1,3-Dipolar cycloadditions. Part XII - Selective cycloaddition route to 4-nitroisoxazolidine ring systems

Article abstract of DOI:10.1002/jhet.5570440511

(Chemical Equation Presented) Cycloadditions of C,N-diarylnitrones to β-nitrostyrenes occurred to yield two diastereoisomeric cycloadducts, the 3,4-trans-4,5-trans substituted isoxazolidine derivatives being formed selectively as the major products. These

Full text of DOI:10.1002/jhet.5570440511

Sep-Oct 2007
1045
1,3-Dipolar Cycloadditions. Part XII - Selective Cycloaddition
Route to 4-Nitroisoxazolidine Ring Systems 1
Avijit Banerji* [1], Maya Gupta [1], Pizush Kanti Biswas[1],
Thierry Prangé [2] and Alain Neuman [2]
[1] Centre of Advanced Studies on Natural Products including Organic Synthesis, Department of Chemistry,
University Colleges of Science and Technology, University of Calcutta, 92, Acharya Prafulla Chandra Road,
Kolkata-700009, India.
[2] Laboratoire de Chimie Structurale Biomoleculaire(UMR 7033CNRS), Université Paris Nord, 74 rue M.
Cachin F-93012 Bobigny, France.
Received October 17, 2006
H
NO2
R
H
Toluene
C
N
+
+
H
110 °C, 15-25 hrs, N2
_
O
R
1
R
H
R
H
H
H
NO2
H
NO2
H
+
N
N
O
O
R
R
1
1
Cycloadditions of C,N-diarylnitrones to ꢀ-nitrostyrenes occurred to yield two diastereoisomeric
cycloadducts, the 3,4-trans-4,5-trans substituted isoxazolidine derivatives being formed selectively as the
major products. These were characterised by spectroscopic and X-ray data. Conformational studies were
carried out by X-ray crystallography and Molecular Modelling.
J. Heterocyclic Chem., 44, 1045 (2007).
and for selected products, - X-ray crystallographic,
analysis. We were also interested in the conformational
aspects of these compounds, and carried out computer-
assisted energy minimisations.
INTRODUCTION
Isoxazolidines can be regarded as templates for 1,3-
difunctionalised compounds which can be used in the
synthesis of several types of biologically active molecules
[2-12]. These isoxazolidines become even more attractive
as intermediates if a nitro group, which can be trans-
formed into several functionalities, is present in the ring.
With the objective of synthesising substituted 4-nitroisox-
azolidines, we have carried out a series of 1,3-dipolar
cycloadditions of nitrones with trans-ꢀ-nitrostyrene and
its p-nitro derivative. Due to the presence of the
conjugated nitro group, the ꢀ–nitrostyrenes have low-
lying LUMOs, and these cycloadditions would be
RESULTS AND DISCUSSION
Cycloadditions of six C-aryl-N-phenyl aldonitrones
(1a-f) with ꢀ-nitrostyrene 2a and 4-nitro-ꢀ-nitrostyrene
2b were investigated. Five of these nitrones (1a-e) had C-
aryl rings with substituents varying from the electron
withdrawing nitro-group to the electron-donating methoxy
group, whereas the C-furyl-N-phenyl nitrone was new.
The cycloadditions were performed by refluxing the
nitrones with equimolar amounts or with slight molar
excess of the dipolarophiles under nitrogen atmosphere
for 15-25 hrs. Conversions to products were usually above
80%. The 3,4-trans-4,5-trans-3,5-diaryl-2-phenyl-4-nitro-
isoxazolidine cycloadducts (Type A) were the major
cycloadducts in all the reactions. The corresponding
diastereoisomeric 3,4-cis-4,5-trans-3,5-diaryl-2-phenyl-4-
nitroisoxazolidine cycloadducts (Type B) were obtained
as the minor products in almost all the reactions. The
essentially of Sustmann Type
I
(DipoleHOMO-
DipolarophileLUMO) [13]. In view of the highly polarised
nature of the dipolarophile frontier orbitals, a high degree
of regioselectivity is expected to yield the desired 4-
nitroisoxazolidines.
We report here the synthesis of a number of 3,4-trans-
4,5-trans-3,5-diaryl-2-phenyl-4-nitroisoxazolidine cyclo-
adducts with high regio- and stereo-selectivity. The
structures and stereochemistry of these cycloadducts as
well as the minor cycloadducts, with 3,4-cis-4,5-trans
stereochemistry were settled by detailed spectroscopic,
1
product ratios of the cycloadducts were determined by H
NMR analysis of the crude reaction mixtures. The IR

1046
A. Banerji , M. Gupta, P. K. Biswas,T. Prange and A. Neuman
Vol 44
spectra of all the isolated pure compounds in all series of
cycloadducts showed the expected bands for the nitro
group (ca. 1500-1550, 1350 cm-1) and for the aromatic
moieties. The UV spectra of the cycloadducts lacked the
strong absorptions characteristic of the conjugated nitro
groups, thus indicating that cycloadditions had occurred.
The EI-MS analysis of a typical example 3aa, showed
the molecular ion-peak at m/z 391 (87%). Other important
peaks appeared at m/z 344 (8%; M+-HNO2), 285 (25%;
M+-PhCHO) and the fragments obtained from electron-
impact induced cycloreversion at m/z 242 (10%), and 149
(7.5%). The loss of the elements of PhCHO, and a peak at
m/z 238 from concomitant cleavage at N-2/C-3 and C-
4/C-5, confirmed the presence of a phenyl group at C-5.
The 300 MHz 1H NMR spectra of the products belonging
of J3,4 seemed to indicate a 3,4-trans orientation for 3aa.
The relative stereochemistry and conformation of 3aa was
confirmed by its X-ray crystallographic analysis [14]. The
ORTEP projection of this molecule is shown in Figure 1.
Compound 3aa crystallised in the triclinic system with the
space group P-1. The heterocyclic ring is in the distorted
envelope conformation, with 3,4- and 4,5-substituents
trans, as well as the nitrogen phenyl substituent with
respect to the 3-aryl group. The oxygen forms the tip of
the envelope. Cycloadducts 3 (ba, ca, da, ea, fa, cb and
ab), which were the major cycloadducts in the reactions
of 1(a-f) respectively, showed 1H and 13C NMR
characteristics very similar to those of 3aa. Thus, all these
belonged to the 3,4-trans-4,5-trans-series (Type A
cycloadducts). Cycloadducts 3cb and 3ab, also belonging
Scheme-1
NO2
H
H
Ar
NO2
H
H
H
NO2
Ar
Ar
H
H
/ Reflux
Toluene
+
H
R'
N
_
3
+
4
3
4
O
15-25 hours / N2
+
N
2
N
2
5
O
1
R'
5
O
1
H
R'
1a: Ar = p-NO2C6H4 2a: R'=H
3,4-trans-4,5-trans-
(3RS)-2-phenyl-3,5-diaryl-
4-nitroisoxazolidines
3,4-cis-4,5-trans-
(3RS)-2-phenyl-3,5-diaryl-
4-nitroisoxazolidines
b: Ar = p-ClC6H4
c: Ar = C6H5
b: R'=NO2
d: Ar = p-OCH3C6H4
e: Ar = m-NO2C6H4
f: Ar= 2-furyl
3aa: Ar=p-NO2C6H4;
ba: Ar=p-ClC6H4;
ca: Ar=C6H5;
da: Ar=p-OCH3C6H4; R'=H
ea: Ar=m-NO2C6H4; R'=H
fa: Ar=2-furyl;
cb: Ar=C6H5;
ab: Ar=p-NO2C6H4; R'=NO2
R'=H
R'=H
R'=H
4aa: Ar=p-NO2C6H4;
ba: Ar=p-ClC6H4;
ca: Ar=C6H5;
da: Ar=p-OCH3C6H4;
ea: Ar=m-NO2C6H4;
fa: Ar=2-furyl;
R'=H
R'=H
R'=H
R'=H
R'=H
R'=H
R'=H
R'=NO2
cb: Ar=C6H5;
ab: Ar=p-NO2C6H4;
R'=NO2
R'=NO2
to both types A and B showed that H-3 and H-5 protons
appeared as doublets and there was no coupling between
them. Further, the H-3, H-5 protons showed long-range
coupling with aromatic protons in COSY-LR spectrum,
thereby showing their benzylic nature. The H-4 proton
coupled to both H-3 and H-5 and appeared as double
doublet. H-4 correlations to aromatic protons were not
observed in the COSY-LR. This established the structure
of the major isomers to be 2-phenyl-3,5-diaryl-4-nitro-
isoxazolidine derivatives. A typical representative of the
major cycloadducts, viz. 3aa, showed the presence of the
to Type A, were obtained from 4-nitro-trans-ꢀ-
nitrostyrene 2b and nitrones 1c and 1a respectively. The
300 MHz H NMR spectrum of 3cb in d6-DMSO showed
1
that H-3 and H-5 protons appeared at ꢀ5.75 and ꢀ6.16 as
doublets and the H-4 proton as ꢀ5.93 as a double doublet;
J3,4 and J4,5 were respectively 3.2 and 4.2 Hz. The relative
stereochemistry of 3cb as 3,4-trans-4,5-trans was
confirmed by X-ray crystallographic analyses [14]. This
compound crystallised in the monoclinic form in the
space group P21/n. The ORTEP diagram for 3cb is shown
in Figure 2. The five-membered heterocyclic ring exists as
a twist envelope, in between the two idealised envelope
conformations with the tips being at N2 and O1. Owing to
significant ring puckering all substituents come in quasi-
axial or quasi-equatorial positions. The nitrogen atom of
1
H-3 doublet at ꢀ5.77 in its H NMR spectrum. This was
coupled to a double- doublet H-4 at ꢀ5.27, which in turn
was coupled with the downfield H-5 doublet at ꢀ5.84; J3,4
and J4,5 were respectively 3.7 and 5.8 Hz. The magnitude

Sep-Oct 2007
1,3-Dipolar Cycloadditions. Part XII
1047
the isoxazolidine ring is pure pyramidal. In the relative
configurations shown, the lone pair on N(2) is set above
the plane by convention. A statistical disorder of the
orientation of the nitro group at C(4) was observed in the
crystal lattice at room temperature. This is a dynamic
process but X-ray diffraction gives only an "average"
static view of the phenomenon. During refinements, this
group was modelised as a three static-component group
(three positions with the sum of occupancies equal to one,
for the two rotating oxygens, i.e. 0.4:0.35:0.25).
Cycloadduct 3ab showed similar spectroscopic properties
and hence also belonged to Type A.
O3 4 B
N3 4
Figure 2. Structure of 3cb as determined by X-Ray crystallographic
analysis (ORTEP Projection. Only one rotamer of the nitro group
at C4 is shown for clarity).
C3 3
C3 2
O3 4 A
O4 A
N4
C3 4
The relative potential energy of 4aa compared to
3aa was calculated to be 2.15 kcal/mol. The X-ray
structure of all-trans isomer (compound 3aa) has close
similarity with the model structure of minimum energy.
The reaction of the new nitrone C-furfuryl-N-phenyl
nitrone (1f) with trans ꢀ-nitrostyrene was carried out by
refluxing for 16 hrs. in dry toluene under nitrogen
atmosphere. The major product was confirmed as 3fa, i.e.
3,4-trans-4,5-trans isomer from its NMR characteristics.
Thus the selectivity of the cycloaddition process of this C-
2-furfuryl nitrone was similar to the C-phenyl nitrone.
This nitrones was prepared by reacting furfural with N-
phenylhydroxylamine.
C3 1
C3 5
C3 6
C4
C5 6
C5 5
C3
C5 4
O4 B
C5 1
C5
C5 3
N2
C5 2
O1
C2 1
C2 2
C2 6
C2 3
C2 4
C2 5
Figure 1. Structure of 3aa as determined by X-Ray crystallographic
analysis (ORTEP Projection).
EXPERIMENTAL
General. Melting points were recorded on an electrically
heated Kofler Block and are uncorrected. UV spectra were
recorded on a Hitachi U-3501 spectrophotometer in 95%
aldehyde free spectroscopic ethanol. IR spectra were recorded
on KBr disc or as a thin film on a Perkin-Elmer FT-IR model.
Mass spectra were recorded on a JEOL JMS-600 Mass
spectrometer. Column chromatography (CC) was carried out
using neutral alumina and silica gel. TLC was performed using
silica gel G. Petrol refers to the fraction, b.p. 60-80°. Anhydrous
sodium sulphate was used for drying extracts. Analytical
samples were routinely dried over anhydrous calcium chloride in
vacuo at room temperature. The starting materials prepared were
identified by comparison of their melting points with those
reported in the literature; as well as from elemental analyses and
from IR spectra. NMR spectra were recorded in CDCl3 or in d6-
DMSO solution on a Bruker AM-300L equipped with an
ASPECT-3000 computer and an Array Processor using a
switchable dual 1H-13C 5 mm dual probe (normal and inverse) at
ambient temperature. X-Ray crystallographic data were recorded
at room temperature at the LURE synchrotron facility, Orsay,
France (MoKꢀ ꢁ= 0.953 Å ) for 3aa, and on a PHILIPS PW
1100 diffractometer (operating the CuKꢀ radiation, ꢁ= 1.5418
Å) for 3cb. The two structures were solved using the SHELXS
program [16] and anisotropically refined using SHELXL [17].
The minor cycloadducts Type B were established to
have 3,4-cis-4,5-trans-configuration. COSY-LR spectra
of this type of cycloadducts showed long range
correlations of H-3 and H-5 with aromatic protons. This
established the overall structure as 3,4-cis-4,5-trans-3,5-
diaryl-2-phenyl-4-nitroisoxazolidine. The signals of H-3,
H-4, H-5 are situated close together. Cycloadducts 4(aa,
ba, ca, da, ea, fa, cb and ab) belong to this type of
cycloadduct.
Conformational analysis and energy minimisation of
the all-trans isomer along with its minor stereoisomer 3,4-
cis, 3,4-trans have been carried out by taking advantage
of the X-ray crystallographic data of the Type A isomers.
Energy minimisation of the 3,4-trans-4,5-trans isomer
3aa (Type A), 3,4-cis-4,5-trans 4aa (Type B) was carried
out by conjugate gradient method using DISCOVER
Molecular Simulation Program (Version 2.98) [15]. In all
cases normal completion of conjugate gradient was
achieved in less than 2000 steps of energy evaluations; the
energy minimisation was stopped when the RMS
derivative of energy reached a value of 0.001 kcal/mol.

1048
A. Banerji , M. Gupta, P. K. Biswas,T. Prange and A. Neuman
Vol 44
General procedure for the Cycloaddition Reactions. A
(CC-4), 129.5 (CA-3,5), 134.6 (CC-1), 135.3 (CB-4), 136.7 (CB-1),
148.9 (CA-1). Anal. Calcd. for C21H17N2O3Cl: C, 66.23; H, 4.50;
N, 7.36%. Found: C, 66.10; H, 4.66; N, 7.45%.
solution of the nitrone (3.5-5.4 mM) in anhydrous toluene (10-
15 ml) was added at a time to a solution of the dipolarophile
(usually 1 to 1.5 molar proportions) in anhydrous toluene (10-15
ml). The reaction mixture was refluxed for several hours under
nitrogen atmosphere. The progress of the reaction was
Reaction of C-phenyl-N-phenyl nitrone with ꢀ-nitrostyrene.
3RS(3R*,4S*,5R*)-2,3,5-Triphenyl-4-nitroisoxazolidine
(3ca). Yellow amorphous solid (yield 86%) was obtained from
1
monitored by TLC and 300 MHz H NMR. After the reaction
1
period solvent was removed from the reaction mixture by
distillation under reduced pressure in a Büchi rotary evaporator.
The residue was analysed by 300 MHz 1H NMR and then
subjected to Column Chromatography over silica gel, and
sometimes over neutral alumina.
30% benzene in petrol. IR (KBr): 1554, 1360, 756, 697; H
NMR (CDCl3, ꢁ, 300 MHz): 5.32 (1H, dd, J=4.2, 5.9, H-4), 5.60
(1H, d, J=4.2, H-3), 5.78 (1H, d, J=5.9 H-5), 7.04 (H, t, J=7.5),
7.10 (2H, d, J=8.4, HA-2,6), 7.30 (2H, t, J=8.0, HA-3,5), 7.36-7.44
(other Aromatic-H), 7.53 (2H, d, J=6.5, HB-2,6); 13C NMR
(CDCl3, ꢁ, 75.5 MHz ): 74.2 (C-3), 83.2 (C-5), 101.7 (C-4),
115.3 (CA-2,6), 129.3 (CA-3,5), 123.1 (CA-4), 126.6 (CC-2,6), 126.7
(CB-2,6), 128.6 (CB-4), 129.0 (CC-3,5), 129.2 (CB-3,5), 129.2 (CC-4),
135.5 (CC-1), 138.2 (CB-1), 149.2 (CA-1). Anal Calcd. for
C21H18N2O3: C, 72.81; H, 5.24; N, 8.09%. Found: C, 72.93; H,
5.10; N, 8.01%.
Reaction of C-(4-nitrophenyl)-N-phenyl nitrone with ꢀ-nitro-
styrene).
3RS(3R*,4S*,5R*)-2,5-Diphenyl-3-(4-nitro-phenyl)-4-nitro
isoxazolidine (3aa). Light yellowish crystals, m.p. 126 ºC (yield
84%) from 30% benzene in petrol; IR (KBr): 1556, 1347, 834,
1
750, 693 cm-1; H NMR (CDCl3, ꢁ, 300 MHz): 5.26 (1H, dd,
Reaction of C-(4-methoxyphenyl)-N-phenyl nitrone with ꢀ-
J=3.8, 5.9, H-4), 5.77 (1H, d, J=3.8, H-3), 5.84 (1H, d, J=5.9, H-
5), ~7.02 (1H, obscured by H-2, H-6, Hꢂꢃ4), 7.09 (2H, d, J=7.9 HA-
2,6), 7.34 (2H, dis. dd, HA-3,5), 7.37-7.42 (5H, br. s, HC-2,6,3,5,4), 7.77
(2H, d, J=8.8, HB-2,6), 8.28 (2H, d, J=8.8, HB-3,5); 13C NMR
(CDCl3, ꢁ, 75.5 MHz): 73.5 (C-3), 83.6 (C-5), 101.4 (C-4), 115.3
(CA-2,6), 124.0 (CA-4), 124.9 (CB-3,5), 127.0 (CC-2,6), 128.2 (CB-2,6),
129.6 (CC-3,5), 129.9 (CA-3,5), 130.0 (CC-4), 135.0 (CC-1), 145.7
(CB-1), 148.5 (CA-1), 148.8 (CB-4), EI-MS: m/z 391 (M+), 285, 238,
226, 192, 165, 105, and 77. Anal. Calcd for C21H17N3O5: C, 64.44;
H, 4.34; N, 10.73 %. Found: C, 64.29; H, 4.43; N, 10.92%.
X-ray data. Triclinic, P-1 (Z=2) with a=7.242(2);
b=8.371(2); c=16.587(2) Å; ꢄ=84.32(4); ꢀ=78.72(4) and
ꢅ=70.01(4)°. Final R (1639 observed F) = 0.079 and R (all 1652
F data) = 0.085. Energy minimisations done by DISCOVER
Molecular Simulation Program (Version 2.98) [15] for 3aa and
4aa were accurate to the extent of + 0.2 kcal/mole.
nitrostyrene
3RS(3R*,4S*,5R*)-2,5-Diphenyl-3-(4-methoxyphenyl)-4-
nitro isoxazolidine (3da). Orange red amorphous solid (yield
72%) was obtained from 30% benzene in petrol; IR (KBr): 1554,
1362, 836, 759, 696 cm-1; H NMR (CDCl3, ꢁ, 300 MHz ): 5.30
(1H, dd, J=4.4, 5.8, H-4), 5.49 (1H, d, J=4.4, H-3), 5.77 (1H, d,
J=5.8, H-5), 6.90 ( 2H, d, J=8.7, HB-3,5), 7.06 (1H, dis. t, HA-4),
7.09 (2H, d, J=8.0, HA-2,6), 7.30 (2H, d, J=8.0, HA-3,5), obscured
(2H, HB-2,6), 7.38-7.45 (5H, br. s, HC-2,6,3,5,4); 13C NMR (CDCl3, ꢁ,
75.5 MHz): 74.1 (C-3), 83.0 (C-5), 101.8 (C-4), 114.8 (CB-3,5),
115.6 (CA-2,6), 123.2 (CA-4), 126.6 (CC-2,6), 128.1(CB-2,6), 129.0
(CC-4), 129.1 (CA-3,5), 129.1 (CC-3,5), 130.0 (CB-1), 135.9 (CC-1),
149.3 (CA-1), 159.8 (CB-4). Anal. Calcd. for C22H20N2O4: C,
70.20; H, 5.36; N, 7.44%. Found: C, 70.08; H, 5.43; N, 7.58%.
1
Reaction of C-(3-Nitrophenyl)-N-phenyl nitrone with ꢀ-
3RS(3R*,4R*,5S*)-2,5-Diphenyl-3-(4-nitrophenyl)-4-
nitro isoxazolidine (4aa). Canary yellow crystals, m.p.192 ºC
(yield 16%) from 75% benzene in petrol. IR (KBr): 1552, 1347,
837, 749, 695 cm-1; 1H NMR (CDCl3, ꢁ, 300 MHz): 5.41 (2H, m,
H-3,4), 5.75 (1H, d, J=3.3, H-5), 7.09 (2H, d, J=8.0, HA-2,6), 7.13
(1H, t, 7.4, HA-4 ), 7.30 (2H, br.t, J= ~7.8, HA-3,5 ), 7.40 (5H, br.
s, HC-2,6,3,5,4), 7.76 ( 2H, d, J=8.6, HB-2,6 ), 8.32 (2H, d, J=8.6, HB-
3,5); 13C NMR (CDCl3, ꢁ, 75.5 MHz): 73.7 (C-3), 81.8 (C-5),
99.6 (C-4), 118.4 (CA-2,6), 125.1 (CB-3,5), 125.4 (CA-4), 126.9 (CC-
2,6), 128.8 (CB-2,6), 129.2 (CA-3,5), 129.4 (CC-3,5), 130.2 (CC-1),
130.2 (CC-4), 148.2 (CA-1), 148.2 (CB-4), not found (CB-1). Anal.
Calcd. for C21H17N3O5: C, 64.44; H, 4.34; N, 10.73%. Found: C,
64.46; H, 4.48; N, 10.80%.
nitrostyrene.
3RS(3R*,4S*,5R*)-2,5-Diphenyl-3-(3-nitrophenyl)-4-nitro
isoxazolidine (3ea). Yellow amorphous solid (yield 68%) was
obtained from 30% benzene in petrol; IR (KBr): 1541, 1352,
812, 756, 693 cm-1; H NMR (CDCl3, ꢁ, 300 MHz ): 5.28 (1H,
1
dd, J=3.65, 5.9, H-4), 5.76 (1H, d, J=3.65, H-3), 5.83 (1H, d,
J=5.9, H-5), 7.07 (1H, t, 7.4, HA-4), 7.10 (2H, d, J=7.8, HA-2,6),
7.33 (2H, dd, 7.8, 7.4 HA-3,5), 7.38-7.40 (5H, brd. s, HC-2,6,3,5,4),
7.60 (1H, t, ~8.0, HB-5), 7.89 (1H, d, 7.7, HB-6), 8.21 (1H, dd,
J=1.1, 8.2, HB-4), 8.45 (1H, s, HB-2); 13C NMR (CDCl3, ꢁ, 75.5
MHz): 73.4 (C-3), 83.7 (C-5), 101.4 (C-4), 115.4 (CA-2,6), 122.4
(CB-2), 124.0 (CA-4), 124.1 (CB-4), 127.0 (CC-2,6), 129.6 (CC-3,5),
129.9 (CA-3,5), 130.0 (CC-4), 130.8(CB-5), 133.2 (CB-6), 135.0
(CC-1), 141.0 (CB-1), 148.9 (CA–1), 149.3(CB-3). Anal. Calcd. for
C21H17N3O5: C, 64.44; H, 4.34; N, 10.73%. Found: C, 64.55; H,
4.45; N, 10.64%.
Reaction of C-(4-chlorophenyl)-N-phenyl nitrone with ꢀ-
nitrostyrene.
3RS(3R*,4S*,5R*)-2,5-Diphenyl-3-(4-chlorophenyl)-4-nitro
isoxazolidine (3ba). Yellow microcrystalline solid (yield 82%)
was obtained from 20% benzene in petrol. IR (KBr): 1555,
3RS(3R*,4R*,5S*)-2,5-Diphenyl-3-(3-nitrophenyl)-4-nitro
isoxazolidine (4ea). Yellow amorphous solid (yield 18%) from
75% benzene in petrol. IR (KBr): 1538, 1347, 812, 748, 693
1
1361, 834, 785, 695 cm-1; H NMR (CDCl3, ꢁ, 300 MHz ): 5.26
1
cm-1; H NMR (CDCl3, ꢁ, 300 MHz): 5.42 (2H, m, H-3,4), 5.78
(1H, dd, J=4.0, 5.7, H-4), 5.57 (1H, d, J=4.0, H-3), 5.78 (1H, d,
J=5.7, H-5), 7.08 (2H, d, J=7.9, HA-2,6), 7.29-7.49 (3H, m,
(1H, d, 5.5, H-5), 7.11 (2H, d, J=7.0, HA-2,6), 7.14 (1H, t, 7.0,
HA-4), 7.30 (2H, t, J= 7.5, HA-3,5), 7.39-7.44 (5H, brd. s, HC-
2,6,3,5,4), 7.65 (H, t, ~8.0, HB-5), 7.87 (H, d, 7.5, HB-6), 8.28 (H, dd,
J=1.5,7.5, HB-4), 8.47 ( H, br. t, 1.5 HB-2); 13C NMR (CDCl3, ꢁ,
75.5 MHz): 73.7 (C-3), 81.8 (C-5), 99.7 (C-4), 118.6 (CA-2,6),
122.8 (CB-2), 124.6 (CB-4),125.4 (CA-4), 126.9 (CC-2,6), 129.2
H
A-3,4,5), 7.35 (2H, d, J=8.2, HB-2,6), 7.37-7.42( br. s, Hc-2,3,4,5,6),
7.47 (2H, d, J=8.2, HB-3,5 ); 13C NMR (CDCl3, ꢁ, 75.5 MHz):
73.4 (C-3 ), 83.1(C-5 ), 101.5 (C-4 ), 115.3 (CA-2,6), 123.4 (CA-4),
126.6 (CC-2,6), 128.3 ('CB-2,6), 129.0 (CB-3,5), 129.3 (CC-3,5), 129.3

Sep-Oct 2007
1,3-Dipolar Cycloadditions. Part XII
1049
(CA-3,5), 129.5 (CC-3,5), 130.1 (CC-4), 131.1 (CB-5), 131.4 (CC-1),
133.8 (CB-6), 140.1 (CB-1), 148.3 (CA-1), 149.5 (CB-3). Anal.
Calcd. for C21H17N3O5: C, 64.44; H, 4.34; N, 10.73%. Found: C,
64.46; H, 4.48; N, 10.80%.
Ratio of 3ea:4ea in crude reaction mixture by H NMR -
77:23
Final R (2743 observed F) = 0.064 and R (all 3149 F data) =
0.081
Reaction of C-(4-Nitrophenyl)-N-(4'-chlorphenyl) nitrone)
with 4-nitro -ꢀ-nitrostyrene).
1
3RS(3R*,4S*,5R*)-2-(Chlorophenyl)-3-(4-nitrophenyl)-4-
nitro-5-phenyl isoxazolidine (3ab). Canary yellow crystals,
m.p. 212º (yield 87%) was obtained from 50% benzene in petrol.
Reaction of C-(2-Furyl)-N-phenyl nitrone with ꢀ-nitrostyrene.
1
IR (KBr) 1519, 1346, 841, 687 cm-1; H NMR (CDCl3, ꢁ, 300
3RS(3R*,4S*,5R*)-2,5-Diphenyl-3-furyl-4-nitroisoxazoli-
dine (3fa). Yellow amorphous solid (yield 68.5%) was obtained
from 10% benzene in petrol. IR (KBr): 1556, 1361, 754, 695 cm-
1; 1H NMR (CDCl3, ꢁ, 300 MHz): 5.54 (1H, dd, J=3.3, 6.0, H-4),
5.71 (1H, d, J=6.0, H-5), 5.77 (1H, d, J=3.3, H-3), 6.39 (1H, dd,
J=3.1, 1.8, HB-4), 6.45 (1H, d, 3.1, HB-3), 7.07 (1H, t, 7.4, HA-4),
7.15 (2H, d, J=7.8, HA-2,6), 7.34 (2H, dd, 7.8, 7.4, HA-3,5), 7.40-
7.45 (3H, m, HC-3,5,4), 7.46 (1H, dis. d, HB-5), 7.50 (2H, dd, J=7.6,
1.8, HB-2,6): 13C NMR (CDCl3, ꢁ, 75.5 MHz): 68.6 (C-3), 84.0
(C-5), 98.1 (C-4), 109.7 (CB-3), 111.2 (CB-4), 115.7 (CA-2,6), 123.8
(CA-4), 127.4 (CC-2,6), 129.4 (CA-3,5), 129.8 (CC-4), 129.6 (CC-3,5),
135.5 (CC–1), 143.8 (CB-5), 148.8 (CA-1), 150.0 (CB-2). Anal
Calcd. for C19H16N2O4: C, 67.84; H, 4.79; N, 8.33%. Found: C,
67.65; H, 4.66; N, 8.00%.
MHz): 6.07 (1H, dd, J=4.7, 2.2, H-4), 6.16 (1H, d, J=4.7, H-3),
6.21 (1H, d, J=2.2, H-5), 7.23 (2H, d, J=8.9, HA-2,6), 7.35 ( 2H,
d, 8.9, H A-3,5), 7.65 (1H, d, J=8.7, HB-2,6), 7.77 (2H, d, J=8.7, HB-
3,5), 8.21 (2H, d, J=8.5, HC-2,6), 8.24 (2H, d, J=8.4, HB-3,5); 13C-
NMR (d6-DMSO, ꢁ, 75.5 MHz): 71.5 (C-3), 81.6 (C-5), 98.6
(C-4), 117.4 (CA-2,6), 123.9 (CC-3,5), 124.0 (CB-3,5), 127.3 (CA-4),
128.5 (CC-2,6), 128.7 (CB-2,6), 129.1 (CA-3,5), 142.6 (CC-1), 144.8
(CB-1), 147.0 (CA-1), 147.5 (CC-4), 147.9 (CB-4). Anal. Calcd for
C21H15N4O7Cl: Calc. for C, 53.57; H, 3.21; N, 11.9%. Found: C,
53.72; H, 3.53; N, 9.89%.
REFERENCES AND NOTES
3RS(3R*,4R*,5S*)-2,5-Diphenyl-3-furyl-4-nitroisoxazoli-
dine (4fa). Canary yellowish amorphous solid (yield 25%) was
obtained from 30% benzene in petrol. IR (KBr): 1555, 1370,
[1] Banerji, A.; Biswas, P. K.; Bandyopadhyay, D.; Gupta, M.;
Prangé, T.; Neuman, A.; J. Heterocyclic Chemistry , (Part XI) 2007, 44, 137.
[2] Black; D. St. C. Crozier, R. F.; Davis, V. C. ; Synthesis
1975, 205.
1
745, 695 cm-1; H NMR (CDCl3, ꢁ, 300 MHz): 5.15 (1H, d, 8.9,
[3] Tufariello, J. J. ; 1,3-Dipolar Cycloaddition Chemistry; John
Wiley and Sons, Inc.: New York, 1984.
[4] Houk, K.N.; Yamaguchi, L. in “1,3-Dipolar Cycloaddition
Chemistry”, ed. A. Padwa, Wiley-Interscience, New York, Vol. III, p.
407, 1984.
[5] Banerji, A.; Sahu, A.; J. Sci. Ind. Res., 1986, 45, 355.
[6] B.M. Trost, Ian Fleming, “Comprehensive Organic
Synthesis” Pergamon Press, Vols. IV and V, 1991.
[7] Torsell, K.B.G.; “Nitrile Oxides, Nitrones and Nitronates in
Organic Synthesis”, VCH, New York, 1988.
H-5), 5.44 (1H, dd, J=7.1, 8.9, H-4), 6.09 (1H, d, J=7.1, H-3),
6.37 (1H, dd, J=3.2, 1.9, HB-4), 6.51 (1H, d, 3.3, HB-3), 7.07 (1H,
dd, 8.2, 1.0, H A-4), 7.09 (2H, d, J=7.4, HA-2,6), 7.28 (2H, t, J =
~7.5, H A-3,5 ), 7.40-7.51 (5H, m, HC-2,6,3,5,4), 7.48 (H, d, 3.3, HB-5).
13C NMR (CDCl3, ꢁ, 75.5 MHz): 67.6 (C-3), 81.2 (C-5), 95.1
(C-4), 111.5 (CB-3), 111.9 (CB-4), 118.5 (CA-2,6), 125.0 (CA-3,5), not
found (CA-4), not found (CB-2), not found (CC-1), 127.1 (CC-2,6),
129.5 (CC-3,5), 129.8 (CC-4), 144.2 (CB-5), 149.2 (CA-1). Anal
Calcd. for C19H16N2O4: C, 67.84; H, 4.79; N, 8.33%. Found: C,
67.65; H, 4.76; N, 8.20%.
[8]. Iralapati, N.R.; Baldwin, J.E.; Adlington, R.M.; Pritchard
G.J.; Cowley, A.R.; Tetrahedron 2005, 61, 1773.
Reaction of C,N-Diphenyl nitrone with 4-nitro ꢀ-
nitrostyrene.
[9] O'Neil, I. A.; Ramos, V.E.; Ellis, G.L;. Cleator, E.; Chorlton,
A.P.. Kalindjian, S. B; Tetrahedron Lett., 2004, 45, 3659.
[10] Banerji, A.; Bandyopadhyay, D.; Prangé, T.; Neuman, A D.
Bandyopadhyay; Tetrahedron Letters, 2005, 46, 2619..
[11] Saito, A. T.; Yamada, T.; Miyazaki, S.; Otani, T.;
Tetrahedron Lett. 2004, 45, 9581.
3RS(3R*,4S*,5R*)-2,3-Diphenyl-5-(4-nitrophenyl)-4-nitro
isoxazolidine (3cb). Yellow crystals, m.p.170º (yield 40%) was
obtained from 50% benzene in petrol. IR (KBr): 1550, 1344,
849, 754, 693 cm-1; 1H NMR (CDCl3, ꢁ, 300 MHz): 5.75 (1H, d,
J=3.2, H-3), 5.93 (1H, dd, J=3.2, 4.2, H-4), 6.16 (1H, d, J=4.2,
H-5), 7.01 (2H, t, 7.3, H A-3,5), 7.11 (2H, d, J=8.5, HB-3,5), 7.27
(2H, d, J=8.0, HB-2,6), 7.29-7.32 (1H, m, HB-4), 7.37 (1H, d,
J=7.6, HA-4), 7.45 (2H, d, J=7.7, HA-2,6), 7.75 (2H, d, J=8.7, HC-
2,6), 8.24 (2H, d, J=8.7, HB-3,5); 13C-NMR (d6-DMSO, ꢁ, 75.5
MHz): 72.7 (C-3), 80.8 (C-5), 99.6 (C-4), 116.1 (CA-2,6), 123.4
(CA-4), 123.8 (CC-3,5), 127.2 (CB-3,5), 128.2 (CC-2,6), 128.4 (CB-4),
129.0 (CB-2,6), 129.2 (CA-3,5), 137.5 (CB–1), 143.8 (CC-1), 147.7
(CA-1), 148.3 (CC-4). Anal. Calcd. for C21H17N3O5: C, 64.44; H,
4.34; N, 10.73%. Found: C, 64.24; H, 4.43; N, 10.67%.
[12] Saito, A. T.; Yamada, T.; Miyazaki, S.; Otani, T.;
Tetrahedron Lett. 2004, 45, 9585.
[13] Sustmann, R.’ Tetrahedron Lett, 1978, 29, 2717.
[14] Crystallographic Data for compound 3aa and 3cb have been
deposited with the Cambridge Crystallographic Data Centre as CCDC
235162 and 248040 respectively. Copies of the data can be obtained,
free of charge, on application to CCDC, 12 Union Road, Cambridge
CB2 1EZ, UK (fax: +44 1223 336033 or e-mail:deposit@ccdc.cam.ac.uk).
[15] G. H. Grant, W. G. Richard, Computational Chemistry.
Oxford Chemistry Primers, Oxford University Press, 1995.
[16] Sheldrick, G. M.; SHELXS-86. Program for Solution of
Crystal Structures. University of Göttingen, Germany, 1986.
[17] Sheldrick, G. M.; Schneider, T. R.;Methods Enzymol. 1997,
277, 319.
X-ray data. Monoclinic, space group P21/n (Z=4) with
a=11.140(3); b=18.123(3); c=10.113(3) Å and ꢀ=110.99(5)°.