Synthesis of 2′,3′,4′-triaryl-5,6-dihydro-8H-spiro[indolizine-7,5′-isoxazolidin]-8-ones via 1,3-dipolar cycloaddition reaction involving (Z)-C-aryl-N-phenylnitrones

Article abstract of DOI:10.1007/s10593-020-02774-6

[Figure not available: see fulltext.] The 1,3-dipolar cycloaddition of C-aryl-N-phenylnitrones to 7-arylmethylidene-6,7-dihydroindolizin-8(5H)-ones afforded novel 2′,3′,4′-triaryl-5,6-dihydro-8H-spiro[indolizine-7,5′-isoxazolidin]-8-ones in moderate yield

Full text of DOI:10.1007/s10593-020-02774-6

DOI 10.1007/s10593-020-02774-6
Chemistry of Heterocyclic Compounds 2020, 56(8), 1062–1066
Synthesis of 2',3',4'-triaryl-5,6-dihydro-8H-spiro[indolizine-
7,5'-isoxazolidin]-8-ones via 1,3-dipolar cycloaddition reaction
involving (Z)-C-aryl-N-phenylnitrones
Youfeng Li1*, Jin Tang2, Xiaofang Li2
1 School of Chemistry and Chemical Engineering, Zunyi Normal University,
Zunyi Pingan Road, Zunyi 563006, China; e-mail: 490742310@qq.com
2 Key Laboratory of Theoretical Organic Chemistry and Functional Molecules,
Ministry of Education, School of Chemistry and Chemical Engineering,
Hunan University of Science and Technology,
Xiangtan Taoyuan Road, Hunan 411201, China; e-mail: 850469131@qq.com
Submitted January 27, 2020
Accepted after revision June 22, 2020
Published in Khimiya Geterotsiklicheskikh Soedinenii,
2020, 56(8), 1062–1066
The 1,3-dipolar cycloaddition of C-aryl-N-phenylnitrones to 7-arylmethylidene-6,7-dihydroindolizin-8(5H)-ones afforded novel 2',3',4'-
triaryl-5,6-dihydro-8H-spiro[indolizine-7,5'-isoxazolidin]-8-ones in moderate yields. The structures of all the products were proved by
NMR and IR spectroscopy, HRMS, and X-ray analysis.
Keywords: indolizine, isoxazolidine, nitrone, 1,3-dipolar cycloaddition.
Isoxazolidines are presented in many known pharmaco-
logical alkaloids such as pyrinodemin A,1 lycojaponicumin B,2
flueggine A,3 setigerumine I,4 and dactylicapnosinine.5 The
derivatives of isoxazolidine possess an extensive spectrum
of biological activities such as antiviral, antifungal, and
antimicrobial,6 and are also used as hypoglycemic agents7
and reductase inhibitors.8 The isoxazolidines are important
intermediates for the concise synthesis of pharmaceutically
important building blocks such as 1,3-aminocarbonyls,
1,3-amino alcohols, β-lactams and a variety of natural
products.8 The 1,3-dipolar cycloaddition reaction of
nitrones with electrophilic olefins is one of the most
convenient methods to construct isoxazolidines.9
methylidene-6,7-dihydroindolizin-8(5H)-ones in conti-
nuation of our work regarding 1,3-dipolar cycloaddition
reactions20 and synthesis of indolizine derivatives.21
1,3-Dipolar cycloaddition of compounds 1a–c with
nitrones 2a–d in refluxing PhMe yielded the corresponding
spiroisooxazolines 3a–k in satisfactory yields with high
regioselectivity (Scheme 1) .
Scheme 1. Synthesis of spiro[indolizine-7,5'-isoxazolidin]-
8-ones 3a–k
Indolizine cycle is a ubiquitous fragment of many
biologically significant alkaloids: kinganone,10 (+)-mono-
morine,11 indolizidine 209D,12 and polygonatines A, B.13
Indolizine derivatives have been widely studied due to their
biological
activities
(antiHIV,14
hypoglycemic,15
antitumor,16 and antimicrobial17), ability to act as glycogen
synthase kinase-3β inhibitors18 and 5-hydroxytryptamine
receptor antagonists.19
Herein, we report the synthesis of 2',3',4'-triaryl-5,6-
dihydro-8H-spiro[indolizine-7,5'-isoxazolidin]-8-ones by
the cycloaddition of C-aryl-N-phenylnitrones with 7-aryl-
0009-3122/20/56(8)-1062©2020 Springer Science+Business Media, LLC
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Chemistry of Heterocyclic Compounds 2020, 56(8), 1062–1066
The structures of products 3a–k were established by IR
1
and H, 13C NMR spectroscopy and HRMS. The high-
resolution mass spectrum of product 3a contained a signal
of protonated molecular ion with m/z 499.1018. The
IR spectrum of the product 3a displayed a characteristic
absorption of carbonyl group at 1650 cm–1, isoxazolidine
ring (C–N) at 1176 cm–1, as well as N–O fragment at
945 cm–1. The 1H NMR spectrum of compound 3a revealed
a doublet of doublets of doublets at 1.84 ppm (J = 14.0,
J = 12.5, J = 5.0 Hz) and a doublet of triplets at 2.14 ppm
(J = 14.0, J = 2.5 Hz) assigned to the 6-CH2 protons; a
doublet of doublets of doublets at 3.98 ppm (J = 12.5, J = 5.0,
J = 2.0 Hz) and a triplet of doublets at 4.43 ppm (J = 12.5,
J = 3.0 Hz) corresponding to the 5-CH2 protons; a doublet
at 4.84 ppm and a doublet at 5.08 ppm assigned to the
3'-CH and 4'-CH protons, respectively; a doublet of
doublets at 6.29 (J = 4.0, J = 2.0 Hz) and a triplet at
6.84 ppm assigned to the H-2 and H-3 protons of the
pyrrole cycle, respectively.
The 13C NMR spectrum of product 3a exhibited the
presence of carbonyl group at 180.2 ppm. Signals at 30.8
and 41.4 ppm were assigned to the C-6 and C-5 atoms,
respectively. The signal at 83.1 corresponded to the spiro
carbon atom C-7. In addition, signals at 73.9 and 59.2 ppm
Figure 2. The molecular structure of compound 3e with atom
represented by thermal vibration ellipsoids of 50% probability.
attack to the less substituted carbon atom of dipolarophile 1
should provide products 3'' and 3''' which were not
detected. In our point of view, the regioselectivity was
determined by the attack of the most nucleophilic center of
diarylnitrone 2 on the most activated atom of the C=C
moiety of dipolarophile 1.23 On the other hand, the
stereoselectivity was influenced by steric effects which
favored 3,4-trans configuration in the transition state.24
1
represented C-3' and C-4' atoms, respectively. The H–13C
HMBC spectrum of compound 3a confirmed the
correlation between carbonyl group and 6-CH2 and 4'-CH
protons, the cross peak of C-5 carbon and H-3 proton was
also detected, the C-7 carbon atom with the signal at 83.1 ppm
correlated with 3'-CH and 5-CH2 protons. Some significant
2D NMR correlations for the assignment of H and C atoms
and confirmation of the structure of compound 3a are
shown in Figure 1. Further, the X-ray analysis of
compound 3e allowed to make the final assignment of the
structure of cycloaddition reaction product and identify it
as product 3 in contrast to products 3', 3'', or 3''' (Fig. 2,
Scheme 2).
Scheme 2. Possible reaction pathways for the formation
of compound 3
The possible pathways of the cycloaddition reaction
between dipolarophile 1 and nitrone 2 is shown in Scheme 2.
Thus, there are four different variations of nitrone 2 attack
to the double bond of dipolarophile 1. Addition of the
O atom of nitrone 2 to the the most substituted carbon of
dipolarophiles should lead to the formation of products 3
and/or 3' which could be distinguished and proved by
NMR data. Thus, possessing two characteristic signals of
protons of isoxazolidine cycle at 4.84 and 5.08 ppm
assigned to 3'-CH and 4'-CH atoms gave coupling constant
J = 10.0 Hz which confirmed the trans location of 3'-CH
and 4'-CH hydrogen atoms in the cycle.22 The O atom
Figure 1. The main correlations in the 1H–1H COSY and
1H–13C HMBC spectra of compound 3a.
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Chemistry of Heterocyclic Compounds 2020, 56(8), 1062–1066
In conclusion, we have developed an efficient [3+2]-regio-
5.01 (1H, d, J = 10.0, CH); 6.29 (1H, dd, J = 4.0, J = 2.0,
H pyrrole); 6.85 (1H, t, J = 1.5, H pyrrole); 6.92–6.99 (3H,
m, H pyrrole, H Ar); 7.15–7.16 (1H, m, H Ar); 7.18–7.21
(2H, m, H Ar); 7.27–7.29 (6H, m, H Ar); 7.42–7.43 (2H,
m, H Ar). 13C NMR spectrum, δ, ppm: 30.9; 41.4; 59.0;
73.9; 83.0; 111.5; 116.3; 116.7; 122.9; 126.6; 128.7; 129.0;
129.1; 129.5; 130.7; 133.3; 133.8; 133.9; 137.5; 149.9;
180.2. Found, m/z: 489.1134 [M+H]+. C28H23Cl2N2O2.
Calculated, m/z: 489.1131.
selective cycloaddition reaction of 7-arylmethylidene-6,7-
dihydroindolizin-8(5H)-ones to arylnitrones, affording a
variety of 2',3',4'-triaryl-5,6-dihydro-8H-spiro[indolizine-
7,5'-isoxazolidin]-8-ones in moderate yields.
Experimental
IR spectra were recorded on a PerkinElmer Spectrum
1
One spectrometer using KBr pellets. H, 13C NMR spectra
1
(500 and 125 MHz, respectively) and H–13C HMQC,
3'-(4-Bromophenyl)-4'-(4-fluorophenyl)-2'-phenyl-5,6-
dihydro-8H-spiro[indolizine-7,5'-isoxazolidin]-8-one (3c).
Yield 237 mg (46%), white solid, mp 223–225°C.
IR spectrum, ν, cm–1: 1655, 1598, 1509, 1485, 1395, 1184,
1
1H–13C HMBC, and H–1H COSY spectra were acquired
on a Bruker Avance II 500 spectrometer in CDCl3 solution
using TMS as internal standard. HRMS analyses were
conducted on a Finnigan LCQ Advantage MAX mass
spectrometer (ESI). Melting points were determined on a
Yanaco MP-500 melting point apparatus and are uncor-
rected. TLC analyses were performed on Merck TLC Silica
gel 60 F254 plates using petroleum ether – EtOAc, 4:1.
Crude products were purified by column chromatography
using silica gel (100–200 mesh, Beijing Innochem Company).
Starting compounds 1a–c were synthesized according to
literature method,25 C-aryl-N-phenylnitrones 2a–d were
synthesized by the reaction of nitrobenzene and aryl-
aldehyde in the presence of zinc as previously reported.26
All other chemicals were obtained from commercial
suppliers and were used without additional purification.
Synthesis of 2',3',4'-triaryl-5,6-dihydro-8H-spiro-
[indolizine-7,5'-isoxazolidin]-8-ones 3a–k (General method).
A mixture of the corresponding 7-arylmethylidene-6,7-
dihydroindolizin-8(5H)-one 1a–c (1 mmol) and C-aryl-
N-phenylnitrones 2a–d (1.5 mmol) in PhMe (20 ml) was
refluxed for 72 h. The solvent was removed under reduced
pressure, and the reaction mixture was purified by flash column
chromatography, eluent petroleum ether – EtOAc, 4:1.
4'-(4-Bromophenyl)-2',3'-diphenyl-5,6-dihydro-8H-
spiro[indolizine-7,5'-isoxazolidin]-8-one (3a). Yield 214 mg
(43%), white solid, mp 215–217°C. IR spectrum, ν, cm–1:
1650, 1592, 1525, 1485, 1391, 1176, 1066, 945, 754, 693.
1H NMR spectrum, δ, ppm (J, Hz): 1.84 (1H, ddd, J = 14.0,
J = 12.5, J = 5.0, CH2); 2.14 (1H, dt, J = 14.0, J = 2.5,
CH2); 3.98 (1H, ddd, J = 12.5, J = 5.0, J = 2.0, CH2); 4.43
(1H, td, J = 12.5, J = 3.0, CH2); 4.84 (1H, d, J = 10.0, CH);
5.08 (1H, d, J = 10.0, CH); 6.29 (1H, dd, J = 4.0, J = 2.0,
H pyrrole); 6.84 (1H, t, J = 1.5, H pyrrole); 6.93–6.96 (3H,
m, H pyrrole, H Ar); 7.14–7.16 (1H, m, H Ar); 7.18–7.22
(4H, m, H Ar); 7.25–7.31 (3H, m, H Ar); 7.40–7.42 (2H,
m, H Ar); 7.48–7.50 (2H, m, H Ar). 13C NMR spectrum,
δ, ppm: 30.8; 41.4; 59.2; 73.9; 83.1; 111.5; 116.1; 116.7;
121.8; 122.6; 126.7; 127.4; 128.2; 128.7; 128.9; 129.7; 131.3;
131.8; 133.9; 138.9; 150.5; 180.2. Found, m/z: 499.1018
[M+H]+. C28H24BrN2O2. Calculated, m/z: 499.1016.
1
1070, 940, 752, 699. H NMR spectrum, δ, ppm (J, Hz):
1.84 (1H, ddd, J = 14.0, J = 12.5, J = 5.0, CH2); 2.13 (1H,
dt, J = 14.0, J = 2.5, CH2); 4.00 (1H, ddd, J = 12.5, J = 5.0,
J = 2.0, CH2); 4.43 (1H, td, J = 12.5, J = 3.0, CH2); 4.77
(1H, d, J = 10.0, CH); 5.01 (1H, d, J = 10.0, CH); 6.29 (1H,
dd, J = 4.0, J = 2.5, H pyrrole); 6.84 (1H, t, J = 1.5,
H pyrrole); 6.92–6.94 (2H, m, H pyrrole, H Ar); 6.97–7.02
(3H, m, H Ar); 7.14–7.16 (1H, m, H Ar); 7.18–7.21 (2H,
m, H Ar); 7.27–7.30 (2H, m, H Ar); 7.35–7.37 (2H, m,
H Ar); 7.41–7.43 (2H, m, H Ar). 13C NMR spectrum,
δ, ppm (J, Hz): 30.8; 41.4; 59.0; 74.0; 83.0; 111.5; 115.8
(d, J = 21.0); 116.2; 116.7; 122.0; 122.8; 126.6; 128.7;
128.8; 129.0; 129.6; 130.4; 130.9 (d, J = 8.0); 132.0; 138.2;
150.1; 163.3 (d, J = 246.0); 180.3. Found, m/z: 517.0916
[M+H]+. C28H23BrFN2O2. Calculated, m/z: 517.0921.
4'-(4-Bromophenyl)-3'-(4-chlorophenyl)-2'-phenyl-
5,6-dihydro-8H-spiro[indolizine-7,5'-isoxazolidin]-8-one
(3d). Yield 271 mg (51%), white solid, mp 233–235°C.
IR spectrum, ν, cm–1: 1653, 1594, 1528, 1486, 1395, 1185,
1
1070, 942, 752, 697. H NMR spectrum, δ, ppm (J, Hz):
1.84 (1H, ddd, J = 14.0, J = 12.5, J = 5.0, CH2); 2.14 (1H,
dt, J = 14.0, J = 2.5, CH2); 4.01 (1H, ddd, J = 12.5, J = 5.0,
J = 2.0, CH2); 4.43 (1H, td, J = 12.5, J = 3.0, CH2); 4.79
(1H, d, J = 10.0, CH); 5.08 (1H, d, J = 10.0, CH); 6.30 (1H,
dd, J = 4.0, J = 2.0, H pyrrole); 6.85 (1H, t, J = 2.0,
H pyrrole); 6.93–6.97 (3H, m, H pyrrole, H Ar); 7.15–7.16
(1H, m, H Ar); 7.18–7.21 (4H, m, H Ar); 7.27–7.28 (2H,
m, H Ar); 7.41–7.44 (4H, m, H Ar). 13C NMR spectrum,
δ, ppm: 30.9; 41.4; 59.1; 73.8; 82.9; 111.5; 116.4; 116.8;
122.0; 122.9; 126.6; 128.7; 129.1; 129.5; 131.1; 131.9;
133.9; 137.5; 149.9; 180.2. Found, m/z: 533.0624 [M+H]+.
C28H23BrClN2O2. Calculated, m/z: 533.0626.
4'-(4-Chlorophenyl)-2'-phenyl-3'-(p-tolyl)-5,6-dihydro-
8H-spiro[indolizine-7,5'-isoxazolidin]-8-one (3e). Yield
192 mg (41%), white solid, mp 226–228°C. IR spectrum,
ν, cm–1: 1656, 1598, 1527, 1488, 1396, 1186, 1067, 956,
1
760, 697. H NMR spectrum, δ, ppm (J, Hz): 1.83 (1H,
ddd, J = 14.0, J = 12.5, J = 5.0, CH2); 2.13 (1H, dt, J = 14.0,
J = 2.5, CH2); 2.29 (3H, s, CH3); 3.97 (1H, ddd, J = 12.5, J =
5.0, J = 2.0, CH2); 4.43 (1H, td, J = 12.5, J = 3.0, CH2);
4.81 (1H, d, J = 10.0, CH); 5.09 (1H, d, J = 10.0, CH); 6.28
(1H, dd, J = 4.0, J = 2.5, H pyrrole); 6.84 (1H, t, J = 2.0,
H pyrrole); 6.93–6.95 (3H, m, H pyrrole, H Ar); 7.08–7.09
(2H, m, H Ar); 7.14–7.16 (1H, m, H Ar); 7.17–7.19 (2H,
m, H Ar); 7.24–7.28 (4H, m, H Ar); 7.37 (2H, d, J = 8.0,
H Ar). 13C NMR spectrum, δ, ppm: 21.2; 30.8; 41.4; 59.0;
3',4'-Bis(4-chlorophenyl)-2'-phenyl-5,6-dihydro-8H-
spiro[indolizine-7,5'-isoxazolidin]-8-one (3b). Yield 229 mg
(47%), white solid, mp 240–242°C. IR spectrum, ν, cm–1:
1654, 1595, 1528, 1487, 1395, 1183, 1068, 941, 752, 698.
1H NMR spectrum, δ, ppm (J, Hz): 1.84 (1H, ddd, J = 14.0,
J = 12.5, J = 5.0, CH2); 2.12 (1H, dt, J = 14.0, J = 2.5,
CH2); 4.00 (1H, ddd, J = 12.5, J = 5.0, J = 2.0, CH2); 4.44
(1H, td, J = 12.5, J = 3.0, CH2); 4.79 (1H, d, J = 10.0, CH);
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Chemistry of Heterocyclic Compounds 2020, 56(8), 1062–1066
73.8; 83.0; 111.4; 116.2; 116.7; 122.5; 126.5; 127.3; 128.6;
4'-(4-Chlorophenyl)-2',3'-diphenyl-5,6-dihydro-8H-
spiro[indolizine-7,5'-isoxazolidin]-8-one (3i). Yield 181 mg
(40%), white solid, mp 191–192°C. IR spectrum, ν, cm–1:
1655, 1595, 1527, 1487, 1395, 1182, 1067, 942, 755, 696.
1H NMR spectrum, δ, ppm (J, Hz): 1.83 (1H, ddd, J = 18.0,
J = 12.5, J = 5.0, CH2); 2.12 (1H, dt, J = 14.0, J = 3.0,
CH2); 3.98 (1H, ddd, J = 12.5, J = 5.0, J = 2.0, CH2); 4.43
(1H, td, J = 12.5, J = 3.0, CH2); 4.85 (1H, d, J = 10.0, CH);
5.10 (1H, d, J = 10.0, CH); 6.28 (1H, dd, J = 4.0, J = 2.0,
H pyrrole); 6.83 (1H, t, J = 1.5, H pyrrole); 6.93–6.95 (3H,
m, H pyrrole, H Ar); 7.14–7.19 (3H, m, H Ar); 7.27–7.31
(7H, m, H Ar); 7.48–7.49 (2H, m, H Ar). 13C NMR
spectrum, δ, ppm: 30.8; 41.4; 59.1; 74.0; 83.1; 111.5; 116.0;
116.7; 122.5; 126.6; 127.3; 128.2; 128.6; 128.8; 128.9;
129.7; 130.8; 133.3; 133.6; 138.9; 150.5; 180.2. Found, m/z:
455.1522 [M+H]+. C28H24ClN2O2. Calculated, m/z: 455.1521.
3'-(4-Chlorophenyl)-4'-(4-fluorophenyl)-2'-phenyl-
5,6-dihydro-8H-spiro[indolizine-7,5'-isoxazolidin]-8-one
(3j). Yield 208 mg (44%), white solid, mp 229–231°C.
IR spectrum, ν, cm–1: 1658, 1598, 1527, 1488, 1396, 1187,
128.8; 129.5; 129.7; 130.7; 133.5; 133.6; 135.7; 137.8;
150.6; 180.3. Found, m/z: 469.1675 [M+H]+. C29H26ClN2O2.
Calculated, m/z: 469.1677.
4'-(4-Fluorophenyl)-2',3'-diphenyl-5,6-dihydro-8H-
spiro[indolizine-7,5'-isoxazolidin]-8-one (3f). Yield 171 mg
(39%), white solid, mp 202–204°C. IR spectrum, ν, cm–1:
1657, 1598, 1510, 1486, 1396, 1183, 1068, 941, 755, 698.
1H NMR spectrum, δ, ppm (J, Hz): 1.84 (1H, ddd, J = 14.0,
J = 12.5, J = 5.0, CH2); 2.15 (1H, dt, J = 14.0, J = 2.5,
CH2); 3.98 (1H, ddd, J = 12.5, J = 5.0, J = 2.0, CH2); 4.43
(1H, td, J = 12.5, J = 3.0, CH2); 4.86 (1H, d, J = 10.0, CH);
5.10 (1H, d, J = 10.0, CH); 6.29 (1H, dd, J = 4.0, J = 2.0,
H pyrrole); 6.84 (1H, t, J = 2.0, H pyrrole); 6.93–6.99 (5H,
m, H pyrrole, H Ar); 7.15–7.16 (1H, m, H Ar); 7.17–7.20
(2H, m, H Ar); 7.27–7.32 (5H, m, H Ar); 7.49–7.50 (2H,
m, H Ar). 13C NMR spectrum, δ, ppm (J, Hz): 30.8; 41.4;
59.0; 74.1; 83.1; 111.4; 115.6 (q, J = 21.0); 116.0; 116.7;
122.5; 126.5; 127.3; 128.1; 128.6; 128.8; 129.7; 130.5 (d,
J = 3.0); 131.0 (d, J = 7.5); 139.0; 150.6; 163.2 (d, J = 245.0);
180.3. Found, m/z: 439.1819 [M+H]+. C28H24FN2O2.
Calculated, m/z: 439.1816.
1
1069, 941, 759, 700. H NMR spectrum, δ, ppm (J, Hz):
1.84 (1H, ddd, J = 14.0, J = 12.5, J = 5.0, CH2); 2.13 (1H,
dt, J = 14.0, J = 3.0, CH2); 4.00 (1H, ddd, J = 12.5, J = 5.0,
J = 2.0, CH2); 4.43 (1H, td, J = 12.5, J = 3.0, CH2); 4.79
(1H, d, J = 10.0, CH); 5.01 (1H, d, J = 10.0, CH); 6.29 (1H,
dd, J = 4.0, J = 2.5, H pyrrole); 6.85 (1H, t, J = 1.5,
H pyrrole); 6.92–6.94 (2H, m, H pyrrole, H Ar); 6.95–7.02
(3H, m, H Ar); 7.15–7.16 (1H, m, H Ar); 7.18–7.22 (2H,
m, H Ar); 7.27–7.31 (4H, m, H Ar); 7.42–7.44 (2H, m,
H Ar). 13C NMR spectrum, δ, ppm (J, Hz): 30.9; 41.4;
59.0; 73.9; 83.0; 111.5; 115.7 (d, J = 21.0); 116.2; 116.7;
122.8; 126.5; 128.6; 128.7; 129.0; 129.6; 130.4 (d, J = 3.0);
131.0 (d, J = 8.0); 133.8; 137.6; 150.1; 163.3 (d, J = 246.0);
180.3. Found, m/z: 473.1424 [M+H]+. C28H23ClFN2O2.
Calculated, m/z: 473.1427.
3'-(4-Bromophenyl)-4'-(4-chlorophenyl)-2'-phenyl-
5,6-dihydro-8H-spiro[indolizine-7,5'-isoxazolidin]-8-one
(3g). Yield 239 mg (45%), white solid, mp 253–255°C.
IR spectrum, ν, cm–1: 1653, 1596, 1527, 1488, 1395, 1183,
1
1068, 941, 759, 697. H NMR spectrum, δ, ppm (J, Hz):
1.84 (1H, ddd, J = 14.0, J = 12.5, J = 5.0, CH2); 2.13 (1H,
dt, J = 14.0, J = 3.0, CH2); 3.99 (1H, ddd, J = 12.5, J = 5.0,
J = 2.0, CH2); 4.43 (1H, td, J = 12.5, J = 3.0, CH2); 4.77
(1H, d, J = 10.0, CH); 5.01 (1H, d, J = 10.0, CH); 6.29 (1H,
dd, J = 4.0, J = 2.5, H pyrrole); 6.85 (1H, t, J = 1.5,
H pyrrole); 6.92–6.93 (2H, m, H pyrrole, H Ar); 6.95–6.98
(1H, m, H Ar); 7.14–7.16 (1H, m, H Ar); 7.18–7.21 (2H,
m, H Ar); 7.26–7.28 (4H, m, H Ar); 7.35–7.37 (2H, m,
H Ar); 7.42–7.44 (2H, m, H Ar). 13C NMR spectrum,
δ, ppm: 30.9; 41.4; 59.1; 73.9; 83.0; 111.5; 115.2; 116.3;
116.8; 122.1; 122.9; 126.6; 128.0; 128.6; 128.7; 128.8;
129.0; 129.1; 129.2; 129.5; 130.7; 131.6; 132.0; 133.3;
133.8; 138.1; 150.0; 180.2. Found, m/z: 533.0624 [M+H]+.
C28H23BrClN2O2. Calculated, m/z: 533.0626.
4'-(4-Bromophenyl)-2'-phenyl-3'-(p-tolyl)-5,6-dihydro-
8H-spiro[indolizine-7,5'-isoxazolidin]-8-one (3k). Yield
251 mg (49%), white solid, mp 229–231°C. IR spectrum,
ν, cm–1: 1655, 1596, 1527, 1488, 1396, 1186, 1067, 943,
1
760, 696. H NMR spectrum, δ, ppm (J, Hz): 1.83 (1H,
ddd, J = 14.0, J = 12.5, J = 5.0, CH2); 2.13 (1H, dt, J = 14.0,
J = 2.5, CH2); 2.29 (3H, s, CH3); 3.98 (1H, ddd, J = 12.5,
J = 5.0, J = 2.0, CH2); 4.43 (1H, td, J = 12.5, J = 3.0, CH2);
4.81 (1H, d, J = 10.0, CH); 5.08 (1H, d, J = 10.0, CH); 6.28
(1H, dd, J = 4.0, J = 2.0, H pyrrole); 6.84 (1H, t, J = 1.5,
H pyrrole); 6.92–6.94 (3H, m, H pyrrole, H Ar); 7.09–7.10
(2H, m, H Ar); 7.14–7.21 (5H, m, H Ar); 7.36–7.41 (4H,
m, H Ar). 13C NMR spectrum, δ, ppm: 21.1; 30.9; 41.4;
59.0; 73.7; 82.9; 111.4; 116.1; 116.7; 121.7; 122.5; 126.6;
127.3; 128.6; 129.5; 129.7; 131.1; 131.8; 134.0; 135.7;
137.8; 150.5; 180.3. Found, m/z: 513.1176 [M+H]+.
C29H26BrN2O2. Calculated, m/z: 513.1172.
3',4'-Bis(4-bromophenyl)-2'-phenyl-5,6-dihydro-8H-
spiro[indolizine-7,5'-isoxazolidin]-8-one (3h). Yield 277 mg
(48%), white solid, mp 230–232°C. IR spectrum, ν, cm–1:
1654, 1594, 1528, 1488, 1395, 1185, 1068, 943, 759, 695.
1H NMR spectrum, δ, ppm (J, Hz): 1.84 (1H, ddd, J = 14.0,
J = 12.5, J = 5.0, CH2); 2.12 (1H, dt, J = 14.0, J = 2.5,
CH2); 4.00 (1H, ddd, J = 12.5, J = 5.0, J = 2.0, CH2); 4.43
(1H, td, J = 12.5, J = 3.0, CH2); 4.77 (1H, d, J = 10.0, CH);
5.00 (1H, d, J = 10.0, CH); 6.29 (1H, dd, J = 4.0, J = 2.5,
H pyrrole); 6.85 (1H, t, J = 1.5, H pyrrole); 6.92–6.93 (2H,
m, H pyrrole, H Ar); 6.95–6.98 (1H, m, H Ar); 7.14–7.15
(1H, m, H Ar); 7.18–7.21 (4H, m, H Ar); 7.35–7.37 (2H,
m, H Ar); 7.41–7.44 (4H, m, H Ar). 13C NMR spectrum,
δ, ppm: 30.9; 41.4; 59.1; 73.8; 82.9; 111.5; 116.3; 116.8;
122.9; 126.6; 128.3; 128.7; 129.0; 129.5; 131.1; 131.5;
131.9; 132.0; 133.8; 138.0; 149.9; 180.2. Found, m/z:
577.0121 [M+H]+. C28H23Br2N2O2. Calculated, m/z:
577.0121.
X-ray structural analysis of compound 3e. A suitable
crystal was obtained by slow diffusion of hexane into a
solution of compound 3e in EtOAc. Single crystal X-ray
crystallographic data were collected on a Bruker Apex II
CCD diffractometer with monochromatic MoKα radiation
(λ 0.71073 Å) at 296(2) K. The data set was integrated and
reduced applying the SAINT program with absorption and
1065

Chemistry of Heterocyclic Compounds 2020, 56(8), 1062–1066
Jasiński, R. Chem. Heterocycl. Compd. 2020, 56, 120. [Khim.
scaling correction being undertaken with the SADABS
program. The structure was resolved by the direct method,
all non-hydrogen atoms were refined by the full-matrix
least-square procedure on F2 using the SHELXL-2014
program set in conjunction with the Olex2 program.27
Crystal data for compound 3e: C29H25ClN2O2, Mr 468.96,
monoclinic space group P2yn; a 13.2609(15), b 11.7853(14),
c 15.4849(18) Å; β 94.116(2)°; V 2413.8(5) Å3; T 296 (2) K;
Z 4; dcalc 1.290 g·cm–3; μ 0.187 mm–1; F(000) 984;
Rint 0.0394, 4247 reflections, 2991 with I > 2σ(I) for 308
parameters, GOF 1.024, R1 0.0406, wR2 0.0987 (I > 2σ(I))
and R1 0.0648, wR2 0.1133 (all data). The complete
crystallogrpahic dataset was deposited at the Cambridge
Crystallographic Data Center (deposit CCDC 1983953).
Geterotsikl. Soedin. 2020, 56, 120.]
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