2-Substituted 3-nitro-2H-chromenes in reaction with azomethine ylide derived from ninhydrin and proline: regio- and stereoselective synthesis of spiro[chromeno[3,4-a]pyrrolizidine-11,2'-indene]-1',3'-diones

Article abstract of DOI:10.1007/s10593-018-2193-2

Regio- and stereoselective 1,3-dipolar cycloaddition of stabilized azomethine ylides, generated in situ from ninhydrin and proline, occurred at the double bond activated by nitro group in 3-nitro-2-(trifluoromethyl)- and 3-nitro-2-phenyl-2H-chromenes upon heating in ethanol. This reaction produced high yields of spiro[chromeno[3,4-a]pyrrolizidine-11,2'-indene]-1',3'-diones. The structure of the obtained products was confirmed by the method of X-ray crystallography.

Full text of DOI:10.1007/s10593-018-2193-2

DOI 10.1007/s10593-018-2193-2
Chemistry of Heterocyclic Compounds 2017, 53(11), 1192–1198
2-Substituted 3-nitro-2H-chromenes in reaction with azomethine ylide
derived from ninhydrin and proline: regio- and stereoselective synthesis
of spiro[chromeno[3,4-a]pyrrolizidine-11,2'-indene]-1',3'-diones
Vladislav Yu. Korotaev1*, Igor B. Kutyashev1,
Alexey Yu. Barkov1, Vyacheslav Ya. Sosnovskikh1
1
Institute of Natural Sciences and Mathematics,
Ural Federal University named after the first President of Russia B. N. Yeltsin,
51 Lenina St., Yekaterinburg 620000, Russia; е-mail: korotaev.vladislav@urfu.ru
Translated from Khimiya Geterotsiklicheskikh Soedinenii,
2017, 53(11), 1192–1198
Submitted August 1, 2017
Accepted October 11, 2017
O
O
OH
OH
O
R1
NO2
R
N
EtOH
O
H
R1
+
50°C, 1 h
80–90%
O
NO2
R
R2
O
CO2H
N
H
R2
R = CF3, Ph; R1, R2 = H, Me, MeO, EtO, Cl, Br, NO2
Regio- and stereoselective 1,3-dipolar cycloaddition of stabilized azomethine ylides, generated in situ from ninhydrin and proline,
occurred at the double bond activated by nitro group in 3-nitro-2-(trifluoromethyl)- and 3-nitro-2-phenyl-2H-chromenes upon heating in
ethanol. This reaction produced high yields of spiro[chromeno[3,4-a]pyrrolizidine-11,2'-indene]-1',3'-diones. The structure of the
obtained products was confirmed by the method of X-ray crystallography.
Keywords: 3-nitro-2H-chromenes, spiro[chromeno[3,4-a]pyrrolizidine-11,2'-indene]-1',3'-diones, stabilized azomethine ylides, 1,3-dipolar
cycloaddition.
Fused ring systems containing chromene and chromane
(3,4-dihydro-2H-1-benzopyran) motifs are often found in
natural compounds, as well are included in biologically
active synthetic molecules.1 The notable biological activity
of these compounds is primarily related to the simultaneous
presence of several pharmacophoric fragments in one fused
heterocyclic system. In particular, benzopyran 1 containing
Δ3-annulated pyrrolidine ring is an antagonist of 5-HT2C
receptors showing selectivity with regard to 5-HT2А
receptors,2a while its structural analog 2 is selective toward
α1A and α1B adrenergic receptors, and has been proposed
as a promising pharmaceutical agent for the treatment of
benign prostatic hyperplasia2b (Fig. 1).
contain a reactive β-nitrostyrene moiety. The reactions of
nitrochromenes with unstabilized and stabilized azomethine
ylides derived from aldehydes and α-amino acids or their
esters have been studied in considerable detail, resulting in
the preparation of a broad range of chromane derivatives
fused with pyrrolidine or pyrrolizidine rings.4 However,
their reactions with ylides of polycarbonyl compounds
have been little studied: only two brief reports describe
[3+2] addition of ylides derived from isatin and
acenaphthenequinone to 2-substituted 3-nitro-2H-chromenes.5
One of the most effective direct methods for the
synthesis of pyrrolidines and pyrrolizidines, which has
received an increasing attention from researchers over the
recent years, relies on 1,3-dipolar cycloaddition of
azomethine ylides at alkene double bonds.3 Suitable
examples of alkenes include 3-nitro-2H-chromenes that
Figure 1. Biologically active chromeno[3,4-c]pyrrolidines.
0009-3122/17/53(11)-1192©2017 Springer Science+Business Media, LLC
1192

Chemistry of Heterocyclic Compounds 2017, 53(11), 1192–1198
Scheme 1
The reactions of nitrochromenes with ylides prepared from
ninhydrin have not been previously examined. At the same
time, it has been reported that the azomethine ylide derived
from ninhydrin and proline added regio- and stereo-
selectively to β-nitrostyrenes by attacking the electrophilic
α-carbon atom of styrene with its more substituted part.6
These reactions provided high yields of the respective endo-
spirocycloadducts, the molecules of which contained
pyrrolizidine ring along with the pharmacophoric indane-
1,3-dione moiety.6,7
In
a continuation of our studies aimed at the
development of new methods for Δ3-annulation of 3-nitro-
2-(trihalomethyl)-2H-chromenes,8 in the current work we
studied a three-component reaction involving 2-substituted
3-nitro-2H-chromenes, ninhydrin, and proline, proposed a
single-step method for the preparation of previously
undescribed spiro[chromeno[3,4-a]pyrrolizidine-11,2'-inde-
ne]-1',3'-diones, and studied their behavior in CHCl3 and
DMSO solutions.
It was found that the [3+2] cycloaddition of azomethine
ylide, generated in situ from ninhydrin and proline, at the
double bond of 3-nitro-2-(trifluoromethyl)-2H-chromenes
3a‒i in ethanol at 50°C over 1 h produced endo-spiro-
[chromeno[3,4-a]pyrrolizidine-11,2'-indene]-1',3'-diones
4a‒i in 80‒90% yields. The formation of regioisomeric
adducts 4'a‒i did not occur due to the unfavorable dipole-
dipole interaction arising between the C=O and NO2
groups in the transition state6 (Scheme 1, Table 1).
As shown in Table 1, the yields of products 4a‒i were
little affected by the electron donor-acceptor properties of the
substituents R1 and R2. When using other solvents (benzene,
methanol, 2-propanol) in the reaction with chromene 3a, the
yields of adduct 4a were lower by 10‒30%.
3-Nitro-2-phenyl-2H-chromenes 3j‒l reacted with
azomethine ylide obtained from ninhydrin and proline
under analogous conditions, forming spirocycloadducts 4j‒l
with the same regio- and stereospecificity (Scheme 1,
Table 1). Again, the high yields of compounds 4j‒l (84‒
90%) were not affected by the nature of substituents in the
starting chromenes.
Table 1. Yields of chromeno[3,4-a]pyrrolizidines 4a–l
Yield,
%
Adduct
R
R1
R2 Yield, % Adduct
R
R1 R2
CF3 Br Br
CF3 NO2
CF3 NO2 NO2
CF3
H
H
H
83
86
80
80
83
83
90
87
89
88
84
90
4a
4b
4c
4d
4e
4f
4g
4h
4i
CF3 Me
CF3 MeO
H
H
CF3
H
EtO
H
Ph
H
H
H
H
4j
CF3 Cl
CF3 Br
Ph MeO
Ph Br
4k
4l
H
The regio- and stereochemistry of products 4a‒l was
confirmed by X-ray structural analysis of compound 4a
(Fig. 2). As shown in Figure 2, cycloadduct 4a was indeed
the regioisomer formed by addition of the С-2 atom of
azomethine ylide at the more electrophilic С-4 atom of
chromene. The trifluoromethyl substituent, nitro group, and
the hydrogen atom at the C-11а position were in a cis
configuration, while the hydrogen atom at the C-6b
position was in a transoid orientation. The pyran ring had a
half-chair conformation, while the five-membered ring
annulated to it, as well as the next five-membered ring of
the pyrrolizidine system assumed twist and envelope
conformations, respectively.
Since the most favorable conformation for 2-substituted
3-nitro-2H-chromenes is half-chair with a pseudoaxial
orientation of substituent,9 the attack by azomethine ylide
at the double bond of chromenes 3a‒l occurred from the
side of pseudoequatorial 2-CH hydrogen atom (Scheme 1).
As a result, the nitro group and substituent R in
Figure 2. The molecular structure of compound 4a with atoms
represented by thermal vibration ellipsoids of 30% probability.
1193

Chemistry of Heterocyclic Compounds 2017, 53(11), 1192–1198
chromenopyrrolizidines 4a‒l were found in
a
cis
in transition state between the bulky substituents at position
2 of chromene and the 1,3-indanedione moiety of ylide.
Spirocycloadducts also could not be obtained in a reaction
involving 2-CCl3 analogs13a of nitrochromenes 3a‒i, with a
high degree of resinification occurring in all of the cases.
This was probably associated with the elimination of HCl
molecule from 3-nitro-2-(trichloromethyl)-2H-chromenes
by the action of basic azomethine ylide 5, followed by the
formation of unstable 2-(dichloromethylidene)chromenes.
A similar process was observed by us upon treatment of
2-CCl3-nitrochromenes with sodium azide.8e
relationship to each other, which is characteristic for the
majority of adducts obtained by 1,3-dipolar cycloaddition
involving 2-monosubstituted 3-nitro-2H-chromenes.4,5,10
1H NMR spectra of compounds 4a‒l in CDCl3 solution
contained a characteristic singlet signal of the 1a-CH
proton signal in the range of 4.68‒5.12 ppm and a triplet or
double doublet of the pyrrolizidine 6b-CH proton at the
range of 4.04‒4.60 ppm. The signal of the 6-CH proton
appeared as a quartet at 5.78‒6.22 ppm with spin-spin
3
coupling constant JHF = 5.5‒6.2 Hz in spectra of
compounds 4a‒i or a singlet at 6.34‒6.46 ppm in the spectra
of compounds 4j‒l. The signal of trifluoromethyl group, which
was bonded to an sp3-hybridized carbon atom, appeared in
19F NMR spectra of 6-CF3-chromenopyrrolizidines 4a–i as
a doublet in the range of 91.7–93.7 ppm with spin-spin
Thus, 3-nitro-2-(trifluoromethyl)- and 3-nitro-2-phenyl-
2H-chromenes reacted with azomethine ylide obtained
from ninhydrin and proline, and the reaction proceeded as
easily as the analogous reaction with β-nitrostyrenes. In
contrast to 6-Ph-spirocycloadducts, the 6-CF3-substituted
products were unstable in DMSO solution. The molecules
of the obtained compounds contained a combination of
three pharmacophoric moieties and clearly should be of
interest to researchers in the field of medicinal chemistry.
3
coupling constant JFH = 5.5–6.2 Hz. 13C NMR spectra of
compounds 4a–i featured quartet signals of CF3 group and
С-6 carbon atom in the ranges of 121.6–122.8 and 75.3–
75.8 ppm, respectively, with spin-spin coupling constants
2
1JCF = 280.3–286.7 and JCF = 33.1–34.3 Hz. IR spectra of
Experimental
products 4a‒l contained absorption bands due to the
stretching vibrations of carbonyl group (1701‒1709 cm‒1)
and NO2 group (1531‒1554, 1339‒1359 cm‒1).
IR spectra were recorded on
a Bruker Alpha
spectrometer equipped with an ATR accessory (ZnSe
1
In contrast to 6-phenylchromenopyrrolizidines 4j‒l,
which remain stable also in DMSO-d6 solution, the 6-tri-
fluoromethyl-substituted adducts 4a–i were unstable in this
solvent and existed in equilibrium with the respective
starting chromene 3 and azomethine ylide 5 (Scheme 2).
Indeed, the dissolution of these compounds in DMSO-d6
was immediately followed by the appearance of two new
crystal). Н and 19F NMR spectra were acquired on Bruker
DRX-400 (400 and 376 MHz, respectively) and Bruker
Avance 500 (500 and 471 MHz, respectively)
spectrometers in CDCl3 or DMSO-d6, using TMS and C6F6
as internal standards. 13C NMR spectra were acquired on a
Bruker Avance-500 spectrometer (126 MHz) in CDCl3
solution, using residual solvent signal (77.0 ppm) as
internal standard. High-resolution mass spectra with
electrospray ionization were recorded on a Waters Xevo
QTof instrument. Elemental analysis was performed on an
automatic PE 2400 elemental analyzer. Melting points were
determined on an SMP40 apparatus.
1
sets of H NMR signals besides those of products 4a–i,
which were assigned to chromenes 3a–i and azomethine
ylide 511 in the ratio of 3:5 = 1:1. The equilibrium
compositions of mixtures containing compounds 3a–i, 4a–i,
and 5 in DMSO-d6 solution at 22°C are given in Table 2.
In conclusion, it should be noted that sterically hindered
3-nitro-2-phenyl-2-(trifluoromethyl)-2H-chromenes,12 repre-
senting hybrid structures of chromenes 3a‒l, did not react
with azomethine ylide 5 due to the steric hindrance arising
The starting nitrochromenes 3a–l were obtained
according to previously published procedures.13
Preparation of spiro[chromeno[3,4-a]pyrrolizidine-11,2'-
indene]-1',3'-diones 4a–l (General method). A mixture of
nitrochromene 3a–l (1.0 mmol), ninhydrin (0.18 g,
1.0 mmol), and proline (0.17 g, 1.5 mmol) in ethanol (5 ml)
was stirred at 50°C for 1 h. The reaction mixture was then
cooled to room temperature, the precipitate was filtered off,
washed first with ethanol (3×3 ml) and then with water
(3×1 ml), and dried at 60°C. Products 4a–l were isolated as
greenish-yellow powders.
Scheme 2
Table 2. The equilibrium 4a‒i ⇌ 3a‒i + 5 in DMSO-d6 solution
(6S*,6aS*,6bS*,11aR*)-6a-Nitro-6-trifluoromethyl-
6a,6b,7,8,9,11a-hexahydro-6H-spiro[chromeno[3,4-a]pyrro-
lizidine-11,2'-indene]-1',3'-dione (4a). Yield 0.38 g (83%),
mp 162–163°C (decomp.). IR spectrum, ν, cm−1: 1705,
1554, 1490, 1459, 1397, 1370, 1354, 1329. 1H NMR
spectrum (500 MHz, CDCl3), δ, ppm (J, Hz): 1.84–3.33
(6H, m, 3CH2); 4.60 (1H, t, J = 7.3, 6b-СH); 5.12 (1H, s,
11a-СH); 5.84 (1H, q, J = 6.2, 6-CH); 6.34 (1H, d, J = 7.7,
H-1); 6.64 (1H, t, J = 6.4, H-2); 7.03 (1H, d, J = 8.2, H-4);
7.12 (1H, t, J = 7.8, H-3); 7.83 (1H, d, J = 7.6,
H-4'(7')); 7.93 (1H, t, J = 7.5, H-5'(6')); 7.99 (1H, t, J = 7.5,
H-6'(5')); 8.17 (1H, d, J = 7.6, H-7'(4')). 1H NMR spectrum
Abundance of components, mol %
The composition of
mixture
4
3
5
4a + 3a + 5
4b + 3b + 5
4c + 3c + 5
4d + 3d + 5
4e + 3e + 5
4f + 3f + 5
4g + 3g + 5
4h + 3h + 5
4i + 3i + 5
26
24
34
26
32
32
38
26
40
37
38
33
37
34
34
31
37
30
37
38
33
37
34
34
31
37
30
1194

Chemistry of Heterocyclic Compounds 2017, 53(11), 1192–1198
(500 MHz, DMSO-d6), δ, ppm (J, Hz): 1.69–2.85 (6H, m,
J = 9.0, H-4); 7.82 (1H, d, J = 7.6, H-4'(7')); 8.06 (1H, td,
J = 7.6, J = 1.0, H-5'(6)'); 8.14 (1H, td, J = 7.6, J = 1.0,
H-6'(5')); 8.22 (1H, d, J = 7.6, H-7'(4')). 19F NMR spectrum
(471 MHz, CDCl3), δ, ppm (J, Hz): 93.2 (d, J = 6.1, CF3).
19F NMR spectrum (471 MHz, DMSO-d6), δ, ppm (J, Hz):
93.5 (d, J = 6.2, CF3). 13C NMR spectrum, δ, ppm (J, Hz):
24.6; 28.7; 48.7; 50.1; 58.7; 69.5; 74.1; 75.9 (q, J = 33.4,
C-6); 93.4; 110.8; 115.9; 118.6; 120.1; 122.7 (q, J = 281.3,
CF3); 123.9; 124.5; 131.8; 136.8; 137.5; 141.7; 142.0;
154.8; 197.1; 197.4. Found, m/z: 489.1267 [М+Н]+.
C24H20F3N2O6. Calculated, m/z: 489.1268.
3CH2); 4.26 (1H, br. t, J = 7.9, 6b-СH); 4.86 (1H, s,
11a-СH); 6.01 (1H, q, J = 6.2, 6-CH); 6.31 (1H, d, J = 7.6,
H-1); 6.69 (1H, t, J = 7.6, H-3); 7.05 (1H, d, J = 8.1, H-4);
7.16 (1H, br. t, J = 7.5, H-2); 7.81 (1H, d, J = 7.6, H-4'(7'));
8.05 (1H, t, J = 7.5, H-5'(6')); 8.14 (1H, t, J = 7.5, H-6'(5'));
8.22 (1H, d, J = 7.6, H-7'(4')). 19F NMR spectrum (471 MHz,
CDCl3), δ, ppm (J, Hz): 93.6 (d, J = 6.2, CF3). 19F NMR
spectrum (471 MHz, DMSO-d6), δ, ppm (J, Hz): 93.4 (d,
J = 6.2, CF3). 13C NMR spectrum, δ, ppm (J, Hz): 24.8;
29.1; 48.1; 50.0; 69.5; 74.6; 75.6 (q, J = 33.4, C-6); 93.1;
117.7; 120.0; 122.7; 122.8 (q, J = 281.5, CF3); 123.8;
124.3; 126.6; 129.1; 131.8; 136.7; 137.2; 141.8; 151.9;
197.6; 197.7. Found, %: С 59.31; Н 3.83; N 6.05.
C23H17F3N2O5·0.33H2O. Calculated, %: С 59.49; Н 3.83;
N 6.03.
(6S*,6aS*,6bS*,11aR*)-4-Ethoxy-6a-nitro-6-trifluoro-
methyl-6a,6b,7,8,9,11a-hexahydro-6H-spiro[chromeno-
[3,4-a]pyrrolizidine-11,2'-indene]-1',3'-dione (4d). Yield
0.40 g (80%), mp 169–170°C (decomp.). IR spectrum,
1
ν, cm−1: 1708, 1553, 1390, 1359, 1337. H NMR spectrum
(500 MHz, CDCl3), δ, ppm (J, Hz): 1.40 (3H, t, J = 7.0,
CH3); 1.81–3.27 (6H, m, 3CH2); 4.01 (1H, dq, J = 10.6,
J = 7.0, OCH2); 4.03 (1H, dq, J = 10.6, J = 7.0, OCH2);
4.54 (1H, t, J = 7.0, 6b-СH); 5.11 (1H, s, 11a-СH); 5.80
(1H, q, J = 6.2, 6-CH); 5.90 (1H, d, J = 7.8, H-1); 6.53 (1H,
t, J = 7.9, H-2); 6.68 (1H, d, J = 8.0, H-3); 7.85 (1H, d,
J = 7.6, H-4'(7')); 7.91 (1H, t, J = 7.5, H-5'(6')); 7.97 (1H, t,
(6S*,6aS*,6bS*,11aR*)-2-Methyl-6a-nitro-6-trifluoro-
methyl-6a,6b,7,8,9,11a-hexahydro-6H-spiro[chromeno-
[3,4-a]pyrrolizidine-11,2'-indene]-1',3'-dione (4b). Yield
0.41 g (86%), mp 150–151°C (decomp.). IR spectrum,
ν, cm−1: 1705, 1551, 1504, 1399, 1369, 1354, 1333. 1H NMR
spectrum (500 MHz, CDCl3), δ, ppm (J, Hz): 1.82–3.29
(6H, m, 3CH2); 1.86 (3H, s, CH3); 4.57 (1H, t, J = 7.3,
6b-СH); 5.04 (1H, s, 11a-СH); 5.79 (1H, q, J = 6.2, 6-CH);
6.07 (1H, br. s, H-1); 6.87‒6.92 (2H, m, H-3,4); 7.86 (1H,
d, J = 7.6, H-4'(7')); 7.92 (1H, td, J = 7.5, J = 1.0, H-5'(6'));
7.99 (1H, td, J = 7.5, J = 1.0, H-6'(5')); 8.18 (1H, d, J = 7.6,
H-7'(4')). 1H NMR spectrum (400 MHz, DMSO-d6), δ, ppm
(J, Hz): 1.68–2.87 (6H, m, 3CH2); 1.79 (3H, s, CH3); 4.26
(1H, dd, J = 8.9, J = 6.7, 6b-СH); 4.77 (1H, s, 11a-СH);
5.95 (1H, q, J = 6.2, 6-CH); 6.01 (1H, br. s, H-1); 6.92 (1H,
d, J = 8.4, H-4); 6.94 (1H, br. d, J = 8.4, H-3); 7.79 (1H, d,
J = 7.6, H-4'(7')); 8.06 (1H, t, J = 7.5, H-5'(6')); 8.14 (1H, t,
J = 7.5, H-6'(5')); 8.23 (1H, d, J = 7.6, H-7'(4')). 19F NMR
spectrum (471 MHz, CDCl3), δ, ppm (J, Hz): 93.6 (d,
J = 6.2, CF3). 19F NMR spectrum (376 MHz, DMSO-d6),
δ, ppm (J, Hz): 93.4 (d, J = 6.2, CF3). 13C NMR spectrum,
δ, ppm, (J, Hz): 20.3; 24.8; 29.0; 48.2; 50.0; 69.4; 75.1;
75.5 (q, J = 33.1, C-6'); 92.9; 117.3; 120.0; 122.6; 122.7 (q,
J = 281.0, CF3); 123.8; 124.3; 126.9; 130.0; 132.1; 136.7;
137.2; 141.7; 149.8; 198.2; 198.4. Found, m/z: 473.1320
[М+Н]+. C24H20F3N2O5. Calculated, m/z: 473.1319.
1
J = 7.5, H-6'(5')); 8.15 (1H, d, J = 7.6, H-7'(4')). H NMR
spectrum (400 MHz, DMSO-d6), δ, ppm (J, Hz): 1.31 (3H,
t, J = 6.9, CH3); 1.66–2.83 (6H, m, 3CH2); 4.09 (1H, dq,
J = 9.8, J = 6.9, OCHH); 4.13 (1H, dq, J = 9.8, J = 6.9,
OCHH); 4.26 (1H, br. t, J = 7.8, 6b-СH); 4.84 (1H, s, 11a-
СH); 5.84 (1H, d, J = 7.8, H-1); 5.94 (1H, q, J = 6.2,
6-CH); 6.60 (1H, t, J = 8.1, H-2); 6.84 (1H, d, J = 8.4,
H-3); 7.83 (1H, d, J = 7.6, H-4'(7')); 8.05 (1H, t, J = 7.5,
H-5'(6')); 8.14 (1H, t, J = 7.5, H-6'(5')); 8.22 (1H, d,
J = 7.6, H-7'(4')). 19F NMR spectrum (471 MHz, CDCl3),
δ, ppm (J, Hz): 93.7 (d, J = 6.2, CF3). 19F NMR spectrum
(376 MHz, DMSO-d6), δ, ppm (J, Hz): 93.8 (d, J = 6.2,
CF3). 13C NMR spectrum, δ, ppm (J, Hz): 14.7; 24.8; 28.9;
48.2; 49.9; 65.2; 69.5; 75.0; 75.3 (q, J = 33.7, C-6); 93.4;
113.7; 117.7; 118.1; 122.5; 122.8 (q, J = 280.3, CF3);
123.9; 124.3; 136.6; 137.2; 141.7; 141.8; 142.4; 148.2;
198.0; 198.2. Found, m/z: 503.1423 [М+Н]+.
C25H22F3N2O6. Calculated, m/z: 503.1424.
(6S*,6aS*,6bS*,11aR*)-2-Chloro-6a-nitro-6-trifluoro-
methyl-6a,6b,7,8,9,11a-hexahydro-6H-spiro[chromeno-
[3,4-a]pyrrolizidine-11,2'-indene]-1',3'-dione (4e). Yield
0.41 g (83%), mp 167–168°C (decomp.). IR spectrum,
(6S*,6aS*,6bS*,11aR*)-2-Methoxy-6a-nitro-6-trifluoro-
methyl-6a,6b,7,8,9,11a-hexahydro-6H-spiro[chromeno-
[3,4-a]pyrrolizidine-11,2'-indene]-1',3'-dione (4c). Yield
0.39 g (80%), mp 175–176°C (decomp.). IR spectrum,
ν, cm−1: 1703, 1553, 1503, 1466, 1399, 1370, 1355, 1333.
1H NMR spectrum (500 MHz, CDCl3), δ, ppm (J, Hz):
1.78–3.18 (6H, m, 3CH2); 3.27 (3H, s, CH3O); 4.47 (1H, t,
J = 7.2, 6b-СH); 5.02 (1H, s, 11a-СH); 5.77 (1H, d, J = 2.9,
H-1); 5.78 (1H, q, J = 6.2, 6-CH); 6.65 (1H, dd, J = 9.0,
J = 2.9, H-3); 6.94 (1H, d, J = 9.0, H-4); 7.86 (1H, d,
J = 7.6, H-4'(7')); 7.92 (1H, td, J = 7.6, J = 1.0, H-5'(6'));
7.97 (1H, td, J = 7.6, J = 1.0, H-6'(5')); 8.16 (1H, d, J = 7.6,
1
ν, cm−1: 1701, 1552, 1486, 1382, 1353. H NMR spectrum
(500 MHz, CDCl3), δ, ppm (J, Hz): 1.79–3.15 (6H, m,
3CH2); 4.46 (1H, t, J = 7.3, 6b-СH); 4.96 (1H, s, 11a-СH);
5.87 (1H, q, J = 6.1, 6-CH); 6.29 (1H, d, J = 2.3, H-1); 6.97
(1H, d, J = 8.8, H-4); 7.07 (1H, dd, J = 8.8, J = 2.3, H-3);
7.88 (1H, d, J = 7.6, H-4'(7')); 7.95 (1H, td, J = 7.5, J = 1.0,
H-5'(6')); 8.01 (1H, td, J = 7.5, J = 1.0, H-6'(5')); 8.18 (1H,
d, J = 7.6, H-7'(4')). 1H NMR spectrum (400 MHz, DMSO-d6),
δ, ppm (J, Hz): 1.71–2.89 (6H, m, 3CH2); 4.23 (1H, dd,
J = 9.2, J = 6.5, 6b-СH); 4.87 (1H, s, 11a-СH); 6.02 (1H, q,
J = 6.1, 6-CH); 6.25 (1H, d, J = 2.6, H-1); 7.10 (1H, d,
J = 8.8, H-4); 7.58 (1H, dd, J = 8.8, J = 2.6, H-3); 7.81
(1H, d, J = 7.6, H-4'(7')); 8.07 (1H, td, J = 7.5, J = 1.0,
H-5'(6')); 8.16 (1H, td, J = 7.5, J = 1.0, H-6'(5')); 8.23 (1H,
1
H-7'(4')). H NMR spectrum (500 MHz, DMSO-d6), δ, ppm
(J, Hz): 1.68–2.86 (6H, m, 3CH2); 3.14 (3H, s, CH3O);
4.25 (1H, dd, J = 8.8, J = 6.5, 6b-СH); 4.80 (1H, s,
11a-СH); 5.71 (1H, d, J = 2.9, H-1); 5.91 (1H, q, J = 6.2,
6-CH); 6.72 (1H, dd, J = 9.0, J = 2.9, H-3); 6.99 (1H, d,
1195

Chemistry of Heterocyclic Compounds 2017, 53(11), 1192–1198
d, J = 7.6, H-7'(4')). 19F NMR spectrum (471 MHz,
137.6; 141.6; 148.2; 198.1; 198.3. Found, %: С 44.61; Н 2.38;
N 4.56. C23H15Br2F3N2O5. Calculated, %: С 44.83; Н 2.45;
N 4.55.
CDCl3), δ, ppm (J, Hz): 93.0 (d, J = 6.1, CF3). 19F NMR
spectrum (376 MHz, DMSO-d6), δ, ppm (J, Hz): 92.9 (d,
J = 6.1, CF3). 13C NMR spectrum, δ, ppm (J, Hz): 24.6;
28.9; 47.7; 50.1; 69.3; 74.4; 75.5 (q, J = 33.6, C-6); 92.2;
117.7; 117.8; 119.1; 122.5 (q, J = 281.6, CF3); 124.2; 124.6;
126.3; 129.6; 137.2; 137.7; 141.6; 141.8; 150.5; 197.2; 197.3.
Found, m/z: 493.0771 [М+Н]+. C23H17ClF3N2O5.
Calculated, m/z: 493.0773.
(6S*,6aS*,6bS*,11aR*)-2,6a-Dinitro-6-trifluoromethyl-
6a,6b,7,8,9,11a-hexahydro-6H-spiro[chromeno[3,4-a]-
pyrrolizidine-11,2'-indene]-1',3'-dione (4h). Yield 0.44 g
(87%), mp 147–148°C (decomp.). IR spectrum, ν, cm−1:
1
1707, 1589, 1564, 1533, 1346, 1329. H NMR spectrum
(500 MHz, CDCl3), δ, ppm (J, Hz): 1.84–3.06 (6H, m,
3CH2); 4.43 (1H, t, J = 7.7, 6b-СH); 4.91 (1H, s, 11a-СH);
6.05 (1H, q, J = 5.8, 6-CH); 7.16 (1H, d, J = 9.1, H-4); 7.25
(1H, d, J = 2.1, H-1); 7.80 (1H, d, J = 7.7, H-4'(7')); 7.93 (1H,
td, J = 7.6, J = 1.0, H-5'(6')); 8.00–8.05 (2H, m, H-6'(5'),
(6S*,6aS*,6bS*,11aR*)-2-Bromo-6a-nitro-6-trifluoro-
methyl-6a,6b,7,8,9,11a-hexahydro-6H-spiro[chromeno-
[3,4-a]pyrrolizidine-11,2'-indene]-1',3'-dione (4f). Yield
0.45 g (83%), mp 152–153°C (decomp.). IR spectrum,
1
1
ν, cm−1: 1702, 1551, 1484, 1370, 1351, 1329. H NMR
H-3); 8.22 (1H, d, J = 7.7, H-7'(4')). H NMR spectrum
spectrum (500 MHz, CDCl3), δ, ppm (J, Hz): 1.81–3.19
(6H, m, 3CH2); 4.49 (1H, t, J = 7.4, 6b-СH); 4.96 (1H, s,
11a-СH); 5.86 (1H, q, J = 6.0, 6-CH); 6.42 (1H, d, J = 2.2,
H-1); 6.91 (1H, d, J = 8.8, H-4); 7.21 (1H, dd, J = 8.8,
J = 2.2, H-3); 7.88 (1H, d, J = 7.6, H-4'(7')); 7.96 (1H, td,
J = 7.5, J = 1.1, H-5'(6')); 8.01 (1H, td, J = 7.5, J = 1.1,
H-6'(5')); 8.18 (1H, d, J = 7.6, H-7'(4')). 1H NMR spectrum
(400 MHz, DMSO-d6), δ, ppm (J, Hz): 1.70–2.90 (6H, m,
3CH2); 4.22 (1H, br. t, J = 7.2, 6b-СH); 4.87 (1H, s,
11a-СH); 6.01 (1H, q, J = 6.1, 6'-CH); 6.36 (1H, br. s,
H-1); 7.16 (1H, d, J = 8.6, H-4); 7.70 (1H, dd, J = 8.6,
J = 2.2, H-3); 7.81 (1H, d, J = 7.6, H-4'(7')); 8.07 (1H, t,
J = 7.5, H-5'(6')); 8.16 (1H, t, J = 7.5, H-6'(5')); 8.23 (1H,
d, J = 7.6, H-7'(4')). 19F NMR spectrum (471 MHz,
CDCl3), δ, ppm (J, Hz): 93.0 (d, J = 6.0, CF3). 19F NMR
spectrum (376 MHz, DMSO-d6), δ, ppm (J, Hz): 92.8 (d,
J = 6.1, CF3). 13C NMR spectrum, δ, ppm, (J, Hz): 24.8;
29.2; 47.6; 50.1; 69.1; 75.1; 75.3 (q, J = 33.6, C-6); 91.9;
114.9; 118.6; 119.3; 122.5 (q, J = 281.6, CF3); 124.0; 124.4;
129.4; 132.3; 137.0; 137.6; 141.6; 141.7; 150.9; 198.0;
198.1. Found, m/z: 537.0267 [М+Н]+. C23H17BrF3N2O5.
Calculated, m/z: 537.0267.
(400 MHz, DMSO-d6), δ, ppm (J, Hz): 1.76–2.91 (6H, m,
3CH2); 4.23 (1H, dd, J = 9.5, J = 6.3, 6b-СH); 5.10 (1H, s,
11a-СH); 6.16 (1H, q, J = 5.7, 6-CH); 7.12 (1H, d, J = 2.3,
H-1); 7.34 (1H, d, J = 9.1, H-4); 7.72 (1H, d, J = 7.8,
H-4'(7')); 8.01 (1H, br. t, J = 7.8, H-5'(6')); 8.05 (1H, dd,
J = 9.1, J = 2.3, H-3); 8.14 (1H, t, J = 7.8, H-6'(5')); 8.25
(1H, d, J = 7.7, H-7'(4')). 19F NMR spectrum (471 MHz,
CDCl3), δ, ppm (J, Hz): 92.2 (d, J = 5.8, CF3). 19F NMR
spectrum (471 MHz, DMSO-d6), δ, ppm (J, Hz): 92.4 (d,
J = 5.7, CF3). 13C NMR spectrum, δ, ppm (J, Hz): 24.8;
29.6; 47.4; 50.1; 69.0; 75.1; 75.4 (q, J = 34.2, C-6); 90.3;
117.5; 118.3; 120.3; 122.2 (q, J = 281.6, CF3); 124.3;
125.1; 128.5; 131.9; 137.4; 137.8; 141.5; 141.7; 142.4;
198.2; 198.4. Found, %: С 54.73; Н 3.15; N 8.31.
C23H16F3N3O7. Calculated, %: С 54.88; Н 3.20; N 8.35.
(6S*,6aS*,6bS*,11aR*)-2,4,6a-Trinitro-6-trifluoro-
methyl-6a,6b,7,8,9,11a-hexahydro-6H-spiro[chromeno-
[3,4-a]pyrrolizidine-11,2'-indene]-1',3'-dione (4i). Yield
0.49 g (89%), mp 154–155°C (decomp.). IR spectrum, ν, cm−1:
1
1706, 1538, 1401, 1339. H NMR spectrum (500 MHz,
CDCl3), δ, ppm (J, Hz): 1.80–2.98 (6H, m, 3CH2); 4.33
(1H, dd, J = 8.3, J = 7.3, 6b-СH); 4.90 (1H, s, 11a-СH);
6.22 (1H, q, J = 5.5, 6-CH); 7.46 (1H, d, J = 2.6, H-1); 7.84
(1H, d, J = 7.7, H-4'(7')); 7.96 (1H, td, J = 7.6, J = 1.0,
H-5'(6')); 8.05 (1H, td, J = 7.6, J = 1.0, H-6'(5')); 8.22 (1H,
(6S*,6aS*,6bS*,11aR*)-2,4-Dibromo-6a-nitro-6-tri-
fluoromethyl-6a,6b,7,8,9,11a-hexahydro-6H-spiro[chro-
meno[3,4-a]pyrrolizidine-11,2'-indene]-1',3'-dione (4g).
1
Yield 0.55
g
(90%), mp 173–174°C (decomp.).
d, J = 7.7, H-7'(4')); 8.67 (1H, d, J = 2.6, H-3). H NMR
1
IR spectrum, ν, cm−1: 1701, 1554, 1408, 1355. H NMR
spectrum (500 MHz, CDCl3), δ, ppm (J, Hz): 1.77–3.05
(6H, m, 3CH2); 4.39 (1H, t, J = 7.5, 6b-СH); 4.92 (1H, s,
11a-СH); 5.92 (1H, q, J = 5.9, 6-CH); 6.37 (1H, d, J = 2.1,
H-1); 7.49 (1H, d, J = 2.1, H-3); 7.88 (1H, d, J = 7.5,
H-4'(7')); 7.96 (1H, dd, J = 7.5, J = 1.1, H-5'(6')); 8.01 (1H,
dd, J = 7.5, J = 1.1, H-6'(5')); 8.17 (1H, d, J = 7.5, H-7'(4')).
1H NMR spectrum (400 MHz, DMSO-d6), δ, ppm (J, Hz):
1.72–2.91 (6H, m, 3CH2); 4.22 (1H, dd, J = 9.1, J = 6.3,
6b-СH); 4.96 (1H, s, 11a-СH); 6.08 (1H, q, J = 5.9, 6-CH);
6.39 (1H, d, J = 2.0, H-1); 7.84 (1H, d, J = 7.6, H-4'(7'));
7.76 (1H, d, J = 2.0, H-3); 8.07 (1H, t, J = 7.5, H-5'(6'));
8.16 (1H, t, J = 7.5, H-6'(5')); 8.22 (1H, d, J = 7.6, H-7'(4')).
19F NMR spectrum (471 MHz, CDCl3), δ, ppm (J, Hz): 92.7
(d, J = 5.9, CF3). 19F NMR spectrum (376 MHz, DMSO-d6),
δ, ppm (J, Hz): 92.6 (d, J = 5.9, CF3). 13C NMR spectrum,
δ, ppm (J, Hz): 24.8; 29.3; 47.7; 49.9; 69.1; 74.5; 75.8 (q,
J = 34.0, C-6); 91.9; 112.7; 114.7; 120.0; 122.3 (q,
J = 287.6, CF3); 124.0; 124.5; 128.5; 131.9; 135.3; 137.1;
spectrum (400 MHz, DMSO-d6), δ, ppm (J, Hz): 1.77–3.07
(6H, m, 3CH2); 4.26 (1H, dd, J = 9.6, J = 6.3, 6b-СH); 5.32
(1H, s, 11a-СH); 6.28 (1H, q, J = 5.6, 6-CH); 7.43 (1H, d,
J = 2.6, H-1); 7.79 (1H, d, J = 7.7, H-4'(7')); 8.71 (1H, d,
J = 2.6, H-3); 8.07 (1H, t, J = 7.6, H-5'(6')); 8.16 (1H, t,
J = 7.6, H-6'(5')); 8.26 (1H, d, J = 7.7, H-7'(4')). 19F NMR
spectrum (471 MHz, CDCl3), δ, ppm (J, Hz): 91.7 (d,
J = 5.5, CF3). 19F NMR spectrum (471 MHz, DMSO-d6),
δ, ppm (J, Hz): 92.4 (d, J = 5.6, CF3). 13C NMR spectrum,
δ, ppm (J, Hz): 24.7; 29.7; 46.6; 50.1; 68.7; 74.9; 75.8 (q,
J = 34.3, C-6'); 88.9; 121.4; 121.5; 121.6 (q, J = 282.0,
CF3); 124.4; 124.7; 125.8; 137.8; 138.1; 138.2; 140.7;
141.4; 141.6; 149.8; 197.7; 197.9. Found, %: С 50.35;
Н 2.76; N 10.04. C23H15F3N4O9. Calculated, %: С 50.38;
Н 2.76; N 10.22.
(6R*,6aS*,6bS*,11aR*)-6a-Nitro-6-phenyl-
6a,6b,7,8,9,11a-hexahydro-6H-spiro[chromeno[3,4-a]-
pyrrolizidine-11,2'-indene]-1',3'-dione (4j). Yield 0.41 g
(88%), mp 163–164°C (decomp.). IR spectrum, ν, cm−1:
1196

Chemistry of Heterocyclic Compounds 2017, 53(11), 1192–1198
1709, 1621, 1592, 1547, 1489, 1457, 1407, 1354, 1325.
s, 6-CH); 6.86 (1H, d, J = 8.7, H-4); 7.18 (1H, dd, J = 8.7,
J = 2.3, H-3); 7.43–7.49 (3H, m, H Ph); 7.50–7.55 (2H, m,
H Ph); 7.87 (1H, br. d, J = 7.5, H-4'(7')); 7.97 (1H, td,
J = 7.5, J = 1.0, H-5'(6')); 8.01 (1H, td, J = 7.5, J = 1.0,
H-6'(5')); 8.18 (1H, br. d, J = 7.5, H-7'(4')). 1H NMR spectrum
(500 MHz, DMSO-d6), δ, ppm (J, Hz): 1.63–2.96 (6H, m,
3CH2); 3.74 (1H, dd, J = 10.5, 5.7, 6b-СH); 4.65 (1H, s,
11a-СH); 6.28 (1H, d, J = 2.4, H-1); 6.44 (1H, s, 6-CH);
6.93 (1H, d, J = 8.7, H-4); 7.16 (1H, dd, J = 8.7, J = 2.4,
H-3); 7.32–7.37 (2H, m, H Ph); 7.47–7.53 (3H, m, H Ph);
7.84 (1H, br. d, J = 7.6, H-4'(7')); 8.09 (1H, td, J = 7.5,
J = 1.0, H-5'(6')); 8.16 (1H, td, J = 7.6, J = 1.0, H-6'(5'));
8.22 (1H, br. d, J = 7.6, H-7'(4')). 13C NMR spectrum, δ, ppm:
24.8; 30.0; 47.5; 50.7; 69.0; 76.4; 78.2; 93.0; 113.4; 119.4;
119.5; 123.8; 124.2; 127.8 (2C); 128.3 (2C); 129.5; 130.1;
131.9; 134.1; 136.8; 137.6; 141.4; 141.9; 153.2; 198.7;
200.2. Found, %: С 61.53; Н 3.88; N 5.34. C28H21BrN2O5.
Calculated, %: С 61.66; Н 3.88; N 5.14.
X-ray structural study of compound 4a was
performed at 22°C on an Xcalibur diffractometer with an
Eos CCD detector according to standard procedure (MoKα
radiation, graphite monochromator, ω-scanning, 2θmax
56.4°. Crystals suitable for X-ray structural analysis were
obtained by slowly evaporating a chloroform solution of
compound 4a. The structure of compound 4a was solved
by direct method using the SHELX97 software suite.14 The
positions of all non-hydrogen atoms were independently
refined in anisotropic approximation, the hydrogen atoms
were placed in geometrically calculated positions and
included in the refinement according to the ''rider'' model
with dependent temperature parameters. The complete
X-ray structural dataset for compound 4a was deposited at
the Cambridge Crystallographic Data Center (deposit
CCDC 1565370).
1H NMR spectrum (500 MHz, CDCl3), δ, ppm (J, Hz): 1.82–
3.37 (6H, m, 3CH2); 4.34 (1H, dd, J = 9.1, J = 6.9, 6b-СH);
4.89 (1H, s, 11a-СH); 6.24 (1H, br. d, J = 7.4, H-1); 6.46
(1H, s, 6-CH); 6.57 (1H, td, J = 7.6, J = 1.1 H-2); 6.97 (1H,
dd, J = 8.2, J = 1.1, H-4); 7.16 (1H, td, J = 7.7, J = 1.3
H-3); 7.45–7.49 (3H, m, Н Ph); 7.59–7.64 (2H, m, H Ph);
7.88 (1H, br. d, J = 7.6, H-4'(7')); 7.94 (1H, td, J = 7.5,
J = 1.0, H-5'(6')); 8.00 (1H, td, J = 7.5, J = 1.0, H-6'(5'));
1
8.17 (1H, br. d, J = 7.6, H-7'(4')). H NMR spectrum
(500 MHz, DMSO-d6), δ, ppm (J, Hz): 1.62–2.95 (6H, m,
3CH2); 3.76 (1H, dd, J = 10.3, J = 5.8, 6b-СH); 4.62 (1H, s,
11a-СH); 6.21 (1H, dd, J = 7.9, J = 1.5, H-1); 6.49 (1H, s,
6-CH); 6.69 (1H, td, J = 7.6, J = 1.1 H-2); 6.94 (1H, dd,
J = 8.2, J = 1.1, H-4); 7.16 (1H, td, J = 7.8, J = 1.5, H-3);
7.33–7.39 (2H, m, H Ph); 7.48–7.53 (3H, m, H Ph); 7.81
(1H, br. d, J = 7.6, H-4'(7')); 8.06 (1H, td, J = 7.5, J = 1.1,
H-5'(6')); 8.14 (1H, td, J = 7.6, J = 1.0, H-6'(5')); 8.21 (1H,
br. d, J = 7.7, H-7(4)). 13C NMR spectrum, δ, ppm: 24.7;
29.9; 47.7; 50.8; 69.2; 76.0; 78.0; 93.6; 117.1; 117.7;
121.5; 123.7; 124.2; 127.2; 127.8 (2C); 128.2 (2C); 128.9;
129.4; 134.5; 136.7; 137.4; 141.5; 142.0; 154.0; 198.4;
200.0. Found, %: С 72.13; Н 4.90; N 6.27. C28H22N2O5.
Calculated, %: С 72.09; Н 4.75; N 6.01.
(6R*,6aS*,6bS*,11aR*)-2-Methoxy-6a-nitro-6-phenyl-
6a,6b,7,8,9,11a-hexahydro-6H-spiro[chromeno[3,4-a]-
pyrrolizidine-11,2'-indene]-1',3'-dione (4k). Yield 0.42 g
(84%), mp 179–180°C (decomp.). IR spectrum, ν, cm−1:
1708, 1622, 1590, 1539, 1501, 1456, 1408, 1353, 1325.
1H NMR spectrum (500 MHz, CDCl3), δ, ppm (J, Hz): 1.88–
3.48 (6H, m, 3CH2); 3.24 (3H, s, CH3O); 4.50 (1H, br. t,
J = 7.7, 6b-СH); 4.91 (1H, s, 11a-СH); 5.71 (1H, d, J = 2.9,
H-1); 6.34 (1H, s, 6-CH); 6.67 (1H, dd, J = 9.0, J = 2.9,
H-3); 6.90 (1H, d, J = 9.0, H-4); 7.45–7.49 (3H, m, H Ph);
7.61–7.66 (2H, m, H Ph); 7.93 (1H, br. d, J = 7.3, H-4'(7'));
7.97 (1H, td, J = 7.3, J = 1.1, H-5'(6')); 8.01 (1H, td, J = 7.3,
The work was performed with financial support from the
Russian Science Foundation (project 17-73-20070).
1
J = 1.4, H-6'(5')); 8.19 (1H, br. d, J = 7.4, H-7'(4')). H NMR
spectrum (500 MHz, DMSO-d6), δ, ppm (J, Hz): 1.62–2.95
(6H, m, 3CH2); 3.09 (3H, s, CH3O); 3.75 (1H, dd, J = 10.4,
J = 5.8, 6b-СH); 4.56 (1H, s, 11a-СH); 5.64 (1H, d, J = 2.9,
H-1); 6.37 (1H, s, 6-CH); 6.67 (1H, dd, J = 8.9, J = 2.9
H-3); 6.87 (1H, d, J = 8.9, H-4); 7.32–7.38 (2H, m, H Ph);
7.47–7.52 (3H, m, H Ph); 7.83 (1H, br. d, J = 7.6, H-4'(7'));
8.07 (1H, td, J = 7.5, J = 1.1, H-5(6)); 8.14 (1H, td, J = 7.6,
J = 1.0, H-6(5)); 8.21 (1H, br. d, J = 7.7, H-7(4)). 13C NMR
spectrum, δ, ppm: 24.7; 29.8; 48.3; 50.9; 55.1; 69.2; 75.7;
78.2; 93.8; 111.3; 115.7; 118.7; 123.7; 124.4; 127.8 (2C);
128.2 (2C); 129.4; 131.7; 134.5; 136.7; 137.5; 141.4;
142.2; 148.1; 153.8; 197.7; 199.6. Found, %: С 70.17; Н
5.00; N 5.80. C29H24N2O6. Calculated, %: С 70.15; Н 4.87;
N 5.64.
References
1. (a) The Chemistry of Heterocyclic Compounds: Chromans
and Tocopherols; Ellis, G. P.; Lockhart, I. M., Eds.; John
Wiley & Sons: New York, 1981, Vol. 36. (b) Goel, A.;
Ram, V. J. Tetrahedron 2009, 65, 7865. (c) Costa, M.;
Dias, T. A.; Brito, A.; Proença, F. Eur. J. Med. Chem. 2016,
123, 487. (d) Unangst, P. C.; Capiris, T.; Connor, D. T.;
Heffner, T. G.; MacKenzie, R. G.; Miller, S. R.; Pugsley, T. A.;
Wise, L. D. J. Med. Chem. 1997, 40, 2688.
2. (a) Lavielle, G.; Dubuffet, T.; Millan, M.; Newman-Tancredi, A.
US Patent 5663191; Chem. Abstr. 1996, 124, 261014.
(b) Haight, A. R.; Bailey, A. E.; Baker, W. S.; Cain, M. H.;
Copp, R. R.; DeMattei, J. A.; Ford, K. L.; Henry, R. F.;
Hsu, M. C.; Keyes, R. F.; King, S. A.; McLaughlin, M. A.;
Melcher, L. M.; Nadler, W. R.; Oliver, P. A.; Parekh, S. I.;
Patel, H. H.; Seif, L. S.; Staeger, M. A.; Wayne, G. S.;
Wittenberger, S. J.; Zhang, W. Org. Process Res. Dev. 2004,
8, 897.
(6R*,6aS*,6bS*,11aR*)-2-Bromo-6a-nitro-6-phenyl-
6a,6b,7,8,9,11a-hexahydro-6H-spiro[chromeno[3,4-a]-
pyrrolizidine-11,2'-indene]-1',3'-dione (4l). Yield 0.49 g
(90%), mp 194–195°C (decomp.). IR spectrum, ν, cm−1:
3. (a) Döndas, H. A.; Retamosa, M. G.; Sansano, J. M. Synthesis
2017, 2819. (b) Singh, M. S.; Chowdhury, S.; Koley, S.
Tetrahedron 2016, 72, 1603.
4. (a) Nyerges, M.; Virányi, A.; Marth, G.; Dancsó, A.; Blaskó, G.;
Tőke, L. Synlett 2004, 2761. (b) Virányi, A.; Marth, G.;
1
1707, 1590, 1545, 1481, 1456, 1410, 1353, 1330. H NMR
spectrum (500 MHz, CDCl3), δ, ppm (J, Hz): 1.71–3.19
(6H, m, 3CH2); 4.04 (1H, dd, J = 10.4, J = 6.1, 6b-СH);
4.68 (1H, s, 11a-СH); 6.28 (1H, d, J = 2.3, H-1); 6.46 (1H,
1197

Chemistry of Heterocyclic Compounds 2017, 53(11), 1192–1198
Dancsó, A.; Blaskó, G.; Tőke, L.; Nyerges, M. Tetrahedron
Sosnovskikh, V. Ya. Tetrahedron 2013, 69, 9642.
(d) Korotaev, V. Yu.; Barkov, A. Yu.; Kutyashev, I. B.;
Kotovich, I. V.; Ezhikova, M. A.; Kodess, M. I.;
Sosnovskikh, V. Ya. Tetrahedron 2015, 71, 2658.
(e) Korotaev, V. Yu.; Kutyashev, I. B.; Barkov, A. Yu.;
Sosnovskikh, V. Ya. Chem. Heterocycl. Compd. 2017, 53,
597. [Khim. Geterotsikl. Soedin. 2017, 53, 597.]
2006, 62, 8720. (c) Korotaev, V. Yu.; Barkov, A. Yu.;
Moshkin, V. S.; Matochkina, E. G.; Kodess, M. I.;
Sosnovskikh, V. Ya. Tetrahedron 2013, 69, 8602. (d) Xie, J.-W.;
Fan, L.-P.; Li, X.-S.; Xu, D.-C. Org. Biomol. Chem. 2010, 8, 2117.
5. (a) Rao, J. N. S.; Raghunathan, R. Tetrahedron Lett. 2013, 54,
6568. (b) Rao, J. N. S.; Raghunathan, R. Tetrahedron Lett.
2015, 56, 2276.
9. (a) Kodukulla, R. P. K.; Hariharan, S.; Trivedi, G. K.
Tetrahedron 1994, 50, 4623. (b) Yan, L.-J.; Zhang, S.-Y. Acta
Crystallogr., Sect. E: Crystallogr. Commun. 2013, 69, о877.
10. Korotaev, V. Yu.; Sosnovskikh, V. Ya.; Barkov, A. Yu. Russ.
Chem. Rev. 2013, 82, 1081. [Usp. Khim. 2013, 82, 1081.]
11. Kaupp, G.; Naimi-Jamal, M. R.; Schmeyers, J. Chem.–Eur. J.
2002, 8, 594.
12. Barkov, A. Yu.; Korotaev, V. Yu.; Kotovich, I. V.;
Zimnitskiy, N. S.; Kutyashev, I. B.; Sosnovskikh, V. Ya.
Chem. Heterocycl. Compd. 2016, 52, 814. [Khim. Geterotsikl.
Soedin. 2016, 52, 814.]
13. (a) Korotaev, V. Yu.; Kutyashev, I. B.; Sosnovskikh, V. Ya.
Heteroat. Chem. 2005, 16, 492. (b) Sakakibara, T.; Koezuka, M.;
Sudoh, R. Bull. Chem. Soc. Jpn. 1978, 51, 3095.
14. Sheldrick, G. M. Acta Crystallogr., Sect. A: Found. Adv.
2008, A64, 112.
6. (a) Poornachandran, M.; Raghunathan, R. Synth. Commun.
2007, 37, 2507. (b) Barkov, A. Yu.; Zimnitskiy, N. S.;
Korotaev, V. Yu.; Kutyashev, I. B.; Moshkin, V. S.;
Sosnovskikh, V. Ya. Chem. Heterocycl. Compd. 2017, 53,
451. [Khim. Geterotsikl. Soedin. 2017, 53, 451.]
7. (a) Kathiravan, S.; Raghunathan, R.; Suresh, G.; Siva, G. V.
Med. Chem. Res. 2012, 21, 3170. (b) Ajmi, N. S.; Ali, M. A.;
Rusli, I.; Hasnah, O.; Kumar, R. S.; Tan, S. C.; Yeong, K. Y.
WO Patent 2012099452 A1; Chem. Abstr. 2012, 157, 261573.
8. (a) Korotaev, V. Yu.; Sosnovskikh, V. Ya.; Barabanov, M. A.;
Yasnova, E. S.; Ezhikova, M. A.; Kodess, M. I.; Slepukhin, P. A.
Tetrahedron 2010, 66, 1404. (b) Korotaev, V. Yu.;
Sosnovskikh, V. Ya.; Barkov, A. Yu.; Slepukhin, P. A.;
Ezhikova, M. A.; Kodess, M. I.; Shklyaev, Yu. V. Tetrahedron
2011, 67, 8685. (c) Korotaev, V. Yu.; Barkov, A. Yu.;
1198