Tandem Ring Opening/Cyclization of trans-2-Aryl-3-nitrocyclopropane-1,1-dicarboxylates with 2-Aminopyridines: Access to Pyrido[1,2-a]pyrimidin-4-one Derivatives

Article abstract of DOI:10.1002/ejoc.201700765

A tandem ring-opening/cyclization reaction of trans-2-aryl-3-nitrocyclopropane-1,1-dicarboxylates with 2-aminopyridines was discovered. The reaction did not require the assistance of any catalyst and proceeded more efficiently in water than in organic solvents. This strategy afforded pyrido[1,2-a]pyrimidin-4-one derivatives having a carboxylate group at C3 in 62–90 % yields.

Full text of DOI:10.1002/ejoc.201700765

A Journal of
Accepted Article
Title: Tandem Ring-Opening/Cyclization of trans-2-Aryl-3-nitro-
cyclopropane -1,1-dicarboxylates with 2-Aminopyridines: Access
to Pyrido[1,2-a]pyrimidin-4-one Derivatives
Authors: Selvi Subramani and Srinivasan Kannupal
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201700765
Link to VoR: http://dx.doi.org/10.1002/ejoc.201700765
Supported by

10.1002/ejoc.201700765
European Journal of Organic Chemistry
COMMUNICATION
Tandem Ring-Opening/Cyclization of trans-2-Aryl-3-nitro-
cyclopropane -1,1-dicarboxylates with 2-Aminopyridines: Access
to Pyrido[1,2-a]pyrimidin-4-one Derivatives
Subramani Selvi[a] and Kannupal Srinivasan*[a]
Abstract: A novel tandem ring-opening/cyclisation reaction of trans-
2-aryl-3-nitrocyclopropane-1,1-dicarboxylates with 2-aminopyridines
is described. The reaction does not require the assistance of any
catalyst and proceeds more efficiently in water than in organic
solvents. The strategy afforded pyrido[1,2-a]pyrimidin-4-one
derivatives having a carboxylate group at C-3 in 62-90% yields.
became interested in studying their ring-opening reaction with 2-
aminopyridine and its derivatives. It may be noted that 2-
aminopyridine is a versatile building block for the synthesis of
biologically important pyrido-fused heterocycles.14 Reissig et al.,
have previously used 2-aminopyridine for the ring-opening of
siloxycyclopropanedicarboxylates and obtained pyridoimidazole
derivatives.15 In the present study, we found that the tandem
ring-opening/cyclisation of trans-2-aryl-3-nitrocyclopropane-1,1-
dicarboxylates with 2-aminopyridines proceeds smoothly in
Introduction
water and affords
a series of pyrido[1,2-a]pyrimidin-4-one
derivatives. Although numerous simpler methods are available
for the synthesis of pyrido[1,2-a]pyrimidin-4-ones,16 the present
method is unique as it provides the products with a carboxylate
group at C-3, which could be used for either tuning the solubility
or linking other auxo-pharmacophores. It is also worth noting
that many pharmaceutically important pyrido[1,2-a]pyrimidin-4-
one derivatives possess an attachment at C-3 (Figure 1).17
The diverse reactivity of donor-acceptor (D-A) cyclopropanes
has made them popular building blocks in organic synthesis.1
They undergo a number of ring-opening,2 ring-expansion3 and
formal cycloaddition4 reactions thereby providing access to a
wide variety of acyclic products, carbocycles, heterocycles and
natural products. In the realm of D-A cyclopropane chemistry,
the synthetic potential of nitro-substituted D-A cyclopropanes
has been less explored as compared to others, despite their
NH
N
unique reactivity.5
Yet,
certain nitro-substituted D-A
O
O
N
N
cyclopropanes have been subjected to nucleophilic ring-opening
with amines6 and phenols,7 ring-expansion to isoxazoline-N-
oxides8 and formal cycloaddition reaction with nitrones.9
N
3
N
N
O
4
F
CH3
N
Mast cell stabilizer
3
(Pemirolast)
O
trans-2-Aryl-3-nitrocyclopropane-1,1-dicarboxylates are a kind of
nitro-substituted D-A cyclopropanes which were first prepared by
Sopova and co-workers in 1969.10 Though the ring-opening
reactions of these cyclopropanes with nucleophiles such as
sodium malonate, sodium methoxide and ammonia were studied
by the Sopova group,11 no other reasonable synthetic
applications of these cyclopropanes have been reported
thereafter. Recently, we developed a convenient procedure for
the synthesis of these cyclopropanes and explored their
synthetic utility.12 We found that these cyclopropanes upon
treatment with Lewis acids give aroylmethylidene malonates,
which could be synthetically manipulated for the access of
important heterocycles such as imidazoles, quinoxalines,
oxazoles and thiophenes.12 He et al., have recently reported the
reaction of these cyclopropanes with Huisgen zwitterions for the
access of pyrazolines.13
2
N
1
CH3
N
S
O
5-HT2 Serotonin
receptor antagonist
(Pirenperone)
O
CO2Et
N
3
N
Me
Antiulcerative agent
Figure 1. Pharmaceutically important pyrido[1,2-a]pyrimidin-4-ones.
Results and Discussion
We began the study by reacting an equimolar amount of
nitrocyclopropane dicarboxylate 1a with 2-aminopyridine (2a) in
different solvents (Table 1, entries 1-14). Pleasingly, the reaction
gave pyrido[1,2-a]pyrimidin-4-one 3a in 90% yield when carried
out in water under reflux condition for 1 h (entry 4). The structure
of 3a was confirmed by NMR and MS spectra and further by X-
ray analysis (Figure 2).18 The reaction did not take place at room
temperature and also gave inferior yields when performed at
lower temperatures (for example, entry 5). In the initial stage of
the reaction, 2a was in solution while 1a was practically ‘on
water’. As the reaction progressed, the reaction mixture became
homogeneous and towards the end, the product started
appearing ‘on water’. Although the product could be isolated by
simple filtration, it led to much loss of the product. Hence the
product was extracted with dichloromethane and then purified.
In continuation of our interest in exploring the synthetic potential
of
trans-2-aryl-3-nitrocyclopropane-1,1-dicarboxylates,
we
[a]
School of Chemistry
Bharathidasan University
Tiruchirappalli-620024, Tamil Nadu, India
E-mail: srinivasank@bdu.ac.in
http://www.bdu.ac.in/schools/chemistry/chemistry/dr_k_srinivasan.
php
Supporting information for this article is given via a link at the end of
the document.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201700765
European Journal of Organic Chemistry
COMMUNICATION
A simpler alternative method:
Among various solvents screened, only AcOH, dichloromethane
and nitromethane gave 3a in 50% or more yields (entries 3, 7
and 12). The reaction did not occur in 1,4-dioxane and DMF
even after 24 h (entries 10 and 13). In all other cases [MeOH,
EtOH, toluene, 1,2-dichloroethane (1,2- DCE), THF, acetonitrile
and DMSO], the yield of 3a ranged from 20-42% (entries 1, 2, 6,
8, 9, 11 and 14). Therefore, we selected heating the reaction
mixture under reflux in water as the optimal condition for the
transformation.
CO2Et
CO2Et
CH2(CO2Et)2
O
2a, DDQ
3a
Ph
Ph
piperidine, AcOH
CH2Cl2, rt
2 h, 61%
n-heptane, reflux
18 h, 86%
Overall yield: 52%
Present method:
EtO2C
Ph
CO2Et
NO2
I2, DBU
1a
CH2(CO2Et)2
NO2
Ph
CH2Cl2
LiClO4, Et3N
2a, H2O
reflux
rt, 15 min
94%
Neat, rt
30 min, 92%
Table 1. Optimisation of reaction conditions
1 h, 90%
O
2a
3a
Overall yield: 78%
EtO2C
Ph
CO2Et
NO2
CO2Et
Ph
N
NH2
N
Scheme 1. Comparison of the present method with an alternative route.
N
1a
3a
Next, we investigated the scope of the reaction for various
nitrocyclopropane dicarboxylates 1 with 2-aminopyridine (2a)
and the results are summarized in Table 2. The transformation
tolerated the presence of various electron donating, halogen and
Entry
Solvent and conditionsa
MeOH, reflux, 5 h
EtOH, reflux, 3 h
Yield (%)b
26
1
2
32
3
AcOH, reflux, 3 h
H2O, reflux, 1 h
50
Table 2. Scope of the reaction for various nitrocyclopropane dicarboxylatesa
4
90
O
5
H2O, 60 C, 48 h
10c
2a
EtO2C
Ar
CO2Et
NO2
CO2Et
Ar
6
Toluene, reflux, 3 h
CH2Cl2, reflux, 1 h
1,2-DCE, reflux, 2 h
THF, reflux, 4 h
40
N
NH2
N
7
68
H2O, reflux
N
3
8
20
1
O
9
28
NRd
O
N
CO2Et
CO2Et
10
11
12
13
14
1,4-Dioxane, reflux, 24 h
MeCN, reflux, 4 h
MeNO2, reflux, 5 h
DMF, 80 C, 24 h
DMSO, 120 C, 4 h
N
N
Me
25
N
55
NRd
entry 2: 3b, 88% (1 h)
entry 1: 3a, 90% (1 h)
O
O
42
CO2Et
N
CO2Et
N
[a] No reaction occurs at room temperature in any of the solvents. [b] Isolated
yield. [c] About 70% of the starting material was recovered. [d] No reaction.
OMe
N
N
entry 4: 3d, 76% (1 h)
entry 3: 3c, 74% (3 h)
O
O
CO2Et
N
CO2Et
N
Cl
Br
N
N
entry 6: 3f, 62% (1 h)
entry 5: 3e, 80% (2 h)
O
O
CO2Et
N
CO2Et
N
Cl
Figure 2. X-ray structure of 3a.
N
N
Cl
Cl
entry 8: 3h, 68% (2 h)
entry 7: 3g, 84% (0.5 h)
Before investigating the scope of the reaction for other
substrates, we decided to evaluate the merits of the
O
O
CO2Et
N
CO2Et
N
transformation by comparing it with
a simpler alternative
F
CO2Me
N
N
synthetic route to 3a. As shown in Scheme 1, 3a could be
obtained in 52% overall yield over two steps (Knoevenagel
condensation19 and conjugate addition/cyclisation/aromatisation)
from commercially available phenylacetaldehyde. On the other
hand, the present transformation involves three steps from
trans--nitrostyrene (conjugate addition,20 cyclisation12a and ring-
opening/cyclisation) and affords 3a in 78% overall yield. Clearly,
the present transformation, though involves an extra step, is
superior to the alternative route in terms of overall yield and
reaction time.
entry 9: 3i, 78% (2 h)
entry 10: 3j, 72% (2.5 h)
O
O
CO2Et
N
CO2Et
N
NO2
N
N
entry 12: 3l, 80% (1 h)
entry 11: 3k, 82% (1 h)
[a] Isolated yield.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201700765
European Journal of Organic Chemistry
COMMUNICATION
electron withdrawing substituents at different positions of the aryl
ring of the cyclopropanes and the expected pyridopyrimidinones
3a-k are produced in 62-90% yields (entries 1-11). Notably, the
presence of ester group on the aryl ring of the cyclopropane did
not interfere in the transformation (entry 10). The reaction also
worked well when the aryl ring of the cyclopropane was 1-
naphthyl and the respective pyridopyrimidinone 3l was isolated
in 80% yield (entry 12). However, when two or three electron
donating methoxy groups were present on the aryl ring, the
reaction led to a complicated mixture. For cyclopropanes having
heteroaromatic 2-furyl and 2-thienyl rings, the reactions gave the
respective pyridopyrimidinones only in trace amounts (detected
by MS only).
Accordingly, the abstraction of the acidic proton in 1 by 2a
triggers the ring-opening of 1 leading to the intermediate B via A
(the intermediate B is different from the usual aroylmethylidene
malonate intermediate, Ar−C(=O)−CH=C(CO2Et)2 obtained by
treatment of 1 with Lewis acids12). The nucleophilic substitution
of nitro group in B by 2 (by addition elimination mechanism) and
subsequent cyclization with the loss of ethanol afforded
pyridopyrimidinones 3. We envisage that the formation of the
polar intermediate, A is more facilitated in water than in organic
solvents and hence the reaction proceeded more efficiently in
water.
EtO2C
CO2Et
H2N
N
H
We also explored the scope of the reaction for nitrocyclopropane
dicarboxylate 1a with various substituted 2-aminopyridines 2 and
related compounds (Table 3). The reactions proceeded nicely
with aminopyridines having 4-methyl, 6-methyl and 5-bromo
NH2
NO2
H
Ar
CO2Et
CO2Et
N
Ar
1
2a
NO2
A
O
substituents
with
the
formation
the
corresponding
CO2Et
O
EtO
O2N
pyridopyrimidinones 3m-o in 66-76% yields (entries 1-3).
Surprisingly, the presence of unprotected hydroxyl or amino
group on the aminopyridine nucleus was also tolerated in the
reaction and the respective pyridopyrimidinones 3p and 3q were
CO2Et
Ar
EtO
N
Ar
B
N
-HNO2
NO2
N
NH2
O
H
H
obtained in good yields (entries
4
and 5).
When 2-
O
EtO
aminopyrazine (4) was used instead of 2-aminopyridines in the
reaction, the expected pyrazinopyrimidinone 5 was produced in
70% yield (entry 6). However, the reaction did not take place
with related compounds such as 2-aminopyrimidine, 2-
aminothiazole, acetamidine, benzamidine and guanidine.
CO2Et
Ar
CO2Et
Ar
N
N
3
-EtOH
N
H
N
H
Scheme 2. Mechanism for the formation of pyridopyrimidinones 3.
Organic transformations are rarely performed in water owing to
the insolubility of most organic substrates in water and also the
deterioration of many reagents and catalysts in water. The
present transformation is therefore a valuable addition to a
handful of organic reactions that proceed more efficiently in
water than in organic solvents.22 It may also be noted that
though water has been utilized as a nucleophile for the ring-
opening of aryl-diester D-A cyclopropanes,2f it has not been
previously used as solvent for carrying out any types of
reactions of D-A cyclopropanes.
Table 3. Scope of the reaction for substituted 2-aminopyridines and 2-
aminopyrazinea
X
R
N
NH2
O
N
2: X= CH
4: X= N, R = H
EtO2C
Ph
CO2Et
NO2
CO2Et
Ph
N
X
H2O, reflux
1a
3/5
O
N
Me
O
N
CO2Et
CO2Et
N
Me
N
Conclusions
entry 1: 3m, 76% (1 h)
entry 2: 3n, 66% (1 h)
O
O
We have studied tandem ring-opening/cyclization reactions of
CO2Et
N
Br
CO2Et
N
trans-2-aryl-3-nitrocyclopropane-1,1-dicarboxylates
with
aminopyridines and obtained several pyrido[1,2-a]pyrimidin-4-
ones derivatives having a carboxylate group at C-3 in good
yields. The reactions proceeded more efficiently in water than in
organic media and did not require any other reagents or
catalysts. The transformation takes place through the formation
of nitroarylethylidene malonate intermediate from the
cyclopropane, nucleophilic displacement of nitro group in the
intermediate by aminopyridine and subsequent cyclization. Work
is underway to explore further scope of the methodology.
N
N
OH
entry 3: 3o, 68% (1h)
entry 4: 3p, 72% (2 h)
O
NH2
O
CO2Et
N
CO2Et
N
N
N
N
entry 5: 3q, 69% (2 h)
entry 6: 5, 70% (1.5 h)
[a] Isolated yield.
We propose
formation
a
mechanism outlined in Scheme
2
for the
from
of
pyrido[1,2-a]pyrimidin-4-ones
3
nitrocyclopropane dicarboxylates 1 and 2-aminopyridine (2a).21
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201700765
European Journal of Organic Chemistry
COMMUNICATION
D. Schmidt, M. Mumby, D. Kratzert, D. Stalke, D. B. Werz, Chem.
Commun. 2013, 49, 4403-4405; e) G. Sathishkannan, K. Srinivasan,
Adv. Synth. Catal. 2014, 356, 729-735; f) A. Ghosh, S. Mandal, P. K.
Chattaraj, P. Banerjee, Org. Lett. 2016, 18, 4940-4943.
Experimental Section
General procedure for the synthesis of pyridopyrimidinones 3: A
mixture of nitrocyclopropane 1 (1 mmol) and 2-aminopyridine 2 (1 mmol)
in water (5 mL) was heated under reflux for 0.5 to 2 h. After the reaction
was complete, the reaction mixture was cooled to room temperature and
extracted with dichloromethane. The organic layer was washed with
water, dried (over anhydrous Na2SO4) and the solvent was removed
under reduced pressure. The crude product was purified by column
[4]
a) V. K. Yadav, V. Sriramurthy, Angew. Chem. Int. Ed. 2004, 43, 2669-
2671; b) C. A. Carson, M. A. Kerr, J. Org. Chem. 2005, 70, 8242-8244;
c) Y.-B. Kang, Y. Tang, X.-L. Sun, Org. Biomol. Chem. 2006, 4, 299-
301; d) K. Sapeta, M. A. Kerr, J. Org. Chem. 2007, 72, 8597-8599; e)
O. A. Ivanova, E. M. Budynina, Y. K. Grishin, I. V. Trushkov, P. V.
Verteletskii, Angew. Chem. Int. Ed. 2008, 47, 1107-1110; f) A. T.
Parsons, J. S. Johnson, J. Am. Chem. Soc. 2009, 131, 3122-3123; g)
F. de Nanteuil, J. Waser, Angew. Chem. Int. Ed. 2011, 50, 12075-
12079; h) J.-P. Qu, Y. Liang, H. Xu, X.-L. Sun, Z.-X. Yu, Y. Tang,
Chem. Eur. J. 2012, 18, 2196-2201; i) H. Xiong, H. Xu, S. Liao, Z. Xie,
Y. Tang, J. Am. Chem. Soc. 2013, 135, 7851-7854; j) S. Chakrabarty, I.
Chatterjee, B. Wibbeling, C. G. Daniliuc, A. Studer, Angew. Chem. Int.
Ed. 2014, 53, 5964-5968; k) E. M. Budynina, O. A. Ivanova, A. O.
Chagarovskiy, Y. K. Grishin, I. V. Trushkov, M. Y. Melnikov, J. Org.
Chem. 2015, 80, 12212-12223; l) L.K. Garve, M. Petzold, P.G. Jones,
D. B. Werz, Org. Lett. 2016, 18, 564-567.
chromatography
using
EtOAc/hexane
(3:2)
to
give
pure
pyridopyrimidinone 3.
Ethyl
2-(benzyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine-3-carboxylate
(3a): Black solid. Yield: 277 mg (90%). M. p.: 106-108 °C. UV (max
,
EtOAc): 354 nm ( = 4310 M-1cm-1). IR (Neat): 1630, 1672, 1719 cm-1.
1H NMR (400 MHz, CDCl3): δ 9.02 (d, J = 7.2 Hz, 1H), 7.76-7.72 (m, 1H),
7.61 (d, J = 8.8 Hz, 1H), 7.35-7.11 (m, 6H), 4.39-4.34 (m, 2H), 4.20 (s,
2H), 1.32 (t, J = 7.2 Hz, 3H) ppm. 13C NMR (100 MHz, CDCl3): δ 166.1,
165.7, 155.8, 150.6, 137.7, 137.6, 129.3, 128.6, 128.4, 127.7, 126.6,
126.4, 116.1, 109.7, 61.6, 42.4, 14.2 ppm. HRMS (ESI) calcd. for
[5]
[6]
a) R. Ballini, A. Palmieri, D. Fiorini, ARKIVOC 2007, vii, 172-194; b) E.
B. Averina, N. V. Yashin, T. S. Kuznetsova, N. S. Zefirov, Russ. Chem.
Rev. 2009, 78, 887-902.
C18H16N2O3: 309.1234 [M
+
H+], found: 309.1244. Anal. calcd. for
C18H16N2O3: C 70.12, H 5.23, N 9.09; found: C 70.25, H 5.33, N 9.21.
a) R. P. Wurz, A. B. Charette, Org. Lett. 2005, 7, 2313-2316; b) O.
Lifchits, A. B. Charette, Org. Lett. 2008, 10, 2809-2812; c) S. S. So, T.
J. Auvil, V. J. Garza, A. E. Mattson, Org. Lett. 2012, 14, 444-447.
O. Lifchits, D. Alberico, I. Zakharian, A. B. Charette, J. Org. Chem.
2008, 73, 6838-6840.
Supporting Information: Experimental details, characterization data
and copies of the 1H and 13C NMR spectra of all products.
[7]
[8]
[9]
A. B. Charette, R. P. Wurz, T. Ollevier, Helv. Chim. Acta. 2002, 85,
4468-4484.
Acknowledgements
A. M. Hardman, S. S. So and A. E. Mattson, Org. Biomol. Chem., 2013,
11, 5793-5797.
The authors thank Science and Engineering Research Board
(SERB), India for financial support and DST-FIST for
instrumentation facilities at School of Chemistry, Bharathidasan
University. S. S. thanks the University Grants Commission
(UGC) for a BSR-RFSMS fellowship.
[10] A. S. Sopova, V. V. Perekalin, O. L. Yurchenko, G. M. Arnautova, Zh.
Org. Khim. 1969, 5, 858-863; Chem. Abstr. 1969, 71, 38394k.
[11] A. S. Sopova, O. S. Bakova, K. L. Metelkina, V. V. Perekalin, Zh. Org.
Khim. 1975, 11, 68-71. Chem. Abstr. 1975, 83, 9406h.
[12] a) T. Selvi, K. Srinivasan, J. Org. Chem. 2014, 79, 3653-3658; b)
T.Selvi, K. Srinivasan, Chem. Commun. 2014, 50, 10845-10848; c) T.
Selvi, K. Srinivasan, Adv. Synth. Catal. 2015, 357, 2111-2118; d) T.
Selvi, G. Vanmathi, K. Srinivasan, RSC Adv. 2015, 5, 49326-49329.
[13] C. Yang, W. Liu, Z. He, Z. He, Org. Lett. 2016, 18, 4936-4939.
[14] a) A. K. Bagdi, S. Santra, K. Monir, A. Hajra, Chem. Commun. 2015,
51, 1555-1575; b) K. Pericherla, P. Keswan, K. Pandey, A. Kumar,
Synthesis 2015, 47, 887-912.
Keywords Donor acceptor cyclopropanes
•
Nitrogen
heterocycles • Ring opening cyclisation • Synthetic methods •
Water chemistry
[1]
a) H.-U. Reissig, R. Zimmer, Chem. Rev. 2003, 103, 1151-1196; b) M.
Yu, B. L. Pagenkopf, Tetrahedron 2005, 61, 321-347; c) M. Y. Mel’nikov,
E. M. Budynina, O. A. Ivanova, I. V. Trushkov, Mendeleev Commun.
2011, 21, 293-301; d) M. A. Cavitt, L. H. Phun, S. France, Chem. Soc.
Rev. 2014, 43, 804-818; e) T. F. Schneider, J. Kaschel, D. B. Werz,
Angew. Chem. Int. Ed. 2014, 53, 5504-5523; f) F. D. Nanteuil, F. D.
Simone, R. Frei, F. Benfatti, E. Serrano, J. Waser, Chem. Commun.
2014, 50, 10912-10928; g) H. K. Grover, M. R. Emmett, M. A. Kerr,
Org. Biomol. Chem. 2015, 13, 655-671; h) N. R. O’Connor, J. L. Wood,
B. M. Stoltz, Isr. J. Chem. 2016, 56, 431-444.
[15] I. Veljkovic, R. Zimmer, H.-U. Reissig, I. Brudgam, H. Hartl, Synthesis
2006, 2677-2684.
[16] For recent examples, see: a) Y. Yang, W.-M. Shu, S.-B. Yu, F. Ni, M.
Gao, A.-X. Wu, Chem. Commun. 2013, 49, 1729-1731; b) A. V.
Gulevich, V. Helan, D. J. Wink, V. Gevorgyan, Org. Lett. 2013, 15, 956-
959; c) Y. Xie, T. Chen, S. Fu, H. Jiang, W. Zeng, Chem. Commun.
2015, 51, 9377-9380; d) J. Zhang, X. Meng, C. Yu, G. Chen, P. Zhao,
RSC Adv. 2015, 5, 87221-87227; e) S. N. Basahel, N. S. Ahmed, K.
Narasimharao, Mokhtar, RSC Adv. 2016, 6, 11921-11932; f) Z. Chen,
Y. Wen, H. Ding, G. Luo, M. Ye, L. Liu, J.Xue, Tetrahedron Lett. 2017,
58, 13-16.
[2]
a) M. R. Emmett, M. A. Kerr, Org. Lett. 2011, 13, 4180-4183; b) M. R.
Emmett, H. K. Grover, M. A. Kerr, J. Org. Chem. 2012, 77, 6634-6637;
c) Y.-Y. Zhou, L.-J. Wang, J. Li, X.-L. Sun, Y. Tang, J. Am. Chem. Soc.
2012, 134, 9066-9069; d) L. K. B.Garve, P. Barkawitz, P. G. Jones, D.
B. Werz, Org. Lett. 2014, 16, 5804-5807; e) Y. Xia, L. Lin, F. Chang, X.
Fu, X. Liu, X. Feng, Angew. Chem. Int. Ed. 2015, 54, 13748-13752; f)
Q.-K. Kang, L. Wang, Q.-J. Liu, J.-F. Li, Y. Tang, J. Am. Chem. Soc.
2015, 137, 14594-14597; g) G. Sathishkannan, V. J. Tamilarasan, K.
Srinivasan, Org. Biomol. Chem. 2016, 15, 1400-1406.
[17] a) M. M. Foreman, J. L. Hall, R. L. Love, Life Sci. 1989, 45, 1263-1270;
b) T. Kawashima, I. Iwamoto, N. Nakagawa, H. Tomioka, S. Yoshida,
Int. Arch. Allergy Immunol. 1994, 103, 405-409; c) G. S. Kumar, G. J.
Dev, N. R. Kumar, D. K. Swaroop, Y. P. Chandra, C. G. Kumar, B.
Narasaiah, Chem. Pharm. Bull. 2015, 63, 584-590.
[18] CCDC 1534729 for compound 3a. See the Supporting Information.
[19] H. Mukherjee, C. A. Martinez, ACS Catal. 2011, 1, 1010-1013.
[20] M. R. Saidi, N. Azizi, E. Akbari, F. Ebrahimi, J. Mol. Catal. A: Chem.
2008, 292, 44-48.
[3]
a) G.-Q. Li, L.-X. Dai, S.-L. You, Org. Lett. 2009, 11, 1623-1625; b) T.
F. Schneider, J. Kaschel, B. Dittrich, D. B. Werz, Org. Lett. 2009, 11,
2317-2320; c) J. Kaschel, T. F. Schneider, D. Kratzert, D. Stalke, D. B.
Werz, Angew. Chem. Int. Ed. 2012, 51, 11153-11156; d) J. Kaschel, C.
[21] The following reaction reported by Sopova and co-workers (Ref. 11)
provided the basic idea for the mechanism.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201700765
European Journal of Organic Chemistry
COMMUNICATION
CO2Me
CO2Me
MeO2C
Ph
CO2Me
NO2
NH3
Ph
MeOH
NH2
[22] a) C. J. Li, L. Chen, Chem. Soc. Rev. 2006, 35, 68-82; b) A. Chanda, V.
V. Fokin, Chem. Rev. 2009, 109, 725-748.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201700765
European Journal of Organic Chemistry
COMMUNICATION
Entry for the Table of Contents (Please choose one layout)
Layout 2:
COMMUNICATION
Donor-Acceptor Cyclopropanes
O
R
R
Subramani Selvi and Kannupal
Srinivasan*
EtO2C
Ar
CO2Et
NO2
CO2Et
Ar
N
N
NH2
H2O, reflux
62-90%
N
Page No. – Page No.
Tandem Ring-Opening/Cyclization of
trans-2-Aryl-3-nitro-cyclopropane -
1,1-dicarboxylates with 2-
Aminopyridines: Access to
Pyrido[1,2-a]pyrimidin-4-one
Derivatives
trans-2-Aryl-3-nitrocyclopropane-1,1-dicarboxylates
underwent tandem ring-
opening/cyclization with 2-aminopyridines in water to afford pyrido[1,2-a]pyrimidin-
4-one derivatives.
This article is protected by copyright. All rights reserved.