Remarkable stereocontrol in 1,3-dipolar cycloaddition of acyclic nitrones: Investigation of the cycloaddition of C,N-diaryl nitrones to methyl cinnamate under different reaction conditions

Article abstract of DOI:10.1080/00397911003797858

Investigation of the cycloaddition of C,N-diarylnitrones to methyl cinnamate under different reaction conditions were carried out. Two diastereoisomeric and one regioisomeric cycloadducts were isolated and characterized by spectroscopic and X-ray data. Re

Full text of DOI:10.1080/00397911003797858

This article was downloaded by: [University of Wisconsin - Madison]
On: 09 September 2014, At: 02:30
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered
office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Synthetic Communications: An
International Journal for Rapid
Communication of Synthetic Organic
Chemistry
Publication details, including instructions for authors and
subscription information:
http://www.tandfonline.com/loi/lsyc20
Remarkable Stereocontrol in 1,3-Dipolar
Cycloaddition of Acyclic Nitrones:
Investigation of the Cycloaddition of
C,N-Diaryl Nitrones to Methyl Cinnamate
Under Different Reaction Conditions
Pizush Kanti Biswas a , Debasish Bandyopadhyay a , Thierry Prangé b ,
Alain Neuman b & Avijit Banerji a
a Centre of Advanced Studies on Natural Products Including Organic
Synthesis, Department of Chemistry , Calcutta University , Kolkata ,
India
b LCRB, UMR 8015–Université Paris Descartes–CNRS, Faculté de
Pharmacie , Paris , France
Published online: 21 Mar 2011.
To cite this article: Pizush Kanti Biswas , Debasish Bandyopadhyay , Thierry Prangé , Alain Neuman
& Avijit Banerji (2011) Remarkable Stereocontrol in 1,3-Dipolar Cycloaddition of Acyclic Nitrones:
Investigation of the Cycloaddition of C,N-Diaryl Nitrones to Methyl Cinnamate Under Different
Reaction Conditions, Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 41:8, 1146-1159, DOI: 10.1080/00397911003797858
To link to this article: http://dx.doi.org/10.1080/00397911003797858
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the
“Content”) contained in the publications on our platform. However, Taylor & Francis,
our agents, and our licensors make no representations or warranties whatsoever as to
the accuracy, completeness, or suitability for any purpose of the Content. Any opinions
and views expressed in this publication are the opinions and views of the authors,
and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content
should not be relied upon and should be independently verified with primary sources
of information. Taylor and Francis shall not be liable for any losses, actions, claims,
proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or

howsoever caused arising directly or indirectly in connection with, in relation to or arising
out of the use of the Content.
This article may be used for research, teaching, and private study purposes. Any
substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing,
systematic supply, or distribution in any form to anyone is expressly forbidden. Terms &
Conditions of access and use can be found at http://www.tandfonline.com/page/terms-
and-conditions

Synthetic Communications1, 41: 1146–1159, 2011
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911003797858
REMARKABLE STEREOCONTROL IN 1,3-DIPOLAR
CYCLOADDITION OF ACYCLIC NITRONES:
INVESTIGATION OF THE CYCLOADDITION OF
C,N-DIARYL NITRONES TO METHYL CINNAMATE
UNDER DIFFERENT REACTION CONDITIONS
Pizush Kanti Biswas,1 Debasish Bandyopadhyay,1
2
Thierry Prange, Alain Neuman, and Avijit Banerji
2
1
´
1Centre of Advanced Studies on Natural Products Including Organic
Synthesis, Department of Chemistry, Calcutta University, Kolkata, India
2
´
LCRB, UMR 8015–Universite Paris Descartes–CNRS, Faculte de
´
Pharmacie, Paris, France
GRAPHICAL ABSTRACT
Abstract Investigation of the cycloaddition of C,N-diarylnitrones to methyl cinnamate
under different reaction conditions were carried out. Two diastereoisomeric and one regioi-
someric cycloadducts were isolated and characterized by spectroscopic and x-ray data.
Remarkable change in selectivity was noticed in solvent-free condition and in the presence
of ytterbium triflate as catalyst.
Keywords Cycloaddition; isoxazolidine; methyl cinnamate; nitrone; ytterbium triflate
Received December 28, 2009.
Present affiliation for Debasish Bandyopadhyay: Department of Chemistry, University of Texas–
Pan American, Edinburg, Texas, USA.
Address correspondence to Avijit Banerji, Centre of Advanced Studies on Natural Products
Including Organic Synthesis, Department of Chemistry, Calcutta University, 92 Acharya Prafulla
Chandra Road, Kolkata 700 009, India. E-mail: ablabccu@yahoo.co.uk
1146

STEREOCONTROL IN 1,3-DIPOLAR CYCLOADDITION
1147
INTRODUCTION
The 1,3-dipolar cycloaddition (1,3-DC) of nitrones to electron-deficient olefins
is the best procedure for the synthesis of isoxazolidines.[1–4] By exploiting this strat-
egy as the key step, several classes of biologically active compounds as well as natural
products have been synthesized.[2–5] As a part of our investigation in this particular
field,[6–11] we have recently carried out the p4s þ p2s cycloaddition of C,N-diaryl
nitrones to methyl cinnamate under different conditions. The main objective of this
investigation was to study the regio- and stereochemical courses of nitrone cycload-
dition reaction to 1,2-disubstituted olefin as well as the substitution effect on the aryl
ring of the substrate. The effect of rare-earth triflate (yitterbium triflate) as catalyst
on 1,3-DC of nitrones has also been studied. This article gives a concise report of this
investigation.
RESULTS AND DISCUSSION
Three nitrones [viz., C-(4-nitrophenyl)-N-(40-chlorophenyl), C-phenyl-N-
(4-chlorophenyl) and C,N-diphenyl nitrone] were chosen for the present cycloaddition
studies. A total of 12 reactions were carried out under different reaction conditions
(Schemes 1 and 2). The nitrones were initially synthesized by the conventional
Scheme 1. Reaction conditions: (i) in refluxing toluene (ꢀ110 ꢁC); molar ratio nitrone=methyl cinnamate
1:3; time 15 h, nitrogen atmosphere; and (ii) solvent-free condition; molar ratio nitrone=methyl cinnamate
1:5; temperature ꢀ110 ꢁC, time 4 h, nitrogen atmosphere. ꢂCorresponding carbocyclic acid (5a) was
obtained.

1148
P. K. BISWAS ET AL.
Scheme 2. 1,3-Dipolar cycloaddition of C,N-diaryl nitrones to methyl cinnamate in the presence of
Yb(OTf)3.
procedure of heating the corresponding hydroxylamines with the appropriate alde-
hydes in ethanol. Subsequently, an improved microwave-assisted procedure similar
to that developed by the authors for the C-aryl-N-methyl nitrones[11] was used.
1,3-DC of C-(4-nitrophenyl)-N-(40-chlorophenyl) nitrone to methyl cinnamate
was performed in the usual way in refluxing toluene (ꢀ110 ꢁC) and also in
solvent-free conditions at 110 ꢁC, with excess of the dipolarophile. When the reaction
was carried out in refluxing toluene, three-fold molar excess of the dipolarophile was
used to enhance the reaction rates and hence yields in 15 h. This afforded a mixture
of diastereoisomeric products (types I, II) and small amounts of regioisomaric
product (type III). The same reaction was performed under solvent-free conditions
for about 4 h, resulting only one compound (type I). The all-trans isomer (type I)
was the major product isolated from all the reactions [condition (i), Scheme 1].
The diastereoisomeric 3,4-cis 4,5-trans (type II) 5-aryl-4-carbomethoxyisoxazolidine
and the regioisomeric (type III) 4-aryl-5-carbomethoxyisoxazolidine were isolated as
minor products from the reaction where toluene used as solvent. The product ratio
was found to be as 85:8:7 (5a=8=11), but in solvent-free conditions only the all-trans
product was obtained. An identical protocol was followed for the reactions between
the other two nitrones (2 and 3) with methyl cinnamate (4) either in solvent (toluene)
or in solvent-free conditions, and the same result was obtained.
All the isolated products showed ester bands at 1736–1706 cmꢃ1 in their
respective infrared (IR) spectra. The three types of cycloadducts (viz., type I,

STEREOCONTROL IN 1,3-DIPOLAR CYCLOADDITION
1149
Figure 1. X-ray crystallographic structure (ORTEP projection) of 5a.
type II, and type III) could be differentiated from their 1H and 13C NMR character-
istics. The C(3)H appeared at d 5.54 ppm in 5a and d 5.72 ppm in 8. C(4)H were
shielded by ꢀ2.0 and 1.85 ppm respectively, compared to 5a in which the benzylic
H-4 (triplet) was deshielded by ꢀ1.0 ppm. These relationships were typical of all
the compounds belonging to different series.
The x-ray crystallographic analysis of the representative compound of type I
(viz., 5a) showed (ORTEP projection, Fig. 1) that it had a carboxyl group at C-4,
and 3,4-trans configuration between H-3 and H-4 protons and also trans configur-
ation between H-4 and H-5 protons. Thus the inferences regarding the relative
stereochemistry of 5a made from the magnitude of the NMR coupling constant in
the isoxazolidine ring are fully supported by x-ray crystallographic data. Interest-
ingly, compound 5a exists in intermolecular association as a classic head-to-head
dimer (PLUTO projection, Fig. 2) via hydrogen bonding of the carboxylate group.
The relative configuration of the minor cycloadducts [viz., 3,4-cis (type II) and the
Figure 2. X-ray crystallographic structure (PLUTO projection) of 5a (dimer).

1150
P. K. BISWAS ET AL.
regioisomer of type I (i.e., type III)] were obtained on the basis of NMR comparisons
with the similar cycloadducts derived from C-aryl-N-phenyl nitrones,[10,11] for which
the x-ray crystallographic analysis was performed.
The all-trans isomer is obtained by the favorable endo-mode of approach of
the dipolarophile with respect to the carbonyl group. Several publications have
analyzed the regioselectivity and diastereoselectivity of the 1,3-dipolar cycloaddi-
tions of nitrones on the basis of frontier molecular orbital (FMO) interac-
tions.[12–15] Most authors have explained the favored endo-mode of approach,
with respect to the carbonyl group, to be due to favorable secondary orbital inter-
actions. Accordingly, type I should be the major product, which gets support from
our experimental findings when the cycloadditions were carried out in solvent
(toluene). On the other hand, our experimental results seem to indicate that steric
and dipolar factors, which favor exclusively the all-trans-cycloadduct, might play a
significant role in the transition state, resulting in type I cycloadducts as the sole
products in each of the three cases.
In addition to these reactions, the effect of rare-earth triflate (ytterbium triflate)
as catalyst on 1,3-DC of nitrones has been studied. As of now, very little infor-
mation[16,17] exists on this aspect of 1,3-DCs; hence, to study the effect of ytterbium
triflate (20 mol% of nitrone) as a catalyst, the following cycloadditions were per-
formed.
Cycloadition of C-(4-nitrophenyl)-N-(40-chlorophenyl) nitrone (1) with methyl
cinnamate in the presence of Yb(OTf)3 (20 mol% of nitrone) was carried out both in
solvent (toluene) and solvent-free conditions. In both cases, only one compound (8)
corresponding to type II was identified, which could be confirmed from the chemical
shift, and the coupling values of H-3 (5.72 ppm, J3,4 ¼ 9.6 Hz) and H-5 (5.05 ppm,
J4,5 ¼ 10.2 Hz) indicated the 3,4-cis, 4,5-trans configuration for this regioisomeric
compound (8).
Following a similar sequence, the reactions of C-phenyl-N-(4-chlorophenyl)
nitrone (2) and C-phenyl-N-phenyl nitrone (3) with methyl cinnamate in the pres-
ence of Yb(OTf)3 in dry toluene afforded only type II compounds (9 and 10,
respectively). The nonaromatic protons H-3 and H-5 of compound 9 appeared
at d 5.37 ppm and d 5.17 ppm respectively as doublets [J3,4 ¼ 8.7 Hz and
J4,5 ¼ 6.6 Hz], and for compound 10 H-3 appeared at d 5.39 ppm and H-5 appeared
d 5.24 ppm, both as doublets [J3,4 ¼ 8.7 Hz and J4,5 ¼ 9.5 Hz respectively]. The
coupling constant values J3,4 of H-3 and H-4 protons confirm compounds 9 and
10 to be the cis isomer.
In conclusion, a critical study regarding the regio- and stereoselectivity in
the 1,3-DC of three acyclic nitrones with methyl cinnamate has been carried
out, which revealed the following: (i) Uncatalyzed thermal reaction (a) in solvent
(toluene) yields type I cycloadducts as the major isomer, in addition to the stereo-
isomeric type II and regioisomeric type III cycloadducts as minor products, (b) in
solvent-free conditions, type I cycloadducts are obtained as sole products; that is,
the reaction becomes regio- as well as stereoselective. This may be because the all-
trans isomer (i.e., type I) is obtained by the favorable endo-mode of approach of
the dipolarphile with respect to the carbonyl group, stabilized further by favor-
able secondary orbital interactions. (ii) In the presence of ytterbium triflate
[Yb(OTf)3] as a catalyst (20 mol% of nitrone) and in the presence of solvent

STEREOCONTROL IN 1,3-DIPOLAR CYCLOADDITION
1151
and solvent-free conditions, type II cycloadducts were obtained as the sole
products in all the cases. The probable reason may be like that the reaction is
primarily controlled by the interaction between highest occupied molecular orbital
(HOMO)nitrone and lowest unoccupied molecular orbital (LUMO)dipolarophile. By
the application of ytterbium triflate, a Lewis acid catalyst that acts as an electron
acceptor, the LUMO energy of the dipolarophile was lowered by coordination of
the a,b-unsaturated carbonyl to the ytterbium triflate. As a result of the decreased
energy gap between the interacting FMOs, a rate acceleration of the reaction is
achieved. The selectivity may also be due to this concomitant coordination. So,
with 1,3-dipolar cycloaddition in the presence of ytterbium triflate, the selectivity
of the reaction changed significantly, and the endo- type II was obtained as a
single diastereoisomer. Most recently, Ess and Houk reported[18] that the
energy to distort the 1,3-dipole and dipolarophile to the transition-state geometry
is the major factor that actually controls reactivity differences of 1,3-dipoles.
Interaction energies between the 1,3-dipole and the dipolarophile differentiate
reactivity for a series of substituted alkenes when the distortion energies are
nearly constant.
EXPERIMENTAL
Melting points were recorded on a Ko¨fler block apparatus and are uncorrected.
Neutral alumina was used for column chromatography, and silica gel (60–120 mesh)
was used for thin-layer chromatography (TLC). Petrol refers to the petroleum ether
AR (bp 60–80 ꢁC). Analytical samples were routinely dried over CaCl2 in vacuo at
room temperature. IR spectra were recorded in KBr pellets with a Perkin-Elmer
RX-1 Fourier transform (FT)-IR, and ultraviolet spectra were measured in
spectroscopic-grade ethanol (Merck) with a Hitachi U-3501 instrument. Elemental
analysis (C, H, N) were conducted using the Perkin-Elmer 2400 series II elemental
analyzer, and their results were found to be in good agreement (ꢄ0.2%) with the cal-
culated values for C, H, and N. 1H NMR (300 MHz) and 13C NMR (75.5 MHz) were
recorded in CDCl3 and dimethylsulfoxide (DMSO)-d6 solution with a Bruker
AM-300L spectrometer (chemical shift in d ppm and J in hertz).
The compound N-(4-chlorophenyl)hydroxylamine, mp 89–90 ꢁC, was pre-
pared from 4-chloronitrobenzene by adopting the method used for obtaining N-
phenylhydroxylamine from nitrobenzene.[19] Initially the nitrones were prepared
as described in our early communications.[9–11] The C-aryl-N-(40-chlorophenyl)
nitrones were also synthesized by a more convenient method using microwave
irradiation techniques from the appropriate aromatic aldehyde and N-(40-
chlorophenyl)hydroxylamine. This improved procedure was similar to that developed
by the authors for C-aryl-N-methyl nitrones.[11] In this procedure, the aromatic alde-
hyde was taken with a small excess of N-(4-chlorophenyl)hydroxylamine (1:1.2 molar
ratio) in dry dichloromethane in an Erlenmeyer flask. The reaction mixture was sub-
jected to microwave irradiation for periods varying from 1–4 min (yield 91.5%). At
the end of the reaction period, the postreaction mixture was worked up, and the residue
was analyzed by 1H NMR. The nitrones were crystallized from ethanol, methanol, or
1
petrol–benzene mixture and characterized from their FT-IR, H NMR, and 13C
NMR spectra.

1152
P. K. BISWAS ET AL.
General Method for the Reaction of Nitrones (1–3) with Methyl
Cinnamate
A hot solution of nitrones 1–3 (0.0066 mol) in anhydrous toluene (20 ml) was
added to a solution of methyl cinnamate (3 ꢅ 0.0066 mol) in anhydrous toluene
(20 ml). In solvent-free conditions, the nitrone 1 (0.0022 mol) was directly added to
methyl cinnamate (5 ꢅ 0.0022 mol). The reaction mixture was refluxed under a nitro-
1
gen atmosphere for 4–15 h. The reaction was monitored by TLC and by H NMR
analyses. The solvent was removed from the crude reaction mixture, and the mixture
was chromatographed over neutral alumina to separate the products. In the catalytic
reactions, both in solvent and solvent-free conditions, ytterbium triflate (20 mol% of
nitrone) was used.
Reaction of C-(4-Nitrophenyl)-N-(4’-chlorophenyl) Nitrone (1) with
Methyl Cinnamate (4) in Refluxing Toluene
3RS-(3Rꢂ,4Sꢂ,5Rꢂ)-2-(4’-Chlorophenyl)-3-(4’’-nitrophenyl)-5-phenyl-4-
carboxyisoxazolidine (5a). C22H17N2O5Cl, white crystals, mp 192 ꢁC, yield:
1.63 g (85%). IR: n ¼ 2931, 2830 (m, aliphatic –CH– stretching), 1706 (s, carboxylic
=
acid >C O), 1522, 1340 (s, aromatic –NO2), 1097 (m, aryl-Cl), 834 (m, 1,4-disubsti-
tuted benzene ring), 757, 694 (m, monosubstituted benzene ring) cmꢃ1; UV: kmax (log
1
e) ¼ 253 (4.37) nm; H NMR (DMSO-d6, d, 300 MHz): 5.54 (1H, d, J ¼ 8.4, H-3),
3.54 (1H, dd, J ¼ 8.4, 8.7, H-4), 5.33 (1H, d, J ¼ 8.7, H-5), 7.10 (2H, d, J ¼ 9.0,
A,H-2,6), 7.35 (2H, d, J ¼ 9.0, A,H-3,5), 7.82 (2H, d, J ¼ 8.7, B,H-2,6), 8.26 (2H,
d, J ¼ 8.7, B,H-3,5), 7.36–7.39 (5H, m, C,H-2,3,4,5,6) ppm; 13C NMR (DMSO-
=
d6, d, 75.5 MHz): 72.3 (C-3), 65.0 (C-4), 83.1 (C-5), 171.1 (>C O), 149.3 (A,C-1),
115.9 (A,C-2,6), 127.9 (A,C-3,5), 136.0 (A,C-4), 147.1 (B,C-1), 127.3 (B,C-2,6),
124.1 (B,C-3,5), 149.2 (B,C-4), 125.9 (C,C-1), 128.7 (C,C-2,6), 129.9 (C,C-3,5),
129.1 (C,C-4) ppm. The structure has been finally confirmed[18] by x-ray crystallo-
graphic analysis. Anal. calcd. for C22H17N2O5Cl: C, 63.11; H, 4.40; N, 6.38. Found:
C, 62.98; H, 4.31; N, 6.33.
1RS-(1Rꢂ,2Rꢂ,3Sꢂ)-1’-[N-Hydroxy-N-(4-chlorophenyl) amino]-1’-(4’-nitro-
phenyl)-3-hydroxy-2-phenyl propanoyl cinnamate (8). C23H21N2O6Cl, colorless
solid, mp 175 ꢁC, yield: 0.22 g (8.0%). IR: n ¼ 3420–3340 (m, -OH), 2934, 2825 (m,
=
aliphatic –CH– stretching), 1726 (s, ester >C O), 1520, 1345 (s, aromatic –NO2),
1090 (m, aryl-Cl), 830 (m, 1,4-disubstituted benzene ring), 760, 690 (m, monosubsti-
1
tuted benzene ring) cmꢃ1; UV: kmax (log e) ¼ 250 (4.35) nm; H NMR (CDCl3, d,
300 MHz): 5.72 (1H, d, J ¼ 9.7, H-3), 3.47 (1H, t, J ¼ 9.5, H-4), 4.45 (1H, d,
J ¼ 9.5, H-5), 3.19 (3H, s, -OCH3), 7.06 (1H, d, J ¼ 2.3, >N-OH), 3.70 (1H, s,
5-OH), 6.77 (2H, d, J ¼ 8.3, A,H-2,6), 7.65 (2H, d, J ¼ 8.3, A,H-3,5), 7.74 (2H, d,
J ¼ 8.7, B,H-2,6), 8.30 (2H, d, J ¼ 8.7, B,H-3,5), 7.34 (2H, dd, J ¼ 6.8, 3.2,
C,H-2,6), 6.98–6.95 (3H, m, C,H-3,4,5) ppm. 13C NMR (CDCl3, d, 75.5 MHz):
=
72.0 (C-3), 65.5 (C-4), 83.5 (C-5), 51.25 (-OCH3), 172.1 (>C O), 150.0 (A,C-1),
115.0 (A,C-2,6), 127.0 (A,C-3,5), 136.5 (A,C-4), 147.4 (B,C-1), 127.4 (B,C-2,6),
124.3 (B,C-3,5), 149.0 (B,C-4), 125.3 (C,C-1), 128.6 (C,C-2,6), 129.4 (C,C-3,5),
129.2 (C,C-4) ppm. Anal. calcd. for C23H21N2O6Cl: C, 60.52; H, 4.60; N, 6.14.
Found: C, 60.30; H, 4.46; N, 6.21.

STEREOCONTROL IN 1,3-DIPOLAR CYCLOADDITION
1153
3RS-(3Rꢂ,4Sꢂ5Rꢂ)-2-(4-Chlorophenyl)-3-(4’-nitrophenyl)-4-phenyl-5-
carbomethoxyisoxazolidine (11). C23H19N2O5Cl, microcrystalline solid, mp
180 ꢁC, yield: 0.1 g (7%). IR: n ¼ 2921, 2853 (m, aliphatic –CH– stretching), 1734
=
(s, ester, >C O), 1517, 1347 (s, aromatic –NO2), 1095 (m, aryl-Cl), 816 (m, 1,4-
disubstituted benzene ring), 701 (m, monosubstituted benzene ring) cmꢃ1; UV: kmax
1
log e) ¼ 252 (3.82) nm; H NMR (CDCl3, d, 300 MHz): 5.03 (1H, d, J ¼ 7.4, H-3),
3.25 (1H, t, J ¼ 7.8, H-4), 4.97 (1H, d, J ¼ 8.3, H-5), 3.16 (3H, s, -OCH3), 6.33
(2H, d, J ¼ 8.8, A,H-2,6), 6.97 (2H, d, J ¼ 8.8, A,H-3,5), 7.47 (2H, d, J ¼ 8.7,
B,H-2,6), 8.08 (2H, d, J ¼ 8.7, B,H-3,5), 7.27–7.19 (5H, m, C, H,2,3,4,5,6) ppm.
13C NMR (CDCl3, d, 75.5 MHz): 74.16 (C-3), 59.26 (C-4), 85.0 (C-5), 51.64
=
(-OCH3), 172.0 (>C O), 147.0 (A,C-1), 115.3 (A,C-2,6), 128.2 (A,C-3,5), 135
(A,C-4), 143.0 (B,C-1), 126.6 (B,C-2,6), 123.7 (B,C-3,5), 146.5 (B,C-4), 128.3
(C,C-1), 127.8 (C,C-2,6), 129.1 (C,C-3,5), 129.0 (C,C-4) ppm. Anal. calcd. for
C23H19N2O5Cl: C, 63.01; H, 4.37; N, 6.40. Found: C, 63.08; H, 4.42; N, 6.48.
Reaction of C-Phenyl-N-(4-chlorophenyl) Nitrone (2) with Methyl
Cinnamate (4) in Refluxing Toluene
3RS-(3Rꢂ,4Sꢂ,5Rꢂ)-2-(4-Chlorophenyl)-3-phenyl-5-phenyl-4-carbomethoxy-
isoxazolidine (6). C23H20NO3Cl, white crystals, mp 180 ꢁC, yield: 1.52 g (81%). IR:
=
n ¼ 2929, 2835 (m, aliphatic –CH– stretching), 1730 (s, ester >C O), 1090 (m,
aryl-Cl), 830 (m, 1,4-disubstituted benzene ring), 753, 692 (m, monosubstituted ben-
1
zene ring) cmꢃ1; UV: kmax (log e) ¼ 251 (4.32) nm; H NMR (CDCl3, d, 300 MHz):
5.51 (1H, d, J ¼ 8.1, H-3), 3.52 (1H, dd, J ¼ 8.1, 8.5, H-4), 5.31 (1H, d, J ¼ 8.5, H-5),
3.15 (3H, s, -OCH3), 7.11 (2H, d, J ¼ 8.9, A,H-2,6), 7.32 (2H, d, J ¼ 8.9, A,H-3,5),
7.52 (2H, d, J ¼ 8.1, B,H-2,6), 7.30–7.40 (3H, m, B,H-3,4,5), 7.32–7.42 (5H, m,
C,H-2,3,4,5,6) ppm; 13C NMR (CDCl3, d, 75.5 MHz): 72.1 (C-3), 65.2 (C-4), 83.3
=
(C-5), 50.62 (-OCH3), 172.1 (>C O), 149.1 (A,C-1), 115.2 (A,C-2,6), 127.3
(A,C-3,5), 136.2 (A,C-4), 147.3 (B,C-1), 127.5 (B,C-2,6), 124.5 (B,C-3,5), 128.2
(B,C-4), 125.4 (C,C-1), 128.2 (C,C-2,6), 129.2 (C,C-3,5), 129.5 (C,C-4) ppm. Anal.
calcd. for C23H20NO3Cl: C, 70.14; H, 5.12; N, 3.56. Found: C, 69.91; H, 5.10; N,
3.48.
3RS-(3Rꢂ,4Rꢂ,5Sꢂ)-2-(4-Chlorophenyl)-3-phenyl-5-phenyl-4-carbomethoxy-
isoxazolidine (9). C23H20NO3Cl, colorless solid; mp 172 ꢁC; yield: 0.20 g (6.8%).
=
IR: n ¼ 2932, 2822 (m, aliphatic –CH– stretching), 1723 (s, ester >C O), 1091 (m,
aryl-Cl), 832 (m, 1,4-disubstituted benzene ring), 761, 692 (m, monosubstituted ben-
1
zene ring) cmꢃ1; UV: kmax (log e) ¼ 251 (4.36) nm; H NMR (CDCl3, d, 300 MHz):
4.72 (1H, d, J ¼ 9.6, H-3), 3.46 (1H, t, J ¼ 9.2, H-4), 4.43 (1H, d, J ¼ 9.2, H-5), 3.17
(3H, s, -OCH3), 6.75 (2H, d, J ¼ 8.1, A,H-2,6), 7.62 (2H, d, J ¼ 8.1, A,H-3,5), 7.72
(2H, d, J ¼ 8.3, B,H-2,6), 7.28–7.39 (3H, m, B,H-3,4,5), 7.32 (2H, dd, J ¼ 6.6, 3.1,
C,H-2,6), 6.96–6.93 (3H, m, C,H-3,4,5) ppm. 13C NMR (CDCl3, d, 75.5 MHz):
=
72.1 (C-3), 65.4 (C-4), 83.3 (C-5), 51.23 (-OCH3), 172.0 (>C O), 150.1 (A,C-1),
115.2 (A,C-2,6), 127.2 (A,C-3,5), 136.4 (A,C-4), 147.2 (B,C-1), 127.2 (B,C-2,6),
124.1 (B,C-3,5), 149.2 (B,C-4), 125.2 (C,C-1), 128.3 (C,C-2,6), 129.2 (C,C-3,5),
129.3 (C,C-4) ppm. Anal. calcd. for C23H20NO3Cl: C, 70.14; H, 5.12; N, 3.56.
Found: C, 69.88; H, 5.06; N, 3.51.

1154
P. K. BISWAS ET AL.
3RS-(3Rꢂ,4Sꢂ5Rꢂ)-2-(4-Chlorophenyl)-3,4-diphenyl-5-carbomethoxyisoxa-
zolidine (12). C23H20NO3Cl, microcrystalline solid, mp 175 ꢁC, yield: 0.12 g (5.4%).
=
IR: n ¼ 2918, 2845 (m, aliphatic –CH– stretching), 1730 (s, ester, >C O), 1090 (m,
aryl-Cl), 814 (m, 1,4-disubstituted benzene ring), 705 (m, monosubstituted benzene
ring) cmꢃ1; UV: kmax (log e) ¼ 250 (3.80) nm; 1H NMR (CDCl3, d, 300 MHz):
5.01 (1H, d, J ¼ 7.2, H-3), 3.22 (1H, t, J ¼ 7.6, H-4), 4.95 (1H, d, J ¼ 8.1, H-5),
3.14 (3H, s, -OCH3), 6.31 (2H, d, J ¼ 8.6, A,H-2,6), 6.93 (2H, d, J ¼ 8.6, A,H-3,5),
7.43 (2H, d, J ¼ 8.4, B,H-2,6), 7.27–7.39 (3H, m, B,H-3,4,5), 7.25–7.22 (5H, m, C,
H,2,3,4,5,6) ppm. 13C NMR (CDCl3, d, 75.5 MHz): 74.14 (C-3), 59.23 (C-4), 85.3
=
(C-5), 51.62 (-OCH3), 172.5 (>C O), 147.2 (A,C-1), 115.5 (A,C-2,6), 128.4
(A,C-3,5), 136 (A,C-4), 143.3 (B,C-1), 126.4 (B,C-2,6), 123.5 (B,C-3,5), 146.2
(B,C-4), 128.2 (C,C-1), 127.5 (C,C-2,6), 129.0 (C,C-3,5), 129.2 (C,C-4) ppm. Anal.
calcd. for C23H20NO3Cl: C, 70.14; H, 5.12; N, 3.56. Found: C, 69.85; H, 5.02; N,
3.48.
Reaction of C,N-Diphenyl Nitrone (3) with Methyl Cinnamate
(4) in Refluxing Tolune
3RS-(3Rꢂ,4Sꢂ,5Rꢂ)-2,3,5-Triphenyl-4-carbomethoxyisoxazolidine
(7).
C23H21NO3, white crystals, mp 175 ꢁC, yield: 1.50 g (80%). IR: n ¼ 2931, 2830 (m,
=
aliphatic –CH– stretching), 1715 (s, ester >C O), 750, 690 (m, mono-substituted
benzene ring) cmꢃ1; UV: kmax (log e) ¼ 252 (4.33) nm; 1H NMR (CDCl3, d,
300 MHz): 5.52 (1H, d, J ¼ 8.2, H-3), 3.53 (1H, dd, J ¼ 8.2, 8.5, H-4), 5.32 (1H, d,
J ¼ 8.5, H-5), 3.19 (3H, s, -OCH3), 7.15 (2H, d, J ¼ 9.2, A,H-2,6), 7.12–7.22 (3H,
m, A,H-3,4,5), 7.35 (2H, d, J ¼ 8.2, B,H-2,6), 7.25–7.32 (3H, m, B,H-3,4,5),
7.31–7.35 (5H, m, C,H-2,3,4,5,6) ppm; 13C NMR (CDCl3, d, 75.5 MHz): 72.1
=
(C-3), 65.2 (C-4), 83.2 (C-5), 50.25 (-OCH3), 172.3 (>C O), 149.1 (A,C-1), 115.7
(A,C-2,6), 127.5 (A,C-3,5), 136.2 (A,C-4), 147.3 (B,C-1), 127.1 (B,C-2,6), 124.3
(B,C-3,5), 149.3 (B,C-4), 125.7 (C,C-1), 128.5 (C,C-2,6), 129.7 (C,C-3,5), 129.2
(C,C-4) ppm. Anal. calcd. for C23H21NO3: C, 76.86; H, 5.89; N, 3.89. Found: C,
76.76; H, 5.81; N, 3.79.
3RS-(3Rꢂ,4Rꢂ,5Sꢂ)-2,3,5-Triphenyl-4-carbomethoxyisoxazolidine (10).
C23H21NO3, Colorless solid, mp 160 ꢁC, yield: 0.21 g (6.5%). IR: n ¼ 2930, 2820
=
(m, aliphatic –CH– stretching), 1720 (s, ester >C O), 761, 691 (m, monosubstituted
benzene ring) cmꢃ1; UV: kmax (log e) ¼ 252 (4.35) nm; 1H NMR (CDCl3, d,
300 MHz); 4.77 (1H, d, J ¼ 9.5, H-3), 3.45 (1H, t, J ¼ 9.3, H-4), 4.43 (1H, d,
J ¼ 9.3, H-5), 3.17 (3H, s, -OCH3), 6.77 (2H, d, J ¼ 8.1, A,H-2,6), 7.15–7.21 (3H,
m, A,H-3,4,5), 7.72 (2H, d, J ¼ 8.3, B,H-2,6), 7.30–7.36 (3H, m, B,H-3,4,5), 7.32
(2H, dd, J ¼ 6.6, 3.1, C,H-2,6), 6.96–6.93 (3H, m, C,H-3,4,5) ppm. 13C NMR
(CDCl3, d, 75.5 MHz): 72.1 (C-3), 65.3 (C-4), 83.3 (C-5), 51.22 (-OCH3), 172.2
=
(>C O), 150.1 (A,C-1), 115.2 (A,C-2,6), 127.3 (A,C-3,5), 136.2 (A,C-4), 147.3
(B,C-1), 127.2 (B,C-2,6), 124.1 (B,C-3,5), 149.2 (B,C-4), 125.1 (C,C-1), 128.3
(C,C-2,6), 129.3 (C,C-3,5), 129.2 (C,C-4) ppm. Anal. calcd. for C23H21NO3: C,
76.86; H, 5.89; N, 3.89. Found: C, 76.79; H, 5.83; N, 3.82.
3RS-(3Rꢂ,4Sꢂ,5Rꢂ)-2,3,4-Triphenyl-5-carbomethoxyisoxazolidine (13).
C23H21NO3, microcrystalline solid, mp 182 ꢁC, yield: 0.13 g (5.5%). IR: n ¼ 2921,

STEREOCONTROL IN 1,3-DIPOLAR CYCLOADDITION
1155
=
2855 (m, aliphatic –CH– stretching), 1731 (s, ester, >C O), 703 (m,
1
mono-substituted benzene ring) cmꢃ1; UV: kmax (log e) ¼ 253 (3.83) nm; H NMR
(CDCl3, d, 300 MHz): 5.13 (1H, d, J ¼ 7.5, H-3), 3.22 (1H, t, J ¼ 7.6, H-4), 4.95
(1H, d, J ¼ 8.2, H-5), 3.16 (3H, s, -OCH3), 6.30 (2H, d, J ¼ 8.6, A,H-2,6),
7.31–7.41 (3H, m, A,H-3,4,5), 7.45 (2H, d, J ¼ 8.4, B,H-2,6), 7.25–7.33 (3H, m,
B,H-3,4,5), 7.23–7.19 (5H, m, C, H,2,3,4,5,6) ppm. 13C NMR (CDCl3, d,
=
75.5 MHz): 74.15 (C-3), 59.24 (C-4), 85.3 (C-5), 51.63 (-OCH3), 172.5 (>C O),
147.6 (A,C-1), 115.6 (A,C-2,6), 128.4 (A,C-3,5), 137.0 (A,C-4), 143.2 (B,C-1),
126.3 (B,C-2,6), 123.5 (B,C-3,5), 146.2 (B,C-4), 128.1 (C,C-1), 127.5 (C,C-2,6),
129.3 (C,C-3,5), 129.2 (C,C-4) ppm. Anal. calcd. for C23H21NO3: C, 76.86; H,
5.89; N, 3.89. Found: C, 76.82; H, 5.84; N, 3.81.
Reaction of C-(4-Nitrophenyl)-N-(4’-chlorophenyl) Nitrone (1) with
Methyl Cinnamate (4) in Solvent-Free Conditions
3RS-(3Rꢂ,4Sꢂ,5Rꢂ)-2-(4-Chlorophenyl)-3-(4’-nitrophenyl)-5-phenyl-4-
carbomethoxyisoxazolidine (5). C23H19N2O5Cl, white crystals, mp 130 ꢁC,
yield: 0.86 g (90%). IR: n ¼ 2954, 2830 (m, aliphatic –CH– stretching), 1736 (s, ester,
=
>C O), 1495, 1343 (s, aromatic –NO2), 1100 (m, aryl –Cl), 825 (m, 1,4-disubstituted
benzene ring), 749, 695 (m, monosubstituted benzene ring) cmꢃ1; UV: kmax (log
e) ¼ 250 (4.22) nm; 1H NMR (CDCl3, d, 300 MHz): 5.41 (1H, d, J ¼ 8.5, H-3),
3.53 (1H, dd, J ¼ 8.5, 6.1, H-4), 5.35 (1H, d, J ¼ 6.1, H-5), 3.70 (3H, m, -OCH3),
7.70 (2H, d, J ¼ 8.9, A,H-2,6), 7.75 (2H, d, J ¼ 8.9, A,H-3,5), 7.76 (2H, d, J ¼ 8.7,
B,H-2,6), 8.26 (2H, d, J ¼ 8.7, B,H-3,5), 7.36–7.41 (5H, m, C,H-2,3,4,5,6) ppm;
13C NMR (CDCl3, d, 75.5 MHz): 72.91 (C-3), 65.88 (C-4), 83.15 (C-5), 52.82
=
(-OCH3), 170.2 (>C O), 148.9 (A,C-1), 115.8 (A,C-2,6), 128.7 (A,C-3,5), 136.2
(A,C-4), 147.8 (B,C-1), 127.4 (B,C-2,6), 124.2 (B,C-3,5), 148.2 (B,C-4), 127.7
(C,C-1), 128.9 (C,C-2,6), 129.1 (C,C-3,5), 126.7 (C,C-4) ppm. Anal. calcd. for
C23H19N2O5Cl: C, 63.01; H, 4.37, N, 6.40. Found: C, 62.95; H, 4.32; N, 6.34.
Reaction of C-Phenyl-N-(4-chlorophenyl) Nitrone (2) with Methyl
Cinnamate (4) in Solvent-Free Conditions
3RS-(3Rꢂ,4Sꢂ,5Rꢂ)-2-(4-Chlorophenyl)-3-phenyl-5-phenyl-4-carbomethoxy-
isoxazolidine (6). C23H20NO3Cl, white crystals, mp 180 ꢁC; yield: 1.52 g (81%). IR:
=
n ¼ 2929, 2835 (m, aliphatic –CH– stretching), 1730 (s, ester >C O), 1090 (m,
aryl-Cl), 830 (m, 1,4-disubstituted benzene ring), 753, 692 (m, monosubstituted ben-
1
zene ring) cmꢃ1; UV: kmax (log e) ¼ 251 (4.32) nm; H NMR (CDCl3, d, 300 MHz):
5.52 (1H, d, J ¼ 8.1, H-3), 3.51 (1H, dd, J ¼ 8.1, 8.5, H-4), 5.32 (1H, d, J ¼ 8.5, H-5),
3.15 (3H, s, -OCH3), 7.11 (2H, d, J ¼ 8.9, A,H-2,6), 7.32 (2H, d, J ¼ 8.9, A,H-3,5),
7.52 (2H, d, J ¼ 8.1, B,H-2,6), 7.30–7.40 (3H, m, B,H-3,4,5), 7.32–7.42 (5H, m,
C,H-2,3,4,5,6) ppm; 13C NMR (CDCl3, d, 75.5 MHz): 72.2 (C-3), 65.1 (C-4), 83.2
=
(C-5), 50.62 (-OCH3), 172.1 (>C O), 149.1 (A,C-1), 115.2 (A,C-2,6), 127.3
(A,C-3,5), 136.2 (A,C-4), 147.3 (B,C-1), 127.5 (B,C-2,6), 124.5 (B,C-3,5), 128.2
(B,C-4), 125.4 (C,C-1), 128.2 (C,C-2,6), 129.2 (C,C-3,5), 129.5 (C,C-4) ppm. Anal.
calcd. for C23H20NO3Cl: C, 70.14; H, 5.12; N, 3.56. Found: C, 69.91; H, 5.10;
N, 3.48.

1156
P. K. BISWAS ET AL.
Reaction of C,N-Diphenyl Nitrone (3) with Methyl Cinnamate (4) in
Solvent-Free Conditions
3RS-(3Rꢂ,4Sꢂ,5Rꢂ)-2,3,5-Triphenyl-4-carbomethoxyisoxazolidine
(7).
C23H21NO3, white crystals, mp: 175 ꢁC; yield: 1.50 g (80%). IR: n ¼ 2931, 2830 (m,
=
aliphatic –CH– stretching), 1715 (s, ester >C O), 750, 690 (m, monosubstituted ben-
zene ring) cmꢃ1; UV: kmax (log e) ¼ 252 (4.33) nm; H NMR (CDCl3, d, 300 MHz):
1
5.52 (1H, d, J ¼ 8.2, H-3), 3.51 (1H, dd, J ¼ 8.2, 8.5, H-4), 5.32 (1H, d, J ¼ 8.5, H-5),
3.19 (3H, s, -OCH3), 7.15 (2H, d, J ¼ 9.2, A,H-2,6), 7.12–7.22 (3H, m, A,H-3,4,5),
7.35 (2H, d, J ¼ 8.2, B,H-2,6), 7.25–7.32 (3H, m, B,H-3,4,5), 7.31–7.35 (5H, m,
C,H-2,3,4,5,6) ppm; 13C NMR (CDCl3, d, 75.5 MHz): 72.1 (C-3), 65.2 (C-4), 83.2
=
(C-5), 50.25 (-OCH3), 172.3 (>C O), 149.1 (A,C-1), 115.7 (A,C-2,6), 127.5
(A,C-3,5), 136.2 (A,C-4), 147.3 (B,C-1), 127.1 (B,C-2,6), 124.3 (B,C-3,5), 149.3
(B,C-4), 125.7 (C,C-1), 128.5 (C,C-2,6), 129.7 (C,C-3,5), 129.2 (C,C-4) ppm. Anal.
calcd. for C23H21NO3: C, 76.86; H, 5.89; N, 3.89. Found: C, 76.76; H, 5.81; N, 3.79.
Reaction of C-(4-Nitrophenyl)-N-(4’-chlorophenyl) Nitrone (1) with
Methyl Cinnamate (4) in the Presence of Yb(OTf)3, Using Toluene
as Solvent
1RS-(1Rꢂ,2Rꢂ,3Sꢂ)-1’-[N-Hydroxy-N-(4-chlorophenyl)amino]-1’-(4’-nitro-
phenyl)-3-hydroxy-2-phenyl propanoyl cinnamate (8). C23H21N2O6Cl, color-
less solid, mp 175 ꢁC, yield: 0.22 g (7.0%). IR: n ¼ 3420–3340 (m, -OH), 2934, 2825
=
(m, aliphatic –CH– stretching), 1726 (s, carboxylic acid >C O), 1520, 1345 (s, aro-
matic –NO2), 1090 (m, aryl-Cl), 830 (m, 1,4-disubstituted benzene ring), 760, 690 (m,
1
monosubstituted benzene ring) cmꢃ1; UV: kmax (log e) ¼ 250 (4.35) nm; H NMR
(CDCl3, d, 300 MHz): 4.78 (1H, d, J ¼ 9.7, H-3), 3.48 (1H, t, J ¼ 9.5, H-4), 4.46
(1H, d, J ¼ 9.5, H-5), 3.19 (3H, s, -OCH3), 7.06 (1H, d, J ¼ 2.3, >N-OH), 3.70
(1H, s, 5-OH), 6.77 (2H, d, J ¼ 8.3, A,H-2,6), 7.65 (2H, d, J ¼ 8.3, A,H-3,5), 7.74
(2H, d, J ¼ 8.7, B,H-2,6), 8.30 (2H, d, J ¼ 8.7, B,H-3,5), 7.34 (2H, dd, J ¼ 6.8, 3.2,
C,H-2,6), 6.98–6.95 (3H, m, C,H-3,4,5) ppm. 13C NMR (CDCl3, d, 75.5 MHz):
=
72.1 (C-3), 65.6 (C-4), 83.6 (C-5), 51.25 (-OCH3), 172.1 (>C O), 150.0 (A,C-1),
115.0 (A,C-2,6), 127.0 (A,C-3,5), 136.5 (A,C-4), 147.4 (B,C-1), 127.4 (B,C-2,6),
124.3 (B,C-3,5), 149.0 (B,C-4), 125.3 (C,C-1), 128.6 (C,C-2,6), 129.4 (C,C-3,5),
129.2 (C,C-4) ppm. Anal. calcd. for C23H21N2O6Cl: C, 60.52; H, 4.60; N, 6.14.
Found: C, 60.30; H, 4.46; N, 6.21.
Reaction of C-Phenyl-N-(4-chlorophenyl) Nitrone (2) with Methyl
Cinnamate (4) in the Presence of Yb(OTf)3, Using Toluene as Solvent
3RS-(3Rꢂ,4Rꢂ,5Sꢂ)-2-(4-Chlorophenyl)-3-phenyl-5-phenyl-4-carbomethoxy-
isoxazolidine (9). C23H20NO3Cl, Colorless solid, mp 172 ꢁC, yield: 0.20 g (6.8%).
=
IR: n ¼ 2932, 2822 (m, aliphatic –CH– stretching), 1723 (s, ester >C O), 1091 (m,
aryl-Cl), 832 (m, 1,4-disubstituted benzene ring), 761, 692 (m, monosubstituted ben-
1
zene ring) cmꢃ1; UV: kmax (log e) ¼ 251 (4.36) nm; H NMR (CDCl3, d, 300 MHz);
4.71 (1H, d, J ¼ 9.6, H-3), 3.45 (1H, t, J ¼ 9.2, H-4), 4.44 (1H, d, J ¼ 9.2, H-5), 3.17
(3H, s, -OCH3), 6.75 (2H, d, J ¼ 8.1, A,H-2,6), 7.62 (2H, d, J ¼ 8.1, A,H-3,5), 7.72

STEREOCONTROL IN 1,3-DIPOLAR CYCLOADDITION
1157
(2H, d, J ¼ 8.3, B,H-2,6), 7.28–7.39 (3H, m, B,H-3,4,5), 7.32 (2H, dd, J ¼ 6.6, 3.1,
C,H-2,6), 6.96–6.93 (3H, m, C,H-3,4,5) ppm. 13C NMR (CDCl3, d, 75.5 MHz):
=
72.2 (C-3), 65.5 (C-4), 83.4 (C-5), 51.23 (-OCH3), 172.0 (>C O), 150.1 (A,C-1),
115.2 (A,C-2,6), 127.2 (A,C-3,5), 136.4 (A,C-4), 147.2 (B,C-1), 127.2 (B,C-2,6),
124.1 (B,C-3,5), 149.2 (B,C-4), 125.2 (C,C-1), 128.3 (C,C-2,6), 129.2 (C,C-3,5),
129.3 (C,C-4) ppm. Anal. calcd. for C23H20NO3Cl: C, 70.14; H, 5.12; N, 3.56.
Found: C, 69.88; H, 5.06; N, 3.51.
Reaction of C,N-Diphenyl Nitrone (3) with Methyl Cinnamate (4) in
the Presence of Yb(OTf)3, Using Toluene as Solvent
3RS-(3Rꢂ,4Rꢂ,5Sꢂ)-2,3,5-Triphenyl-4-carbomethoxyisoxazolidine (10).
C23H21NO3, colorless solid, mp 160 ꢁC, yield: 0.21 g (6.5%). IR: n ¼ 2930, 2820 (m,
=
aliphatic –CH– stretching), 1720 (s, ester >C O), 761, 691 (m, monosubstituted ben-
zene ring) cmꢃ1; UV: kmax (log e) ¼ 252 (4.35) nm; H NMR (CDCl3, d, 300 MHz);
1
4.76 (1H, d, J ¼ 9.5, H-3), 3.46 (1H, t, J ¼ 9.3, H-4), 4.42 (1H, d, J ¼ 9.3, H-5), 3.17
(3H, s, -OCH3), 6.77 (2H, d, J ¼ 8.1, A,H-2,6), 7.15–7.21 (3H, m, A,H-3,4,5), 7.72
(2H, d, J ¼ 8.3, B,H-2,6), 7.30–7.36 (3H, m, B,H-3,4,5), 7.32 (2H, dd, J ¼ 6.6, 3.1,
C,H-2,6), 6.96–6.93 (3H, m, C,H-3,4,5) ppm. 13C NMR (CDCl3, d, 75.5 MHz):
=
72.2 (C-3), 65.4 (C-4), 83.4 (C-5), 51.22 (-OCH3), 172.2 (>C O), 150.1 (A,C-1),
115.2 (A,C-2,6), 127.3 (A,C-3,5), 136.2 (A,C-4), 147.3 (B,C-1), 127.2 (B,C-2,6),
124.1 (B,C-3,5), 149.2 (B,C-4), 125.1 (C,C-1), 128.3 (C,C-2,6), 129.3 (C,C-3,5),
129.2 (C,C-4) ppm. Anal. calcd. for C23H21NO3: C, 76.86; H, 5.89; N, 3.89. Found:
C, 76.79; H, 5.83; N, 3.82.
Reaction of C-(4-Nitrophenyl)-N-(4’-Chlorophenyl) Nitrone (1) with
Methyl Cinnamate (4) in the Presence of Yb(OTf)3 and in the
Absence of Any Solvent
1RS-(1Rꢂ,2Rꢂ,3Sꢂ)-1’-[N-Hydroxy-N-(4-chlorophenyl)amino]-1’-(4’-nitro-
phenyl)-3-hydroxy-2-phenyl propanoyl cinnamate (8). C23H21N2O6Cl, color-
less solid, mp 175 ꢁC, yield: 0.22 g (7.0%). The IR and NMR data are identical to
those of compound 8.
Reaction of C-Phenyl-N-(4-chlorophenyl) Nitrone (2) with Methyl
Cinnamate (4) in the Presence of Yb(OTf)3 and in the Absence of Any
Solvent
3RS-(3Rꢂ,4Rꢂ,5Sꢂ)-2-(4-Chlorophenyl)-3-phenyl-5-phenyl-4-carbomethoxy-
isoxazolidine (9). C23H20NO3Cl, colorless solid, mp 172 ꢁC, yield: 0.20 g (6.8%).
The IR and NMR data are identical to those of compound 9.
Reaction of C,N-Diphenyl Nitrone (3) with Methyl Cinnamate (4) in
the Presence of Yb(OTf)3 and in the Absence of Any Solvent
3RS-(3Rꢂ,4Rꢂ,5Sꢂ)-2,3,5-Triphenyl-4-carbomethoxyisoxazolidine (10).
C23H21NO3, colorless solid, mp 160 ꢁC, yield: 0.21 g (6.5%). The IR and NMR data
are identical to those of compound 10.

1158
P. K. BISWAS ET AL.
X-Ray Crystallographic Data
X-ray crystallographic data were recorded with an automatic charge coupled
device (CCD) Nonius diffractometer. The wavelength of MoKa radiation is
˚
0.7107 A. The structure was solved by the direct method and refined with the
SHELXS program. Recording was done under cryotemperature conditions, at
ꢃ50 ꢁC. The crystals were triclinic, space group P-1, with molecule asymmetric unit.
An ORTEP projection is shown in Fig. 1. Crystallographic data for compound 5a
have been deposited with the Cambridge Crystallographic Data Centre as CCDC
251186. Copies of the data can be obtained, free of charge, on application to CCDC,
12 Union Road, Cambridge CB2 IEZ, UK (fax: þ44 1223 336033 or e-mail:
deposit@ccdc.cam.ac.uk).
ACKNOWLEDGMENT
The authors thank the Indian Council for Cultural Relations (ICCR) for finan-
cial assistance to P. K. Biswas (present address: BCSIR Laboratory, Dhanmondi,
Dhaka-1205, Bangladesh).
REFERENCES
1. Tufariello, J. J. 1,3-Dipolar Cycloaddition Chemistry; John Wiley and Sons: New York,
1984.
2. Torssell, K. B. G. Nitrile Oxide-Nitrones and Nitronates in Organic Synthesis; VCH:
Weinheim, 1988.
3. Kobayashi, S.; Jørgensen, K. A. Cycloaddition Reactions in Organic Synthesis; Wiley-
VCH Verlag GmbH: Weinheim, 2002.
4. Gothelf, K. V.; Jørgensen, K. A. Asymmetric 1,3-dipolar cycloaddition reaction. Chem.
Rev. 1998, 98, 863–909.
5. Frederickson, M. Optically active isoxazolidines via asymmetric cycloaddition reactions
of nitrones with alkenes: Applications in organic synthesis. Tetrahedron 1997, 53, 403–425.
´
6. Banerji, A.; Bandyopadhyay, D.; Prange, T.; Neuman, A. Unexpected cycloadducts from
1,3-dipolar cycloaddition of 3,4-dehydromorpholine N-oxide to N-cinnamoyl piperi-
dines—First report of the novel formation of 2:1 cycloadducts. Tetrahedron Lett. 2005,
46, 2619–2622.
´
7. Banerji, A.; Bandyopadhyay, D.; Sengupta, P.; Basak, B.; Prange, T.; Neuman, A. The
first report of unusual flipping of the cycloadducts from 1,3-dipolar cycloaddition of
3,4,5,6-tetrahydropyridine N-oxide to N-cinnamoyl piperidines. Tetrahedron Lett. 2006,
47 (23), 3827–3830.
´
8. Banerji, A.; Biswas, P. K.; Bandyopadhyay, D.; Gupta, M.; Prange, T.; Neuman, A.
1,3-Dipolar cycloadditions: Investigation of cycloadditions of C-aryl-N-(4-chlorophenyl)
nitrones to N-cinnamoyl piperidines. J. Heterocycl. Chem. 2007, 44(1), 137–143.
´
9. Banerji, A.; Maiti, K. K.; Halder, S.; Mukhopadhyay, C.; Banerji, J.; Prange, T.;
Neuman, A. 1,3-Dipolar cycloadditions, VI: Structure and conformation of cycloadducts
from reactions of C-aryl-N-phenylnitrones with substituted cinnamic acid amides.
Monatsh. Chem. 2000, 131, 901–911.
´
10. Banerji, A.; Banerji, J.; Halder, S.; Maiti, K. K.; Basu, S.; Prange, T.; Neuman, A.
1,3-Dipolar cycloadditions, part III: Cycloaddition of C,N-diarylnitrones to
N-cinnamoylpiperidines. Indian J. Chem. 1998, 37B, 105–119.

STEREOCONTROL IN 1,3-DIPOLAR CYCLOADDITION
1159
11. Banerji, A.; Biswas, P. K.; Sengupta, P.; Dasgupta, S.; Gupta, M. 1,3-Dipolar cycioaddi-
tions, part VIII: Microwave irradiation–assisted synthesis of N-methyl-C-arylnitrones.
Indian J. Chem. 2004, 43B, 880–881.
´
12. Joucla, M.; Tonnard, F.; Gree, D.; Hamelin, J. 1,3-Dipolar cycloadditions, part 26:
Experimental study and interpretation of the stereochemistry of the approach of nitrones
to activated olefins. J. Chem. Res., Synop. 1978, 240.
13. Sustmann, R. Simple model for substituent effects in cycloaddition reactions: 1,3-Dipolar
cycloadditions. Tetrahedron Lett. 1971, 29, 2717–2720.
14. Brandi, A.; Cardona, F.; Cicchi, S.; Cordero, F. M.; Goti, A. Stereocontrolled cyclic
nitrone cycloaddition strategy for the synthesis of pyrrolizidine and indolizidine alkaloids.
Chem. Eur. J. 2009, 15(32), 7808–7821.
15. Stephens, B. E.; Liu, F. A regio- and diastereoselective intramolecular nitrone cycloaddi-
tion for practical 3- and 2,3-disubstituted piperidine synthesis from c-butyrolactone.
J. Org. Chem. 2009, 74(1), 254–263.
16. Kobayashi, S.; Akiyama, R. Lanthanide triflate–catalyzed 1,3-dipolar cycloaddition
reactions of polymer-suppoprted nitrones with alkenes for the preparation of diverse
2-isoxazoline derivatives. Tetrahedron Lett. 1998, 39, 9211–9214.
17. Kobayashi, S.; Jørgensen, K. A. Cycloaddition Reactions in Organic Synthesis;
Wiley-VCH Verlag GmbH: Weinheim, 2002, pp. 323–326.
18. Ess, D. H.; Houk, K. N. Theory of 1,3-dipolar cycloadditions: Distortion interaction and
frontier molecular orbital models. J. Am. Chem. Soc. 2008, 130(31), 10187–10198.
19. Vogel, A. I. A Textbook of Practical Organic Chemistry, 4th ed.; Longman: London, 1978;
p. 722.