Dipolar cycloaddition of N-aryl-C-(2,2-dichloro-1-phenylcyclopropyl) nitrones to N-arylmaleimides

Article abstract of DOI:10.1134/S1070428011010076

1,3-Dipolar cycloaddition of N-aryl-C-(2,2-dichloro-1-phenylcyclopropyl) nitrones to N-arylmaleimides stereoselectively gives substituted pyrrolo[3,4-d]isoxazolidines as mixtures of two diastereoisomers differing by configuration at the C^1′ atom of the cyclopropane ring in the substituent on C³. Substituents in the aromatic rings of the initial nitrone and maleimide do not affect the stereochemistry of the process.

Full text of DOI:10.1134/S1070428011010076

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2011, Vol. 47, No. 1, pp. 66–73. © Pleiades Publishing, Ltd., 2011.
Original Russian Text © A.P. Molchanov, P.S. Sorokoumov, J. Kopf, R.R. Kostikov, 2011, published in Zhurnal Organicheskoi Khimii, 2011, Vol. 47, No. 1,
pp. 69–76.
Dipolar Cycloaddition of N-Aryl-C-(2,2-dichloro-1-phenyl-
cyclopropyl)nitrones to N-Arylmaleimides
A. P. Molchanova, P. S. Sorokoumova, J. Kopfb, and R. R. Kostikova
a St. Petersburg State University, Universitetskii pr. 26, St. Petersburg, 198504 Russia
e-mail: s.lab@pobox.spbu.ru
b Institut für Anorganische Chemie, Martin-Luter-King Platz 6, Hamburg, D-20146 Germany
Received May 26, 2010
Abstract—1,3-Dipolar cycloaddition of N-aryl-C-(2,2-dichloro-1-phenylcyclopropyl)nitrones to N-arylmale-
imides stereoselectively gives substituted pyrrolo[3,4-d]isoxazolidines as mixtures of two diastereoisomers
differing by configuration at the C1′ atom of the cyclopropane ring in the substituent on C3. Substituents in the
aromatic rings of the initial nitrone and maleimide do not affect the stereochemistry of the process.
DOI: 10.1134/S1070428011010076
1,3-Dipolar cycloaddition of nitrones to unsaturated
compounds underlies one of the most important meth-
ods for building up five-membered heterocyclic sys-
tems [1]. A necessary condition for the synthesis of
compounds with required properties is the possibility
to control the reaction stereochemistry, which may be
achieved by proper selection of the corresponding sub-
strates and reaction conditions (solvent and catalyst). It
is known that in reactions of C,N-diaryl nitrones with
N-arylmaleimides the ratio of the resulting endo/exo
diastereoisomers changes from 1.4 to 3.9, depending
on the substituent in the aromatic ring of the initial
nitrone and mealeimide [2]. Enhanced diastereoselec-
tivity was observed in reactions of C-aryl-N-(aryl-
methyl)nitrones with maleimides having both electron-
withdrawing and electron-donating substituents in the
aromatic ring of the imide [3], as well as with o,o′-di-
substituted N-arylmaleimides due to increase of steric
interaction in the transition state [4]. The selectivity of
cycloaddition also changed in the presence of ZnBr2
[3] and upon variation of the solvent [5].
propenes [10] and 2-methylidenecyclopropane-1,3-di-
carboxylates [11]) to form adducts which readily
undergo secondary processes involving opening of the
strained ring.
In the present work we examined the reaction of
N-aryl-C-(2,2-dichloro-1-phenylcyclopropyl)nitrones
Ia–Ic with N-arylmaleimides IIa–IIe. Nitrones Ia–Ic
were synthesized by reaction of 2,2-dichloro-1-phenyl-
cyclopropane-1-carbaldehyde with N-arylhydroxyl-
amines. Nitrones readily undergo hydrolysis, and their
1H NMR spectra recorded after several hours con-
tained signals from protons of the corresponding aro-
matic amine and initial aldehyde. The steric configura-
tion of nitrones Ia–Ic was determined on the basis of
the NOESY spectrum of compound Ic which displayed
cross peaks between the 3-H proton and ortho-protons
in both aromatic rings, as well as between one ortho-
proton in the unsubstituted aromatic ring and one
proton in the cyclopropane fragment (see the structure
shown below). These findings allowed us to assign
Z-configuration at the C=N bond of nitrone Ic.
Compounds containing a cyclopropyl group attract
interest due to broad spectrum of their biologically
important properties [6, 7]. However, published data on
cycloaddition of nitrones having a cyclopropyl group
to unsaturated compounds are very limited [8, 9],
whereas nitrones containing a geminal dihalocyclo-
propane fragment have not been reported. We previ-
ously found that nitrones react with compounds pos-
sessing a strained three-membered ring (e.g., cyclo-
In the reaction of nitrones Ia–Ic with maleimides in
methylene chloride or benzene at room temperature,
Cl
H
O
N
H
Cl
H
3
H
Cl
H
H
66

DIPOLAR CYCLOADDITION OF N-ARYL-C-(2,2-DICHLORO-1-PHENYL-...
67
Scheme 1.
O
O
H
H
Ar1
O
O
O–
O
N
Ar1
N
Ar2
Ar1
Cl
N
Ar2
Cl
Cl
Ar2
+
+
N
H
H
H
Ph
H
Ph
O
O
Ph
Cl
O
Cl
Cl
Ia–Ic
IIa–IIe
IIIa–IIIo
IVa–IVo
I, Ar1 = Ph (a), 4-MeC6H4 (b), 4-ClC6H4 (c); II, Ar2 = Ph (a), 4-MeC6H4 (b), 4-MeOC6H4 (c), 4-FC6H4 (d), 3-O2NC6H4 (e); III, IV,
Ar1 = Ph (a–e), 4-MeC6H4 (f–j), 4-ClC6H4 (k–o), Ar2 = Ph (a, f, k), 4-MeC6H4 (b, g, l), 4-MeOC6H4 (c, h, m), 4-FC6H4 (d, i, n),
3-O2NC6H4 (e, j, o).
a solid separated from the reaction mixture in several
hours; it was filtered off and subjected to column
chromatography on silica gel. H NMR analysis of the
reaction mixtures revealed the presence of two com-
pounds at a ratio of ~3:1 to 4:1 (Scheme 1). The major
products were isolated as individual substances and
completely characterized, whereas the minor products
in some cases were characterized only by spectral
parameters.
reactions of other nitrones with maleimides [2–4]. The
configuration of compounds III and IV was deter-
mined by X-ray analysis. The X-ray diffraction data
were obtained for compounds IIIa and IVc (Figs. 1,
2). As follows from these data, compounds III and IV
both are characterized by trans configuration of the
pyrrolo[3,4-d]isoxazolidine skeleton, and the only dif-
1
The structure of compounds IIIa–IIIo and IVa–IVo
was determined on the basis of their elemental com-
1
positions and spectral parameters. The H NMR spec-
C3
O2
N1
C3a
tra of IIIa–IIIo contained doublet signals from protons
in the cyclopropane ring at δ 2.2 and 2.5 ppm with
a coupling constant J of 8.0 Hz, a singlet from proton
on C3 at δ 5.2 ppm, and doublets from protons at C3a
(δ 4.3–4.6 ppm) and C6a (δ 3.8–4.0 ppm, J = 7–8 Hz).
In the 13C NMR spectra of these compounds we ob-
served signals at δC 53.7 (C3a), 71.5 (C6), and 77.4 ppm
C4
N5
C6a
C6
(C6a). In the H NMR spectra of adducts IVa–IVo in
1
Fig. 1. Structure of the molecule of (3RS,3aSR,6aRS)-3-
[(RS)-2,2-dichloro-1-phenylcyclopropyl]-2,5-diphenyltetra-
hydropyrrolo[3,4-d]isoxazole-4,6-dione (IIIa) according to
the X-ray diffraction data.
CDCl3, doublet signals from protons in the cyclopro-
pane ring appeared at δ 2.10 and 2.20 ppm, and signals
from protons in the isoxazolidine ring were singlets at
1
δ 3.95 (2H) and 4.90 ppm (1H). The H NMR spectra
of the same compounds in C6D6 contained signals from
protons in the cyclopropane ring as doublets at δ 1.65
and 1.76 ppm (J = 8 Hz); protons in the isoxazolidine
ring resonated as doublets at δ 3.16 (J = 7.3 Hz) and
3.62 ppm (J = 8 Hz) and a singlet at δ 4.99 ppm (3a-H,
6a-H, and 3-H, respectively).
C6a C6
N5
C3a
O1
C4
C3
N2
The spectral parameters of compounds IIIa–IIIo
and IVa–IVo allowed us to assign them trans-orienta-
tion of 3-H with respect to 3a-H and 6a-H. Insofar as
nitrones Ia–Ic possess a chiral center at the C1 atom in
the three-membered ring, the formation of two dia-
stereoisomeric products differing by relative configu-
rations of that center and chiral C3 atom of the pyrrolo-
[3,4-d]isoxazolidine system might be expected, as in
Fig. 2. Structure of the molecule of (3RS,3aSR,6aRS)-3-
[(SR)-2,2-dichloro-1-phenylcyclopropyl]-5-(4-methoxy-
phenyl)-2-phenyltetrahydropyrrolo[3,4-d]isoxazole-4,6-
dione (IVc) according to the X-ray diffraction data.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 1 2011

MOLCHANOV et al.
68
ference is configuration of C1′ in the cyclopropane ring
with respect to the substituents on C3.
ν, cm–1: 3060, 1600, 1560, 1490, 1380, 1100, 1050.
1H NMR spectrum (acetone-d6), δ, ppm: 2.36 d (1H,
CH2, J = 8.7 Hz), 2.58 d (1H, CH2, J = 8.7 Hz), 7.27–
7.47 (6H, Harom), 7.67 m (2Harom), 7.75 m (2H, Harom),
8.06 s (1H, =CH). 13C NMR spectrum (acetone-d6), δC,
ppm: 31.5 (CH2), 38.1 (C), 65.8 (CCl2), 121.8 (CH),
128.4 (CH), 128.6 (CH), 129.4 (C), 148.3 (N–C=).
Thus the addition of nitrones Ia–Ic to substituted
maleimides IIa–IIe is cis-stereoselective, and the
imide fragment is oriented endo with respect to (Z)-ni-
trone in the transition state. Analogous stereochemistry
of adducts with trans orientation of protons in the pyr-
rolo[3,4-d]isoxazolidine ring was observed previously
in reactions of maleimides with sterically hindered
nitrones [12]. Diastereoisomeric adducts III and IV are
formed at a ratio different from equimolar. According
Compounds Ib and Ic were synthesized in a similar
way. As noted above, nitrones Ia–Ic readily undergo
hydrolysis with atmospheric moisture; therefore, they
were not isolated as analytically pure substances.
1
to the H NMR spectra of the reaction mixtures the
N-(2,2-Dichloro-1-phenylcyclopropylmethyli-
dene)-4-methylaniline N-oxide (Ib). Yield 73%.
1H NMR spectrum, δ, ppm: in acetone-d6: 2.34 d (1H,
CH2, J = 8.0 Hz), 2.37 s (3H, CH3), 2.56 d (1H, CH2,
J = 8.0 Hz), 7.26–7.47 (6H, Harom), 7.62–7.69 (3H,
ratio III:IV weakly depends on the substituent in the
aromatic ring in both nitrone Ia–Ic and maleimide IIa–
IIe. It is the same for the following couples: IIIa/IVa,
IIIe/IVe, 3.3; IIIb/IVb, 3.2; IIIc/IVc, IIIh/IVh,
IIIm/IVm, 3.7; IIId/IVd, 3.1; IIIf/IVf, IIIi/IVi,
IIIl/IVl, 4.0; IIIg/IVg, IIIj/IVj, IIIo/IVo, 3.6;
IIIk/IVk, 3.8; IIIn/IVn 3.0. Presumably, preferential
formation of diastereoisomers III is related to their
higher stability as compared to isomers IV. In fact, van
der Waals repulsion between the chlorine atoms and
N-phenyl group is inherent to the latter. Estimation of
the enthalpies of formation of diastereoisomers IIIa
and IVa in terms of the MM2 approximation showed
that the former is more stable by 1 kcal/mol; this value
is close to 0.7 kcal/mol, calculated on the basis of the
ratio of diastereoisomers IIIa and IVa in the reaction
mixture.
Harom), 8.02 s (1H, =CH); in CDCl3: 2.39 s (3H), 2.41 d
(1H, J = 8.0 Hz), 2.50 d (1H, J = 8.0 Hz), 7.17–7.44
(6H), 7.50–7.60 (3H), 7.67 s (1H). 13C NMR spectrum
(CDCl3), δC, ppm: 21.1 (CH3), 31.7 (CH2), 37.5 (C),
65.0 (C), 121.4 (CH), 128.2 (CH), 128.5 (CH), 129.5
(CH), 129.9 (CH), 133.1 (C), 135.4 (C), 140.8 (N–C=).
4-Chloro-N-(2,2-dichloro-1-phenylcyclopropyl-
methylidene)aniline N-oxide (Ic). Yield 75%.
1H NMR spectrum (CDCl3), δ, ppm: 2.40 d (1H, CH2,
J = 8.0 Hz), 2.51 d (1H, CH2, J = 8.0 Hz), 7.35–7.46 m
(5H, Harom), 7.53 m (2H, Harom), 7.62 m (2H, Harom),
7.67 s (1H, =CH). 13C NMR spectrum (CDCl3), δC,
ppm: 31.7 (CH2), 37.4 (C), 64.8 (C), 122.9 (CH), 128.4
(CH), 128.6 (CH), 129.2 (CH), 129.9 (CH), 130.7 (C),
135.0 (C), 136.4 (N–C=).
EXPERIMENTAL
The elemental compositions were determined on
a Hewlett–Packard 185-B CHN analyzer. The IR spec-
tra were measured from 2% solutions in chloroform on
Compounds IIIa–IIIo and IVa–IVo (general
procedure). Maleimide IIa–IIe, 1 mmol, was added to
a solution of 1 mmol of nitrone Ia–Ic in 20 ml of
methylene chloride (or benzene). The mixture was left
to stand for 12 h at room temperature, the solvent was
evaporated, and the residue was recrystallized from
ethanol or subjected to column chromatography on
silica gel using hexane–ethyl acetate as eluent.
1
a UR-20 spectrometer. The H and 13C NMR spectra
were recorded on a Bruker DPX-300 instrument at 300
and 75 MHz, respectively. X-Ray analysis of single
crystals of compounds IIIa and IVc was performed on
an ApexCCD diffractometer using SHELXL97 soft-
ware package. The purity of compounds was checked,
and the progress of reactions was monitored, by thin-
layer chromatography on Silufol UV-254 plates.
(3RS,3aSR,6aRS)-3-[(RS)-2,2-Dichloro-1-phenyl-
cyclopropyl]-2,5-diphenyltetrahydropyrrolo[3,4-d]-
isoxazole-4,6-dione (IIIa). Yield 166 mg (35%),
mp 195°C. IR spectrum (CHCl3), ν, cm–1: 3070,
1720 v.s, 1600, 1500 s, 1380, 1310, 1240 s, 1190.
1H NMR spectrum (DMSO-d6), δ, ppm: 2.22 d (1H,
CH2, J = 8.0 Hz), 2.48 d (1H, CH2, J = 8.0 Hz), 4.00 d
(1H, CH, J = 7.3 Hz), 4.56 d (1H, CH, J = 7.3 Hz),
5.09 s (1H, CH), 6.33 m (2H, Harom), 6.94–7.55 (12H,
N-(2,2-Dichloro-1-phenylcyclopropylmethyli-
dene)aniline N-oxide (Ia). A solution of 2.4 g
(18 mmol) of N-phenylhydroxylamine in ethanol was
added to a solution of 2.5 g (12 mmol) of 2,2-dichloro-
1-phenylcyclopropane-1-carbaldehyde in 30 ml of
ethanol, and the mixture was left to stand for 12 h at
4°C. The precipitate was filtered off and recrystallized
from ethanol. Yield 2.3 g (62%). IR spectrum (CHCl3),
H
arom), 7.78 m (1H, Harom). 13C NMR spectrum (CDCl3),
δC, ppm: 32.0 (CH2), 41.5 (C), 53.8 (CH), 64.5 (C),
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 1 2011

DIPOLAR CYCLOADDITION OF N-ARYL-C-(2,2-DICHLORO-1-PHENYL-...
69
71.6 (CH), 77.4 (CH), 113.7 (CH), 123.1 (CH), 125.9
(CH), 128.6 (CH), 128.8 (CH), 128.9 (CH), 129.6
(CH), 130.6 (CH), 136.6 (C), 148.9 (C), 172.3 (C=O),
173.7 (C=O). Found, %: C 64.95; H 4.30; N 5.81.
C26H20Cl2N2O3. Calculated, %: C 65.15; H 4.21;
N 5.84.
215 mg (42%), mp 169°C. IR spectrum (CHCl3), ν,
cm–1: 3070, 1715 v.s, 1600, 1520, 1490, 1390, 1305,
1
1270, 1030. H NMR spectrum, δ, ppm: in CDCl3:
2.11 d (1H, CH2, J = 8.0 Hz), 2.32 d (1H, CH2, J =
8.0 Hz), 3.75 s (3H, CH3), 3.88 d (1H, CH, J =
7.3 Hz), 4.37 d (1H, CH, J = 7.3 Hz), 5.21 s (1H, CH),
6.28 d (2H, Harom, J = 8.7 Hz), 6.76 d (2H, Harom, J =
9.4 Hz), 6.96–7.66 (10H, Harom); in C6D6: 1.77 d (1H,
CH2, J = 8.0 Hz), 2.11 d (1H, CH2, J = 8.0 Hz), 3.25 s
(3H, CH3), 3.29 d (1H, CH, J = 7.3 Hz), 3.95 d (1H,
(3RS,3aSR,6aRS)-3-[(SR)-2,2-Dichloro-1-phenyl-
cyclopropyl]-2,5-diphenyltetrahydropyrrolo[3,4-d]-
isoxazole-4,6-dione (IVa). 1H NMR spectrum (CDCl3),
δ, ppm: 2.06 d (1H, CH2, J = 7.3 Hz), 2.20 d (1H, CH2,
J = 7.3 Hz), 3.97 s (2H, CH), 4.89 s (1H, CH), 6.30 m
(2H, Harom), 7.04 m (1H, Harom), 7.20–7.53 (11H,
Harom), 7.87 m (1H, Harom). 13C NMR spectrum (CDCl3),
δC, ppm: 32.2 (CH2), 43.3 (C), 53.8 (CH), 64.5 (C),
71.6 (CH), 77.4 (CH), 113.7 (CH), 123.1 (CH), 125.9
(CH), 128.6 (CH), 128.8 (CH), 128.9 (CH), 129.6
(CH), 130.6 (C), 136.6 (C), 148.9 (C), 172.3 (C=O),
173.7 (C=O).
CH, J = 7.3 Hz), 5.29 s (1H, CH), 6.25 d (2H, Harom
,
J = 8.0 Hz), 7.05 m (2H, Harom), 7.15 d (2H, Harom, J =
8.0 Hz), 7.35–7.40 (4H, Harom), 7.42–7.60 (4H, Harom).
13C NMR spectrum (CDCl3), δC, ppm: 32.0 (CH2),
41.4 (C), 53.7 (CH), 55.3 (Me), 64.4 (C), 71.4 (CH),
77.4 (CH), 113.7 (CH), 114.1 (CH), 123.0 (CH), 123.2
(CH), 127.1 (CH), 128.5 (CH), 129.5 (CH), 130.6
(CH), 136.6 (C), 148.8 (C), 159.6 (C), 172.5 (C=O),
173.9 (C=O). Found, %: C 63.68; H 4.31; N 5.35.
C27H22Cl2N2O4. Calculated, %: C 63.66; H 4.35;
N 5.50.
(3RS,3aSR,6aRS)-3-[(RS)-2,2-Dichloro-1-phenyl-
cyclopropyl]-5-(4-methylphenyl)-2-phenyltetrahy-
dropyrrolo[3,4-d]isoxazole-4,6-dione (IIIb). Yield
200 mg (56%), mp 168°C. IR spectrum (CHCl3), ν,
cm–1: 3080, 1720 v.s, 1600, 1530, 1500, 1385 s, 1310,
1230. 1H NMR spectrum (CDCl3), δ, ppm: 2.12 d (1H,
CH2, J = 8.0 Hz), 2.27 s (3H, CH3), 2.32 d (1H, CH2,
J = 8.0 Hz), 3.89 d (1H, CH, J = 7.3 Hz), 4.37 d (1H,
(3RS,3aSR,6aRS)-3-[(SR)-2,2-Dichloro-1-phenyl-
cyclopropyl]-5-(4-methoxyphenyl)-2-phenyltetrahy-
dropyrrolo[3,4-d]isoxazole-4,6-dione (IVc). 1H NMR
spectrum (C6D6), δ, ppm: 1.65 d (1H, CH2, J =
8.0 Hz), 1.76 d (1H, CH2, J = 8.0 Hz), 3.16 d (1H, CH,
J = 7.3 Hz), 3.25 s (3H, CH3), 3.62 d (1H, CH, J =
7.3 Hz), 4.99 s (1H, CH), 6.63 d (2H, Harom, J =
8.0 Hz), 6.72–7.35 (9H, Harom), 7.51 d (2H, Harom, J =
8.0 Hz), 8.02 m (1H, Harom). 13C NMR spectrum
(CDCl3), δC, ppm: 32.2 (CH2), 43.3 (C), 54.0 (CH),
55.4 (Me), 65.5 (C), 73.8 (CH), 77.4 (CH), 114.2
(CH), 123.2 (CH), 127.2 (CH), 127.8 (CH), 128.0
(CH), 128.7 (CH), 129.4 (CH), 134.5 (C), 134.6 (C),
149.6 (C), 159.7 (C), 172.6 (C=O), 174.2 (C=O).
CH, J = 7.3 Hz), 5.21 s (1H, CH), 6.23 d (2H, Harom
,
J = 8.7 Hz), 6.96–7.65 (12H, Harom). 13C NMR spec-
trum (CDCl3), δC, ppm: 21.1 (CH3), 32.0 (CH2), 41.4
(C), 53.7 (CH), 64.4 (C), 71.4 (CH), 77.4 (CH), 113.7
(CH), 123.0 (CH), 125.6 (CH), 128.0 (CH), 128.6
(CH), 129.5 (CH), 129.6 (CH), 130.6 (CH), 136.6 (C),
139.0 (C), 148.8 (C), 172.3 (C=O), 173.8 (C=O).
Found, %: C 65.57; H 4.65; N 5.54. C27H22Cl2N2O3.
Calculated, %: C 65.73; H 4.49; N 5.68.
(3RS,3aSR,6aRS)-3-[(RS)-2,2-Dichloro-1-phenyl-
cyclopropyl)-5-(4-fluorophenyl)-2-phenyltetrahy-
dropyrrolo[3,4-d]isoxazole-4,6-dione (IIId). Yield
190 mg (44%), mp 204°C. IR spectrum (CHCl3), ν,
cm–1: 3080, 1720 v.s, 1600, 1515 s, 1390 s, 1245,
1200. 1H NMR spectrum (CDCl3), δ, ppm: 2.13 d (1H,
CH2, J = 8.0 Hz), 2.33 d (1H, CH2, J = 8.0 Hz), 3.94 d
(1H, CH, J = 7.3 Hz), 4.43 d (1H, CH, J = 7.3 Hz),
5.26 s (1H, CH), 6.83 d (1H, Harom, J = 8.0 Hz), 6.95–
7.65 (12H, Harom), 8.16 m (1H, Harom). 13C NMR spec-
trum (CDCl3), δC, ppm: 31.8 (CH2), 41.4 (C), 53.7
(CH), 64.4 (C), 71.5 (CH), 77.4 (CH), 113.7 (CH),
115.9 (CH, JCF = 22.8 Hz), 123.1 (CH), 126.5 (CH),
127.7 (CH), 127.9 (CH), 128.3 (CH), 129.3 (CH),
(3RS,3aSR,6aRS)-3-[(SR)-2,2-Dichloro-1-phenyl-
cyclopropyl]-5-(4-methylphenyl)-2-phenyltetrahy-
dropyrrolo[3,4-d]isoxazole-4,6-dione (IVb). 1H NMR
spectrum (CDCl3), δ, ppm: 2.10 d (1H, CH2, J =
7.3 Hz), 2.21 d (1H, CH2, J = 7.3 Hz), 2.41 s (3H,
CH3), 3.95 s (2H, CH), 4.89 s (1H, CH), 6.37 m (2H,
H
arom), 6.95–7.65 (12H, Harom). 13C NMR spectrum
(CDCl3), δC, ppm: 21.1 (Me), 32.2 (CH2), 43.3 (C),
54.1 (CH), 65.6 (C), 73.8 (CH), 77.4 (CH), 114.3
(CH), 123.2 (CH), 125.7 (CH), 126.0 (CH), 127.9
(CH), 128.6 (CH), 129.8 (CH), 134.2 (CH), 134.6 (C),
138.1 (C), 149.6 (C), 169.7 (C=O), 172.5 (C=O).
(3RS,3aSR,6aRS)-3-[(RS)-2,2-Dichloro-1-phenyl-
cyclopropyl]-5-(4-methoxyphenyl)-2-phenyltetra-
hydropyrrolo[3,4-d]isoxazole-4,6-dione (IIIc). Yield
130.5 (CH), 136.5 (C), 148.8 (C), 162.5 (C, JCF
=
248 Hz), 172.1 (C=O), 173.6 (C=O). Found, %:
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MOLCHANOV et al.
70
C 62.68; H 3.85; N 5.75. C26H19Cl2FN2O3. Calculated,
%: C 62.79; H 3.85; N 5.63.
(CH3), 31.9 (CH2), 41.4 (C), 53.8 (CH), 64.5 (C), 71.4
(CH), 77.4 (CH), 114.0 (CH), 121.0 (CH), 128.6 (CH),
128.8 (CH), 128.9 (CH), 130.0 (CH), 130.6 (CH),
132.8 (C), 136.7 (C), 146.5 (C), 172.4 (C=O), 173.8
(C=O). Found, %: C 65.44; H 4.31; N 5.80.
C27H22Cl2N2O3. Calculated, %: C 65.73; H 4.49;
N 5.68.
(3RS,3aSR,6aRS)-3-[(SR)-2,2-Dichloro-1-phenyl-
cyclopropyl)-5-(4-fluorophenyl)-2-phenyltetrahydro-
1
pyrrolo[3,4-d]isoxazole-4,6-dione (IVd). H NMR
spectrum (C6D6), δ, ppm: 1.64 d (1H, CH2, J =
8.0 Hz), 1.72 d (1H, CH2, J = 8.0 Hz), 3.11 d (1H, CH,
J = 7.5 Hz), 3.57 d (1H, CH, J = 7.5 Hz), 4.95 s (1H,
CH), 6.50 m (2H, Harom), 6.67–7.05 m (6H, Harom),
7.10–7.20 m (4H, Harom), 7.45 m (2H, Harom). 13C NMR
spectrum (CDCl3), δC, ppm: 32.2 (CH2), 43.2 (C), 54.0
(CH), 65.5 (C), 73.9 (CH), 77.4 (CH), 114.3 (CH),
116.0 (CH, JCF = 22.8 Hz), 123.2 (CH), 127.8 (CH),
128.0 (CH), 128.7 (CH), 129.5 (CH), 134.2 (CH),
134.5 (C), 149.5 (C), 162.3 (C, JCF = 248 Hz), 172.3
(C=O), 174.0 (C=O).
(3RS,3aSR,6aRS)-3-[(SR)-2,2-Dichloro-1-phenyl-
cyclopropyl]-2-(4-methylphenyl)-5-phenyltetrahy-
1
dropyrrolo[3,4-d]isoxazole-4,6-dione (IVf). H NMR
spectrum (CDCl3), δ, ppm: 2.05 d (1H, CH2, J =
7.6 Hz), 2.18 d (1H, CH2, J = 7.8 Hz), 2.26 s (3H,
CH3), 3.93 s (2H, CH), 4.84 s (1H, CH), 6.29 m (2H,
H
arom), 6.99–7.18 (4H, Harom), 7.20–7.31 (4H, Harom),
7.34–7.47 (3H, Harom), 7.86 m (1H, Harom). 13C NMR
spectrum (CDCl3), δC, ppm: 20.3 (CH3), 32.3 (CH2),
43.2 (C), 54.1 (CH), 65.5 (C), 74.0 (CH), 77.4 (CH),
114.5 (CH), 126.0 (CH), 127.8 (CH), 128.0 (CH),
128.7 (CH), 129.0 (CH), 130.7 (CH), 134.6 (C), 134.7
(C), 147.2 (C), 172.5 (C=O), 174.1 (C=O).
(3RS,3aSR,6aRS)-3-[(RS)-2,2-Dichloro-1-phenyl-
cyclopropyl]-5-(3-nitrophenyl)-2-phenyltetrahydro-
pyrrolo[3,4-d]isoxazole-4,6-dione (IIIe). Yield
210 mg (40%), mp 179°C. IR spectrum (CHCl3), ν,
cm–1: 3070, 1720 v.s, 1595, 1530, 1500, 1380, 1360,
(3RS,3aSR,6aRS)-3-[(RS)-2,2-Dichloro-1-phenyl-
cyclopropyl]-2,5-bis(4-methylphenyl)tetrahydropyr-
rolo[3,4-d]isoxazole-4,6-dione (IIIg). Yield 248 mg
1
1240, 1200. H NMR spectrum (CDCl3), δ, ppm:
2.13 d (1H, CH2, J = 8.0 Hz), 2.33 d (1H, CH2, J =
8.0 Hz), 3.94 d (1H, CH, J = 7.3 Hz), 4.43 d (1H, CH,
J = 7.3 Hz), 5.26 s (1H, CH), 6.83 d (1H, Harom, J =
8.0 Hz), 6.95–7.65 (12H, Harom), 8.16 m (1H, Harom).
13C NMR spectrum (CDCl3), δC, ppm: 31.9 (CH2),
41.2 (C), 53.8 (CH), 64.4 (C), 71.6 (CH), 77.4 (CH),
113.7 (CH), 121.3 (CH), 123.7 (CH), 128.4 (CH),
128.7 (CH), 129.3 (CH), 129.7 (CH), 130.5 (CH),
131.5 (CH), 131.9 (CH), 136.5 (C), 148.2 (C), 148.5
(C), 171.6 (C=O), 173.2 (C=O). Found, %: C 59.91;
H 3.60; N 8.07. C26H19Cl2N3O5. Calculated, %:
C 59.56; H 3.65; N 8.01.
1
(48%), mp 180°C. H NMR spectrum (CDCl3), δ,
ppm: 2.10 d (1H, CH2, J = 7.6 Hz), 2.28 s (3H, CH3),
2.30 s (3H, CH3), 2.33 d (1H, CH2, J = 7.6 Hz), 3.85 d
(1H, CH, J = 7.3 Hz), 4.41 d (1H, CH, J = 7.3 Hz),
5.20 s (1H, CH), 6.22 m (2H, Harom), 6.97–7.11 (6H,
Harom), 7.32–7.7 (5H, Harom). 13C NMR spectrum
(CDCl3), δC, ppm: 20.3 (CH3), 21.2 (CH3), 31.8 (CH2),
41.4 (C), 53.8 (CH), 64.5 (C), 71.3 (CH), 77.4 (CH),
114.0 (CH), 125.7 (CH), 128.1 (CH), 128.5 (CH),
129.4 (CH), 130.0 (CH), 130.5 (CH), 132.7 (C), 136.7
(C), 139.0 (C), 146.5 (C), 172.5 (C=O), 173.9 (C=O).
Found, %: C 65.94; H 4.60; N 5.85. C28H24Cl2N2O3.
Calculated, %: C 66.28; H 4.77; N 5.52.
(3RS,3aSR,6aRS)-3-[(SR)-2,2-Dichloro-1-phenyl-
cyclopropyl]-5-(3-nitrophenyl)-2-phenyltetrahydro-
1
pyrrolo[3,4-d]isoxazole-4,6-dione (IVe). H NMR
(3RS,3aSR,6aRS)-3-[(SR)-2,2-Dichloro-1-phenyl-
spectrum (CDCl3), δ, ppm (in a mixture with com-
pound IIIe): 2.08 d (1H, CH2, J = 8.0 Hz), 2.22 d (1H,
CH2, J = 8.0 Hz), 4.01 m (2H, CH), 4.92 s (1H, CH).
cyclopropyl]-2,5-bis(4-methylphenyl)tetrahydro-
pyrrolo[3,4-d]isoxazole-4,6-dione (IVg). H NMR
1
spectrum (CDCl3), δ, ppm: 2.02 d (1H, CH2, J =
7.3 Hz), 2.20 d (1H, CH2, J = 7.3 Hz), 2.28 s (3H,
CH3), 2.30 s (3H, CH3), 3.93 s (2H, CH), 4.85 s (1H,
CH), 6.19 m (2H, Harom), 7.03–7.22 (7H, Harom), 7.31–
7.50 (3H, Harom), 7.90 m (1H, Harom). 13C NMR spec-
trum (CDCl3), δC, ppm: 20.4 (CH3), 21.2 (CH3), 32.3
(CH2), 43.2 (C), 54.1 (CH), 65.5 (C), 77.1 (CH), 114.5
(CH), 125.8 (CH), 127.8 (CH), 128.0 (CH), 128.6
(CH), 129.5 (CH), 129.9 (CH), 132.8 (C), 134.5
(CH), 134.7 (C), 139.1 (C), 147.2 (C), 172.6 (C=O),
174.2 (C=O).
(3RS,3aSR,6aRS)-3-[(RS)-2,2-Dichloro-1-phenyl-
cyclopropyl]-2-(4-methylphenyl)-5-phenyltetrahy-
dropyrrolo[3,4-d]isoxazole-4,6-dione (IIIf). Yield
213 mg (43%), mp 161°C. 1H NMR spectrum (CDCl3),
δ, ppm: 2.11 d (1H, CH2, J = 7.8 Hz), 2.27 s (3H,
CH3), 2.33 d (1H, CH2, J = 7.8 Hz), 3.88 d (1H, CH,
J = 7.4 Hz), 4.38 d (1H, CH, J = 7.4 Hz), 5.20 s (1H,
CH), 6.35 m (2H, Harom), 7.00–7.10 (4H, Harom), 7.20–
7.30 (3H, Harom), 7.33–7.54 (4H, Harom), 7.62 m (1H,
H
arom). 13C NMR spectrum (CDCl3), δC, ppm: 20.3
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 1 2011

DIPOLAR CYCLOADDITION OF N-ARYL-C-(2,2-DICHLORO-1-PHENYL-...
71
(3RS,3aSR,6aRS)-3-[(RS)-2,2-Dichloro-1-phenyl-
cyclopropyl]-5-(4-methoxyphenyl)-2-(4-methyl-
phenyl)tetrahydropyrrolo[3,4-d]isoxazole-4,6-dione
(IIIh). Yield 230 mg (44%), mp 191°C. 1H NMR spec-
trum (CDCl3), δ, ppm: 2.10 d (1H, CH2, J = 8.0 Hz),
2.30 s (3H, CH3), 2.33 d (1H, CH2, J = 8.0 Hz), 3.76 s
(3H, CH3), 3.84 d (1H, CH, J = 7.3 Hz), 4.37 d (1H,
CH, J = 7.3 Hz), 5.19 s (1H, CH), 6.25 m (2H, Harom),
6.75 m (2H, Harom), 6.97–7.08 (4H, Harom), 7.37–7.62
(5H, Harom). 13C NMR spectrum (CDCl3), δC, ppm:
20.4 (CH3), 31.8 (CH2), 41.4 (C), 53.7 (CH), 55.4
(CH3), 64.5 (C), 71.3 (CH), 77.4 (CH), 114.0 (CH),
114.1 (CH), 123.3 (CH), 125.7 (CH), 128.3 (CH),
128.5 (CH), 129.2 (CH), 132.7 (C), 136.7 (C), 146.5
(C), 159.6 (C), 172.6 (C=O), 174.0 (C=O). Found, %:
C 64.61; H 4.82; N 5.41. C28H24Cl2N2O4. Calculated,
%: C 64.25; H 4.62; N 5.35.
(CH), 132.9 (C), 134.2 (CH), 147.2 (C), 162.2 d (C,
JCF = 250 Hz), 169.4 (C=O), 174.1 (C=O).
(3RS,3aSR,6aRS)-3-[(RS)-2,2-Dichloro-1-phenyl-
cyclopropyl]-2-(4-methylphenyl)-5-(3-nitrophenyl)-
tetrahydropyrrolo[3,4-d]isoxazole-4,6-dione (IIIj).
1
Yield 285 mg (53%), mp 173°C. H NMR spectrum
(CDCl3), δ, ppm: 2.11 d (1H, CH2, J = 7.8 Hz), 2.22 s
(3H, CH3), 2.33 d (1H, CH2, J = 7.8 Hz), 3.90 d (1H,
CH, J = 7.6 Hz), 4.41 d (1H, CH, J = 7.6 Hz), 5.23 s
(1H, CH), 6.89 d (1H, Harom, J = 8.0 Hz), 6.99–7.10
(4H, Harom), 7.24 s (1H, Harom), 7.32–7.54 (5H, Harom),
7.62 m (1H, Harom), 7.80 d (1H, Harom, J = 8.0 Hz).
13C NMR spectrum (CDCl3), δC, ppm: 20.4 (CH3),
31.8 (CH2), 41.3 (C), 53.9 (CH), 64.4 (C), 71.5 (CH),
77.3 (CH), 113.9 (CH), 121.3 (CH), 123.7 (CH), 128.7
(CH), 129.3 (CH), 129.6 (CH), 130.1 (CH), 133.5
(CH), 136.6 (C), 146.2 (C), 148.2 (C), 171.7 (C=O),
173.3 (C=O). Found, %: C 60.62; H 3.78; N 7.70.
C27H21Cl2N3O5. Calculated, %: C 60.24; H 3.93;
N 7.80.
(3RS,3aSR,6aRS)-3-[(SR)-2,2-Dichloro-1-phenyl-
cyclopropyl]-5-(4-methoxyphenyl)-2-(4-methyl-
phenyl)tetrahydropyrrolo[3,4-d]isoxazole-4,6-dione
1
(IVh). H NMR spectrum (CDCl3), δ, ppm (in a mix-
(3RS,3aSR,6aRS)-3-[(SR)-2,2-Dichloro-1-phenyl-
cyclopropyl]-2-(4-methylphenyl)-5-(3-nitrophenyl)-
tetrahydropyrrolo[3,4-d]isoxazole-4,6-dione (IVj).
1H NMR spectrum (CDCl3), δ, ppm: 2.08 d (1H, CH2,
J = 7.3 Hz), 2.21 d (1H, CH2, J = 7.3 Hz), 2.23 s (3H,
CH3), 3.97 d (1H, CH, J = 7.3 Hz), 4.00 d (1H, CH,
J = 7.8 Hz), 4.90 s (1H, CH), 6.84 d (1H, Harom, J =
7.8 Hz), 7.07–7.18 (4H, Harom), 7.18–7.26 (2H, Harom),
7.30–7.51 (4H, Harom), 7.90 m (1H, Harom), 8.25 m (1H,
ture with compound IIIh): 3.93 s (2H, CH), 4.84 s
(1H, CH).
(3RS,3aSR,6aRS)-3-[(RS)-2,2-Dichloro-1-phenyl-
cyclopropyl]-5-(4-fluorophenyl)-2-(4-methylphenyl)-
tetrahydropyrrolo[3,4-d]isoxazole-4,6-dione (IIIi).
1
Yield 220 mg (44%), mp 190°C. H NMR spectrum
(CDCl3), δ, ppm: 2.11 d (1H, CH2, J = 8.0 Hz), 2.27 s
(3H, CH3), 2.32 d (1H, CH2, J = 8.0 Hz), 3.86 d (1H,
CH, J = 7.3 Hz), 4.38 d (1H, CH, J = 7.3 Hz), 5.20 s
(1H, CH), 6.38 m (2H, Harom), 6.90–7.08 (6H, Harom),
7.33–7.55 (4H, Harom), 7.62 m (1H, Harom). 13C NMR
spectrum (CDCl3), δC, ppm: 20.3 (CH3), 31.8 (CH2),
41.3 (C), 53.7 (CH), 64.5 (C), 71.4 (CH), 77.3 (CH),
114.0 (CH), 116.2 d (CH, JCF = 23 Hz), 126.6 (CH),
127.9 (CH), 128.6 (CH), 130.0 (CH), 130.5 (CH),
H
arom). 13C NMR spectrum (CDCl3), δC, ppm: 20.3
(CH3), 32.4 (CH2), 43.1 (C), 54.1 (CH), 65.1 (C), 77.1
(CH), 114.4 (CH), 121.4 (CH), 123.7 (CH), 128.1
(CH), 128.8 (CH), 129.6 (CH), 130.1 (CH), 132.0 (C),
133.6 (C), 134.6 (CH), 147.0 (C), 171.8 (C=O), 173.6
(C=O).
(3RS,3aSR,6aRS)-2-(4-Chlorophenyl)-3-[(RS)-
2,2-dichloro-1-phenylcyclopropyl]-5-phenyltetrahy-
dropyrrolo[3,4-d]isoxazole-4,6-dione (IIIk). Yield
205 mg (40%), mp 181°C. 1H NMR spectrum (CDCl3),
δ, ppm: 2.12 d (1H, CH2, J = 7.8 Hz), 2.32 d (1H, CH2,
J = 7.8 Hz), 3.89 d (1H, CH, J = 7.3 Hz), 4.42 d (1H,
CH, J = 7.3 Hz), 5.17 s (1H, CH), 6.39 m (2H, Harom),
7.06 d (2H, Harom, J = 8.9 Hz), 7.22 d (2H, Harom, J =
8.9 Hz), 7.25–7.66 (8H, Harom). 13C NMR spectrum
(CDCl3), δC, ppm: 31.7 (CH2), 41.2 (C), 53.7 (CH),
64.3 (C), 71.5 (CH), 77.4 (CH), 115.2 (CH), 125.6
(CH), 128.4 (CH), 128.7 (CH), 129.0 (CH), 129.4
(CH), 130.5 (C), 136.4 (C), 147.4 (C), 172.0 (C=O),
173.5 (C=O). Found, %: C 60.78; H 3.69; N 5.46.
C26H19Cl3N2O3. Calculated, %: C 60.78; N 3.73;
N 5.45.
132.8 (C), 136.6 (C), 146.5 (C), 162.2 d (C, JCF
=
250 Hz), 172.3 (C=O), 173.8 (C=O). Found, %:
C 63.82; H 4.48; N 5.76. C27H21Cl2FN2O3. Calculated,
%: C 63.42; H 4.14; N 5.48.
(3RS,3aSR,6aRS)-3-[(SR)-2,2-Dichloro-1-phenyl-
cyclopropyl]-5-(4-fluorophenyl)-2-(4-methylphenyl)-
tetrahydropyrrolo[3,4-d]isoxazole-4,6-dione (IVi).
1H NMR spectrum (CDCl3), δ, ppm: 2.06 d (1H, CH2,
J = 8.0 Hz), 2.20 d (1H, CH2, J = 8.0 Hz), 2.27 s (3H,
CH3), 3.94 s (2H, CH), 4.85 s (1H, CH), 6.30 m (2H,
Harom), 6.90–7.12 (6H, Harom), 7.30–7.50 (4H, Harom),
7.87 m (1H, Harom). 13C NMR spectrum (CDCl3), δC,
ppm: 20.3 (CH3), 32.3 (CH2), 43.2 (C), 54.0 (CH),
65.5 (C), 76.9 (CH), 114.5 (CH), 116.0 d (CH, JCF
20 Hz), 127.9 (CH), 128.0 (CH), 128.7 (CH), 129.9
=
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 1 2011

MOLCHANOV et al.
(3RS,3aSR,6aRS)-2-(4-Chlorophenyl)-3-[(SR)-
72
C27H21Cl3N2O3. Calculated, %: C 61.44; H 4.01;
N 5.31.
(3RS,3aSR,6aRS)-2-(4-Chlorophenyl)-3-[(RS)-
2,2-dichloro-1-phenylcyclopropyl]-5-phenyltetrahy-
dropyrrolo[3,4-d]isoxazole-4,6-dione (IVk). Yield
46 mg (9%), mp 194°C. 1H NMR spectrum, δ, ppm: in
CDCl3: 2.08 d (1H, CH2, J = 7.6 Hz), 2.21 d (1H, CH2,
J = 7.6 Hz), 3.97 s (2H, CH), 4.82 s (1H, CH), 6.38 m
(2H, Harom), 7.12–7.52 (11H, Harom), 7.37 m (1H,
2,2-dichloro-1-phenylcyclopropyl]-5-(4-methoxy-
phenyl)tetrahydropyrrolo[3,4-d]isoxazole-4,6-dione
1
(IIIm). Yield 206 mg (38%), mp 194°C. H NMR
spectrum (CDCl3), δ, ppm: 2.11 d (1H, CH2, J =
7.3 Hz), 2.31 d (1H, CH2, J = 7.3 Hz), 3.77 s (3H,
CH3), 3.85 d (1H, CH, J = 7.3 Hz), 4.41 d (1H, CH,
J = 7.3 Hz), 5.16 s (1H, CH), 6.31 d (2H, Harom, J =
8.7 Hz), 6.80 d (2H, Harom, J = 8.7 Hz), 7.05 d (2H,
H
arom); in C6D6: 1.61 d (1H, CH2, J = 7.3 Hz), 1.69 d
(1H, CH2, J = 7.3 Hz), 3.05 d (1H, CH, J = 7.3 Hz),
3.51 d (1H, CH, J = 7.3 Hz), 4.31 s (1H, CH), 6.71 m
(2H, Harom), 6.83 m (2H, Harom), 7.92 d (1H, Harom) (the
other signals were overlapped by those of residual pro-
tons in the solvent). 13C NMR spectrum (CDCl3), δC,
ppm: 32.3 (CH2), 43.2 (C), 54.1 (CH), 65.5 (C), 74.0
(CH), 77.4 (CH), 114.5 (CH), 126.0 (CH), 127.8 (CH),
128.0 (CH), 128.7 (CH), 129.0 (CH), 130.7 (CH),
134.6 (C), 134.7 (C), 147.2 (C), 172.5 (C=O), 174.1
(C=O). Found, %: C 60.67; H 3.78; N 5.55.
C26H19Cl3N2O3. Calculated, %: C 60.78; H 3.73;
N 5.45.
Harom, J = 8.7 Hz), 7.22 d (2H, Harom, J = 8.7 Hz),
7.27–7.65 (5H, Harom). 13C NMR spectrum (CDCl3),
δC, ppm: 31.7 (CH2), 41.1 (C), 53.6 (CH), 55.4 (CH3),
64.3 (C), 71.5 (CH), 77.3 (CH), 114.3 (CH), 115.2
(CH), 126.8 (CH), 128.3 (CH), 128.7 (CH), 129.4
(CH), 136.4 (C), 147.4 (C), 159.7 (C), 172.3 (C=O),
173.8 (C=O). Found, %: C 59.52; H 3.89; N 5.03.
C27H21Cl3N2O4. Calculated, %: C 59.63; H 3.89;
N 5.15.
(3RS,3aSR,6aRS)-2-(4-Chlorophenyl)-3-[(RS)-
2,2-dichloro-1-phenylcyclopropyl]-5-(4-methyl-
phenyl)tetrahydropyrrolo[3,4-d]isoxazole-4,6-dione
(IIIl). Yield 210 mg (40%), mp 183°C. 1H NMR spec-
trum (CDCl3), δ, ppm: 2.12 d (1H, CH2, J = 7.3 Hz),
2.30 d (1H, CH2, J = 7.3 Hz), 2.32 s (3H, CH3), 3.85 d
(1H, CH, J = 8.0 Hz), 4.42 d (1H, CH, J = 8.0 Hz),
(3RS,3aSR,6aRS)-2-(4-Chlorophenyl)-3-[(SR)-
2,2-dichloro-1-phenylcyclopropyl]-5-(4-methoxy-
phenyl)tetrahydropyrrolo[3,4-d]isoxazole-4,6-dione
(IVm). Yield 54 mg (10%), mp 202°C. 1H NMR spec-
trum (CDCl3), δ, ppm: 2.16 d (1H, CH2, J = 7.3 Hz),
2.34 d (1H, CH2, J = 7.3 Hz), 3.80 s (3H, CH3), 3.92 s
(2H, CH), 5.20 s (1H, CH), 6.35 d (2H, Harom, J =
8.7 Hz), 6.81 d (2H, Harom, J = 8.7 Hz), 7.12 d (2H,
5.16 s (1H, CH), 6.26 m (2H, Harom), 7.05 d (2H, Harom
,
J = 8.7 Hz), 7.10 m (2H, Harom), 7.22 d (2H, Harom, J =
8.7 Hz), 7.25–7.63 (5H, Harom). 13C NMR spectrum
(CDCl3), δC, ppm: 21.2 (CH3), 32.3 (CH2), 43.5 (C),
54.3 (CH), 65.8 (C), 74.4 (CH), 77.5 (CH), 116.1
(CH), 125.6 (CH), 128.2 (CH), 128.3 (CH), 129.1
(CH), 129.4 (CH), 130.1 (C), 134.6 (C), 148.4 (C),
172.3 (C=O), 174.4 (C=O). Found, %: C 61.37;
H 4.01; N 5.25. C27H21Cl3N2O3. Calculated, %:
C 61.44; H 4.01; N 5.31.
H
arom, J = 8.7 Hz), 7.24 d (2H, Harom, J = 8.7 Hz),
7.24–7.68 (5H, Harom). 13C NMR spectrum (CDCl3),
δC, ppm: 31.7 (CH2), 41.0 (C), 53.6 (CH), 55.7 (CH3),
64.4 (C), 71.8 (CH), 77.7 (CH), 114.2 (CH), 115.5
(CH), 123.0 (CH), 126.8 (CH), 128.8 (CH), 129.1
(CH), 130.0 (CH), 130.8 (CH), 136.7 (C), 147.4 (C),
150.1 (C), 171.9 (C=O), 174.3 (C=O). Found, %:
C 59.54; H 3.99; N 5.06. C27H21Cl3N2O4. Calculated,
%: C 59.63; H 3.89; N 5.15.
(3RS,3aSR,6aRS)-2-(4-Chlorophenyl)-3-[(SR)-
2,2-dichloro-1-phenylcyclopropyl]-5-(4-methyl-
phenyl)tetrahydropyrrolo[3,4-d]isoxazole-4,6-dione
(3RS,3aSR,6aRS)-2-(4-Chlorophenyl)-3-[(RS)-
2,2-dichloro-1-phenylcyclopropyl]-5-(4-fluorophen-
yl)tetrahydropyrrolo[3,4-d]isoxazole-4,6-dione
(IIIn). Yield 282 mg (53%), mp 185°C. 1H NMR spec-
trum (CDCl3), δ, ppm: 2.10 d (1H, CH2, J = 7.3 Hz),
2.29 d (1H, CH2, J = 7.3 Hz), 3.85 d (1H, CH, J =
7.3 Hz), 4.40 d (1H, CH, J = 7.3 Hz), 5.15 s (1H, CH),
6.36 m (2H, Harom), 6.93–7.64 (11H, Harom). Found, %:
C 58.50; H 3.41; N 5.12. C26H18Cl3FN2O3. Calculated,
%: C 58.72; H 3.41; N 5.27.
1
(IVl). Yield 52 mg (10%), mp 192°C. H NMR spec-
trum (CDCl3), δ, ppm: 2.07 d (1H, CH2, J = 7.3 Hz),
2.20 d (1H, CH2, J = 7.3 Hz), 2.32 s (3H, CH3), 3.95 s
(2H, CH), 4.80 s (1H, CH), 6.24 d (2H, Harom, J =
8.0 Hz), 7.11 d (2H, Harom, J = 8.0 Hz), 7.12–7.54 (8H,
Harom), 7.87 m (1H, Harom). 13C NMR spectrum (CDCl3),
δC, ppm: 21.1 (CH3), 31.2 (CH2), 43.2 (C), 54.0 (CH),
65.4 (C), 74.1 (CH), 77.1 (CH), 115.8 (CH), 125.4
(CH), 127.9 (CH), 129.3 (CH), 129.8 (CH), 134.4 (C),
139.3 (C), 147.2 (C), 148.4 (C), 172.3 (C=O), 173.9
(C=O). Found, %: C 61.33; H 4.02; N 5.28.
(3RS,3aSR,6aRS)-2-(4-Chlorophenyl)-3-[(SR)-
2,2-dichloro-1-phenylcyclopropyl]-5-(4-fluorophen-
yl)tetrahydropyrrolo[3,4-d]isoxazole-4,6-dione
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DIPOLAR CYCLOADDITION OF N-ARYL-C-(2,2-DICHLORO-1-PHENYL-...
73
lengths, Å: O1–N2 1.4460(12), N2–C3a 1.4724(14),
O1–C6a 1.4483(13), N5–C4 1.3910(15), N5–C6
1.4011(15); angles, deg: N2O1C6a 107.44(8), O1N2C3
103.972(8), C4N5C6 112.79(9).
1
(IVn). Yield 70 mg (13%), mp 196°C. H NMR spec-
trum (CDCl3), δ, ppm: 2.06 d (1H, CH2, J = 7.2 Hz),
2.19 d (1H, CH2, J = 7.2 Hz), 3.94 s (2H, CH), 4.79 s
(1H, CH), 6.33 m (2H, Harom), 6.92–7.52 (10H, Harom),
7.83 m (1H, Harom). Found, %: C 58.64; H 3.42;
N 5.21. C26H18Cl3FN2O3. Calculated, %: C 58.72;
H 3.41; N 5.27.
X-Ray diffraction data for compound IVc.
Monoclinic crystal system; C27H22Cl2N2O4; M 509.37;
space group C2/c; unit cell parameters: a = 28.679(4),
b = 6.8631(10), c = 25.398(4) Å; β = 107.699(3)°; V =
4762.4(12) Å3; Z = 8; dcalc = 1.421 g/cm3; Rall = 0.071;
MoKa irradiation, λ = 0.71073 Å, graphite monochro-
mator. Selected bond lengths, Å: O1–N2 1.451(2),
N2–C3 1.468(2), O1–C6a 1.454(2), N5–C4 1.393(2),
N5–C6 1.400(2); angles, deg: N2O1C6a 108.75(13),
O1N2C3 104.19(14), C4N5C6 112.38(16).
(3RS,3aSR,6aRS)-2-(4-Chlorophenyl)-3-[(RS)-
2,2-dichloro-1-phenylcyclopropyl]-5-(3-nitrophenyl)-
tetrahydropyrrolo[3,4-d]isoxazole-4,6-dione (IIIo).
1
Yield 200 mg (36%), mp 196°C. H NMR spectrum
(CDCl3), δ, ppm: 2.13 d (1H, CH2, J = 8.0 Hz), 2.32 d
(1H, CH2, J = 8.0 Hz), 3.92 d (1H, CH, J = 7.3 Hz),
4.47 d (1H, CH, J = 7.3 Hz), 5.21 s (1H, CH), 6.79 m
(1H, Harom), 7.06 d (2H, Harom, J = 8.9 Hz), 7.23 d (2H,
Harom, J = 8.9 Hz), 7.27–7.66 (7H, Harom), 8.18 m (1H,
Harom). 13C NMR spectrum (CDCl3), δC, ppm: 31.7
(CH2), 41.0 (C), 53.7 (CH), 64.2 (C), 71.6 (CH), 77.3
(CH), 115.2 (CH), 121.0 (CH), 123.7 (CH), 128.5
(CH), 128.8 (CH), 129.8 (CH), 130.3 (C), 130.5 (CH),
131.4 (CH), 136.3 (C), 147.1 (C), 148.2 (C), 171.3
(C=O), 173.0 (C=O). Found, %: C 55.89; H 3.25;
N 7.52. C26H18Cl3N3O5. Calculated, %: C 55.88;
H 3.25; N 7.52.
The complete sets of crystallographic parameters of
compounds IIIa and IVc were deposited to the Cam-
bridge Crystallographic Data Centre (entry nos. CCDC
718 571 and CCDC 718572, respectively) and are
available at http://www.ccdc.cam.ac.uk/deposit.
REFERENCES
1. Jones, R.C.F. and Martin, J.N., Synthetic Applications of
1,3-Dipolar Cycloaddition Chemistry toward Hetero-
cycles and Natural Products, Padwa, A. and
Pearson, W.H., Eds., New York: Wiley, 2002, p. 1.
2. Iwakura, Y., Uno, K., Hong, S-J., and Hongu, T., Bull.
Chem. Soc. Jpn., 1972, vol. 45, p. 192.
(3RS,3aSR,6aRS)-2-(4-Chlorophenyl)-3-[(SR)-
2,2-dichloro-1-phenylcyclopropyl]-5-(3-nitrophenyl)-
tetrahydropyrrolo[3,4-d]isoxazole-4,6-dione (IVo).
1
Yield 56 mg (10%), mp 208°C. H NMR spectrum
3. Coşkun, N. and Öztürk, A., Tetrahedron, 2007, vol. 63,
p. 1402.
(CDCl3), δ, ppm: 2.20 d (1H, CH2, J = 8.0 Hz), 2.32 d
(1H, CH2, J = 8.0 Hz), 4.06 s (2H, CH), 5.21 s (1H,
CH), 6.79 m (1H, Harom), 7.06 d (2H, Harom, J =
9.0 Hz), 7.22 d (2H, Harom, J = 9.0 Hz), 7.30–7.65 (7H,
Harom), 8.19 m (1H, Harom). 13C NMR spectrum (CDCl3),
δC, ppm: 31.7 (CH2), 41.0 (C), 53.7 (CH), 64.2 (C),
71.5 (CH), 77.3 (CH), 115.2 (CH), 120.9 (CH), 123.7
(CH), 128.5 (CH), 128.8 (CH), 129.4 (CH), 129.8
(CH), 130.3 (C), 131.4 (CH), 136.3 (C), 140.0 (C),
147.2 (C), 148.2 (C), 171.3 (C=O), 173.0 (C=O).
Found, %: C 55.89; H 3.25; N 7.52. C26H18Cl3N3O5.
Calculated, %: C 55.88; H 3.25; N 7.52.
4. Fišera, L., Al-Timari, U.A.R., Ertl, P., and Pronayo-
va, N., Monatsh. Chem., 1993, vol. 124, p. 1019.
5. Coşkun, N., Mert, H., and Arikan, N., Tetrahedron,
2006, vol. 62, p. 1351.
6. Salaün, J. and Baird, M.S., Curr. Med. Chem., 1995,
vol. 2, p. 511.
7. Brackmann, F. and de Meijere, A., Chem. Rev., 2007,
vol. 107, p. 4493.
8. Caddick, S. and Bush, H., Org. Lett., 2003, vol. 5,
p. 2489.
9. Karlsson, E. and Hadberg, H.-E., Eur. J. Org. Chem.,
2003, p. 2782.
X-Ray diffraction data for compound IIIa.
Monoclinic crystal system; C26H20Cl2N2O3; M 479.34;
space group P21/n; unit cell parameters: a =
12.7788(6), b = 7.8648(4), c = 22.2761(10) Å; β =
10. Diev, V.V., Stetsenko, O.N., Tung, T.Q., Kopf, J., Kos-
tikov, R.R., and Molchanov, A.P., J. Org. Chem., 2008,
vol. 73, p. 2396.
11. Diev, V.V., Tung, T.Q., and Molchanov, A.P., Eur. J.
Org. Chem., 2009, p. 525.
91.3750(10)°; V = 2238.16(18) Å3; Z = 4; dcalc
=
1.423 g/cm3; Rall = 0.034; MoKa irradiation, λ =
12. Dondas, H.A., Grigg, R., and Thibault, S., Tetrahedron,
0.71073 Å, graphite monochromator. Selected bond
2001, vol. 57, p. 7035.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 1 2011