Double nitro-Mannich reaction utilizing in situ generated N-trimethylsilylaldimines: novel four-component one-pot synthesis of nitroimines

Article abstract of DOI:10.1016/j.tet.2007.11.042

Four-component synthesis of nitroimine derivatives (3) via double nitro-Mannich reaction was carried out in which nitroalkane, two moles of aldehyde, and lithium hexamethyldisilazide (LHMDS) were coupled in one-pot. In situ generated N-trimethylsilylaldim

Full text of DOI:10.1016/j.tet.2007.11.042

Available online at www.sciencedirect.com
Tetrahedron 64 (2008) 1388e1396
www.elsevier.com/locate/tet
Double nitro-Mannich reaction utilizing in situ generated
N-trimethylsilylaldimines: novel four-component one-pot
synthesis of nitroimines
a
a
a
b
Seiji Tanaka a, , Yukinari Oguma , Yusuke Tanaka , Hidenori Echizen , Hyuma Masu ,
*
Kentaro Yamaguchi b, Keiki Kishikawa a, Shigeo Kohmoto a, Makoto Yamamoto a
a Department of Applied Chemistry and Biotechnology, Faculty of Engineering, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan
b Faculty of Pharmaceutical Sciences at Kagawa Campus, Tokushima Bunri University, Shido, Sanuki, Kagawa 769-2193, Japan
Received 17 October 2007; accepted 15 November 2007
Available online 19 November 2007
Abstract
Four-component synthesis of nitroimine derivatives (3) via double nitro-Mannich reaction was carried out in which nitroalkane, two moles of
aldehyde, and lithium hexamethyldisilazide (LHMDS) were coupled in one-pot. In situ generated N-trimethylsilylaldimine was reacted with
nitroalkane dianion followed by the second addition of the resulting nitrogen anion to the aldimine and the subsequent elimination of bistrime-
thylsilylamine furnished nitoroimine. The reaction was proceeded with erythro selectivity.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
a base instead of n-BuLi or LDA in the reaction of nitro-
alkanes and aldehydes, nitroimines were obtained instead of
aldol products. The four components, nitroalkane, LHMDS,
and two molecules of aldehydes were coupled to form nitroi-
mines (Scheme 1). The reaction can be interpreted in terms of
the double nitro-Mannich reaction which involves the initial
nitro-Mannich7 process, the addition of a nitroalkane dianion
to N-trimethylsilylaldimine,8 followed by the second Mannich
reaction, and further addition of the resulting anion to N-trime-
thylsilylaldimine. The involvement of N-trimethylsilylaldi-
mine as the intermediacy of the reaction was confirmed by
the reaction of independently prepared N-trimethylsilylaldi-
mine with the nitroalkane dianion. In this stepwise way, nitro-
imines were also obtained in good yields. Herein, we report on
the details of this novel double nitro-Mannich reaction.
Aldimines are versatile synthetic reagents and numerous
examples of addition reactions of electrophiles to them have
been reported,1 generally known as the Mannich type reac-
tion.2 One of the characteristics of Mannich type reaction is
the feasibility of one-pot synthesis, where three components:
amines, carbonyl compounds, and electrophiles, can be cou-
pled in one-pot.3 It is intriguing and synthetically useful if fur-
ther numbers of components are coupled together in one-pot
with some modification of the reaction. Recently, much
attention has been paid to such a four-component one-pot syn-
thesis.4 In some cases, the reactions were carried out in sol-
vent-free conditions as an environmentally benign synthesis.5
During the course of our study of regioselective aldol addi-
tion reaction of nitroalkanes,6 we found a novel four-compo-
nent coupling reaction in one-pot affording nitroimines.
When lithium hexamethyldisilazide (LHMDS) was used as
R1
R2
SiMe3
N
2 R1CHO
LiN
R2CH2NO2
+
+
NO2
SiMe3
R1
2
1
3
* Corresponding author. Tel.: þ81 43 290 3420; fax: þ81 43 290 3422.
E-mail address: tanaka@office.chiba-u.jp (S. Tanaka).
Scheme 1.
0040-4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.11.042

S. Tanaka et al. / Tetrahedron 64 (2008) 1388e1396
1389
2. Results and discussion
of LHMDS to nitroalkane were added (entry 7). Quenching
temperature affected the diastereomeric ratio. erythro Diaste-
reomer was obtained predominantly when quenching was car-
ried out at ꢀ90 ꢁC. The erythro/threo ratio was decreased from
5/1 at ꢀ90 ꢁC (entry 7) to 2/1 at 0 ꢁC (entry 8). For further
study of the double nitro-Mannich reaction of nitroalkanes,
method B (conditions described in entry 7) was employed.
2.1. Optimization of reaction conditions
The order of addition of reagents was important in our dou-
ble nitro-Mannich reaction. Two ways of the addition of re-
agents, the methods A and B were investigated. In the
method A, nitroalkane was added to a solution of LHMDS
and then aromatic aldehyde was added to the resulting mix-
ture. On the contrary, an addition of reagent was carried out
in the sequence of aromatic aldehyde and then nitroalkane to
a solution of LHMDS in the method B. For both methods, ef-
fects of the amount of LHMDS and of the presence of DMPU
(N,N0-dimethylpropylurea), a dipolar aprotic solvent,9 were
examined. A typical reaction was carried out in the following
way to optimize the reaction conditions. To a solution of
LHMDS in THF was added either 1-nitropropane (method
A) or benzaldehyde (method B) at ꢀ90 ꢁC in the presence
or absence of DMPU. The resulting mixture was stirred for
1 h at ꢀ60 ꢁC (method A) or at room temperature (method
B). After cooling to ꢀ90 ꢁC, benzaldehyde (method A) or
1-nitropropane (method B) was added to this mixture and the
solution was stirred for additional 3 h at ꢀ40 ꢁC. The reaction
was quenched by adding acetic acid at ꢀ90 ꢁC in both
methods. The product nitroimine 3a was purified by column
chromatography on silica gel. The structure of 3a was con-
firmed from its spectral and physical data. Its structure was
also supported by its reduction by hydrogenation to the re-
ported amine10 and also by its hydrolysis to benzaldehyde
and the corresponding amine. Isolated yields and diastereo-
meric (erythro/threo) ratios are presented in Table 1. From
these data, it is clear that the addition of DMPU does not affect
neither the product yields nor the diastereomeric ratios. The
best result was obtained by method B when 3 equiv amounts
2.2. Preparation of nitroimines from nitroalkanes
and aromatic aldehydes
In order to demonstrate the usefulness of this double nitro-
Mannich reaction, additional 19 nitroimines were prepared by
method B from 3 nitroalkanes with 8 aromatic aldehydes. The
results are summarized in Table 2. The higher yields were ob-
tained with electron donating substituents. Poor yield was ob-
tained for 3h in the reaction with 9-anthryl aldehyde probably
due to steric hindrance. Diastereomeric ratios were determined
1
based on integrals in their H NMR spectra or by HPLC ana-
lysis. A single diastereomer (erythro) was obtained for 3e, 3h,
and 3m.
2.3. Determination of the stereochemistry of nitroimines
Stereochemistry of nitroimines was determined based on
the comparison of the coupling constants Jbg of both diaste-
reomers (Tables 3 and 4). The assumption was made on the ba-
sis that vicinal coupling constants of threo diastereomers were
larger than those of erythro diastereomers as reported for
b-nitroalcohols (ca. 4 Hz for erythro and ca. 8 Hz for threo).11
However, the differences in coupling constants between some
of our diastereomers (nitroimies derived from 1-nitropropane)
are very small, which makes the assignment of the stereo-
chemistry of diastereomers difficult. The confirmation of the
Table 1
Double nitro-Mannich reaction of 1-nitropropane with benzaldehyde affording
nitroimine 3a
Table 2
Product yields of double nitro-Mannich reaction of nitroalkanes with various
aldehydes
Ph
SiMe3
SiMe3
NO2
N
Product
R1
R2
Yield (%)
erythro/threo ratio
2 PhCHO
1a
+
LiN
+
2a
NO2
Ph
3b
3c
3d
3e
3f
4-CH3OC6H4
4-CH3C6H4
4-NO2C6H4
1-Naphthyl
2-Naphthyl
1-Furfuryl
9-Anthryl
C2H5
C2H5
C2H5
C2H5
C2H5
C2H5
C2H5
CH3
CH3
CH3
CH3
CH3
CH3
H
72
60
43
66
75
60
29
66
81
87
40
58
67
72
96
91
40
85
76
2/1
2/1
3a
2.5/1
erythro only
Entry LHMDSc 1ac
2ac
(mmol) (mmol) (mmol)
DMPUc 3a (%) erythro/threo
(mmol)
4/1
2/1
1a
2a
3a
4a
5b
6b
7b
8b
22
22
22
22
30
15
22
22
20
15
15
20
15
15
15
15
10
7.5
7.5
10
0
0
31
56
39
38
13
49
62
61
2.5/1c
5/1c
2/1c
3/1c
2/1d
2/1d
5/1c
2/1d
3g
3h
3i
erythro only
4.5/1
C6H5
44
44
0
3j
4-CH3OC6H4
4-CH3C6H4
4-NO2C6H4
1-Naphthyl
2-Naphthyl
C6H5
2.5/1
3/1
3k
3l
7.5
7.5
7.5
7.5
2.5/1
erythro only
0
3m
3n
3o
3p
3q
3r
3s
3t
0
2/1
d
d
d
0
a
Method A: 1-nitropropane was added to a solution of LHMDS and then
benzaldehyde was added to the resulting mixture.
4-CH3OC6H4
4-CH3C6H4
4-NO2C6H4
1-Naphthyl
2-Naphthyl
H
H
b
Method B; benzaldehyde was added to a solution of LHMDS and then
1-nitropropane was added to the resulting mixture.
H
d
d
d
H
c
Quenched at ꢀ90 ꢁC.
H
d
Quenched at 0 ꢁC.

1390
S. Tanaka et al. / Tetrahedron 64 (2008) 1388e1396
Table 3
1H NMR chemical shifts and coupling constants of nitroimines 3 derived from
1-nitropropane
R1
C
Hβ
C
Hγ NO2
R1
Hδ
N
C(Hα)3
CH2
Compd
R
Ha
Hb
Hg
Hd
Jbg
9.8
3a
C6H5
threo
erythro
threo
erythro
threo
0.82
0.94
0.88
0.95
0.88
0.95
0.95
1.00
d
4.95
4.93
4.89
4.88
4.93
4.91
4.96
5.01
d
4.65
4.71
4.65
4.62
4.60
4.65
4.92
4.96
d
8.18
8.29
8.11
8.22
8.15
8.26
8.35
8.53
d
8.3
9.9
8.4
9.7
8.4
9.8
8.0
3b
3c
3d
3e
3f
4-CH3OC6H4
4-CH3C6H4
4-NO2C6H4
1-Naphthyl
2-Naphthyl
1-Furfuryl
erythro
threo
erythro
threo
Figure 1. ORTEP diagram of erythro-3b.
difference even though they had the same erythro configura-
tion. Their conformational stabilities were examined by the
AM1 calculations. The results showed that anti-erythro-3b
was 0.2 kcal/mol (the difference in heat of formation between
the two diastereomers) more stable than that of the syn confor-
mation of erythro-3b, while syn-3m was 2.3 kcal/mol more
stable than that of anti-3m. The configuration of 3h was diffi-
cult to determine from its Jbg. Unlike 1-naphthyl derivatives
(3e and 3m), 3h had a large value (10.7 Hz) of Jbg. Since
3h have a large value of Jbg, it should have an anti conforma-
tion. Except a few nitroimines, 3i and 3l, the protons Hb of
threo diastereomers appeared at slightly lower field than those
of erythro diastereomers and Hg of threo diastereomers have
the chemical shifts of slightly up-field than those of erythro
diastereomers. There was a tendency that the methyl protons
and the vinylic protons Hd of threo diastereomers appeared
at higher field than those of erythro diastereomers (Tables 3
and 4).
d
erythro
threo
0.91
0.85
0.96
0.95
0.99
d
5.25
5.11
5.11
5.10
5.09
d
5.69
4.87
4.92
4.83
4.88
d
9.01
8.35
8.42
8.00
8.11
d
5.5
10.1
8.3
erythro
threo
3g
3h
10.0
8.8
erythro
threo
erythro
9-Anthryl
d
0.91
5.25
5.69
9.01
5.5
stereochemistry of nitoroimine was carried out by single crys-
tal X-ray diffraction analysis of erythro-3b (Fig. 1).
Its stereochemistry was unequivocally determined to be
erythro. The molecule has an anti conformation. The torsion
angle (HbeCeCeHg) measured in its single crystal X-ray
structure is 176ꢁ, which supports the observed value of Jbg
(8.4 Hz). Therefore, the other diastereomer (Jbg¼9.9 Hz)
was assigned to be threo. In some cases, single diastereomers
were obtained. In the case of nitroimine 3m, its stereochemis-
try was determined to be erythro from its single crystal X-ray
diffraction analysis (Fig. 2). The syn conformation with the
torsion angle (HbeCeCeHg) of 66ꢁ attests the observed coup-
ling constant of 4.0 Hz. Nitroimine 3e with the same substit-
uent (R¼1-naphthyl) as 3m was assigned to be erythro from
its Jbg. As we observed, the coupling constants of erythro-
3b and 3m were very different due to their conformational
2.4. Mechanism of the double nitro-Mannich reaction
and stereoselectivity
From the fact that even by method A nitroimines were ob-
tained in reasonable yields, the formation of N-trimethylsilyl-
aldimines should be faster than nitro-aldol (Henry) reaction.12
Table 4
1H NMR chemical shifts and coupling constants of nitroimines 3 derived from
1-nitroethane
R1
C
Hβ
C
Hγ NO2
R1
Hδ
N
C(Hα)3
Compd
R
Ha
Hb
Hg
Hd
Jbg
3i
C6H5
threo
erythro
threo
1.40
1.59
1.39
1.58
1.39
1.57
1.39
1.54
d
5.00
5.11
5.05
4.96
5.07
4.98
5.04
4.96
d
4.66
4.90
4.58
4.77
4.60
4.81
5.02
4.80
d
8.23
8.29
8.14
8.22
8.17
8.26
8.30
8.39
d
9.8
6.7
9.7
6.7
9.8
6.7
9.2
6.6
d
3j
4-CH3OC6H4
4-CH3C6H4
4-NO2C6H4
1-Naphthyl
2-Naphthyl
erythro
threo
3k
3l
erythro
threo
erythro
threo
3m
3n
erythro
threo
erythro
1.69
1.43
1.65
5.30
5.26
5.14
5.95
4.89
5.11
9.09
8.41
8.47
4.0
9.8
6.4
Figure 2. ORTEP diagram of erythro-3m.

S. Tanaka et al. / Tetrahedron 64 (2008) 1388e1396
1391
Ph
O
Ph
O
Ph
Si N C Ph
Si
N
Si
N
C
Ph
Si
N
N
N
N
Si
N
O
O
O
O
N
O
O
SiN C Ph
Ph
O
Ph
O
Ph
O
Ph
Si
Si
N
C
Ph
N
C
Ph
N
C
Ph
N
C
H
N
Si
Si
H
Si
N
Si
N
N
NO2
N
O
N
O
N
O
Ph
Si
H
Si
Scheme 2. Proposed mechanism of the double nitro-Mannich reaction.
The proposed mechanism of the double nitro-Mannich reac-
tion is shown in Scheme 2. The reaction involves LHMDS,
one molecule of nitoralkane, and two molecules of aromatic
aldehydes. Prior to the nitro-Mannich reaction, N-trimethylsi-
lylaldimine is formed by the condensation of LHMDS and
aromatic aldehyde followed by the nucleophilic addition of
nitoalkane dianion to the aldimine. The second addition of
the resulting nitrogen anion to the aldimine and the subsequent
elimination of bistrimethylsilylamine furnish nitoroimine. An
involvement of N-trimethylsilylaldimine was confirmed by
the nitro-Mannich reaction of independently prepared N-trime-
thylsilylbenzaldimine with dianions of 1-nitoropropane and ni-
troethane. Nitroimines 3a (erythro/threo¼5/1) and 3i (erythro/
threo¼3/1) were obtained in 65% and 91% yields, respec-
tively. erythro Selectivity13 of the reaction can be explained
by the chelation model. An electrophile should approach
from the side where a small group locates. The protonation
in this transition state affords the erythro isomer (Fig. 3).
This erythro selectivity is strongly depended on the bulkiness
of the aldehyde and the quenching (protonation) temperature.
1-Naphthylaldehyde afforded the corresponding single diaste-
reomers 3e and 3m with 1-nitropropane and nitroethane,
respectively. However, 2-naphthyl derivatives gave poor
erythro selectivity for 3f and 3m. This difference might be
caused by the sterical ease due to the difference in the substi-
tution position of the naphthyl group. Rigidity of the six-mem-
bered-ring lithium chelation complex could be improved at
low temperature, which regulated the protonation process
more efficiently leading preferentially to erythro with sterical
control. This was confirmed by the epimerization experiment.
Nitroimine 3a (erythro/threo¼1/1) was treated with LDA and
then quenched at 0 ꢁC or ꢀ90 ꢁC. The ratio of erythro/threo
was unchanged at 0 ꢁC. However, the epimerization from the
threo to the erythro diastereomer was favorable at ꢀ90 ꢁC
and the erythro/threo ratio was increased to 5/1.
3. Conclusions
The double nitro-Mannich reaction of nitroalkanes with in
situ generated trimethylsilylaldimies was studied. The coupling
of four components: nitroalkane, two molecules of aromatic al-
dehydes, and LHMDS can be carried out in a one-pot affording
nitroimines with erythro selectivity. The present reaction gives
a new type in the family of nitro-Mannich reaction which is
one of the most useful CeCeN bond formation reactions.
4. Experimental
4.1. General
All reactions were performed under an argon atmosphere.
All solvents were distilled prior to use according to the stan-
dard procedures. All melting points were taken with Yanaco
1
MP-S3 melting point apparatus and are uncorrected. H and
13C NMR spectra were recorded at 500 MHZ (or 400 MHZ)
and 125 MHZ with JEOL GSX500 or LA-400 spectrometer.
The chemical shifts were reported in parts per million using
TMS as an internal standard. Mass spectra were recorded on
a JMS-HX110 instrument. The X-ray crystallographic analysis
was performed on Rigaku AFC7S four-circle diffractometer.
For refinement of the structures, structural analysis, and pro-
duction of crystallographic illustration, the program packages
TEXSAN (SIR 97) were used. Column chromatography was
performed on Merk Silica gel 60. HPLC analysis was per-
formed on HITACHI L-6050, L-4000, and L-3350 apparatus
with MERK column Si-60.
Crystallographic data for the structural analysis of com-
pounds reported herein have been deposited at the Cambridge
Crystallographic Data Center, CCDC nos. 6634773 (erythro-
3m) and 663474 (erythro-3b). Copies of this information may
be obtained free of charge from The Director, CCDC, 12 Union
Road, Cambridge, CB2 1EZ, UK (fax: þ44 1233 336 033;
e-mail: deposit@ccdc.cam.ac.uk or http://www.ccdc.cam.ac.uk).
O
H
Li
N
H
O
4.2. Synthetic procedure
N
R
4.2.1. Method A (preparation of 3a)
To a stirred solution of 3.55 g (22 mmol) of 1,1,1,3,3,3-hexa-
methyldisilazane in 30 ml of tetrahydrofuran was added
Figure 3. Chelation model for erythro selectivity.

1392
S. Tanaka et al. / Tetrahedron 64 (2008) 1388e1396
a hexane solution of 1.6 M n-butyllithium (14 ml, 22 mmol) at
ꢀ78 ꢁC. The resulting solution was stirred for 1 h followed by
addition of 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H )-pyrimidi-
none (5.3 ml, 44 mmol). The solution was stirred for 0.5 h at
ꢀ90 ꢁC followed by the addition of a THF solution (5 ml)
of 1-nitropropane (0.7 ml, 7.5 mmol) at a rate that the temper-
ature of the solution did not exceed ꢀ90 ꢁC. The resulting so-
lution of nitronate dianion was stirred for additional 1 h at
ꢀ60 ꢁC and then a THF solution (5 ml) of benzaldehyde
(1.5 ml, 15 mmol) was added. The resulting mixture was al-
lowed to warm up to ꢀ40 ꢁC and stirred for 3 h. The resulting
mixture was again cooled down to ꢀ90 ꢁC. The reaction was
quenched by the addition of a THF solution (5 ml) of acetic
acid (2.5 ml) at ꢀ90 ꢁC. The mixture was stirred at room tem-
perature for 30 min, poured into 100 ml of saturated NaCl so-
lution, and extracted three times with diethyl ether (100 mlꢂ
3). The combined extracts were dried over anhydrous Na2SO4
and the organic layer was concentrated in vacuum. The resi-
dual oil was flash-chromatographed on silica gel eluted with
hexane/ethyl acetate (2/1) to give 829 mg (yield 39%) of imine
derivative 3a (erythro/threo ratio; 2/1), with trace amounts of
1-phenyl-2-nitro-1-butanol,9a,14 and benzaldehyde.
283.1447, found: 283.1428. Anal. Calcd for C17H18N2O2: C,
72.32; H, 6.43; N, 9.92. Found: C, 72.25; H, 6.27; N, 9.98.
4.3.2. threo-(1E )-2-Aza-4-nitro-1,3-diphenylhex-1-ene
(threo-3a)
1H NMR (500 MHz, CDCl3) d 0.82 (t, J¼7.3 Hz, 3H),
1.46e1.51 (m, 2H), 4.65 (d, J¼9.8 Hz, 1H), 4.91e4.99 (m,
1H), 7.20e7.50 (m, 8H), 7.76e7.80 (m, 2H), 8.18 (s, 1H); 13
C
NMR (125 MHz, CDCl3) d 10.0 (q), 24.0 (t), 77.0 (d), 95.2 (d),
127.3 (d), 127.9 (d), 128.1 (d), 128.35 (d), 128.39 (d), 128.76
(d), 128.82 (d), 129.5 (d, 9C), 131.0 (d), 134.2 (s), 138.3 (s),
162.6 (s).
4.3.3. erythro-(1E )-2-Aza-1,3-bis(4-methoxyphenyl)-
4-nitrohex-1-ene (erythro-3b)
Mp 85e86 ꢁC; IR n (KBr) 2971, 2936, 2838, 1639, 1606,
1578, 1549, 1511, 1461, 1441, 1422, 1373, 1304, 1250, 1166,
1
1109, 1031, 832 cmꢀ1; H NMR (500 MHz, CDCl3) d 0.95
(t, J¼7.4 Hz, 3H), 1.92e2.05 (m, 2H), 3.77 (s, 3H), 3.84 (s,
3H), 4.62 (d, J¼8.3 Hz, 1H), 4.88 (ddd, J¼10.2, 8.5, 3.4 Hz,
1H), 6.85 (d, J¼8.9 Hz, 2H), 6.91 (d, J¼8.8 Hz, 2H),
7.32 (d, J¼8.9 Hz, 2H), 7.69 (d, J¼8.8 Hz, 2H), 8.22 (s,
1H); 13C NMR (125 MHz, CDCl3) d 10.3 (q), 24.2 (t), 55.2
(q), 55.4 (q), 76.0 (d), 95.3 (d), 113.9 (d), 114.0 (d), 114.1
(d), 114.4 (d), 128.6 (d), 128.7 (d), 130.2 (s), 130.2 (d),
131.7 (s), 132.0 (d), 159.4 (s), 162.2 (d), 164.6 (s); HRMS
(FAB): calcd for C19H23N2O4 (Mþ1): 343.1658, found:
343.1652. Anal. Calcd for C19H22N2O4: C, 66.65; H, 6.48;
N, 8.18. Found: C, 66.37; H, 6.51; N, 8.15.
4.2.2. Method B (preparation of 3a)
To a stirred THF solution of lithium hexamethyldisilazide
(22 mmol) was added a THF solution (5 ml) of benzaldehyde
(1.5 ml, 15 mmol) at ꢀ90 ꢁC. The resulting solution was
stirred for 1 h at room temperature and then cooled down to
ꢀ90 ꢁC followed by the addition of a THF solution (5 ml)
of 1-nitropropane (0.7 ml, 7.5 mmol). The resulting mixture
was allowed to warm up to ꢀ40 ꢁC and stirred for 3 h. The re-
sulting mixture was again cooled down to ꢀ90 ꢁC. The reac-
tion was quenched by the addition of a THF solution (5 ml)
of acetic acid (2.5 ml) at ꢀ90 ꢁC. The mixture was stirred at
room temperature for 30 min, poured into 100 ml of saturated
NaCl solution, and extracted three times with diethyl ether
(100 mlꢂ3). The combined extracts were dried over anhy-
drous Na2SO4 and concentrated in vacuum. The residual oil
was flash-chromatographed on silica gel eluted with hexane/
ethyl acetate (2/1) to give 1380 mg (yield 65%) of imine deriva-
tive 3a (erythro/threo ratio; 5/1).
4.3.4. threo-(1E )-2-Aza-1,3-bis(4-methoxyphenyl)-
4-nitrohex-1-ene (threo-3b)
1H NMR (500 MHz, CDCl3) d 0.89 (t, J¼7.4 Hz, 3H),
1.51e1.56 (m, 1H), 1.84e1.91 (m, 1H), 3.79 (s, 3H), 3.81
(s, 3H), 4.57 (d, J¼9.8 Hz, 1H), 4.89 (ddd, J¼10.9, 9.8,
3.2 Hz, 1H), 6.86 (d, J¼8.9 Hz, 2H), 6.90 (d, J¼8.9 Hz,
2H), 7.35 (d, J¼8.9 Hz, 2H), 7.64 (d, J¼8.9 Hz, 2H), 8.11
(s, 1H); 13C NMR (125 MHz, CDCl3) d 10.4 (q), 24.3 (t),
55.31 (q), 55.35 (q), 76.7 (d), 95.7 (d), 113.9 (d), 114.0 (d),
114.12 (d), 114.36 (d), 128.73 (d), 129.11 (d), 130.15 (s), 130.23
(d), 130.84 (s), 159.6 (s), 161.6 (d), 164.6 (s).
4.3. Nitroimines
4.3.5. erythro-(1E )-2-Aza-1,3-bis(4-methylphenyl)-
4-nitrohex-1-ene (erythro-3c)
4.3.1. erythro-(1E )-2-Aza-4-nitro-1,3-diphenylhex-1-ene
(erythro-3a)
IR n (NaCl) 3026, 2975, 2937, 2922, 2878, 1643, 1609,
1573, 1549, 1512, 1457, 1372, 1307, 1174, 1037, 1021,
1
Mp 64e65 ꢁC; IR n (KBr) 2970, 2880, 1955, 1640, 1550,
814 cmꢀ1; H NMR (500 MHz, CDCl3) d 0.95 (t, J¼7.4 Hz,
1500, 1455, 1385, 1300, 1255, 1215, 1080, 1025, 970 cmꢀ1
;
3H), 1.83e2.07 (m, 2H), 2.30 (s, 3H), 2.37 (s, 3H), 4.65 (d,
J¼8.3 Hz, 1H), 4.91 (ddd, J¼10.7, 8.3, 3.3 Hz, 1H), 7.13 (d,
J¼7.9 Hz, 2H), 7.20 (d, J¼7.7 Hz, 2H), 7.29 (d, J¼8.3 Hz,
2H), 7.64 (d, J¼8.3 Hz, 2H), 8.26 (s, 1H); 13C NMR
(125 MHz, CDCl3) d 10.3 (q), 21.1 (q), 21.5 (q), 24.1 (t),
76.4 (d), 95.2 (d), 127.4 (d), 128.5 (d), 129.3 (d), 129.5 (d),
133.2 (s), 136.5 (s), 138.0 (s), 141.7 (s), 163.0 (d); HRMS
(FAB): calcd for C19H23N2O2 (Mþ1): 311.1760, found:
311.1763.
1H NMR (500 MHz, CDCl3) d 0.94 (t, J¼7.4 Hz, 3H), 1.88e
1.96 (m, 1H), 1.99e2.09 (m, 1H), 4.71 (d, J¼8.3, 8.3 Hz, 1H),
4.93 (ddd, J¼10.1, 8.3, 3.1 Hz, 1H), 7.23e7.42 (m, 8H), 7.74
(d, J¼1.9 Hz, 1H), 7.76 (d, J¼1.3 Hz, 1H), 8.29 (s, 1H); 13C
NMR (125 MHz, CDCl3) d 10.3 (q), 24.0 (t), 76.5 (d), 95.1
(d), 127.5 (d), 128.1 (d), 128.3 (d), 128.47 (d), 128.54 (d),
128.6 (d), 128.8 (d), 129.0 (d), 131.4 (d), 139.3 (s), 135.6
(s), 163.3 (d); HRMS (FAB): calcd for C17H19N2O2 (Mþ1):

S. Tanaka et al. / Tetrahedron 64 (2008) 1388e1396
1393
4.3.6. threo-(1E )-2-Aza-1,3-bis(4-methylphenyl)-
4-nitrohex-1-ene (threo-3c)
2.17 (m, 1H), 4.92 (d, J¼8.3 Hz, 1H), 5.07e5.14 (m, 1H),
7.38e8.05 (m, 14H), 8.42 (s, 1H); 13C NMR (125 MHz,
CDCl3) d 10.3 (q), 24.0 (t), 76.6 (d), 95.0 (d), 123.7 (d),
124.9 (d), 126.27 (d), 126.31 (d), 126.6 (d), 126.9 (d), 126.5
(d), 126.7 (d), 127.9 (d), 128.5 (d), 128.7 (d), 129.7 (d),
130.9 (d), 132.9 (s), 133.21 (s), 133.28 (s), 135.0 (s), 136.7
(s), 163.7 (d); HRMS (FAB): calcd for C25H23N2O2 (Mþ1):
383.1760, found: 383.1789.
1H NMR (500 MHz, CDCl3) d 0.88 (t, J¼7.5 Hz, 3H),
1.50e1.57 (m, 1H), 1.82e1.93 (m, 1H), 2.33 (s, 3H), 2.34 (s,
3H), 4.60 (d, J¼9.8 Hz, 1H), 4.93 (ddd, J¼11.3, 9.8, 3.1 Hz,
1H), 7.15 (d, J¼7.9 Hz, 2H), 7.18 (d, J¼7.7 Hz, 2H), 7.32
(d, J¼8.2 Hz, 2H), 7.59 (d, J¼7.9 Hz, 2H), 8.15 (s, 1H); 13C
NMR (125 MHz, CDCl3) d 10.2 (q), 21.0 (q), 21.5 (q), 24.4
(t), 76.8 (d), 95.5 (d), 127.9 (d), 128.5 (d), 129.1 (d), 129.6
(d), 133.1 (s), 135.6 (s), 138.2 (s), 141.4 (s), 162.4 (d).
4.3.11. threo-(1E )-2-Aza-1,3-di(2-naphthyl)-
4-nitrohex-1-ene (threo-3f)
4.3.7. erythro-(1E )-2-Aza-1,3-bis(4-nitrophenyl)-
4-nitrohex-1-ene (erythro-3d)
IR n (NaCl) 3078, 2979, 2941, 2884, 1640, 1600, 1550, 1523,
1H NMR (500 MHz, CDCl3) d 0.85 (t, J¼7.3 Hz, 3H),
1.47e1.55 (m, 1H), 1.89e1.98 (m, 1H), 4.87 (d, J¼10.1 Hz,
1H), 5.07e5.14 (m, 1H), 7.38e8.00 (m, 14H), 8.35 (s, 1H);
13C NMR (125 MHz, CDCl3) d 10.3 (q), 24.4 (t), 76.6 (d),
95.4 (d), 123.9 (d), 126.45 (d), 126.53 (d), 127.4 (d), 127.8
(d), 128.0 (d), 128.1 (d), 128.4 (d), 129.0 (d), 132.9 (s),
133.2 (s), 133.3 (s), 135.0 (s), 135.7 (s), 163.0 (d).
1
1376, 1345, 1314, 1105, 1013, 855 cmꢀ1; H NMR (500 MHz,
CDCl3) d 1.00 (t, J¼7.3 Hz, 3H), 1.91e2.01 (m, 1H), 2.05e
2.15 (m, 1H), 4.96 (d, J¼8.0 Hz, 1H), 5.01 (ddd, J¼10.0, 8.0,
3.3 Hz, 1H), 7.67 (d, J¼8.9 Hz, 2H), 8.02 (d, J¼8.9 Hz, 2H),
8.21 (d, J¼8.9 Hz, 2H), 8.29 (d, J¼8.9 Hz, 2H), 8.53 (s, 1H);
13C NMR (125 MHz, CDCl3) d 10.0 (q), 23.8 (t), 75.5 (d),
94.2 (d), 123.8 (d), 124.0 (d), 128.4 (d), 129.3 (d), 140.2 (s),
145.4 (s), 147.7 (s), 149.5 (s), 161.7 (d).
4.3.12. erythro-(1E )-2-Aza-1,3-di(2-furyl)-
4-nitrohex-1-ene (erythro-3g)
IR n (NaCl) 3124, 2975, 2938, 2882, 1644, 1550, 1482,
1
1373, 1277, 1150, 1078, 1014, 933, 884, 810, 748 cmꢀ1; H
4.3.8. threo-(1E )-2-Aza-1,3-bis(4-nitrophenyl)-
4-nitrohex-1-ene (threo-3d)
NMR (500 MHz, CDCl3) d 0.99 (t, J¼7.3 Hz, 3H), 1.95e
2.17 (m, 2H), 4.88 (d, J¼8.8 Hz, 1H), 5.09 (ddd, J¼10.8,
8.8, 3.7 Hz, 1H), 6.31e6.34 (m, 2H), 6.50 (dd, J¼3.4,
1.8 Hz, 1H), 6.86 (d, J¼3.7 Hz, 1H), 7.37 (dd, J¼1.7,
0.6 Hz, 1H), 7.55 (d, J¼1.8 Hz, 1H), 8.11 (s, 1H); 13C NMR
(125 MHz, CDCl3) d 10.1 (q), 24.4 (t), 69.1 (d), 91.6 (d),
108.3 (d), 110.5 (d), 112.0 (d), 116.5 (d), 143.0 (d), 145.7
(d), 150.7 (s), 150.8 (s), 152.7 (d); HRMS (FAB): calcd for
C13H15N2O4 (Mþ1): 163.1032, found: 163.1026.
1
Mp 162e164 ꢁC; H NMR (500 MHz, CDCl3) d 0.94 (t,
J¼7.3 Hz, 3H), 1.49e1.57 (m, 1H), 1.90e2.00 (m, 1H),
4.86 (d, J¼9.8 Hz, 1H), 4.96 (ddd, J¼10.2, 9.8, 3.0 Hz, 1H),
7.70 (d, J¼8.6 Hz, 2H), 7.91 (d, J¼8.6 Hz, 2H), 8.25 (d,
J¼8.6 Hz, 2H), 8.28 (d, J¼8.6 Hz, 2H), 8.35 (s, 1H); 13C
NMR (125 MHz, CDCl3) d 10.1 (q), 24.1 (t), 76.5 (d), 94.5
(d), 123.8 (d), 124.3 (d), 129.0 (d), 129.4 (d), 140.2 (s),
144.5 (s), 148.1 (s), 149.6 (s), 161.7 (d); HRMS (FAB): calcd
for C17H17N4O6 (Mþ1): 373.1148, found: 373.1115. Anal.
Calcd for C17H16N4O6: C, 54.84; H, 4.33; N, 15.05. Found:
C, 54.61; H, 4.49; N, 14.91.
4.3.13. threo-(1E )-2-Aza-1,3-di(2-furyl)-
4-nitrohex-1-ene (threo-3g)
1H NMR (500 MHz, CDCl3) d 0.95 (t, J¼7.3 Hz, 3H),
1.63e1.95 (m, 2H), 4.83 (d, J¼10.1 Hz, 1H), 5.10 (ddd,
J¼10.2, 10.1, 3.4 Hz, 1H), 6.36e6.38 (m, 2H), 6.45 (dd,
J¼3.4, 1.8 Hz, 1H), 6.80 (d, J¼3.4 Hz, 1H), 7.42 (dd, J¼
1.7, 0.7 Hz, 1H), 7.50 (d, J¼1.5 Hz, 1H), 8.00 (s, 1H); 13C
NMR (125 MHz, CDCl3) d 10.1 (q), 24.5 (t), 69.8 (d), 92.8
(d), 109.1 (d), 110.5 (d), 111.8 (d), 116.3 (d), 143.1 (d), 145.6
(d), 150.2 (s), 150.7 (s), 152.2 (d).
4.3.9. erythro-(1E )-2-Aza-1,3-dinaphthyl-
4-nitrohex-1-ene (erythro-3e)
IR n (NaCl) 3051, 2974, 2936, 2879, 1640, 1617, 1547,
;
1509, 1459, 1369, 1215, 1168, 802, 775 cmꢀ1 1H NMR
(500 MHz, CDCl3) d 0.91 (t, J¼7.3 Hz, 3H), 2.03e2.11 (m,
1H), 2.36e2.45 (m, 1H), 5.25 (ddd, J¼11.8, 5.5, 2.5 Hz, 1H),
5.69 (d, J¼5.5 Hz, 1H), 7.44e7.88 (m, 12H), 8.47 (d,
J¼8.6 Hz, 1H), 8.92 (s, 1H), 9.01 (d, J¼8.6 Hz, 1H); 13C
NMR (125 MHz, CDCl3) d 10.7 (q), 22.4 (t), 74.5 (d), 94.0
(d), 123.1 (d), 124.5 (d), 125.1 (d), 125.4 (d), 125.9 (d), 126.2
(d), 126.6 (d), 126.8 (d), 127.5 (d), 128.7 (d), 129.0 (d),
129.30 (d), 130.4 (s), 130.5 (d), 130.9 (d), 131.3 (s), 131.9
(s), 133.8 (s), 134.1 (s), 134.9 (s), 163.6 (d); HRMS (FAB):
calcd for C25H23N2O2 (Mþ1): 383.1760, found: 387.1789.
4.3.14. erythro-(1E )-1,3-Di(9-anthryl)-2-aza-
4-nitrohex-1-ene (erythro-3h)
Mp 206e207 ꢁC; IR n (KBr) 3051, 2967, 2931, 2853, 1635,
1
1549, 1521, 1446, 1371, 891, 728 cmꢀ1; H NMR (500 MHz,
CDCl3) d 0.79 (t, J¼7.3 Hz, 3H), 1.18e1.26 (m, 1H), 2.00e
2.10 (m, 1H), 5.98 (ddd, J¼3.0, 10.9, 10.9 Hz, 1H), 6.79 (d,
J¼10.7 Hz, 1H), 7.23e8.17 (m, 14H), 8.36 (s, 1H), 8.56 (s,
1H), 8.76 (d, J¼9.2 Hz, 1H), 9.18 (d, J¼8.3 Hz, 1H), 9.49 (s,
1H); 13C NMR (125 MHz, CDCl3) d 10.4 (q), 25.0 (t), 72.1
(d), 94.6 (d), 120.9 (d), 121.9 (d), 123.2 (d), 124.7 (d), 124.7
(d), 125.1 (d), 125.2 (d), 125.3 (d), 125.4 (d), 126.4 (s), 126.8
(s), 127.0 (d), 127.7 (d), 127.9 (d), 128.3 (d), 129.0 (d), 129.4
(s), 129.5 (d), 129.6 (s), 129.7 (d), 129.9 (d), 130.1 (s), 131.2
4.3.10. erythro-(1E )-2-Aza-1,3-di(2-naphthyl)-
4-nitrohex-1-ene (erythro-3f)
IR n (NaCl) 3056, 2970, 2929, 2854, 1637, 1547, 1369,
1
1346, 1121, 895, 858, 819, 746 cmꢀ1; H NMR (500 MHz,
CDCl3) d 0.96 (t, J¼7.3 Hz, 3H), 1.98e2.06 (m, 1H), 2.07e

1394
S. Tanaka et al. / Tetrahedron 64 (2008) 1388e1396
(s), 131.6 (s), 132.2 (s), 163.3 (d); HRMS (FAB): calcd for
C33H26N2O4 (Mþ1): 483.2073, found: 483.2029.
1H); 13C NMR (125 MHz, CDCl3) d 15.0 (q), 21.1 (q, 2C),
76.2 (d), 88.3 (d), 127.3 (d), 128.6 (d), 129.3 (d), 129.4 (d),
133.2 (s), 136.6 (s), 137.9 (s), 141.7 (s), 163.2 (d); HRMS
(FAB): calcd for C18H21N2O2 (Mþ1): 297.1603, found:
297.1578. Anal. Calcd for C18H20N2O2: C, 72.95; H, 6.80;
N, 9.45. Found: C, 72.79; H, 6.80; N, 9.30.
4.3.15. erythro-(1E )-2-Aza-4-nitro-1,3-diphenylpent-
1-ene (erythro-3i)
IR n (NaCl) 3050, 2890, 1710, 1645, 1550, 1495, 1460, 1390,
1360, 1220, 1050 cmꢀ1; 1H NMR (500 MHz, CDCl3) d 1.59 (d,
J¼6.5 Hz, 3H), 4.89 (d, J¼6.5 Hz, 1H), 5.00 (q, J¼6.5 Hz, 1H),
7.32e7.45 (m, 8H), 7.78 (d, J¼1.5 Hz, 2H), 8.31 (s, 1H); 13C
NMR (125 MHz, CDCl3) d 14.7 (q), 76.2 (d), 88.1 (d), 127.3
(d), 128.0 (d), 128.1 (d), 128.5 (d), 128.56 (d), 128.58 (d),
128.7 (d), 129.0 (d), 131.3 (d), 135.6 (s), 138.4 (s), 163.6 (d);
HRMS (FAB): calcd for C16H17N2O2 (Mþ1): 269.1290, found:
269.1282. Anal. Calcd for C16H16N2O2: C, 71.62; H, 6.01; N,
10.4. Found: C, 70.69; H, 6.11; N, 10.13.
4.3.20. threo-(1E )-2-Aza-1,3-bis(4-methylphenyl)-
4-nitropent-1-ene (threo-3k)
1H NMR (500 MHz, CDCl3) d 1.39 (d, J¼7.0 Hz, 3H), 2.33
(s, 3H), 2.33 (s, 3H), 4.60 (d, J¼9.8 Hz, 1H), 5.05e5.11 (m,
1H), 7.15e7.32 (m, 6H), 7.59 (d, J¼7.9 Hz, 2H), 8.17 (s, 1H);
13C NMR (125 MHz, CDCl3) d 16.9 (q), 21.50 (q), 21.53 (q),
77.6 (d), 88.6 (d), 127.9 (d), 129.1 (d), 129.2 (d), 129.7 (d),
129.8 (d), 133.1 (s), 135.4 (s), 138.2 (s), 141.5 (s), 162.6 (d).
4.3.16. threo-(1E )-2-Aza-4-nitro-1,3-diphenylpent-
1-ene (threo-3i)
4.3.21. erythro-(1E )-2-Aza-1,3-bis(4-nitrophenyl)-
4-nitropent-1-ene (erythro-3l)
IR n (NaCl) 3109, 3080, 2942, 2858, 1731, 1708, 1644, 1602,
1H NMR (500 MHz, CDCl3) d 1.40 (d, J¼6.7 Hz, 3H), 4.66
(d, J¼9.8 Hz, 1H), 5.11 (dq, J¼9.8, 6.7 Hz, 1H), 7.27e7.45 (m,
8H), 7.76 (d, J¼1.9 Hz, 2H), 8.23 (s, 1H); 13C NMR (125 MHz,
CDCl3) d 16.8 (q), 77.8 (d), 88.5 (d), 127.3 (d), 128.0 (d), 128.1
(d), 128.46 (d), 128.56 (d), 128.58 (d), 128.7 (d), 1289.0 (d),
131.2 (d), 135.6 (s), 138.2 (s), 162.9 (d).
1
1555, 1493, 1453, 1390, 1347, 1295, 1107, 1014 cmꢀ1; H
NMR (500 MHz, CDCl3) d 1.54 (d, J¼6.4 Hz, 3H), 4.96 (quint,
J¼6.4 Hz, 1H), 5.03 (d, J¼6.4 Hz, 1H), 7.58 (d, J¼8.9 Hz, 2H),
7.91 (d, J¼8.9 Hz, 2H), 8.15e8.23 (m, 4H), 8.39 (s, 1H); 13C
NMR (125 MHz, CDCl3) d 14.5 (q), 75.5 (d), 87.4 (d), 124.0
(d), 124.1 (d), 128.3 (d), 130.4 (d), 140.2 (s), 145.5 (s), 149.9
(s), 149.7 (s), 162.7 (d); HRMS (FAB): calcd for C16H15N4O6
(Mþ1): 359.0992, found: 359.1019.
4.3.17. erythro-(1E )-2-Aza-1,3-bis(4-methoxyphenyl)-
4-nitropent-1-ene (erythro-3j)
IR n (NaCl) 2933, 2838, 1642, 1606, 1578, 1548, 1511,
1462, 1423, 1388, 1359, 1250, 1166, 1030, 831 cmꢀ1; 1H NMR
(500 MHz, CDCl3) d 1.58 (d, J¼6.8 Hz, 3H), 3.78 (s, 3H), 3.83
(s, 3H), 4.77 (d, J¼6.8 Hz, 1H), 4.96 (quint, J¼6.8 Hz, 1H),
6.87 (d, J¼8.9 Hz, 2H), 6.92 (d, J¼8.6 Hz, 2H), 7.34 (d,
J¼8.6 Hz, 2H), 7.71 (d, J¼8.9 Hz, 2H), 8.22 (s, 1H); 13C
NMR (125 MHz, CDCl3) d 15.1 (q), 55.3 (q), 55.4 (q), 75.9
(d), 88.4 (d), 114.0 (d), 114.1 (d), 114.3 (d), 128.5 (d), 128.8
(d), 129.1 (d), 130.0 (d), 130.2 (d), 131.7 (s), 132.0 (d), 159.4
(s), 162.2 (s), 162.5 (s); HRMS (FAB): calcd for C18H21N2O4
(Mþ1): 329.1501, found: 329.1498.
4.3.22. threo-(1E )-2-Aza-1,3-bis(4-nitrophenyl)-
4-nitropent-1-ene (threo-3l)
1H NMR (500 MHz, CDCl3) d 1.39 (d, J¼7.1 Hz, 3H), 4.80
(d, J¼9.2 Hz, 1H), 5.02e5.07 (m, 1H), 7.62 (d, J¼8.5 Hz,
2H), 7.84 (d, J¼8.5 Hz, 2H), 8.16e8.21 (m, 4H), 8.30 (s,
1H); 13C NMR (125 MHz, CDCl3) d 16.6 (q), 77.0 (d), 87.7
(d), 123.8 (d), 124.5 (d), 129.0 (d), 129.4 (d), 140.2 (s),
144.3 (s), 148.1 (s), 149.6 (s), 161.9 (d).
4.3.23. erythro-(1E )-(3RS,4SR)-2-Aza-1,3-dinaphthyl-
4-nitropent-1-ene (erythro-3m)
4.3.18. threo-(1E )-2-Aza-1,3-bis(4-methoxyphenyl)-
4-nitropent-1-ene (threo-3j)
Mp 127.5e129 ꢁC; IR n (KBr) 3051, 1734, 1685, 1636,
1615, 1590, 1546, 1508, 1443, 1383, 1361, 1162, 1049,
1H NMR (500 MHz, CDCl3) d 1.40 (d, J¼6.7 Hz, 3H), 3.80
(s, 3H), 3.82 (s, 3H), 4.58 (d, J¼9.5 Hz, 1H), 5.05 (dq, J¼9.5,
6.7 Hz, 1H), 6.87 (d, J¼8.9 Hz, 2H), 6.91 (d, J¼8.9 Hz, 2H),
7.36 (d, J¼8.5 Hz, 2H), 7.65 (d, J¼8.9 Hz, 2H), 8.14 (s, 1H);
13C NMR (125 MHz, CDCl3) d 16.9 (q), 55.3 (q), 55.4 (q),
76.8 (d), 88.8 (d), 113.9 (d), 114.1 (d), 114.2 (d), 114.4 (d),
128.5 (d), 128.7 (d), 129.2 (d), 130.3 (d), 130.6 (s), 132.1 (d),
159.6 (s), 161.9 (s), 162.1 (d).
970 cmꢀ1; H NMR (500 MHz, CDCl3) d 1.69 (d, J¼6.4 Hz,
1
3H), 5.30 (dq, J¼6.4, 4.0 Hz, 1H), 5.95 (d, J¼4.0 Hz, 1H),
7.45e7.95 (m, 12H), 8.42 (d, J¼8.5 Hz, 1H), 8.98 (s, 1H),
9.09 (d, J¼7.9 Hz, 1H); 13C NMR (125 MHz, CDCl3) d 13.2
(q), 73.7 (d), 86.4 (d), 122.5 (d), 124.6 (d), 125.1 (d), 125.5
(d), 125.9 (d), 126.2 (d), 126.3 (d), 127.0 (d), 127.6 (d), 128.7
(d), 128.8 (d), 129.4 (d), 130.1 (s), 130.7 (d), 131.0 (s), 131.3
(s), 132.0 (d), 133.9 (s), 134.0 (s), 134.9 (s), 164.1 (d); HRMS
(FAB): calcd for C24H21N2O2 (Mþ1): 369.1603, found:
369.1584. Anal. Calcd for C24H20N2O2: C, 78.24; H, 5.47;
N, 7.60. Found: C, 77.96; H, 5.48; N, 7.53.
4.3.19. erythro-(1E )-2-Aza-1,3-bis(4-methylphenyl)-
4-nitropent-1-ene (erythro-3k)
IR n (NaCl) 3026, 2922, 2865, 1644, 1607, 1574, 1549,
1512, 1450, 1389, 1359, 1174, 1020, 813 cmꢀ1
;
1H NMR
4.3.24. erythro-(1E )-2-Aza-1,3-di(2-naphtyl)-
4-nitropent-1-ene (erythro-3n)
IR n (NaCl) 3058, 2867, 1734, 1638, 1548, 1450, 1387,
;
1359, 1243, 1122, 1048, 1638 cmꢀ1 1H NMR (500 MHz,
(500 MHz, CDCl3) d 1.57 (d, J¼6.7 Hz, 3H), 2.31 (s, 3H),
2.37 (s, 3H), 4.81 (d, J¼6.7 Hz, 1H), 4.98 (quint, J¼6.7 Hz,
1H), 7.13e7.31 (m, 6H), 7.65 (d, J¼7.9 Hz, 2H), 8.25 (s,

S. Tanaka et al. / Tetrahedron 64 (2008) 1388e1396
1395
CDCl3) d 1.65 (d, J¼6.4 Hz, 3H), 5.11 (d, J¼6.4 Hz, 1H), 5.14
4.3.29. (1E )-2-Aza-1,3-bis(4-nitrophenyl)-
4-nitrobut-1-ene (3r)
IR n (NaCl) 3106, 2915, 1687, 1641, 1600, 1555, 1523,
1415, 1376, 1347, 1315, 1217, 1108, 1072, 857 cmꢀ1 1H
NMR (500 MHz, CDCl3) d 4.75 (dd, J¼12.9, 3.9 Hz, 1H),
4.94 (dd, J¼12.9, 9.8 Hz, 1H), 5.32 (dd, J¼9.8, 3.9 Hz, 1H),
7.72 (d, J¼8.6 Hz, 2H), 7.98 (d, J¼8.6 Hz, 2H), 8.26e8.29
(m, 4H), 8.50 (s, 1H); 13C NMR (125 MHz, CDCl3) d 70.8
(d), 80.0 (t), 123.9 (d), 124.4 (d), 128.2 (d), 129.5 (d), 140.1
(s), 144.5 (s), 148.1 (s), 149.7 (s), 162.7 (d); HRMS (FAB):
calcd for C15H13N4O6 (Mþ1): 345.0835, found: 345.0824.
(quint, J¼6.4 Hz, 1H), 7.44e8.09 (m, 14H), 8.47 (s, 1H); 13C
NMR (125 MHz, CDCl3) d 14.9 (q), 76.4 (d), 88.1 (d), 123.8
(d), 124.9 (d), 126.3 (d), 126.4 (d), 126.6 (d), 126.7 (d), 127.5
(d), 127.7 (d), 127.9 (d), 128.1 (d), 128.5 (d), 128.7 (d),
131.0 (d), 132.9 (s), 133.1 (s), 133.3 (s), 135.0 (s), 136.8 (s),
163.9 (d); HRMS (FAB): calcd for C24H21N2O2 (Mþ1):
369.1603, found: 369.1595.
;
4.3.25. threo-(1E )-2-Aza-1,3-di(2-naphtyl)-
4-nitropent-1-ene (threo-3n)
1H NMR (500 MHz, CDCl3) d 1.43 (d, J¼6.7 Hz, 3H), 4.89
(d, J¼9.8 Hz, 3H), 5.26 (dq, J¼9.8, 6.7 Hz, 1H), 7.43e8.10
(m, 14H), 8.41 (s, 1H); 13C NMR (125 MHz, CDCl3) d 17.0
(q), 78.0 (d), 88.5 (d), 123.9 (d), 125.3 (d), 126.4 (d), 126.5
(d), 127.4 (d), 127.76 (d), 127.83 (d), 128.0 (d), 128.4 (d),
128.7 (d), 129.0 (d), 130.9 (d), 132.9 (s), 133.1 (s), 133.3
(s), 134.9 (s), 135.6 (s), 163.2 (d).
4.3.30. (1E )-2-Aza-1,3-dinaphthyl-4-nitrobut-1-ene (3s)
IR n (NaCl) 3058, 2913, 1732, 1687, 1637, 1618, 1555,
;
1509, 1375, 1340, 1228, 1167, 802 cmꢀ1 1H NMR
(500 MHz, CDCl3) d 4.91 (dd, J¼12.8, 3.1 Hz, 1H), 5.11 (dd,
J¼12.8, 10.1 Hz, 1H), 6.01 (dd, J¼10.1, 3.1 Hz, 1H), 7.48e
7.56 (m, 4H), 7.60e7.66 (m, 2H), 7.83e7.88 (m, 2H), 7.91e
7.95 (m, 4H), 8.36 (d, J¼8.5 Hz, 1H), 8.99 (d, J¼8.5 Hz,
1H), 9.06 (s, 1H); 13C NMR (125 MHz, CDCl3) d 69.4 (d),
80.5 (t), 122.4 (d), 124.5 (d) 125.1 (d), 125.7 (d), 125.9 (d),
126.0 (d), 126.2 (d), 127.0 (d), 127.5 (d), 128.7 (d), 129.0
(d), 129.4 (d), 130.1 (s), 130.3 (d), 130.9 (s), 131.3 (s), 132.0
(d), 133.8 (s), 134.1 (s), 134.1 (s), 164.1 (d); HRMS (FAB):
calcd for C23H19N2O2 (Mþ1): 355.1447, found: 355.1472.
4.3.26. (1E )-2-Aza-4-nitro-1,3-diphenylbut-1-ene (3o)
IR n (NaCl) 3062, 3030, 2873, 1643, 1601, 1579, 1555,
1519, 1493, 1453, 1418, 1376, 1343, 1218, 1027, 969 cmꢀ1
;
1H NMR (500 MHz, CDCl3) d 4.56 (dd, J¼12.7, 3.8 Hz,
1H), 4.82 (dd, J¼12.7, 9.9 Hz, 1H), 5.04 (dd, J¼9.9, 3.8 Hz,
1H), 7.21e7.34 (m, 6H), 7.39 (d, J¼7.4 Hz, 2H), 7.70 (d,
J¼7.9 Hz, 2H), 8.25 (s, 1H); 13C NMR (125 MHz, CDCl3)
d 71.3 (d), 80.9 (t), 127.1 (d), 128.3 (d), 128.5 (d), 128.6
(d), 128.9 (d), 129.2 (d), 131.3 (d), 135.4 (s), 138.4 (s),
163.2 (d); HRMS (FAB): calcd for C15H15N2O2 (Mþ1):
255.1134, found: 255.1151.
4.3.31. (1E )-2-Aza-1,3-di(2-naphthyl)-4-nitrobut-1-ene (3t)
IR n (NaCl) 3056, 2970, 2872, 1692, 1632, 1598, 1547,
1508, 1467, 1419, 1374, 1271, 1215, 1122, 1063, 828 cmꢀ1
;
1H NMR (500 MHz, CDCl3) d 4.77 (dd, J¼12.5, 4.0 Hz, 1H),
5.03 (dd, J¼12.5, 10.0 Hz, 1H), 5.32 (dd, J¼4.0, 10.0 Hz,
1H), 7.4e8.1 (m, 12H), 7.59 (d, J¼7.3 Hz, 1H), 8.06 (d,
J¼8.6 Hz, 1H), 8.50 (s, 1H); 13C NMR (125 MHz, CDCl3)
d 71.7 (d), 81.0 (t), 123.8 (d), 124.7 (d), 126.4 (d), 126.5 (d),
127.5 (d), 127.7 (d), 127.9 (d), 128.0 (d), 128.5 (d), 128.7
(d), 128.9 (d), 131.0 (d), 132.9 (s), 133.2 (s), 133.4 (s), 135.0
(s), 135.8 (s), 163.9 (d); HRMS (FAB): calcd for C23H19N2O2
(Mþ1): 355.1447, found: 355.1429.
4.3.27. (1E )-2-Aza-1,3-bis(4-methoxyphenyl)-
4-nitrobut-1-ene (3p)
IR n (NaCl) 3107, 2928, 1685, 1632, 1605, 1498, 1414,
;
1333, 1264, 1186, 964, 809 cmꢀ1 1H NMR (500 MHz,
CDCl3) d 2.78 (s, 1H), 3.82 (s, 1H), 4.64 (dd, J¼12.4, 4.0 Hz,
1H), 4.86 (dd, J¼12.4, 9.9 Hz, 1H), 5.03 (dd, J¼9.9, 4.0 Hz,
1H), 6.89 (d, J¼8.9 Hz, 2H), 6.90 (d, J¼8.9 Hz, 2H), 7.37 (d,
J¼8.9 Hz, 2H), 7.69 (d, J¼8.9 Hz, 2H), 8.24 (s, 1H); 13C
NMR (125 MHz, CDCl3) d 55.3 (q), 55.4 (q), 71.0 (d), 81.2
(t), 114.0 (d), 114.4 (d), 128.3 (d), 128.6 (s), 130.3 (d), 130.8
(s), 132.0 (d), 159.5 (s), 162.1 (s), 162.5 (d); HRMS (FAB):
calcd for C17H19N2O4 (Mþ1): 315.1345, found: 315.1367.
4.4. Hydrogenation of imine derivative 3a
A suspension of 3a (1300 mg) and 10 wt % PdeC (300 mg)
in ethanol (15 ml) was stirred under hydrogen atmosphere for
5 h at room temperature. Ethanol (10 ml) was added and after
the catalyst had settled the supernatant liquid was carefully
decanted. The solvent was then distilled off in a rotary evapo-
rator to obtain the crude product which was chromatographed
on silica gel to give 617 mg (47%) of (2-nitro-1-phenylbutyl)-
benzylamine (erythro/threo ratio; 1/10).
threo-(2-Nitro-1-phenylbutyl)benzylamine: IR n (NaCl)
3328, 3061, 3027, 2972, 2935, 1551, 1494, 1454, 1374, 1258,
1108, 1078, 1027, 806, 735, 735, 700 cmꢀ1 1H NMR
;
(500 MHz, CDCl3) d 0.82 (t, J¼7.4 Hz, 3H), 1.32e1.40 (m,
1H), 1.75e1.83 (m, 1H), 1.74 (br s, 1H), 3.45 (d, J¼13.3 Hz,
1H), 3.64 (d, J¼13.3 Hz, 1H), 3.99 (d, J¼10.1 Hz, 1H), 4.55
(ddd, J¼3.4, 10.1, 10.7 Hz, 1H), 7.17e7.42 (m, 10H); 13C
NMR (125 Hz, CDCl3) d 10.3 (q), 24.8 (t), 50.8 (t), 64.5 (d),
4.3.28. (1E )-2-Aza-1,3-bis(4-methylphenyl)-
4-nitrobut-1-ene (3q)
IR n (NaCl) 3026, 2920, 2869, 1686, 1642, 1610, 1554,
1
1512, 1375, 1338, 1175, 969, 813 cmꢀ1; H NMR (500 MHz,
CDCl3) d 2.33 (s, 1H), 2.36 (s, 1H), 4.65 (dd, J¼12.3,
3.6 Hz, 1H), 4.89 (dd, J¼12.3, 9.9 Hz, 1H), 5.06 (dd, J¼9.9,
3.6 Hz, 1H), 7.16e7.20 (m, 4H), 7.34 (d, J¼7.8 Hz, 2H),
7.64 (d, J¼7.8 Hz, 2H), 8.28 (s, 1H); 13C NMR (125 MHz,
CDCl3) d 21.1 (q), 21.5 (q), 71.3 (d), 81.1 (t), 127.1 (d),
128.6 (d), 129.2 (d), 129.3 (d), 129.7 (d), 130.2 (d), 133.0 (s),
135.7 (s), 136.3 (d), 138.2 (s), 139.2 (d), 141.7 (s), 163.3 (d);
HRMS (FAB): calcd for C17H19N2O2 (Mþ1): 283.1447, found:
283.1466.

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S. Tanaka et al. / Tetrahedron 64 (2008) 1388e1396
6. (a) Yamada, K.; Tanaka, S.; Kohmoto, S.; Yamamoto, M. J. Chem. Soc., Chem.
Commun. 1989, 110e111; (b) Tanaka, S.; Kohmoto, S.; Yamamoto, M.;
Yamada, K. Nikkashi 1989, 1742e1747; (c) Tanaka, S.; Kawasaki, K.; Hirao,
M.; Kishikawa, K.; Kohmoto, S.; Yamamoto, M. Nikkashi 2002, 475e479.
7. (a) Yamada, K.; Moll, G.; Shibasaki, M. Synlett 2001, 980e982; (b) Qian,
C.; Gao, F.; Chen, R. Tetrahedoron Lett. 2001, 42, 4673e4675; (c)
Sakthivel, K.; Notz, W.; Bui, T.; Barbas, C. F., III. J. Am. Chem. Soc.
2001, 123, 5260e5267; (d) Tsuritani, N.; Yamada, K.; Yoshikawa, N.;
Shibasaki, M. Chem. Lett. 2002, 276e277; (e) Bernardi, L.; Bonini,
B. F.; Dessole, G.; Fochi, M.; Comes-Franchini, M.; Gaviori, S.; Ricci,
A.; Varchi, G. J. Org. Chem. 2003, 68, 1418e1425; (f) Andersion,
J. C.; Blake, A. J.; Howell, G. P.; Wilson, C. J. Org. Chem. 2005, 70,
549e555; (g) Li, Z.; Li, C.-J. J. Am. Chem. Soc. 2005, 127, 3672e3673.
8. (a) Kruger, C.; Rochow, E. G.; Wannagat, U. Chem. Ber. 1963, 96, 2132e
2137; (b) Hart, D. J.; Kanai, K.; Thomas, D. G.; Yang, T.-K. J. Org. Chem.
1983, 48, 289e294; (c) George, G. I.; Herriman, G. C. B.; Peterson, S. A.
J. Org. Chem. 1995, 60, 7366e7368.
95.3 (d), 127.1 (d), 127.7 (d), 128.0 (d), 128.2 (d), 128.29 (d),
128.32 (d), 128.5 (d), 128.6 (d), 129.0 (d), 129.1 (d), 138.5 (s),
139.4 (s); HRMS (FAB): calcd for C17H21N2O2 (Mþ1):
285.1603, found: 285.1606.
References and notes
1. (a) Harada, K. The Chemistry of the CarboneNitrogen Double Bond;
Patai, S., Ed.; John Wiley and Sons: New York, NY, 1970; (b) Tennant,
G. Comprehensive Organic Chemistry; Sutherland, I. O., Ed.; Pergamon:
New York, NY, 1979; Vol. 2, Part 8, pp 385e590.
2. Tramontini, M.; Angiolini, L. Tetrahedron 1990, 50, 1791e1837.
3. Pandey, G.; Singh, R. P.; Garg, A.; Singh, V. K. Tetrahedron Lett. 2005,
46, 2137e2140.
4. (a) Lozanov, M.; Montgomery, J. J. Am. Chem. Soc. 2002, 124, 2106e
2107; (b) Janvier, P.; Sun, X.; Bienayme, H.; Zhu, J. J. Am. Chem. Soc.
2002, 124, 2560e2567; (c) Huang, X.; Vogel, P. Synthesis 2002, 232e
236; (d) Zhao, C.; Lu, J.; Yan, J.; Xi, Z. Tetrahedron Lett. 2003, 44,
6895e6898; (e) Dhawan, R.; Dghaym, R. D.; Arndtsen, B. A. J. Am.
Chem. Soc. 2003, 125, 1474e1475; (f) Rikimaru, K.; Yanagisawa, A.;
Kan, T.; Fukuyama, T. Synlett 2004, 41e44; (g) Tejedor, D.; Santos-Ex-
posito, A.; Gonzalez-Cruz, D.; Marrero-Tellado, J. J.; Garcia-Tellado, F.
J. Org. Chem. 2005, 70, 1042e1045; (h) Bouchez, L. C.; Vogel, P.
Chem.dEur. J. 2005, 11, 4609e4620; (i) Bouchez, L. C.; Turks, M.;
Dubbaka, S. R.; Fonquerne, F.; Craita, C.; Laclef, S.; Vogel, P. Tetra-
hedron 2005, 61, 11473e11487; (j) Karpov, A. S.; Rominger, F.; Mueller,
T. J. J. Org. Biomol. Chem. 2005, 4382e4391; (k) Rivera, D. G.; Pando,
O.; Coll, F. Tetrahedron 2006, 62, 8327e8334; (l) Gwiazda, M.; Reissig,
H.-U. Synlett 2006, 1683e1686; (m) Bonne, D.; Dekhane, M.; Zhu, J.
Angew. Chem., Int. Ed. 2007, 46, 2485e2488; (n) Hu, Q.; Lu, J.; Wang,
C.; Wang, C.; Xi, Z. Tetrahedron 2007, 63, 6614e6624; (o) Song, Q.-Y.;
Yang, B.-L.; Tian, S.-K. J. Org. Chem. 2007, 72, 5407e5410.
9. (a) Mukhopadhyay, T.; Seebach, D. Helv. Chim. Acta 1982, 65, 385e391;
(b) Seebach, D.; Beck, A. K.; Mukhopadhyay, T.; Thomas, T. Helv. Chim.
Acta 1982, 65, 1101e1133.
10. Adams, H.; Anderson, J. C.; Peace, S.; Pennell, A. M. K. J. Org. Chem.
1998, 63, 9932e9934.
11. (a) Baily, K. Tetrahedron 1972, 28, 3981e3986; (b) Eyer, M.; Seebach, D.
J. Am. Chem. Soc. 1985, 107, 3601e3606.
12. (a) Feuer, H. The Chemistry of the Nitro and Nitroso Groups, Part 1; Patai,
S., Ed.; John Wiley and Sons: New York, NY, 1969; (b) The Chemistry of
the Nitro and Nitroso Groups, Part 2; Patai, S., Ed.; John Wiley and Sons:
New York, NY, 1970; (c) Ono, N. The Nitro Group in Organic Synthesis;
John Wiley and Sons: New York, NY, 2001; pp 30e69; (d) Luzzio, F. A.
Tetrahedron 2001, 57, 915e945.
13. (a) Caramella, P.; Rondan, N. G.; Paddon-Row, M. N.; Houk, K. N. J. Am.
Chem. Soc. 1981, 103, 2438e2440; (b) Paddon-Row, M. N.; Rondan, N. G.;
Houk, K. N. J. Am. Chem. Soc. 1982, 104, 7162e7166; (c) Houk, K. N.;
Moses, S. R.; Wu, Y.-D.; Rondan, N. G.; Jager, V.; Schohe, R.; Fronczek,
F. R. J. Am. Chem. Soc. 1984, 106, 3880e3882; (d) Deslongchamps, P.
Stereoelectronic Effects in Organic Chemistry; Pergamon: Oxford, 1983.
14. Lehr, F.; Gonnermann, J.; Seebach, D. Helv. Chim. Acta 1979, 62,
2258e2275.
5. (a) Adib, M.; Mahmoodi, N.; Mahdavi, M.; Bijanzadeh, H. R. Tetrahedron
Lett. 2006, 47, 9365e9368; (b) Regnier, T.; Berree, F.; Lavastre, O.; Carboni,
B. Green Chem. 2007, 9, 125e126; (c) Kantevari, S.; Vuppalapati, S. V. N.;
Biradar, D. O.; Nagarapu, L. J. Mol. Catal. A: Chem. 2007, 266, 109e113.