A highly efficient and stereoselective cycloaddition of nitrones to N-arylitaconimides

Article abstract of DOI:10.1016/j.tetlet.2019.151063

The 1,3-dipolar cycloaddition of keto- and aldonitrones with N-arylitaconimides proceeds regioselectively giving only 5-spiroisoxazolidines. In the case of aldonitrones the reaction proceeds with high diastereoselectivity. A range of the obtained adducts

Full text of DOI:10.1016/j.tetlet.2019.151063

Tetrahedron Letters xxx (xxxx) xxx
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
A highly efficient and stereoselective cycloaddition of nitrones
to N-arylitaconimides
⇑
Polina S. Teterina, Mariia M. Efremova , Ekaterina V. Sirotkina, Alexander S. Novikov,
⇑
Olesya V. Khoroshilova, Alexander P. Molchanov
Saint Petersburg State University, Universitetskaya nab. 7/9, St. Petersburg 199034, Russian Federation
a r t i c l e i n f o
a b s t r a c t
Article history:
The 1,3-dipolar cycloaddition of keto- and aldonitrones with N-arylitaconimides proceeds regioselec-
tively giving only 5-spiroisoxazolidines. In the case of aldonitrones the reaction proceeds with high
diastereoselectivity. A range of the obtained adducts were subjected to reductive cleavage of the NAO
bond using zinc powder in acetic acid to give the corresponding spirolactones and 1,3-amino alcohols.
Ó 2019 Published by Elsevier Ltd.
Received 2 July 2019
Revised 15 August 2019
Accepted 19 August 2019
Available online xxxx
Keywords:
Nitrones
Itaconimides
Cycloaddition
Reduction
Introduction
tions can be unpredictable and depends on both steric and elec-
tronic effects [10–12]. Recently these reactions have attracted
The isoxazolidine ring is an important structural part of a wide
range of heterocyclic systems possessing valuable pharmacological
properties [1], including antiviral [2], antibacterial [3] and antitu-
mor [4] activities. 5-Spiroisoxazolidines have attracted particular
interest in recent years [5]. This structural fragment is also found
in alkaloids extracted from plants [6]. Highly effective and selective
1,3-dipolar cycloadditions of nitrones with exocyclic double bonds
were employed for the synthesis of complex heterocyclic scaffolds
containing the spiroisoxazolidine moiety. Many of these products
were shown to possess valuable biological properties [7] An
undoubted advantage of 1,3-dipolar cycloaddition is the ability to
selectively generate up to three new stereocenters in one step
without the use of catalysts [8], that makes it indispensable in
the synthesis of natural products and their analogues [9].
At the same time, alkylidene succinimides are promising build-
ing blocks for the synthesis of complex spiroheterocyclic scaffolds
containing the pyrrolidine-2,5-dione fragment. It was shown that
their reactions with various 1,3-dipoles: azomethine ylides [10],
azomethine imines [11] and nitrile oxides [12] allow construction
of the corresponding spirocyclic molecules with high efficiency and
diastereoselectivity. However, the regioselectivity of these reac-
interest due to the promising antibacterial [10a,f], including
antimycobacterial [10b,f], and antifungal [10f] activities of the
products. Nevertheless, the reactions of these dipolarophiles with
nitrones have not been previously studied.
A distinct advantage of isoxazolidines is the possibility of using
them as precursors of biologically valuable 1,3-amino alcohols
[13], b-lactams [14] and b-amino acids [15]. For example, one of
the most universal, simple and inexpensive methods for the reduc-
tion of isoxazolidines is the use of zinc powder in acetic acid [16].
In the presence of certain sensitive functional groups or structural
fragments, the amino alcohol intermediates can undergo further
transformations under the reaction conditions [2d,17].
The aim of this work was to investigate the regio- and stereos-
electivity of the 1,3-dipolar cycloaddition of keto- and aldonitrones
with N-arylitaconimides and transformations of the obtained
spiroisoxazolidines under reductive (Zn, acetic acid) conditions.
Results and discussion
Initially, we investigated the regioselectivity of the 1,3-dipolar
cycloaddition of N-arylitaconimides 1a-d with N-aryl-C,C-bis
(methoxycarbonyl)nitrones 2a-d. The reactions were carried out
in dichloromethane at room temperature for three days. It was
found that the reactions proceeds regioselectively giving only
5-spiroisoxazolidines 3a-i in good yields (Table 1).
⇑
Corresponding author.
E-mail addresses: m.efremova@2012.spbu.ru (M.M. Efremova), a.molchanov@
spbu.ru (A.P. Molchanov).
https://doi.org/10.1016/j.tetlet.2019.151063
0040-4039/Ó 2019 Published by Elsevier Ltd.
Please cite this article as: P. S. Teterina, M. M. Efremova, E. V. Sirotkina et al., A highly efficient and stereoselective cycloaddition of nitrones to N-arylita-
conimides, Tetrahedron Letters, https://doi.org/10.1016/j.tetlet.2019.151063

2
P.S. Teterina et al. / Tetrahedron Letters xxx (xxxx) xxx
Table 1
1,3-Dipolar cycloaddition of N-arylitaconimides 1a-d with N-aryl-C,C-bis(methoxycarbonyl)nitrones 2a-d.
O
Entry
Itaconimide
R1
R2
Nitrone
R3
Product
Isolated yield (%)
1
2
3
4
5
6
7
8
9
1a
1a
1a
1b
1b
1b
1b
1c
1d
H
H
H
H
H
H
H
H
Cl
H
H
H
Br
Br
Br
Br
OMe
H
2a
2b
2c
2a
2b
2c
2d
2c
2c
H
Me
Br
H
Me
Br
OMe
Br
Br
3a
3b
3c
3d
3e
3f
3g
3h
3i
74
66
80
89
81
92
76
63
64
The 1H NMR spectra of the crude reaction mixtures did not
show the signals of any other products. The structures of the
adducts were confirmed by spectroscopic methods and addition-
ally proved by X-ray diffraction analysis for compound 3a (Fig. 1)
[18].
Next, the regio- and diastereoselectivities of the cycloaddition
of aldonitrones were investigated. The reactions of highly reactive
N-aryl-C-carbamoylnitrones 4a-d were carried out under the pre-
viously mentioned conditions (r.t., 3 days). It was shown, that the
1,3-dipolar cycloaddition of these nitrones also proceeds regiose-
lectively yielding a mixture of diastereomeric 5-spiroisoxazolidi-
nes 5 and 50. The isomers with cis relative configuration of the
substituent at the C3 position of isoxazolidine ring and the methy-
lene group of the pyrrolidine ring are predominant in all cases
(Table 2). NOESY NMR spectra and X-ray diffraction analysis data
for compound 5d [19] (Fig. 2) were used to determine the relative
configuration of the cycloadducts.
reactions with itaconimide 1a. Only low conversion of the starting
compounds was observed after three days in dichloromethane at
room temperature; therefore the reactions were carried out in
toluene at 110 °C for 3 h. Under these conditions the reactions also
proceeded regioselectively giving only 5-spiroisoxazolidines 7 and
70. The stereoselectivity was lower for 6a, b compared with
nitrones 4a-d (Table 3). Column chromatography on silica gel
was used for purification of the isomers. The diastereomeric
adducts 7a and 70a were difficult to separate completely. However,
a moderate amount of 7a was obtained in pure form, crystallized
and used for X-ray diffraction analysis [20], which established its
relative configuration.
In order to explain the regioselectivity, we carried out quantum
chemical calculations at the DFT level of theory (B3LYP/6-31G*,
geometry optimization in dichloromethane solution, for details
see Computational details section) of global electrophilicity and
nucleophilicity indices and Fukui functions [21] for the model
structures of dipolarophiles 1a and 1b and dipoles 2a, 4a, 6a
(Table S1, see ESI). From the analysis of global electrophilicity
and nucleophilicity indices and the energies of the frontier orbitals,
it can be concluded that different FMO of the dipolarophiles and
dipoles can interact depending on the substituents in the nitrones.
In the case of nitrone 2a bearing two electron withdrawing groups,
the dipole acts as an electrophile (inverse electron demand
cycloaddition). At the same time nitrone 6a acts as a nucleophile
in the reactions with itaconimides. For nitrone 4a both types of
interactions are possible. However, analysis of the Fukui functions
does not allow us to rationalize the reasons of the observed regios-
electivity. Therefore, it can be assumed that the regioselectivity is
determined by steric factors.
In most cases, in the 1H NMR spectra of the crude reaction mix-
tures only signals for major isomer 5 were observed. However, in
the cases of imide 1a and nitrones 4b and 4c the formation of
minor diastereomers 50b and 50c, respectively, was also observed.
The obtained isomers were purified by column chromatography
on silica.
The reactions of itaconimide 1a with C,N-diarylnitrones 6a, b
containing no electron-withdrawing groups were also investi-
gated. Nitrones 6a, b demonstrated diminished reactivity in the
Moreover, our results are consistent with previously
reported data for the cycloaddition of C,N-diphenylnitrone and
3,4-dihydro-2H-pyrrole 1-oxide with exo-methylene heterocyclic
compounds
(3-methylene-5,5-dimethyl-2-pyrrolidinone,
-methylene-d-
3-methylene-5,5-dimethyl-2-pyrrolidinethione,
a
butyrolactone), where the observed regio- and stereoselectivity
appeared to be controlled by steric effects in the transition states
(Scheme S1, see ESI) [7h–m].
The presence of functional groups in isoxazolidines 3 and 5
make them promising substrates for further transformations. In
this work the NAO bond of the isoxazolidine rings were reduced
by employing zinc in acetic acid. First, isoxazolidines 3, containing
two ester groups at the C3 position of the isoxazolidine ring were
reduced. The reactions were carried out in THF at 60 °C and mix-
Fig. 1. Single crystal X-ray structure of 3a.
Please cite this article as: P. S. Teterina, M. M. Efremova, E. V. Sirotkina et al., A highly efficient and stereoselective cycloaddition of nitrones to N-arylita-
conimides, Tetrahedron Letters, https://doi.org/10.1016/j.tetlet.2019.151063

P.S. Teterina et al. / Tetrahedron Letters xxx (xxxx) xxx
3
Table 2
1,3-Dipolar cycloaddition of N-arylitaconimides 1a-b with N-aryl-C-carbamoylnitrones 4a-d.
a
Entry
Itaconimide
R1
Nitrone
R2
R3
Products
Ratio 5:50
Isolated yield (%)
5
50
1
2
3
4
6
5
1a
1a
1a
1b
1b
1b
H
H
H
Br
Br
Br
4a
4b
4c
4a
4b
4d
H
H
5a
–
80
60
69
88
88
84
–
4
Me
Me
H
Me
Me
Cl
Me
H
Cl
H
5b, 50b
5c, 50c
5d
9:1
10:1
–
–
–
9 (5c + 50c)b
–
–
–
5e
5f
a
From 1H NMR spectra of the crude reaction mixture.
Mixture of diastereomers. Ratio 5:50 – 1:1.4.
b
tures of diastereomeric aminolactones 9 were obtained (Table 4).
Attempts to carry out this reaction at room temperature were
unsuccessful and no conversion was observed. For compounds 3e
and 3f full conversion was achieved after 4 h. However, in the case
of 3d, the starting compound was detected in the reaction mixture
after 4 h (Table 4, entry 1), so the reaction time was increased to
8 h. To investigate the possibility of the isomerization of 90a, the
isomer was heated under the standard reaction conditions. Forma-
tion of 9a was not detected (TLC control). After 4 h 90a decomposed
giving an unidentifiable mixture of products. As a result, full con-
version was observed and only major isomer 9a was obtained.
The 1H NMR spectra of the crude reaction mixtures did not show
signals of any other products. NOESY NMR spectra and X-ray
Fig. 2. Single crystal X-ray structure of 5d.
Table 3
1,3-Dipolar cycloaddition of N-arylitaconimide 1a with N-aryl-C-carbamoylnitrones 6a, b.
a
Entry
Nitrone
R
Products
Ratio 7:70
Isolated yield (%)
1
2
6a
6b
H
Cl
7a, 70a
7b, 70b
4.7:1
3.5:1
83 (7a + 70a)
52 (7b), 11 (7b + 70b)b
a
From 1H NMR spectra of the crude reaction mixture.
Mixture of diastereomers. Ratio 7b:7b’ – 1:5.7.
b
Please cite this article as: P. S. Teterina, M. M. Efremova, E. V. Sirotkina et al., A highly efficient and stereoselective cycloaddition of nitrones to N-arylita-
conimides, Tetrahedron Letters, https://doi.org/10.1016/j.tetlet.2019.151063

4
P.S. Teterina et al. / Tetrahedron Letters xxx (xxxx) xxx
Table 4
Reduction of isoxazolidines 3d-f.
a
Entry
3
R
Time h
Products
Ratio 9:90
Isolated yield (%)
9
90
1
2
3
4
3d
3d
3e
3f
H
H
Br
Me
4
8
4
4
9a, 90a
9a
9b, 90b
9c, 90c
5.5:1
–
1.9:1
1.9:1
18
37
34
37
23b
–
18
22
a
From 1H NMR spectra of the crude reaction mixture.
Mixture of 90a and 3d, ratio of 90a:3d – 1:1.6.
b
stance class due to their pharmacological properties [23], strate-
gies based on reductive cleavage of the isoxazolidine ring have
not been previously employed for their synthesis.
Three of the isoxazolidines 5 were also reduced under the same
conditions. The reactions were carried out for 4 h to complete the
conversion of starting isoxazolidines. As a result the corresponding
1,3-amino alcohols 10a-c were obtained in 50–60% yield
(Scheme 1).
Conclusion
In summary, we have demonstrated that the reactions between
the N-arylitaconimides and keto- and aldonitrones proceed regios-
electively and in high yields to give 5-spiroisoxazolidines. The
regioselectivity is assumed to be determined by steric factors.
The reactions with aldonitrones proceed with high diastereoselec-
tivity in most cases. A number of the obtained adducts were
reduced under Zn/AcOH conditions. It was demonstrated that this
strategy can lead not only to 1,3-amino alcohols, but also to amino-
lactones from adducts containing two ester groups. Thus a new
synthesis of this promising substance class was developed.
Fig. 3. Single crystal X-ray structure of 9b.
diffraction analysis data for compound 9b [22] (Fig. 3) were used to
determine the relative configuration of the lactones.
Clearly, aminolactones 9 are formed from 1,3-amino alcohol
intermediate 8, via the reaction of the hydroxyl group with one
of the ester groups. Although 5-spirolactones are a promising sub-
Scheme 1. Reduction of the isoxazolidines 5a, d, e.
Please cite this article as: P. S. Teterina, M. M. Efremova, E. V. Sirotkina et al., A highly efficient and stereoselective cycloaddition of nitrones to N-arylita-
conimides, Tetrahedron Letters, https://doi.org/10.1016/j.tetlet.2019.151063

P.S. Teterina et al. / Tetrahedron Letters xxx (xxxx) xxx
5
g) S.R. Yong, A.T. Ung, S.G. Pyne, B.W. Skelton, A.H. White, Tetrahedron 63
(2007) 5579–5586;
Acknowledgments
h) P. Oravec, L. Fišera, I. Goljer, P. Ertl, Monatsh. Chem. 122 (1991) 977–985;
i) L. Fišera, L. Jarošková, I. Matejková, Heterocycles 40 (1995) 271–278;
j) S.G. Pyne, J., Aust. J. Chem. 48 (1995) 1511–1533;
k) D. Alonso-Perarnau, P. de March, M. el Arrad, M. Figueredo, J. Font, T.
Parella, Tetrahedron 53 (1997) 14763–14772;
NMR, HRMS and XRD studies were performed at the Saint
Petersburg State University Center for Magnetic Resonance, Center
for Chemical analysis and materials research and X-Ray Diffraction
Center, respectively.
l) P. de March, M. Figueredo, J. Font, Heterocycles 50 (1999) 1213–1226;
m) M. Cacciarini, F.M. Cordero, C. Faggi, A. Goti, Molecules 5 (2000) 637–647.
[8] a) I.A. Grigor’ev Nitrile oxides, nitrones, and nitronates in organic synthesis;
Novel Strategies in Synthesis; Editor H. Feier; Wiley: New York, 2008, p. 129.;
b) K.V. Gothelf, K.A. Jørgensen, Chem. Rev. 98 (1998) 863–909;
c) T. Hashimoto, K. Maruoka, Chem. Rev. 115 (2015) 5366–5412;
d) M.S. Singh, S. Chowdhury, S. Koley, Tetrahedron 72 (2016) 1603–1644.
[9] a) R.C.F. Jones, J.N. Martin In Synthetic Application of 1,3-Dipolar
Cycloaddition Chemistry Toward Heterocycles and Natural Products; A.
Padwa, W.H. Pearson, Eds.; Wiley: New York, 2002.;
Appendix A. Supplementary data
1H, 13C NMR spectra of new compounds and computational
details. Supplementary data associated with this article can be
found in the online version, at https://doi.org/10.1016/j.tetlet.
2019.151063.
b) R.W. Bates, K. Sa-Ei, Tetrahedron 58 (2002) 5957–5978.
[10] a) K. Karthikeyan, P.M. Sivakumar, M. Doble, P.T. Perumal, Eur. J. Med. Chem.
45 (2010) 3446–3452;
References
b) S. Haddad, S. Boudriga, F. Porzio, A. Soldera, M. Askri, D. Sriram, P.
Yogeeswari, M. Knorr, Y. Rousselin, M.M. Kubicki, RSC Adv. 4 (2014) 59462–
59471;
[1] M. Berthet, T. Cheviet, G. Dujardin, I. Parrot, J. Martinez, Chem. Rev. 116 (2016)
15235–15283.
c) K.B. Sippy, D.J. Anderson, W.H. Bunnelle, C.W. Hutchins, M.R. Schrimpf,
Bioorg. Med. Chem. Lett. 19 (2009) 1682–1685;
[2] a) B. Loh, L. Vozzolo, B.J. Mok, C.C. Lee, R.J. Fitzmaurice, S. Caddick, A. Fassati,
Chem. Biol. Drug Des. 75 (2010) 461–474;
d) W.-L. Yang, Y.-Z. Liu, S. Luo, X. Yu, J.S. Fossey, W.-P. Deng, Chem. Commun.
51 (2015) 9212–9215;
e) S. Haddad, S. Boudriga, F. Porzio, A. Solderra, M. Askri, M. Knorr, Y.
Rousselin, M.M. Kubicki, C. Golz, C. Strohmann, J. Org. Chem. 80 (2015) 9064–
9075;
f) S. Haddad, S. Boudriga, T.N. Akhaja, J.P. Raval, F. Porzio, A. Soldera, M. Askri,
M. Knorr, Y. Rousselin, M.M. Kubicki, D. Rajani, New J. Chem. 39 (2015) 520–
528.
b) C.L. Lynch, A.L. Gentry, J.J. Hale, S.G. Mills, M. MacCoss, L. Malkowitz, M.S.
Springer, S.L. Gould, J.A. DeMartino, S.J. Siciliano, M.A. Cascieri, G. Doss, A.
Carella, G. Carver, K. Holmes, W.A. Schleif, R. Danzeisen, D. Hazuda, J. Kessler, J.
Lineberger, M. Miller, E. Emini, Bioorg. Med. Chem. Lett. 12 (2002) 677–679;
c) E.V. Sirotkina, M.M. Efremova, A.S. Novikov, V.V. Zarubaev, I.R. Orshanskaya,
G.L. Starova, R.R. Kostikov, A.P. Molchanov, Tetrahedron 73 (2017) 3025–3030;
d) V.A. Dmitriev, M.M. Efremova, A.S. Novikov, V.V. Zarubaev, A.V. Slita, A.V.
Galochkina, G.L. Starova, A.V. Ivanov, A.P. Molchanov, Tetrahedron Lett. 59
(2018) 2327–2331;
e) M. Grabkowska-Dru’zyc, G. Andrei, D. Schols, R. Snoeck, D.G. Piotrowska,
Molecules 23 (2018) 1889;
f) D.G. Piotrowska, G. Andrei, D. Schols, R. Snoeck, M. Łysakowska, Eur. J. Med.
Chem. 126 (2017) 84–100.
[11] a) Yu.B. Koptelov, A.P. Molchanov, R.R. Kostikov, Russ. J. Org. Chem 51 (2015)
1134–1143;
b) A.P. Molchanov, D.I. Sipkin, Yu.B. Koptelov, J. Kopf, R.R. Kostikov, Russ. J.
Org. Chem 40 (2004) 67–78.
[12] a) L. Fišera, M. Konopiková, P. Ertl, N. Pr6nayová, Monatsh. Chem. 125 (1994)
301–312;
[3] a) G.P. Nora, M.J. Miller, U. Möllmann Bioorg, Med. Chem. Lett. 16 (2006)
3966–3970;
b) N. Ben Hamadi, M. Msaddek, J. Soc, Chim. Tunisie 9 (2007) 115–120;
c) M.S. Ledovskaya, A.V. Stepakov, A.P. Molchanov, R.R. Kostikov, Tetrahedron
71 (2015) 7562–7566.
b) M. Yamaguchi, A. Matsuda, S. Ichikawa, Org. Biomol. Chem. 13 (2015)
1187–1197;
[13] a) G. Singh, G. Singh, R. Bhatti, V. Gupta, A. Mahajan, P. Singh, M.P. Singh Ishar,
Eur. J. Med. Chem. 127 (2017) 210–222;
c) M.P. Sadashiva, H. Malleshha, N.A. Hitesh, K.S. Rangappa, Bioorg. Med.
Chem. 12 (2004) 6389–6395.
b) T. Shibue, T. Hirai, I. Okamoto, N. Morita, H. Masu, I. Azumaya, O. Tamura,
Chem. Eur. J. 16 (2010) 11678–11688;
[4] a) O. Bortolini, A. De Nino, T. Eliseo, R. Gavioli, L. Maiuolo, B. Russo, F. Sforza,
Bioorg. Med. Chem. 18 (2010) 6970–6976;
c) D.A. Evans, H.-J. Song, K.R. Fandrick, Org. Lett. 8 (2006) 3351–3354.
[14] a) S. Diethelm, E.M. Carreira, J. Am. Chem. Soc. 137 (2015) 6084–6096;
b) S. Diethelm, F. Schoenebeck, E.M. Carreira, Org. Lett. 16 (2014) 960–963;
c) G. Romeo, D. Iannazzo, A. Piperno, R. Romeo, A. Corsaro, A. Rescifina, U.
Chiacchio, Mini-Rev. Org. Chem. 2 (2005) 59–77;
b) R. Romeo, S.V. Giofrè, C. Carnovale, A. Campisi, R. Parenti, R. Bandini, M.A.
Chiacchio, Bioorg. Med. Chem. 21 (2013) 7929–7937;
c) A. Rescifina, U. Chiacchio, A. Corsaro, A. Piperno, R. Romeo, Eur. J. Med.
Chem. 46 (2011) 129–136;
d) A. Rescifina, M.G. Varrica, C. Carnovale, G. Romeo, U. Chiacchio, Eur. J. Med.
Chem. 51 (2012) 163–173.
d) A. Padwa, K.F. Koehler, A. Rodrigues, J. Am. Chem. Soc. 103 (1981) 4974–
4975;
e) F.M. Cordero, F. Pisaneschi, A. Goti, J. Ollivier, J. Salaün, A. Brandi 122 (2000)
8075–8076.
[5] a) R.R. Kumar, S. Perumal, H.B. Kagan, R. Guillot, Tetrahedron 62 (2006)
12380–12391;
b) E. Gupta, S.R. Nair, R. Cant, K. Mohanan, J. Org. Chem. 83 (2018) 14811–
14819;
c) N. Jegham, A. Bahi, N. El Guesmi, Y. Kacem, B.B. Hassine, Arab. J. Chem. 10
(2017) S3889–S3894;
d) M. Zaki, A. Oukhrib, M. Akssira, S. Berteina-Raboin, RSC Adv. 7 (2017) 6523–
6529.
[15] S. Yadav, C.M. Taylor, J. Org. Chem. 78 (2013) 5401–5409.
[16] a) A.P. Molchanov, R.S. Savinkov, A.V. Stepakov, G.L. Starova, R.R. Kostikov, V.S.
Barnakova, A.V. Ivanov, Synthesis 46 (2014) 771–780;
b) R.W. Bates, J.A. Nemeth, R.H. Snell, Synthesis 7 (2008) 1033–1038;
c) F.M. Cordero, B.B. Khairnar, A. Brandi, Eur. J. Org. Chem. (2014) 7122–7133.
[17] S. Chakrabarty, I. Chatterjee, B. Wibbeling, C.G. Daniliuc, A. Studer, Angew.
Chem. Int. Ed. 53 (2014) 1–6.
[6] a) C. Lee, S. Choe, J.W. Lee, Q. Jin, M.K. Lee, B.Y. Hwang, Bull. Korean Chem. Soc.
34 (2013) 1290–1292;
[18] Suitable crystals were obtained from chloroform. Crystallographic data for
compounds 3a have been deposited at the Cambridge Crystallographic Data
Centre (Deposition No. CCDC 1923084) and can be obtained free of charge via
www.ccdc.cam.ac.uk/data_request/cif.
[19] Suitable crystals were obtained from benzene/acetone. Deposition No.
CCDC 1923083.
b) G.-L. Zhang, G. Rücker, E. Breitmaier, M. Nieger, R. Mayer, C. Steinbeck,
Phytochemistry 40 (1995) 299–305.
[7] a) S.V. Giofrè, S. Cirmi, R. Mancuso, F. Nicolò, G. Lanza, L. Legnani, A. Campisi,
M.A. Chiacchio, M. Navarra, B. Gabriele, R. Romeo, Beilstein J. Org. Chem. 12
(2016) 2793–2807;
b) J. Khazir, P.P. Singh, D.M. Reddy, I. Hyder, S. Shafi, S.D. Sawant, G. Chashoo,
A. Mahajan, M.S. Alam, A.K. Saxena, S. Arvinda, B.D. Gupta, H.M. Sampath
Kumar, Eur. J. Med. Chem. 63 (2013) 279–289;
[20] Suitable crystals were obtained from hexane/methylene chloride. Deposition
No. CCDC 1923085.
[21] a) R.R. Contreras, P. Fuentealba, M. Galvan, P. Perez, Chem. Phys. Lett. 304
(1999) 405–413;
c) R.S. Kumar, S. Perumal, K.A. Shetty, P. Yogeeswari, D. Sriram, Eur. J. Med.
Chem. 45 (2010) 124–133;
b) M.M. Efremova, A.S. Novikov, R.R. Kostikov, T.L. Panikorovsky, A.V. Ivanov,
A.P. Molchanov, Tetrahedron 74 (2018) 174–183.
d) G. Liu, S. Song, S. Shu, Z. Miao, A. Zhang, C. Ding, Eur. J. Med. Chem. 103
(2015) 17–28;
[22] Suitable crystals were obtained from hexane/ethyl acetate. Deposition No.
CCDC 1923085.
[23] a) D. Basavaiah, H. Lingam, H. Babu, Tetrahedron 74 (2018) 2306–2313;
b) S. Rana, E.C. Blowers, C. Tebbe, J.I. Contreras, P. Radhakrishnan, S. Kizhake, T.
Zhou, R.N. Rajule, J. Arnst, A.R. Munkarah, R. Rattan, A. Natarajan, J. Med. Chem.
59 (2016) 5121–5127.
e) S. Malhotra, S. Balwani, A. Dhawan, Y. Raunak, B.J. Kumar, C.E. Singh, A.K.
Olsen, V.S. Prasad, B. Ghosh Parmar, Med. Chem. Commun. 3 (2012) 1536–
1547;
f) D.M. Reddy, N.A. Qazi, S.D. Sawant, A.H. Bandey, J. Srinivas, M. Shankar, S.K.
Singh, M. Verma, G. Chashoo, A. Saxena, D. Mondhe, A.K. Saxena, V.K. Sethi, S.C.
Taneja, G.N. Qazi, H.M. Sampath Kumar, Eur. J. Med. Chem. 46 (2011) 3210–
3217;
Please cite this article as: P. S. Teterina, M. M. Efremova, E. V. Sirotkina et al., A highly efficient and stereoselective cycloaddition of nitrones to N-arylita-
conimides, Tetrahedron Letters, https://doi.org/10.1016/j.tetlet.2019.151063