:iPrOH 85:15, 220 nm, major
tr = 18 min, minor tr = 28 min; 1H NMR (CDCl3, 300 MHz),
d
(ppm): 7.28 (d, J = 8.4 Hz, 2H), 7.14 (d, J = 8.4 Hz, 2H), 6.69 (br s,
NH), 5.50 (dd, J = 23.4 Hz, 12.9 Hz, 1H), 4.71–4.59 (m, 2H), 4.34–
4.00 (m, 4H), 2.12 (s, 3H), 1.26 (t, J = 7.2 Hz, 3H), 1.25
(t, J = 7.2 Hz, 3H). HRMS calcd for C17H21ClN2O7 400.1037. Found
400.1034.
Melting points were taken using a Büchi 510 apparatus and are
uncorrected. Optical rotations were measured on a Perkin–Elmer
241 polarimeter at 20 °C. 1H and 13C NMR spectra were recorded
on a Bruker 300 and a Bruker DRX-500 or a Varian Inova 500
instrument in CDCl3 with TMS as the internal standard. The exact
mass measurements were performed using a Q-TOF Premier mass
spectrometer (Waters Corporation, 34 Maple St, Milford, MA, USA)
in positive electrospray ionization mode. Analytical and prepara-
tive thin layer chromatography was performed on silica gel plates
(60 GF-254, Merck), while column chromatography was carried
out using 70-230 mesh silica gel (Merck). Chemicals were pur-
chased from Aldrich Chem. Co.
4.2.5. Diethyl 2-acetamido-2-(2-nitro-1-(4-nitrophenyl)ethyl)
malonate 5e
Yield: 78%; ½a 2D2
¼ ꢀ22 (c 1, CHCl3) 97% ee; mp 109–112 °C;
ꢁ
HPLC: Chiralpack AD, eluent hexane:iPrOH 85:15, 256 nm, major
tr = 34.3 min, minor tr = 55.6 min; 1H NMR (CDCl3, 500 MHz), d
(ppm): 8.25 (d, J = 8.5 Hz, 2H), 7.53 (d, J = 8.5 Hz, 2H), 6.89 (br s,
NH), 5.52–5.47 (m, 1H), 4.74–4.65 (m, 2H), 4.35–4.24 (m, 2H),
4.20–4.12 (m, 1H), 4.08–4.02 (m, 1H), 2.12 (s, 3H), 1.27 (t,
J = 7 Hz, 3H), 1.25 (t, J = 7 Hz, 3H). HRMS calcd for C17H21N3O9
411.1278. Found 411.1273.
4.2. General procedure for the Michael addition of malonates
The appropriate malonate (1.5 mmol), unsaturated nitro com-
pound (1.0 mmol) and crown catalyst (0.07 g, 0.15 mmol) were
dissolved in a 4:1 mixture of dry diethyl ether and dry THF. After
a short period of stirring, anhydrous Na2CO3 (0.20 g, 1.9 mmol)
was added and the mixture was stirred at rt. The reaction was
monitored by TLC (hexane–ethyl-acetate 5:1). After completion,
the solvents were removed in vacuo, the residue was dissolved in
toluene and filtered. The filtrate was washed with 10% aq HCl
(3 ꢂ 10 ml), and then dried (Na2CO3 and Na2SO4). The crude prod-
uct obtained after evaporating the solvent was purified by prepara-
tive TLC (hexane–ethyl-acetate 10:1). The enantiomeric purity was
determined by chiral HPLC (Chiralpack AD or Chiralpack AS-H col-
umn, Jasco PU-1580 pump, UV-1575 detector, 20 °C, 0.8 ml/min).
4.2.6. Diethyl 2-acetamido-2-(1-(3-methoxyphenyl)-2-nitroethyl)
malonate 5g
Yield: 51%; ½a 2D2
¼ ꢀ14:2 (c 1, CHCl3) 34% ee; mp 91–93 °C;
ꢁ
HPLC: Chiralpack AD, eluent hexane:iPrOH 85:15, 220 nm, major
tr = 16.4 min, minor tr = 22.1 min; 1H NMR (CDCl3, 500 MHz), d
(ppm): 7.21 (t, J = 7.5 Hz, 1H), 6.82 (dd, J = 8 Hz, 1.5 Hz, 1H), 6.76
(d, J = 7.5 Hz, 1H), 6.73–6.70 (m, 1H), 6.70 (br s, NH), 5.50 (dd,
J = 22.5 Hz, 12 Hz, 1H), 4.34–4.23 (m, 2H), 4.23–4.15 (m, 1H),
4.11–4.03 (m, 1H), 3.76 (s, 3H), 2.11 (s, 3H), 1.27 (t, J = 7 Hz, 3H),
1.26 (t, J = 7 Hz, 6H). HRMS calcd for C18H24N2O8 396.1533. Found
396.1537.
4.2.7. Diethyl 2-acetamido-2-(1-(4-methoxyphenyl)-2-nitroethyl)
malonate 5h
4.2.1. Diethyl 2-acetamido-2-(2-nitro-1-phenylethyl)malonate 5a
Yield: 70%; ½a 2D2
¼ ꢀ42:8 (c 1, CHCl3) 99% ee; mp 135–136 °C;
ꢁ
Yield: 49%; ½a 2D2
¼ ꢀ10:6 (c 1, CHCl3) 60% ee; mp 108–110 °C;
ꢁ
HPLC: Chiralpack AD, eluent hexane:iPrOH 85:15, 220 nm, major
tr = 14.6 min, minor tr = 20.5 min; 1H NMR (CDCl3, 500 MHz), d
(ppm): 7.31–7.28 (m, 3H), 7.22–7.18 (m, 2H), 6.89 (br s, NH),
5.54–5.48 (m, 1H), 4.73–4.66 (m, 2H), 4.34–4.23 (m, 2H), 4.20–
4.13 (m, 1H), 4.08–4.01 (m, 1H), 2.12 (s, 3H), 1.27 (t, J = 7 Hz,
3H), 1.25 (t, J = 7 Hz, 3H). HRMS calcd for C17H22N2O7 366.1427.
Found 366.1427.
HPLC: Chiralpack AD, eluent hexane:iPrOH 85:15, 220 nm, major
tr = 15 min, minor tr = 27.5 min; 1H NMR (CDCl3, 500 MHz), d
(ppm): 7.24 (d, J = 8 Hz, 2H), 6.88 (J = 8 Hz, 2H), 6.89 (br s, NH),
5.52–5.47 (m, 1H), 4.74–4.65 (m, 2H), 4.32–4.20 (m, 2H), 4.18–
4.12 (m, 1H), 4.09–4.01 (m, 1H), 3.77 (s, 3H), 2.12 (s, 3H), 1.27 (t,
J = 7 Hz, 3H), 1.25 (t, J = 7 Hz, 3H). HRMS calcd for C18H24N2O8
396.1533. Found 396.1529.
4.2.2. Diethyl 2-acetamido-2-(1-(2-chlorophenyl)-2-nitroethyl)
malonate 5b
4.2.8. Diethyl 2-acetamido-2-(1-benzo[d][1,3]dioxol-5-yl)-2-
nitroethyl)malonate 5i
Yield: 76%; ½a 2D2
¼ ꢀ11:3 (c 1, CHCl3) 67% ee; mp 96–98 °C;
ꢁ
Yield: 52%; ½a 2D2
¼ ꢀ33 (c 1, CHCl3) 72% ee; mp 93–95 °C; HPLC:
ꢁ
HPLC: Chiralpack AD, eluent hexane:iPrOH 85:15, 220 nm, major
tr = 9.4 min, minor tr = 11.2 min; 1H NMR (CDCl3, 500 MHz), d
(ppm): 7.38 (t, J = 2.5 Hz, 1H), 7.36 (t, J = 2.5 Hz, 1H), 7.28–7.30
(m, 2H), 6.89 (br s, NH), 5.55–5.49 (m, 1H), 4.74–4.65 (m, 2H),
4.32–4.23 (m, 2H), 4.19–4.13 (m, 1H), 4.08–4.02 (m, 1H), 2.12
(s, 3H), 1.26 (t, J = 7 Hz, 3H), 1.25 (t, J = 7 Hz, 3H). HRMS calcd for
Chiralpack AD, eluent hexane:iPrOH 85:15, 220 nm, major
tr = 33.2 min, minor tr = 50.1 min; 1H NMR (CDCl3, 300 MHz), d
(ppm): 6.73–6.70 (m, 1H), 6.70 (s, 1H), 6.68 (d, J = 1.5 Hz, 1H),
6.64 (dd, J = 7.8 Hz, 1.5 Hz, 1H), 6.48 (br s, NH), 5.95 (s, 2H),
5.51–5.41 (m, 1H), 4.65–4.44 (m, 2H), 4.35–4.02 (m, 4H), 2.12 (s,
3H), 1.26 (t, J = 6.9 Hz, 6H). HRMS calcd for C18H22N2O9 410.1325.
Found 410.1329.
C17H21ClN2O7 400.1037. Found 400.1035.
4.2.3. Diethyl 2-acetamido-2-(1-(3-chlorophenyl)-2-nitroethyl)
malonate 5c
4.2.9. Diethyl 2-acetamido-2-(1-(naphthalen-2-yl)-2-nitroethyl)
malonate 5j
Yield: 61%; ½a 2D2
¼ ꢀ14 (c 1, CHCl3) 72% ee; mp 107–108 °C;
ꢁ
Yield: 55%; ½a 2D2
¼ ꢀ47:7 (c 1, CHCl3) 45% ee; mp 145–147 °C;
ꢁ
HPLC: Chiralpack AD, eluent hexane:iPrOH 85:15, 220 nm, major
HPLC: Chiralpack AD, eluent hexane:iPrOH 85:15, 254 nm, major

146
Z. Rapi et al. / Tetrahedron: Asymmetry 25 (2014) 141–147
tr = 9.5 min, minor tr = 14.4 min 1H NMR (CDCl3, 300 MHz), d
(ppm): 7.82–7.74 (m, 3H), 7.65–7.62 (m, 1H), 7.51–7.45 (m, 2H),
7.32 (dd, J = 8.4 Hz, 1.8 Hz, 1H), 6.73 (br s, NH), 5.59 (dd,
J = 23.7 Hz, 13.2 Hz, 1H), 4.91–4.77 (m, 2H), 4.38–4.22 (m, 2H),
4.20–4.00 (m, 2H), 2.14 (s, 3H), 1.28 (t, J = 7.2 Hz, 3H), 1.25 (t,
J = 7.2 Hz, 3H). HRMS calcd for C21H24N2O7 416.1584. Found
416.1582.
J = 13.5 Hz, J = 3 Hz, 1H), 4.95 (dd, J = 13.5 Hz, J = 11.5 Hz, 1H),
4.32–4.18 (m, 5H), 1.77 (ddd, J = 12.5 Hz, J = 4.5 Hz, J = 1 Hz, 1H),
1.45 (ddd, J = 12.5 Hz, J = 4.5 Hz, J = 1 Hz, 1H), 1.31 (t, J = 7 Hz,
3H), 1.28 (t, J = 7 Hz, 3H), 1.23–1.10 (m, 4H), 0.83 (t, J = 7 Hz, 3H).
HRMS calcd for C19H27NO6 365.1838. Found 365.1839.
4.2.16. Diethyl 2-acetoxy-2-(2-nitro-1-phenylethyl)malonate 7d
Yield: 81%; ½a 2D2
¼ ꢀ13:1 (c 1, CHCl3) 29% ee; yellow oil. HPLC:
ꢁ
4.2.10. Diethyl 2-acetamido-2-(2-nitro-1-(thiophen-2-yl)ethyl)
malonate 5k
Chiralpack AS-H, eluent hexane:iPrOH 90:10, 256 nm, major
tr = 12.5 min, minor tr = 14.7 min; 1H NMR (CDCl3, 500 MHz), d
(ppm): 7.33–7.28 (m, 5H), 5.16 (dd, J = 14 Hz, J = 4.5 Hz, 1H), 4.85
(dd, J = 14 Hz, J = 9.5 Hz, 1H), 4.38 (dd, J = 9.5 Hz, J = 4.5 Hz, 1H),
4.28 (q, J = 7 Hz, 2H), 4.06–3.89 (m, 2H), 2.22 (s, 3H), 1.30 (t,
J = 7 Hz, 3H), 1.06 (t, J = 7 Hz, 3H). HRMS calcd for C17H21NO8
367.1267. Found 367.1268.
Yield: 88%; ½a 2D2
¼ ꢀ13:8 (c 1, CHCl3) 11% ee; Yellow oil. HPLC:
ꢁ
Chiralpack AD, eluent hexane:iPrOH 85:15, 220 nm, major tr = 12 -
min, minor tr = 14.2 min 1H NMR (CDCl3, 300 MHz), d (ppm) 7.26–
7.24 (m, 1H), 6.95–6.87 (m, 2H), 6.83 (br s, NH), 5.50 (dd,
J = 13.2 Hz, 2.4 Hz, 1H), 5.02 (dd, J = 11.4 Hz, 2.1 Hz, 1H), 4.52 (dd,
J = 13.2 Hz, 11.4 Hz, 1H), 4.35–4.05 (m, 4H), 2.14 (s, 3H), 1.26 (t,
J = 7.2 Hz, 6H). HRMS calcd for C15H20N2O7S 372.0991. Found
372.0995.
4.2.17. Diethyl 2-(1-(2-methoxyphenyl)-2-nitroethyl)-2-methyl-
malonate 8a
Yield: 74%; ½a 2D2
¼ ꢀ20:4 (c 1, CHCl3) 70% ee; yellowish brown
ꢁ
4.2.11. Diethyl 2-acetamido-2-(1-(furan-2-yl)-2-nitroethyl)mal-
onate 5l
oil. HPLC: Chiralpack AS-H, eluent hexane:iPrOH 85:15, 256 nm,
major tr = 7.9 min, minor tr = 11.8 min 1H NMR (CDCl3, 300 MHz),
d (ppm): 7.24 (dd, J = 7.5 Hz, J = 1.5 Hz, 1H), 7.08 (dd, J = 7.5 Hz,
J = 1.5 Hz, 1H), 6.93–6.84 (m, 2H), 5.18–5.00 (m, 2H), 4.74–4.63
(m, 1H), 4.32–4.17 (m, 4H), 3.79 (s, 3H), 1.29 (t, J = 7.2 Hz, 3H),
1.28 (s, 3H), 1.27 (t, J = 7.2 Hz, 3H). HRMS calcd for C17H23NO7
353.1475. Found 353.1477.
Yield: 89%; ½a 2D2
¼ ꢀ19:9 (c 1, CHCl3) 13% ee; Yellow oil. HPLC:
ꢁ
Chiralpack AH, eluent hexane:iPrOH 85:15, 220 nm, major
tr = 11.1 min, minor tr = 12.1 min 1H NMR (CDCl3, 500 MHz), d
(ppm): 7.34 (d, J = 2 Hz, 1H), 6.68 (br s, NH), 6.28 (dd, J = 3 Hz,
2 Hz, 1H), 6.18 (d, J = 3 Hz, 1H), 5.43 (dd, J = 13.5 Hz, 3 Hz, 1H),
4.85 (dd, J = 11.5 Hz, 3 Hz, 1H), 4.66 (dd, J = 13.5 Hz, 11.5 Hz, 1H),
4.34–4.17 (m, 4H), 2.08 (s, 3H), 1.28 (t, J = 7 Hz, 3H), 1.27 (t,
4.2.18. Diethyl 2-(1-(3-methoxyphenyl)-2-nitroethyl)-2-methyl-
malonate 8b
J = 7 Hz, 3H). HRMS calcd for
C15H20N2O8 356.1220. Found
356.1222.
Yield: 51%; ½a 2D2
¼ ꢀ30:8 (c 1, CHCl3) 48% ee; yellow oil. HPLC:
ꢁ
Chiralpack AS-H, eluent hexane:iPrOH 85:15, 256 nm, major
tr = 10.1 min, minor tr = 25.6 min; 1H NMR (CDCl3, 300 MHz), d
(ppm): 7.21 (t, J = 7.1 Hz, 1H), 6.82 (dd, J = 8.1 Hz, J = 1.8 Hz, 1H),
6.75 (d, J = 8.1 Hz, 1H), 6.74–6.70 (m, 1H), 5.03 (d, J = 7.2 Hz, 2H),
4.30–4.10 (m, 5H), 3.77 (s, 3H), 1.34 (s, 3H), 1.29 (t, J = 7.2 Hz,
3H), 1.26 (t, J = 7.2 Hz, 3H). HRMS calcd for C17H23NO7 353.1475.
Found 353.1472.
4.2.12. Diethyl 2-acetamido-2-(1-nitro-4-phenylbutan-2-yl)mal-
onate 5m
Yield: 88%; ½a 2D2
ꢁ
¼ 0racemic; mp 104–107 °C; 1H NMR (CDCl3,
500 MHz), d (ppm): 7.27 (t, J = 7.5 Hz, 2H), 7.19 (t, J = 7.5 Hz, 1H),
7.11 (d, J = 7.5 Hz, 2H), 6.75 (br s, NH), 5.29 (dd, J = 14 Hz, 3.5 Hz,
1H), 4.34–4.19 (m, 4H), 4.15 (dq, J = 10.5 Hz, 7 Hz, 1H), 3.50 (sep,
J = 4 Hz, 1H), 2.64 (ddd, J = 13.5 Hz, 10.5 Hz, 5 Hz, 1H), 2.51 (ddd,
J = 13.5 Hz, 10.5 Hz, 8 Hz, 1H), 2.04 (s, 3H), 1.77–1.70 (m, 1H),
1.65–1.57 (m, 1H), 1.25 (t, J = 7.5 Hz, 3H), 1.24 (t, J = 7.5 Hz, 3H).
HRMS calcd for C19H26N2O7 394.1740. Found 394.1741.
4.2.19. Diethyl 2-(1-(4-methoxyphenyl)-2-nitroethyl)-2-methyl-
malonate 8c
Yield: 52%; ½a 2D2
¼ ꢀ21:6 (c 1, CHCl3) 15% ee; yellow oil. HPLC:
ꢁ
Chiralpack AS-H, eluent hexane:iPrOH 85:15, 256 nm, major
tr = 10.1 min, minor tr = 14.2 min; 1H NMR (CDCl3, 300 MHz), d
(ppm): 7.09 (d, J = 8.7 Hz, 2H), 6.82 (d, J = 8.7 Hz, 2H), 5.01 (d,
J = 7.2 Hz, 2H), 4.29–4.09 (m, 5H), 3.77 (s, 3H), 1.33 (s, 3H), 1.29
(t, J = 7.2 Hz, 3H), 1.26 (t, J = 7.2 Hz, 3H). HRMS calcd for
4.2.13. Diethyl 2-(2-nitro-1-phenylethyl)malonate 7a
Yield: 61%; ½a 2D2
¼ ꢀ3 (c 1, CHCl3) 20% ee; mp 56–58 °C; HPLC:
ꢁ
Chiralpack AS-H, eluent hexane:iPrOH 90:10, 256 nm, major
tr = 18 min, minor tr = 22 min; 1H NMR (CDCl3, 500 MHz),
d
(ppm): 7.33–7.27 (m, 3H), 7.25–7.22 (m, 2H), 4.89 (m, 2H), 4.23
(m, 3H), 4.01 (q, J = 7 Hz, 2H), 3.82 (d, J = 9.5 Hz, 1H), 1.26 (t,
J = 7 Hz, 3H), 1.05 (t, J = 7 Hz, 3H). HRMS calcd for C15H19NO6
309.1212. Found 309.1214.
C17H23NO7 353.1475. Found 353.1474.
4.2.20. Diethyl 2-methyl-2-(2-nitro-1-(2-nitrophenyl)ethyl)mal-
onate 8e
Yield: 72%; ½a 2D2
¼ þ17:5 (c 1, CHCl3) 93% ee; mp 75–78 °C;
ꢁ
4.2.14. Diethyl 2-methyl-2-(2-nitro-1-phenylethyl)malonate 7b
HPLC: Chiralpack AS-H, eluent hexane:iPrOH 85:15, 256 nm, major
tr = 11.9 min, minor tr = 13.3 min; 1H NMR (CDCl3, 500 MHz), d
(ppm): 7.85 (dd, J = 7.5 Hz, J = 1 Hz 1H), 7.58 (td, J = 7.5 Hz,
J = 1 Hz 1H), 7.46 (td, J = 7.5 Hz, J = 1 Hz 1H), 7.40 (dd, J = 7.5 Hz,
J = 1 Hz 1H), 5.13 (td, J = 12 Hz, J = 3 Hz 2H), 5.05–4.98 (m, 1H),
4.29 (q, J = 7 Hz, 2H), 4.24 (q, J = 7 Hz, 2H), 1.39 (s, 3H), 1.31 (t,
J = 7 Hz, 3H), 1.28 (t, J = 7 Hz, 3H). HRMS calcd for C16H20N2O8
368.1220. Found 368.1218.
Yield: 67%; ½a 2D2
¼ ꢀ25:8 (c 1, CHCl3) 42% ee; mp 58–60 °C;
ꢁ
HPLC: Chiralpack AS-H, eluent hexane:iPrOH 85:15, 256 nm, major
tr = 7.5 min, minor tr = 8.4 min; 1H NMR (CDCl3, 300 MHz), d
(ppm): 7.32–7.26 (m, 3H), 7.21–7.16 (m, 2H), 5.05 (d, J = 7.2 Hz,
2H), 4.25 (dd, J = 14.4 Hz, J = 7.2 Hz, 1H), 4.19 (q, J = 7.2 Hz, 2H),
4.18 (q, J = 7.2 Hz, 2H), 1.34 (s, 3H), 1.28 (t, J = 7.2 Hz, 3H), 1.25
(t, J = 7.2 Hz, 3H). HRMS calcd for C16H21NO6 323.1369. Found
323.1366.
4.2.21. Diethyl 2-methyl-2-(2-nitro-1-(3-nitrophenyl)ethyl)mal-
onate 8f
4.2.15. Diethyl 2-butyl-2-(2-nitro-1-phenylethyl)malonate 7c
Yield: 50%; ½a 2D2
ꢁ
¼ ꢀ23:9 (c 1, CHCl3) 22% ee; yellow oil. HPLC:
Yield: 62%; ½a 2D2
¼ ꢀ20 (c 1, CHCl3) 52% ee; mp 52–54 °C; HPLC:
ꢁ
Chiralpack AS-H, eluent hexane:iPrOH 85:15, 256 nm, major
tr = 6.7 min, minor tr = 13.3 min; 1H NMR (CDCl3, 500 MHz), d
(ppm): 7.31–7.27 (m, 3H), 7.12–7.09 (m, 2H), 5.09 (dd,
Chiralpack AS-H, eluent hexane/iPrOH 85:15, 256 nm, major
tr = 17.5 min, minor tr = 22.9 min; 1H NMR (CDCl3, 300 MHz), d
(ppm): 8.18 (d, J = 7.8 Hz, 1H), 8.13–8.10 (m, 1H), 7.62–7.49 (m,

Z. Rapi et al. / Tetrahedron: Asymmetry 25 (2014) 141–147
147
33, 1–18; (c) Petzoldt, K.; Schemiechen, R.; Hamp, K.; Gottwald, M. U.S. Patent
553911, 1996. Mulzer, J. J. Prakt. Chem. 1994, 336, 287–291.; (d) Barrett, A. G.
M.; Graboski, G. G. Chem. Rev. 1986, 86, 751–762.
2H), 5.12–5.06 (m, 2H), 4.34–4.16 (m, 5H), 1.36 (s, 3H), 1.30 (t,
J = 7.2 Hz, 3H), 1.28 (t, J = 7.2 Hz, 3H). HRMS calcd for C16H20N2O8
368.1220. Found 368.1223.
3. (a) Ji, J.; Barnes, D. M.; Zhang, J.; King, S. A.; Wittenberger, S. J.; Morton, H. E. J.
Am. Chem. Soc. 1999, 121, 10215–10216; (b) Barnes, D. M.; Ji, J.; Fickes, M. G.;
Fitzgerald, M. A.; King, S. A.; Morton, H. E.; Plagge, F. A.; Preskill, M.; Wagaw, S.
H.; Wittenberger, S. J.; Zhang, J. J. Am. Chem. Soc. 2002, 124, 13097–13105; (c)
Nichols, P. J.; DeMattei, J. A.; Barnett, B. R.; LeFur, N. A.; Chuang, T.-H.; Piscopio,
A. D.; Koch, K. Org. Lett. 2006, 8, 1495–1498.
4. Evans, D. A.; Mito, S.; Seidel, D. J. Am. Chem. Soc. 2007, 129, 11583–11592.
5. Okino, T.; Hoashi, Y.; Furukawa, T.; Xu, X.; Takemoto, Y. J. Am. Chem. Soc. 2005,
127, 119–125.
6. Tsubogo, T.; Yamashita, Y.; Kobayashi, S. Angew. Chem., Int. Ed. 2009, 48, 9117–
9120.
7. Jin, R.; Liu, K.; Xia, D.; Qian, Q.; Liu, g.; Li, H. Adv. Synth. Catal. 2012, 354, 3265–
3274.
4.2.22. Diethyl 2-methyl-2-(2-nitro-1-(4-nitrophenyl)ethyl)mal-
onate 8g
Yield: 65%; ½a 2D2
¼ ꢀ17:6 (c 1, CHCl3) 8% ee; mp 92–95 °C; HPLC:
ꢁ
Chiralpack AS-H, eluent hexane:iPrOH 85:15, 256 nm, major
tr = 26.1 min, minor tr = 37.4 min; 1H NMR (CDCl3, 500 MHz), d
(ppm): 8.10 (d, J = 8.5 Hz, 2H), 7.36 (d, J = 8.5 Hz, 2H), 5.01 (d,
J = 7.5 Hz, 2H), 4.24–4.10 (m, 5H), 1.28 (s, 3H), 1.21 (t, J = 7 Hz,
3H), 1.19 (t, J = 7 Hz, 3H). HRMS calcd for C16H20N2O8 368.1220.
Found 368.1221.
8. 8 O’Donnell, M. I. Catalytic Asymmetric Synthesis. In Asymmetric Phase-Transfer
Reactions; Ojima, I., Ed., 2nd ed.; Wiley-VCH: New York, 2000; pp 231–280;
(b)Asymmetric Phase Transfer Catalysis; Marouka, K., Ed.; Wiley-VCH:
Weinheim, 2008.
References
}
9. Bakó, P.; Toke, L. J. Inclusion Phenom. 1995, 23, 195–201.
1. Recent reviews: (a) Berner, O. M.; Tedeschi, L.; Enders, D. Eur. J. Org. Chem.
2002, 1877–1894; (b) Krause, N.; Hoffmannn-Röder, A. Synthesis 2001, 171–
196; For some recent examples of enantioselective 1,4-addition to
nitroalkenes, see: (c) Ji, J.; Barnes, D. M.; Zhang, J.; King, S. A.; Wittenberger,
S. J.; Morton, H. E. J. Am. Chem. Soc. 1999, 121, 10215–10216; (d) Barnes, D. M.;
Ji, J.; Fickes, M. G.; Fitzgerald, M. A.; King, S. A.; Morton, H. e.; Plagge, F. A.;
Preskill, M.; Wagaw, S. J.; Wittenberger, S. J.; Zhang, J. J. Am. Chem. Soc. 2002,
124, 13097–13105; (e) Okino, T.; Hoashi, Y.; Takemoto, Y. J. Am. Chem. Soc.
2003, 125, 12672–12673; (f) Li, H.; Wang, Y.; Tang, L.; Deng, L. J. Am. Chem. Soc.
2004, 126, 9906–9907; (g) Watanabe, M.; Ikagawa, A.; Wang, H.; Murata, K.;
Ikariya, T. J. Am. Chem. Soc. 2004, 126, 11148–11149; (h) Evans, D. A.; Seidel, D.
J. Am. Chem. Soc. 2005, 127, 9958–9959; (i) Li, H.; Wang, Y.; Tang, L.; Wu, F.; Liu,
X.; Guo, C.; Foxman, B. M.; Deng, L. Angew. Chem., Int. Ed. 2005, 117, 105–108;
(j) Ye, J.; Dixon, D. J.; Hynes, P. S. Chem. Commun. 2005, 4481–4483; (k)
Luchaco-Cullis, C. A.; Hoveyda, A. M. J. Am. Chem. Soc. 2002, 124, 8192–8193; (l)
Andrey, O.; Alexakis, A.; Bernardinelli, G. Org. Lett. 2003, 5, 2559–2561.
2. (a) Ono, N. The Nitro Group in Organic Synthesis; Wiley-VCH: Weinheim,
Germany, 2001; (b) Seebach, D.; Colvin, E. W.; Lehr, F.; Weller, T. Chimia 1979,
}
10. (a) Bakó, P.; Vízvárdi, K.; Bajor, Z.; Toke, L. Chem. Commun. 1998, 1193–1194;
}
(b) Bakó, P.; Vízvárdi, K.; Toppet, S.; Van der Eycken, E.; Hoornaert, G. J.; Toke, L.
Tetrahedron 1998, 54, 14975–14988; (c) Bakó, P.; Czinege, E.; Bakó, T.; Czugler,
}
M.; Toke, L. Tetrahedron: Asymmetry 1999, 10, 4539–4551; (d) Bakó, T.; Bakó,
}
}
P.; Szöllosy, Á.; Czugler, M.; Keglevich, G.; Toke, L. Tetrahedron: Asymmetry
2002, 13, 203–209; (e) Jászay, Z.; Pham, T. S.; Németh, G.; Bakó, P.; Petneházy,
}
I.; Toke, L. Synlett 2009, 1429–1432; For a review, see (f) Bakó, P.; Keglevich, G.;
Rapi, Z. Lett. Org. Chem. 2010, 7, 645–656.
11. Bakó, P.; Rapi, Z.; Keglevich, G.; Szabó, T.; Sóti, P. L.; Vigh, T.; Grun, A.;
}
Holczbauer, T. Tetrahedron Lett. 2011, 52, 1473–1476.
12. (a) Cai, S.; Wang, D. Z.; Zhang, S.; Zhao, Y. Org. Lett. 2013, 15, 2660–2663; (b)
Fan, R.; Ye, Y.; Li, W.; Wang, L. Adv. Synth. Catal. 2008, 350, 2488–2492.
13. (a) Makosza, M.; Kwast, A.; Kwast, E.; Jonczyk, A. J. Org. Chem. 1985, 50, 3722;
(b) Fedorynski, M.; Wojciechowski, K.; Matacz, Z.; Makosza, M. J. Org. Chem.
1978, 43, 4682.
14. Bakó, P.; Makó, A.; Keglevich, G.; Menyhárt, K. D.; Sefcsik, T.; Fekete, J. J.
Inclusion Phenom. 2006, 55, 295–302.