Synthesis of electron-deficient dienes bearing a chromonyl moiety via the reaction of 3-formylchromones with ylidenemalononitriles and ethyl α-cyano-β-methylcinnamate Dedicated to Professor Oleg N. Chupakhin on his 80th birthday

Article abstract of DOI:10.1016/j.tet.2014.03.105

3-Formylchromones react with ylidenemalononitriles in the presence of triethylamine in dichloromethane to produce the target electron-deficient dienes connected to the chromone system with excellent E-selectivity and in good yields. In a similar manner, t

Full text of DOI:10.1016/j.tet.2014.03.105

Tetrahedron 70 (2014) 3584e3589
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journal homepage: www.elsevier.com/locate/tet
Synthesis of electron-deficient dienes bearing a chromonyl moiety
via the reaction of 3-formylchromones with ylidenemalononitriles
and ethyl a-cyano-b-methylcinnamate
Vladislav Yu. Korotaev, Alexey Yu. Barkov, Igor B. Kutyashev, Alexander V. Safrygin,
*
Vyacheslav Ya. Sosnovskikh
Department of Chemistry, Institute of Natural Sciences, Ural Federal University, 620000 Ekaterinburg, Russian Federation
a r t i c l e i n f o
a b s t r a c t
Article history:
3-Formylchromones react with ylidenemalononitriles in the presence of triethylamine in dichloro-
Received 11 February 2014
Received in revised form 19 March 2014
Accepted 31 March 2014
Available online 4 April 2014
methane to produce the target electron-deficient dienes connected to the chromone system with
excellent E-selectivity and in good yields. In a similar manner, their reaction with ethyl
a-cyano-b-
methylcinnamate gave a mixture of E,Z- and E,E-isomeric chromonyl dienes, from which the former
could be isolated in a pure state by crystallization.
Ó 2014 Elsevier Ltd. All rights reserved.
Dedicated to Professor Oleg N. Chupakhin
on his 80th birthday
Keywords:
3-Formylchromones
3-(Buta-1,3-dienyl)chromones
Ylidenemalononitriles
Electron-deficient dienes
Aldol type condensation
1. Introduction
by condensation of Wittig reagents prepared from 3-
bromomethylchromones with olefinic aldehydes in the presence
3-Formylchromones are widely used in organic synthesis due to
the high reactivity of their three electron-deficient centers at C-2,
C-4, and the C-3 formyl group. The majority of the reactions with
these compounds are nucleophilic additions with concomitant
opening of the pyrone ring leading to various types of heterocyclic
systems. In addition, some of them can react as heterodienes and as
dienophiles.1 As a result, 3-formylchromones have attracted con-
siderable attention in recent years as excellent building blocks in
organic synthesis for the construction of more complex molecules.2
In particular, 3-formylchromone (1) reacts with methyl ketones and
active methylene compounds to give various 3-vinylchromone
derivatives 2,3 while its utility in synthesizing conjugated dienes
3, which are potentially useful intermediates for the synthesis of
biologically active molecules, has not been explored. Earlier, 1,3-
butadiene derivatives 4 and 5 bearing a chromonyl moiety were
obtained by Pd-catalyzed cross-coupling reactions4 and
of n-BuLi5 (Fig. 1).
O
* Corresponding author. Fax: þ7 343 261 59 78; e-mail addresses: sosn1951@
mail.ru, vy.sosnovskikh@urfu.ru (V.Ya. Sosnovskikh).
Fig. 1. 3-Substituted chromones 1e5 (formyl, vinyl, and divinyl derivatives).
0040-4020/$ e see front matter Ó 2014 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2014.03.105

V.Yu. Korotaev et al. / Tetrahedron 70 (2014) 3584e3589
3585
Within the framework of a research program on the synthetic
opportunities offered by the chromone system in the preparation of
organic molecules having potential interest in biomedicinal
chemistry and materials science,6 we were interested in developing
an efficient method for the synthesis of various chromones bearing
a functionalized divinyl unit at the C-3 position. The present paper
describes a novel synthesis of electron-deficient 3-(buta-1,3-
dienyl)chromones 3 based on the reaction of 3-formylchromones
product 7gei with excellent E-selectivity in 45e51% yields
(Scheme 1).
with a number of ylidenemalononitriles and ethyl
methylcinnamate.
a-cyano-b-
Although ylidenemalononitriles 6 have been used extensively in
Michael reactions as vinylogous donors,7 their reactivity in aldol
reactions has not yet been explored to any great extent. Moreover,
information on the reactions of ylidenemalononitriles 6 with aro-
matic aldehydes is rather contradictory. On one hand, it is known
that compounds 6 add to isatins (Et3N, H2O/EtOH, rt),8 aldehydes
(Et3N, ethylene glycol, 40 ꢀC),9 and trifluoromethyl ketones (Et3N,
CH2Cl2, rt)10 to form via vinylogous aldol reaction substituted py-
rans or dienamides depending on the nature of the reactants. In this
reaction, ylidenemalononitriles are commonly employed because
the cyano group can act as both a powerful stabilizer of the in-
termediate anion and as an electrophilic center in the cyclization
forming a pyran ring. In the case of aromatic aldehydes and tri-
fluoromethyl ketones, it would be reasonable to assume the pos-
sibility of the electrocyclic ring-opening of the initially formed 2H-
pyran intermediate occurring with formation of the acyclic dien-
amide system.9,10 On the other hand, it was shown that treatment
of benzaldehydes with 2-(1-phenylethylidene)malononitrile (6b)
in the presence of triethylamine or piperidine in isopropanol does
not provide the dienamide derivatives but gives the corresponding
1,1-dicyanobuta-1,3-diene.11 In connection with our interest in the
development of chromone chemistry,6 we hoped to increase the
synthetic scope of this reaction to include 3-formylchromones
as electrophilic substrates. Although the chemistry of 3-
formylchromone (1) has been well documented,1e3 electron-
deficient dienes 3 containing two terminal electron-withdrawing
substituents are hitherto unreported and their synthetic utility
has not been explored.
Diene 7 R1
R2
H
H
H
H
H
H
Me
Me
Me
H
R3
R4
Time (h) Yield (%)
H
Me
Me
Me
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
CN
CN
CN
CN
CN
CN
CN
CN
CN
1
66
a
b
c
d
e
f
g
h
i
Me
Cl
H
Me
Cl
H
Me
Cl
H
1
58
1
57
1
69
3
64
1
58
24
24
24
45
45
51
CO2Et 16
CO2Et
CO2Et
86 (Z:E = 60:40)
68 (Z:E = 55:45)
65 (Z:E = 70:30)
j
Me
Cl
H
H
8
4
k
l
Scheme 1. Synthesis of chromonyl dienes 7ael.
In a similar manner, reaction with ethyl
a-cyano-b-methyl-
cinnamate (6d, E/Z¼3:2) gave a mixture of isomeric chromonyl
dienes (E,Z)-7jel and (E,E)-7jel in 65e86% yields. Their ratio was
easily determined by 1H NMR analysis (Scheme 1). In all cases ex-
amined, the dominant product was the E,Z-isomer, in spite of the
fact that the starting cinnamate 6d exists predominantly in the E-
isomeric form. This result may imply that the stereochemistry is
controlled by steric effects and in accord with the literature data;16
the percentage of the isomer with the Z-configuration with respect
2. Results and discussion
The reactions of 3-formylchromones
1
with iso-
propylidenemalononitrile (6a)12 and 2-(1-phenylethylidene)malo-
nonitrile (6b)13 were first examined. It should be noted that the
malononitrile derivative 6a has been little studied in the aldol type
reaction with aldehydes and ketones. Only one report is known,
which describes the reaction of 6a with benzylideneacetone to give
1,1-dicyano-2-methyl-4-phenyl-1,3-butadiene,14 probably due to
its easy dimerization in the presence of a base.15 Indeed, our pre-
liminary attempts to synthesize the corresponding electron-
deficient diene from the reaction of 6a with benzaldehyde failed.
However, we found that the reactions of 3-formylchromones 1 with
isopropylidenemalononitrile (6a) and 2-(1-phenylethylidene)
malononitrile (6b) resulted in the formation of 3-(buta-1,3-dienyl)
chromones 7aef as a single E-isomer. The procedure is simple and
the products were obtained in 57e69% yields, merely by standing
a mixture of the reactants and Et3N (as the base) in dichloro-
methane at room temperature for several hours. Substituents R1 on
the chromone ring had no great effect on the reaction course to give
products 7. When these reactions were repeated with ethylene
glycol in place of dichloromethane at 40 ꢀC,5 the starting materials
were consumed but only complex mixtures were obtained. In the
case of 2-(1-phenylpropylidene)malononitrile (6c), the methyl
group (R2¼Me) substantially lowers the rate of reaction, however,
the reaction still proceeded rather efficiently to give the desired
to the C(30)]C(40) bond increases, as the
bulkier (Me<CH]CH). Only the major E,Z-isomer of 7jel could be
isolated in a pure form by recrystallization of the mixture from
b substituent becomes
ethanol. Unfortunately, this reaction did not work for ethyl
ano- -ethylcinnamate, which is less reactive than 6d.
a-cy-
b
This approach represents a new synthesis of electron-deficient
dienes connected to the chromone system and has advantages
with regard to ease of operation and the ready availability of the
starting materials. As chromone derivatives are very useful in or-
ganic synthesis,1e3,6 the reaction described is noteworthy and the
easy accessibility of compounds 7 makes them attractive candi-
dates for further synthetic elaboration. This kind of conjugated
compound can be exploited in such synthetic transformations as
Michael addition, DielseAlder reaction, and so on. We also hoped to
increase the synthetic scope of this reaction to include 2-
cyclohexylidenemalononitrile, however, this malononitrile de-
rivative did not give positive results under our experimental
conditions. In this case, the reaction gave a complex multicompo-
nent mixture, from which no target compounds of type 7 could be
isolated apparently due to steric reasons.
The structures of compounds 7 were established by elemental
analysis and IR, 1O, and 13C NMR spectroscopy. In the 1H NMR

3586
V.Yu. Korotaev et al. / Tetrahedron 70 (2014) 3584e3589
spectra of 7def, protons H-10 and H-20 appeared as a doublet at
conformation was shown; at the same time, the crystal structure of
its analog, in which the methyl group is attached to the C-20 atom,
reveals that this compound has the s-cis,s-trans-conformation.5
d
6.65e6.67 and 8.42e8.47 ppm, respectively, with the vicinal
coupling constants 3J¼15.4e15.5 Hz, whereas the olefinic proton in
compound 7gei resonated at
d 6.89e6.95 ppm as a quintet with
4JH,H¼0.9e1.3 Hz (for 7g: 3JMe,H¼8.0 Hz). The values of the coupling
constants for H-10/H-20 and H-10/Me indicate the E-configuration of
the double bonds in dienes 7aei.17
As noted above, compounds 7jel were formed as a mixture of
E,Z- and E,E-isomers. It is known that the chemical shifts for the
carbethoxy protons occur at a higher field in the cis than in the
trans configuration with respect to the phenyl group due to a long-
range anisotropy effect of the benzene ring, which is not coplanar,
for steric reasons, with the diene fragment.16 In the 1H NMR spectra
of compounds (E,Z)-7jel, the chemical shifts of the signals for the
H-10 and H-20 protons at
d 6.49e6.52 and 8.33e8.36 ppm
Fig. 3. NOE correlations of 7g.
(3J¼15.6 Hz) are very close to those for the corresponding protons
in dienes 7def, whereas the olefinic H-10 and H-20 protons in (E,E)-
7jel appeared as
a pair of doublets at d 6.44e6.48 and
The preferred s-trans,s-trans-conformation of the double bonds
in (E)-7a was deduced from the key NOE correlations between the
H-2 and H-10 protons and the Me group and H-10. In addition, as
depicted in Fig. 4, this compound showed the weak H-2/H-20 and
H-20/Me cross-peaks from several conformational interconversions.
9.24e9.26 ppm (3J¼15.9 Hz), respectively. The downfield shift of
the H-20 proton is associated with the deshielding effect of the two
carbonyl groups in the E,E-isomer with the s-trans,s-trans-confor-
mation with respect to the C(3)eC(10) and C(20)eC(30) single bonds.
These data correlate well with the assumption that compounds
7del exist in CDCl3 as equilibrium mixtures of the s-trans,s-trans-
and s-cis,s-trans-conformers with a predominance of the former.
The 2D NOESY experiment on 7d demonstrates the spatial conti-
guity of H-2 to H-10. In this case, a cross-peak for H-2 with H-10
shows that these protons are sited close to each other, thus
establishing the s-trans-conformation of the dienyl moiety relative
to the pyrone ring. However, in solution the s-cis conformer is also
present to a slight extent, in equilibrium with s-trans, as evidenced
by a very weak effect linking H-2 to H-20 (Fig. 2).
Fig. 4. Diagnostic 1H NMR signals (
d, ppm, CDCl3) and NOE correlations of 7a.
For the formation of products 7 a plausible mechanism is
depicted in Scheme 2. There are three possible routes to these
compounds, as a result of 1,2-, 1,4-additions or their combination.
In the first (path 1,2-AN, vinylogous aldol reaction), initial nucleo-
philic attack of the base-activated ylidenemalononitrile 6 at the
CHO group (intermediate A) followed by dehydration leads to di-
enes 7. Due to the fact that the aldehyde function is chemically
equivalent to the C-2 atom, the second route (path 1,4-AN, Michael
addition) could not be excluded and implies initial nucleophilic
attack at C-2 (intermediate B) followed by ring-opening (C), intra-
molecular cyclization (D), and dehydration. A survey of conjugated
enone literature indicates that under mild conditions the Michael
addition is favored, however, it now seems that the third possibility,
which is the combination of these two routes, may also take place.
The reaction may have proceeded through a Michael addition
pathway followed by 1,2-addition and retro-Michael addition of the
intermediate E during conventional workup. We believe that the
latter route is more preferred, however, further work is necessary to
distinguish between these three pathways (Scheme 2).
Fig. 2. Diagnostic 1H NMR signals (
d, ppm, CDCl3) of 7d,h and NOE correlations of 7d.
The observed NOESY cross-peaks in diene 7g supported the
above E-configuration assignment. Moreover, the s-cis,s-trans-
conformation of the trienyl moiety was deduced on the basis of the
key NOE correlation between H-2 and the Me group. Simultaneous
observation of a weak NOE correlation between the Me and Ph
groups suggested that 7g undergoes fast conformational exchange
between conformations s-cis,s-trans and s-cis,s-cis, however, the
preferred conformation is the s-cis,s-trans in accordance with the
literature data (Fig. 3). Thus, the crystal structure of compound 5
was determined by X-ray diffraction analysis and s-trans,s-trans-

V.Yu. Korotaev et al. / Tetrahedron 70 (2014) 3584e3589
3587
R3
R2
CN
O
O
O
O
R1
CN
OH
R1
CHO
R2
6
R2
1,2-AN
CN
CN
E
B
R3
R3
CN
CN
R1
- 6
OH R3
1,4-AN
O
O
O
R3
R1
CN
CN
1
6
+
R2 CN
R2 CN
-H2O
1,2-AN
O
A
7
1,4-AN
-H2O
R3
O
R3
O
R1
CN
R1
CN
B
R2 CN
CHO R2 CN
OH
OH
O
D
C
Scheme 2. Proposed reaction mechanism.
3. Conclusion
4.2.1. 2-[(E)-1-Methyl-3-(4-oxo-4H-chromen-3-yl)-2-propenylidene]
malononitrile (7a). Yield 0.17 g (66%), mp 244e245 ꢀC (decomp.). IR
(KBr): 2222, 1662, 1617, 1603, 1533, 1463, 1412, 1384, 1357 cmꢁ1; 1H
In conclusion, we have shown, for the first time that 3-
formylchromones react with ylidenemalononitriles and ethyl
cyano- -methylcinnamate in the presence of triethylamine to
a
-
NMR (400 MHz, CDCl3)
d
2.48 (s, 3H, Me), 7.29 (d, J¼15.9 Hz, 1H, H-
b
10), 7.49 (ddd, J¼7.9, 7.1, 1.0 Hz, 1H, H-6), 7.52 (d, J¼8.4 Hz, 1H, H-8),
7.74 (ddd, J¼8.4, 7.1, 1.6 Hz, 1H, H-7), 7.95 (d, J¼15.9 Hz, 1H, H-20),
8.29 (s, 1H, H-2), 8.30 (dd, J¼7.9, 1.6 Hz, 1H, H-5); 1H NMR
produce the hitherto unknown electron-deficient dienes connected
to the chromone system in good yields. In the case of ylidenema-
lononitriles, only one geometric E-isomer was found, while re-
(400 MHz, DMSO-d6)
d
2.47 (s, 3H, Me), 7.44 (d, J¼15.5 Hz,1H, H-10),
actions of ethyl
a
-cyano-
b
-methylcinnamate proceeded with the
7.55 (ddd, J¼8.0, 7.1, 0.8 Hz,1H, H-6), 7.64 (d, J¼8.2 Hz,1H, H-8), 7.82
(ddd, J¼8.2, 7.1, 1.5 Hz, 1H, H-7), 8.20 (dd, J¼8.0, 1.5 Hz, 1H, H-5),
8.35 (d, J¼15.5 Hz, 1H, H-20), 8.83 (s, 1H, H-2); 13C NMR (101 MHz,
formation of E,Z- and E,E-isomers, which could be separated by
crystallization. Taking into account the ability to transform the
chromone system into other compounds, the chromone derivatives
described here are valuable building blocks for the construction of
various heterocycles. Further studies on the reactivity of the com-
pounds obtained are now in progress.
DMSO-d6) d 17.8 (Me), 82.0, 113.2 (CN), 114.2 (CN), 118.9, 119.1, 124.1,
126.1, 126.2, 126.9, 135.3, 138.6, 155.4, 162.8, 171.7, 175.8 (C]O).
Anal. Calcd for C16H10N2O2: S, 73.27; O, 3.84; N, 10.68. Found: S,
73.14; O, 3.95; N, 10.63.
4.2.2. 2-[(E)-1-Methyl-3-(6-methyl-4-oxo-4H-chromen-3-yl)-2-
4. Experimental
4.1. General
propenylidene]malononitrile (7b). Yield 0.16
g
(58%), mp
254e255 ꢀC (decomp.). IR (KBr): 2218, 1652, 1615, 1599, 1564, 1483,
1350 cmꢁ1; 1H NMR (400 MHz, DMSO-d6)
d 2.44 (s, 3H, Me), 2.46 (s,
3H, Me), 7.45 (d, J¼15.3 Hz, 1H, H-10), 7.65 (d, J¼8.5 Hz, 1H, H-8),
7.70 (dd, J¼8.5, 1.5 Hz, 1H, H-7), 8.38 (d, J¼15.3 Hz, 1H, H-20), 7.97
(br s, 1H, H-5), 8.87 (s, 1H, H-2). Anal. Calcd for
NMR spectra were recorded on Bruker DRX-400 (1Hd400 MHz,
13Cd101 MHz) spectrometer in DMSO-d6 and CDCl3 with TMS as an
internal standard. IR spectra were recorded on a PerkineElmer
Spectrum BX-II instrument as KBr discs. Elemental analyses were
performed at the Microanalysis Services of the Institute of Organic
Synthesis, Ural Branch, Russian Academy of Sciences. All solvents
used were dried and distilled per standard procedures.
C17H12N2O2$0.33H2O: S, 72.33; O, 4.52; N, 9.92. Found: S, 72.32; O,
4.50; N, 10.24.
4.2.3. 2-[(E)-1-Methyl-3-(6-chloro-4-oxo-4H-chromen-3-yl)-2-
propenylidene]malononitrile (7c). Yield 0.17
278e279 ꢀC. IR (KBr): 2225, 1652, 1603, 1536, 1468, 1441, 1377,
1347 cmꢁ1; 1H NMR (400 MHz, DMSO-d6)
2.44 (s, 3H, Me), 7.44 (d,
g
(57%), mp
d
4.2. General procedure for the synthesis of compounds (7ael)
J¼15.5 Hz, 1H, H-10), 7.82 (dd, J¼9.0 Hz, 1H, H-8), 7.91 (dd, J¼9.0,
2.6 Hz, 1H, H-7), 8.11 (d, J¼2.6 Hz, 1H, H-5), 8.34 (d, J¼15.5 Hz, 1H,
H-20), 8.90 (s, 1H, H-2). Anal. Calcd for C16H9ClN2O2$0.5H2O: S,
62.86; O, 3.30; N, 9.16. Found: S, 62.89; O, 2.99; N, 9.23.
A solution of 3-formylchromone (1.0 mmol), ylidenemalononi-
trile or ethyl
a-cyano-b-methylcinnamate (1.0 mmol), and trie-
thylamine (0.014 mL, 10%-mol) in dichloromethane (3.0 mL) was
kept for several hours at room temperature (see Scheme 1). After
evaporation of the solvent the product was washed with hot eth-
anol to give compounds 7 as a colorless powder.
4.2.4. 2-[(E)-3-(4-Oxo-4H-chromen-3-yl)-1-phenyl-2-
propenylidene]malononitrile (7d). Yield 0.22
g
(69%), mp
224e225 ꢀC (decomp.). IR (KBr): 2219, 1660, 1649, 1614, 1595, 1561,

3588
V.Yu. Korotaev et al. / Tetrahedron 70 (2014) 3584e3589
1520, 1462, 1414, 1362, 1342 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d
6.67
(d, J¼15.6 Hz, 1H, H-10), 7.12e7.19 (m, 2H, Ph), 7.41e7.49 (m, 5H, H-
6, H-8, Ph), 7.70 (ddd, J¼8.5, 7.2, 1.5 Hz, 1H, H-7), 8.07 (s, 1H, H-2),
8.27 (dd, J¼7.9, 1.5 Hz, 1H, H-5), 8.36 (d, J¼15.6 Hz, 1H, H-20); E,E-
(d, J¼15.4 Hz, 1H, H-10), 7.35e7.40 (m, 2H, Ph), 7.45e7.61 (m, 5H, H-
6, H-8, Ph), 7.72 (ddd, J¼8.4, 7.2, 1.6 Hz, 1H, H-7), 8.09 (s, 1H, H-2),
8.28 (dd, J¼7.9, 1.6 Hz, 1H, H-5), 8.47 (d, J¼15.4 Hz, 1H, H-20); 13C
isomer (40%)
d
1.42 (t, J¼7.1 Hz, 3H, Me), 4.41 (q, J¼7.1 Hz, 2H,
NMR (101 MHz, DMSO-d6)
d
82.0, 113.6 (CN), 114.3 (CN), 118.8, 119.0
CH2O), 6.47 (d, J¼15.9 Hz, 1H, H-10), 7.32e7.36 (m, 2H, Ph),
7.44e7.52 (m, 5H, H-6, H-8, Ph), 7.68 (ddd, J¼8.5, 7.2, 1.5 Hz, 1H, H-
7), 8.04 (s, 1H, H-2), 8.29 (dd, J¼8.0, 1.5 Hz, 1H, H-5), 9.26 (d,
(CH), 124.0, 126.1 (CH), 126.9 (CH), 127.1 (CH), 129.4 (CH), 129.5
(CH), 131.5 (CH), 133.0, 135.3 (CH), 142.1 (CH), 155.3, 163.4 (CH),
172.5, 175.7 (C]O). Anal. Calcd for C21H12N2O2: S, 77.77; O, 3.73; N,
8.64. Found: S, 77.67; O, 3.75; N, 8.85.
J¼15.9 Hz,1H, H-20); 13C NMR (101 MHz, DMSO-d6)
d 13.9 (Me), 61.8
(OCH2), 103.7, 116.2, 119.0, 119.1, 124.0, 126.0, 126.7, 128.5, 128.6,
129.4, 130.1, 135.0, 135.1, 139.4, 155.4, 161.7, 161.9, 166.4, 175.6 (C]
O). Anal. Calcd for C23H17NO4: S, 74.38; O, 4.61; N, 3.77. Found: S,
74.21; O, 4.60; N, 3.51.
4.2.5. 2-[(E)-3-(6-Methyl-4-oxo-4H-chromen-3-yl)-1-phenyl-2-
propenylidene]malononitrile (7e). Yield 0.22
180e181 ꢀC. IR (KBr): 2216, 1643, 1616, 1601, 1590, 1564, 1525, 1484,
1437,1394, 1339 cmꢁ1; 1H NMR (400 MHz, CDCl3)
2.48 (s, 3H, Me),
g
(64%), mp
d
4.2.11. Ethyl 2-cyano-5-(6-methyl-4-oxo-4H-chromen-3-yl)-3-
6.67 (dd, J¼15.4, 0.3 Hz, 1H, H-10), 7.35e7.40 (m, 3H, H-8, Ph),
7.50e7.60 (m, 4H, H-7, Ph), 8.06 (s, 2H, H-2, H-5), 8.45 (d, J¼15.4 Hz,
1H, H-20). Anal. Calcd for C22H14N2O2: S, 78.09; O, 4.17; N, 8.28.
Found: S, 77.85; O, 4.18; N, 8.22.
phenylpenta-2,4-dienoate (7k). Yield 0.26
203e204 ꢀC. IR (KBr): E,Z-isomer (55%) 2220,1719,1702,1652, 1616,
1537, 1478 cmꢁ1; 1H NMR (400 MHz, CDCl3) E,Z-isomer (55%)
1.13
g
(68%), mp
d
(t, J¼7.1 Hz, 3H, Me), 2.46 (s, 3H, Me), 4.08 (q, J¼7.1 Hz, 2H, CH2O),
6.51 (d, J¼15.6 Hz, 1H, H-10), 7.12e7.19 (m, 2H, Ph), 7.35 (d, J¼8.6 Hz,
1H, H-8), 7.42e7.46 (m, 3H, Ph), 7.49 (dd, J¼8.6, 1.3 Hz, 1H, H-7),
8.04 (s, 1H, H-2), 8.06 (br d, 1H, J¼1.3 Hz, 1H, H-5), 8.36 (d,
4.2.6. 2-[(E)-3-(6-Chloro-4-oxo-4H-chromen-3-yl)-1-phenyl-2-
propenylidene]malononitrile (7f). Yield 0.21
233e234 ꢀC. IR (KBr): 2226,1645,1605,1557,1519,1484,1465,1434,
1386, 1344 cmꢁ1 1H NMR (400 MHz, CDCl3)
g
(58%), mp
J¼15.6 Hz, 1H, H-20); E,E-isomer (45%)
d
1.42 (t, J¼7.1 Hz, 3H, Me),
;
d
6.65 (d, J¼15.5 Hz,
2.46 (s, 3H, Me), 4.40 (q, J¼7.1 Hz, 2H, CH2O), 6.48 (d, J¼15.9 Hz, 1H,
H-10), 7.32e7.38 (m, 2H, Ph), 7.41e7.52 (m, 4H, H-8, Ph), 7.70 (dd,
J¼8.4, 1.6 Hz, 1H, H-7), 8.01 (s, 1H, H-2), 8.04 (br s, 1H, H-5), 9.24 (d,
J¼15.9 Hz,1H, H-20). Anal. Calcd for C24H19NO4: S, 74.79; O, 4.97; N,
3.63. Found: S, 74.46; O, 4.98; N, 3.78.
1H, H-10), 7.35e7.40 (m, 2H, Ph), 7.46 (d, J¼8.9 Hz, 1H, H-8),
7.52e7.62 (m, 3H, Ph), 7.66 (dd, J¼8.9, 2.6 Hz, 1H, H-7), 8.08 (s, 1H,
H-2), 8.24 (d, J¼2.6 Hz, 1H, H-5), 8.42 (d, J¼15.5 Hz, 1H, H-20). Anal.
Calcd for C21H11ClN2O2$0.2H2O: S, 69.60; O, 3.17; N, 7.73. Found: S,
69.80; O, 3.00; N, 7.65.
4.2.12. Ethyl 5-(6-chloro-4-oxo-4H-chromen-3-yl)-2-cyano-3-
phenylpenta-2,4-dienoate (7l). Yield 0.24 g (65%), mp 184e185 ꢀC.
IR (KBr): E,Z-isomer (96%) 2220, 1725, 1655, 1605, 1542, 1489, 1469,
4.2.7. 2-[(E)-2-Methyl-3-(4-oxo-4H-chromen-3-yl)-1-phenyl-2-
propenylidene]malononitrile (7g). Yield 0.15
g
(45%), mp
181e182 ꢀC. IR (KBr): 2227, 1645, 1613, 1570, 1548, 1463, 1393,
1441 cmꢁ1 1H NMR (400 MHz, CDCl3) E,Z-isomer (70%)
; d 1.13 (t,
1360 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d
1.98 (d, J¼1.3 Hz, 3H, Me),
J¼7.1 Hz, 3H, Me), 4.09 (q, J¼7.1 Hz, 2H, CH2O), 6.49 (d, J¼15.6 Hz,
1H, H-10), 7.13e7.17 (m, 2H, Ph), 7.44 (d, J¼8.9 Hz, 1H, H-8),
7.45e7.49 (m, 3H, Ph), 7.63 (dd, J¼8.9, 2.6 Hz, 1H, H-7), 8.06 (s, 1H,
H-2), 8.22 (d, J¼2.6 Hz, 1H, H-5), 8.34 (d, J¼15.6 Hz, 1H, H-20); E,E-
6.93 (quint, J¼1.3 Hz,1H, H-10), 7.46 (ddd, J¼8.0, 7.2,1.0 Hz,1H, H-6),
7.50e7.65 (m, 6H, H-8, Ph), 7.73 (ddd, J¼8.5, 7.2, 1.6 Hz, 1H, H-7),
8.10 (d, J¼1.0 Hz, 1H, H-2), 8.26 (dd, J¼8.0, 1.6 Hz, 1H, H-5); 13C NMR
(101 MHz, DMSO-d6)
d
18.0 (qd, J¼129.3, 8.0 Hz, Me), 81.7 (C-40),
isomer (30%)
d
1.42 (t, J¼7.1 Hz, 3H, Me), 4.41 (q, J¼7.1 Hz, 2H,
113.8 (CN), 114.0 (CN), 118.5 (C-8), 119.3 (C-3), 123.1 (C-4a), 125.3 (C-
6), 125.9 (C-5), 129.0 (CH), 129.3 (CH), 129.4 (CH), 132.2 (C-10), 134.1,
134.6 (C-7), 135.7 (C-20), 155.5 (C-8a), 157.0 (C-2), 175.1 (C]O), 177.1
(C-30). Anal. Calcd for C22H14N2O2$0.25H2O: S, 77.07; O, 4.26; N,
8.17. Found: S, 77.32; O, 4.21; N, 8.24.
CH2O), 6.44 (d, J¼16.0 Hz, 1H, H-10), 7.32e7.37 (m, 2H, Ph), 7.43 (d,
J¼8.9 Hz,1H, H-8), 7.49e7.53 (m, 3H, Ph), 7.64 (dd, J¼8.9, 2.6 Hz,1H,
H-7), 8.03 (s,1H, H-2), 8.24 (d, J¼2.6 Hz,1H, H-5), 9.24 (d, J¼16.0 Hz,
1H, H-20). Anal. Calcd for C23H16ClNO4: S, 68.07; O, 3.97; N, 3.45.
Found: S, 67.69; O, 3.95; N, 3.52.
4.2.8. 2-[(E)-2-Methyl-3-(6-methyl-4-oxo-4H-chromen-3-yl)-1-
phenyl-2-propenylidene]malononitrile (7h). Yield 0.16 g (45%), mp
164e165 ꢀC. IR (ATR): 2221, 1638, 1616, 1601, 1572, 1514, 1478, 1439,
Acknowledgements
This work was supported financially by the Russian Foundation
for Basic Research (Grant 14-03-00179).
1387, 1342 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d
1.98 (d, J¼1.2 Hz, 3H,
Me), 2.48 (s, 3H, Me), 6.95 (quint, J¼1.2 Hz, 1H, H-10), 7.40 (d,
J¼8.6 Hz, 1H, H-8), 7.49e7.65 (m, 6H, H-7, Ph), 8.03 (s, 1H, H-5), 8.08
(d, J¼0.9 Hz, 1H, H-2). Anal. Calcd for C23H16N2O2: S, 78.39; O, 4.58;
N, 7.95. Found: S, 78.24; O, 4.62; N, 7.83.
References and notes
1. (a) Sabitha, G. Aldrichimica Acta 1996, 29, 15e25; (b) Ghosh, C. K.; Patra, A. J.
Heterocycl. Chem. 2008, 45, 1529e1547.
4.2.9. 2-[(E)-2-Methyl-3-(6-chloro-4-oxo-4H-chromen-3-yl)-1-
phenyl-2-propenylidene]malononitrile (7i). Yield 0.19 g (51%), mp
186e187 ꢀC. IR (ATR): 2223, 1646, 1605, 1565, 1532, 1468, 1441,
2. (a) Plaskon, A. S.; Grygorenko, O. O.; Ryabukhin, S. V. Tetrahedron 2012, 68,
2743e2757; (b) El-Desoky, E.-S. I.; Al-Shihry, S. S. J. Heterocycl. Chem. 2008, 45,
1855e1864.
3. (a) Nohara, A.; Kuriki, H.; Saijo, T.; Ukawa, K.; Murata, T.; Kanno, M.; Sanno, Y. J.
1388, 1351 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d
1.96 (d, J¼0.9 Hz, 3H,
ꢀ
Med. Chem. 1975, 18, 34e37; (b) Levai, A.; Silva, A. M. S.; Pinto, D. C. G. A.;
Me), 6.89 (quint, J¼0.9 Hz, 1H, H-10), 7.48 (d, J¼8.9 Hz, 1H, H-8),
7.50e7.65 (m, 5H, Ph), 7.67 (dd, J¼8.9, 2.5 Hz, 1H, H-7), 8.09 (s 1H,
H-2), 8.22 (d, J¼2.5 Hz, 1H, H-5). Anal. Calcd for C22H13ClN2O2: S,
70.88; O, 3.51; N, 7.51. Found: S, 70.78; O, 3.43; N, 7.38.
€
Cavaleiro, J. A. S.; Alkorta, I.; Elguero, J.; Jeko, J. Eur. J. Org. Chem. 2004,
4672e4679; (c) Chen, H.; Xie, F.; Gong, J.; Hu, Y. J. Org. Chem. 2011, 76,
8495e8500; (d) Gong, J.; Xie, F.; Ren, W.; Chen, H.; Hu, Y. Org. Biomol. Chem.
2012, 10, 486e489; (e) Dang, A.-T.; Miller, D. O.; Dawe, L. N.; Bodwell, G. J. Org.
Lett. 2008, 10, 233e236; (f) Gong, J.; Xie, F.; Chen, H.; Hu, Y. Org. Lett. 2010, 12,
3848e3851; (g) Zhang, Y.; Lv, Z.; Zhang, M.; Li, K. Tetrahedron 2013, 69,
8839e8846; (h) Kumar, S.; Singh, B. K.; Pandey, A. K.; Kumar, A.; Sharma, S. K.;
Raj, H. G.; Prasad, A. K.; Van der Eycken, E.; Parmar, V. S.; Ghosh, B. Bioorg. Med.
Chem. 2007, 15, 2952e2962.
4. Chen, C.; Wilcoxen, K.; Zhu, Y.-F.; Kim, K.; McCarthy, J. R. J. Org. Chem. 1999, 64,
3476e3482.
5. Sun, W.; Carroll, P. J.; Soprano, D. R.; Canney, D. J. Bioorg. Med. Chem. Lett. 2009,
19, 4339e4342.
4.2.10. Ethyl 2-cyano-5-(4-oxo-4H-chromen-3-yl)-3-phenylpenta-
2,4-dienoate (7j). Yield 0.32 g (86%), mp 217e218 ꢀC (decomp.). IR
(KBr): E,Z-isomer (95%) 2218, 1699, 1654, 1611, 1592, 1538, 1489,
1459, 1407, 1371, 1357 cmꢁ1; 1H NMR (400 MHz, CDCl3) E,Z-isomer
(60%)
d
1.13 (t, J¼7.1 Hz, 3H, Me), 4.08 (q, J¼7.1 Hz, 2H, CH2O), 6.52

V.Yu. Korotaev et al. / Tetrahedron 70 (2014) 3584e3589
3589
6. (a) Sosnovskikh, V. Y. Usp. Khim. 2003, 72, 550e578; Russ. Chem. Rev. 2003, 72,
489e516; (b) Sosnovskikh, V. Y.; Usachev, B. I.; Permyakov, M. N.; Sevenard, D.
V.; Roschenthaler, G.-V. Izv. Akad. Nauk, Ser. Khim. 2006, 1628e1630; Russ.
T. Synlett 2011, 341e344; (d) Li, P.; Luo, L.-L.; Li, X.-S.; Xie, J.-W. Tetrahedron
2010, 66, 7590e7594; (e) Korotaev, V. Y.; Barkov, A. Y.; Sosnovskikh, V. Y. Tet-
rahedron 2013, 69, 9642e9647.
€
Chem. Bull., Int. Ed. 2006, 55, 1687e1689; (c) Sosnovskikh, V. Y.; Korotaev, V. Y.;
Chizhov, D. L.; Kutyashev, I. B.; Yachevskii, D. S.; Kazheva, O. N.; Dyachenko, O.
A.; Charushin, V. N. J. Org. Chem. 2006, 71, 4538e4543; (d) Sosnovskikh, V. Y.;
Irgashev, R. A.; Barabanov, M. A. Synthesis 2006, 2707e2718; (e) Sosnovskikh,
V. Y.; Irgashev, R. A.; Kodess, M. I. Tetrahedron 2008, 64, 2997e3004; (f) Sos-
novskikh, V. Y.; Irgashev, R. A.; Levchenko, A. A. Tetrahedron 2008, 64,
6607e6614; (g) Sosnovskikh, V. Y.; Moshkin, V. S.; Kodess, M. I. Tetrahedron Lett.
2008, 49, 6856e6859; (h) Sosnovskikh, V. Y.; Moshkin, V. S.; Kodess, M. I.
Tetrahedron 2008, 64, 7877e7889; (i) Sosnovskikh, V. Y.; Moshkin, V. S.; Kodess,
M. I. Tetrahedron Lett. 2009, 50, 6515e6518; (j) Sosnovskikh, V. Y.; Safrygin, A.
V.; Anufriev, V. A.; Eltsov, O. S.; Iaroshenko, V. O. Tetrahedron Lett. 2011, 52,
6271e6274.
8. Babu, T. H.; Karthik, K.; Perumal, P. T. Synlett 2010, 1128e1132.
9. Babu, T. H.; Pawar, S.; Muralidharan, D.; Perumal, P. T. Synlett 2010, 2125e2129.
10. Wang, X.-W.; Li, P.; Xiao, H.; Zhu, S.-Z.; Zhao, G. Tetrahedron 2011, 67,
7618e7621.
11. (a) Galil, F. M. A.; Elnagdi, M. H. Liebigs Ann. Chem. 1987, 477e479; (b) Shesto-
palov, A. M.; Sharanin, Y. A.; Nesterov, V. N.; Khoroshilov, G. E.; Shklover, V. E.;
Struchkov, Y. T.; Litvinov, V. P. Chem. Heterocycl. Compd. 1991, 27, 1084e1090.
12. Hard, H.; Kim, Y. C. J. Org. Chem. 1966, 31, 2784e2789.
13. Mowry, D. T. J. Am. Chem. Soc. 1945, 67, 1050e1051.
14. O0Callaghan, C. N.; McMurry, T. B. H. J. Chem. Res., Synop. 1999, 458e459.
15. Williams, J. K. J. Org. Chem. 1963, 28, 2784e2789.
16. Hayashi, T. J. Org. Chem. 1966, 31, 3253e3258.
7. (a) Xie, J.-W.; Chen, W.; Li, R.; Zeng, M.; Du, W.; Yue, L.; Chen, Y.-C.; Wu, Y.; Zhu,
J.; Deng, J.-G. Angew. Chem., Int. Ed. 2007, 46, 389e392; (b) Zhou, R.; Wang, J.;
Tian, J.; He, Z. Org. Biomol. Chem. 2012, 10, 773e781; (c) Babu, T. H.; Perumal, P.
17. Steinhardt, S. E.; Silverston, J. S.; Vanderwal, C. D. J. Am. Chem. Soc. 2008, 130,
7560e7561.