A new domino Knoevenagel-hetero-Diels-Alder reaction: An efficient catalyst-free synthesis of novel thiochromone-annulated thiopyranocoumarin derivatives in aqueous medium

Article abstract of DOI:10.1016/j.tet.2010.09.048

An efficient catalyst-free synthesis of novel pentacyclic thiochromone-annulated thiopyranocoumarin derivatives is achieved via domino Knoevenagel-hetero-Diels-Alder reaction of 4-hydroxy dithiocoumarin and O-acrylated salicylaldehyde derivatives in H

Full text of DOI:10.1016/j.tet.2010.09.048

Tetrahedron 66 (2010) 8615e8622
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
A new domino Knoevenagel-hetero-DielseAlder reaction: an efficient
catalyst-free synthesis of novel thiochromone-annulated thiopyranocoumarin
derivatives in aqueous medium
,
a
a
Firouz Matloubi Moghaddam a , Mostafa Kiamehr , Mohammad Reza Khodabakhshi ,
*
Zohreh Mirjafarya, Shaghayegh Fathi a, Hamdollah Saeidian a
,
b
a Laboratory of Organic Synthesis and Natural Products, Department of Chemistry, Sharif University of Technology, Azadi Street, PO Box 11155-9516, Tehran, Iran
b Department of Science, Payame Noor University (PNU), Zanjan, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 30 June 2010
Received in revised form 21 August 2010
Accepted 13 September 2010
Available online 18 September 2010
An efficient catalyst-free synthesis of novel pentacyclic thiochromone-annulated thiopyranocoumarin
derivatives is achieved via domino Knoevenagel-hetero-DielseAlder reaction of 4-hydroxy dithiocou-
marin and O-acrylated salicylaldehyde derivatives in H2O as solvent. The products are formed in good
yields with high regio- and stereo-selectivity.
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
Domino reaction
Knoevenagel-hetero-DielseAlder
O-acrylated salicylaldehyde
Aqueous medium
3,4-Dihydrocoumarine
Thiopyran
1. Introduction
The hetero-DielseAlder reaction represents an effective
method for the synthesis of heterocyclic compounds, especially
Coumarins and chromones constitute an important class of
compound due to their presence as an important constituent of
natural products1 and synthetic organic chemistry. Members of this
group display a broad range of applications2 as fragrances, phar-
maceuticals, food additives and cosmetics, agrochemicals, optical
brightening agents, dispersal fluorescent, and tunable dye lasers3
and biological activities like antihelminthic, hypnotic, insecticidal,
and anticoagulant4 properties.
Thiochroman-4-one and 1-thiochromone derivatives are in-
teresting classes of heterocycles due to their broad pharmacological
and medicinal importance.5 Also, the 3,4-dihydrocoumarine system
shows a wide range of biological activities,6 such as aldose reductase
inhibition,7 antiherpetic,8 protein kinases,9 and a moderate estro-
genic activity. These wide range of biological applications have
stimulated considerable interest in evolving newer synthetic
methods for the construction of polycycles of 3,4-dihydrocoumarine
and thiochromone derivatives.
natural products.10 In recent years, intramolecular hetero-Dielse
Alder reactions have been used widely in numerous reactions
because of their economical and stereocontrolled nature.11 These
reactions allow the formation of two or more rings in one opera-
tion, thus avoiding sequential chemical transformations. Recently,
domino reactions have been used as highly efficient processes for
the improvement of reaction efficiency.12 Among these reactions,
the domino Knoevenagel-hetero-DielseAlder reaction is a very
efficient process, especially in the field of heterocycles and
natural products.13 A variety of heterocyclic compounds have been
synthesized by domino-Knoevenagel-hetero-DielseAlder reac-
tion.13b,14 Tietze et al. extensively described the domino Knoeve-
nagel-hetero-DielseAlder reaction of unsaturated aromatic and
aliphatic aldehydes (especially O-allylated salicylaldehydes) with
several 1,3-dicarbonyl compounds.12e,d,15 Furthermore, there have
been some reports on domino Knoevenagel-hetero-DielseAlder
reactions of O-propargylated salicylaldehyde derivatives for the
synthesis of polycycles with a pyran ring,16 However, we have also
reported a catalyst-free domino-Knoevenagel-hetero-DielseAlder
reaction of O-acrylated salicylaldehydes.17a In order to expand the
scope of this catalyst-free methodology, we focused our attention
* Corresponding author. Tel.: þ982166165309; fax: þ982166012983; e-mail
address: matloubi@sharif.edu (F.M. Moghaddam).
0040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.09.048

8616
F.M. Moghaddam et al. / Tetrahedron 66 (2010) 8615e8622
on the domino-Knoevenagel-hetero-DielseAlder reaction of O-
acrylated salicylaldehydes with 4-hydroxy dithiocoumarin. To the
best of our knowledge there are no examples of domino Knoeve-
nagel-hetero-DielseAlder reactions using a thioester with O-
acrylated salicylaldehydes in the literature. In the context of our
general interest in the domino-Knoevenagel-hetero-DielseAlder
reaction17 and synthesis of sulfur-containing heterocycles,18 we
herein report a new and highly efficient reaction for the prepara-
tion of polycyclic compounds 5aeh and 6aeh, which consist of
a thiochromone ring (A), a dihydrothiopyran ring (B) annulated to
a dihydrocoumarin ring (C) (Scheme 1).
was also studied. Using various amount of ZnO as catalyst did not
give the desired product. Instead, hydrolysis of the ester moiety of
the intermediate (Knoevenagel adduct) was observed, which led to
low yield of the desired product. After this failure, we tried various
ratios of 3a/4. However, the best result was obtained when the
reaction was carried out under refluxing conditions using 3a
(0.5 mmol, 1 equiv), 4 (0.6 mmol, 1.2 equiv) in H2O (90%, entry 10).
In all the cases the products were obtained as a mixture of cis- and
trans-isomers and changing the reaction conditions did not sig-
nificantly change the ratio of cis/trans isomers. Using these opti-
mized conditions, we investigated the effect of substituents on the
OH
S
S
R2
CHO
A
A
O
H2O/ 3 h
Reflux
O
S
O
S
R3
Ha
+
B
B
Hc
+
Hc
Ha
R3
R2
R2
O
S
S
R3
R1
C
O
C
O
Hb
O
Hb
O
3a-h
4
R1
R1
R1= H, OMe
R2= H, Br, NO2
R3= Ph, Me
6a-h
5a-h
Scheme 1.
2. Results and discussion
ratio of cis/trans and yield of products (Table 2). Reaction of 3a with
1.2 equiv of 4 in refluxing aqueous medium gave the products 5a/6a
in 90% yield as a mixture of trans- and cis-diastereomers (59/41,
respectively, Table 2, entry 1). When the same reaction was carried
out with 3b, the desired products 5b and 6b were obtained in 63/37,
in 86% overall yield (entry 2). The diastereoselectivity varied sig-
nificantly with the substituent on the R2 position. When the re-
action was carried out with 3c and 3d, the products 5c/6c and 5d/
6d were obtained in 60% and 73% yield with a major trans-dia-
stereoselectivity (entries 3 and 4). More contrasted results were
2.1. Preparation of substrates for domino Knoevenagel-
hetero-DielseAlder reaction
The O-acrylated salicylaldehyde derivatives 2aej were prepared
from the corresponding substituted salicylaldehydes and (E)-
acryloyl chloride derivatives (cinnamoyl chloride, crotonoyl chlo-
ride, and acryloyl chloride) using K2CO3 in dry acetone with high
yields and excellent purity at room temperature (Scheme 2).
R1
R2 R3
R2
CHO
Ph
Ph
Ph
Ph
Me
H
H
3a
3b
3c
3d
3e
3f
R2
CHO
OH
O
OMe
H
O
H
K2CO3/ 8-10 h
acetone/ rt
+
Br
NO2
H
Cl
O
R3
H
H
R3
R1
R1
OMe
H
H
Me
Me
1a-d
2a-c
R3= Ph, Me, H
3a-j
Br
3g
3h
3i
R1= H, OMe
NO2 Me
H
R2= H, Br, NO2
OMe
H
H
Br
H
H
3j
Scheme 2.
Table 1
2.2. Domino Knoevenagel-hetero-DielseAlder reaction of
O-acrylated salicylaldehyde derivatives with 4-hydroxy
dithiocoumarin
Effect of catalyst and solvent on the domino Knoevenagel-hetero-DielseAlder re-
action of 3a and 4
Entry Solvent Catalyst
Ratio Temperature Time Yielda Ratiob
3a/4
(h)
(%)
cis/trans
The domino Knoevenagel-hetero-DielseAlder reaction of com-
pound 3a with 4-hydroxy dithiocoumarin 4 was used as a model to
optimize the reaction conditions. The effect of solvent and catalyst
was studied by carrying out the reaction at various conditions. The
experimental results are summarized in Table 1. We first used water
as solvent in the absence of any catalyst under reflux conditions for
3 h, wherein the products were obtained in 65% yield (entry 1).
When the reaction was carried out in the presence of triethyl amine
(1 equiv) in AcOH for 48 or 5 h at room temperature or reflux, re-
spectively, the yield was decreased (Table 1, entries 2 and 3).
According to our previous report,17b the effect of ZnO as Lewis acid
1
2
3
4
5
6
7
8
9
H2O
AcOH
AcOH
CH3CN ZnO (20%)
CH3CN ZnO (20%)
CH3CN ZnO (50%)
d
1/1
1/1
1/1
1/1
1/1
1/1
Reflux
rt
Reflux
rt
Reflux
Reflux
Reflux
3
48
5
24
2
2
2
3
3
65
59/41
Et3N
Et3N
Trace 64/36
23
0
0
0
62/38
d
d
d
CH3CN ZnO (100%) 1/1
0
d
H2O
H2O
H2O
d
d
d
1.5/1 Reflux
1/1.5 Reflux
1/1.2 Reflux
68
90
90
57/43
60/40
59/41
10
3
a
Yield of isolated products.
Based on 1H NMR of the crude.
b

F.M. Moghaddam et al. / Tetrahedron 66 (2010) 8615e8622
8617
Table 2
Domino Knoevenagel-hetero-DielseAlder reactions of 3aeh with 4a
Entry
Aldehyde
Products
Yieldb
Ratioc 5/6
CHO
O
S
S
O
S
O
O
S
H
H
1
90
59/41
63/37
97/03
92/08
07/93
06/94
H
H
H
O
H
O
O
O
3a
6a
5a
S
S
CHO
O
O
S
O
S
H
H
O
H
2
3
4
5
6
86
60
73
73
80
OCH3
H
H
O
H
O
O
O
3b
OCH3
OCH3
5b
6b
Br
CHO
O
S
S
O
S
O
H
S
O
H
H
Br
Br
H
H
O
H
O
O
O
3c
5c
6c
O2N
CHO
O
S
S
O
S
O
H
S
O
H
H
O2N
O2N
H
H
O
H
O
O
O
3d
5d
6d
S
S
CHO
O
O
S
O
S
H
CH3
H
H
H
O
CH3
CH3
H
O
H
O
3e
O
O
5e
6e
S
S
CHO
O
O
S
O
S
H
H
H
CH3
O
CH3
H
CH3
H
O
H
O
OCH3
3f
O
O
OCH3
OCH3
5f
6f
(continued on next page)

8618
F.M. Moghaddam et al. / Tetrahedron 66 (2010) 8615e8622
Table 2 (continued)
Entry
Aldehyde
Products
Yieldb
Ratioc 5/6
S
S
Br
CHO
O
O
S
O
S
H
CH3
H
H
H
7
82
04/96
O
Br
Br
CH3
CH3
H
O
H
O
3g
O
O
5g
6g
S
S
O2N
CHO
O
O
S
O
S
H
H
H
CH3
H
8
75
05/95
O
O2N
O2N
CH3
CH3
H
O
H
O
3h
O
O
5h
6h
a
All the reactions were carried out in H2O at reflux for 3 h, molar ratio 3/4 1:1.2.
Isolated products.
b
c
Based on 1H NMR of the crude.
obtained with the O-crotonoylated salicylaldehyde derivatives
(3eeh), which showed a good reactivity with 4, leading to the
corresponding adducts, but with an unexpected selectivity (entries
5e8). Thus, under the same conditions, whereas the trans-isomer of
5aed (entries 1e4) predominated as product for the O-cinnamoy-
lated salicylaldehyde derivatives (3aed), the products 6eeh were
formed with the predominance of the cis-isomers (entry 5e8). We
also attempted the reaction of O-acrylated salicylaldehyde de-
rivatives 3iej with 4-hydroxy dithiocoumarin 4. But a mixture of
inseparable products was obtained.
A plausible mechanism for the domino-Knoevenagel-hetero-
DielseAlder reaction to produce 5aeh and 6aeh is proposed in
Scheme 3. Aldehydes 3 undergo a Knoevenagel condensation with
4-hydroxy dithiocoumarin 4 in H2O at reflux to afford an alkene
intermediate, which has not been isolated. The alkene intermediate
provides two different heterodiene fragments and therefore, two
pathways can be imagined for the hetero DielseAlder reaction. In
one case, the keto carbonyl group (intermediates 9) could be in-
volved in the cycloaddition reaction leading to the compound 10
(path a). In another form, the thiocarbonyl group of the thioester
could be reacted; affording compounds 5 and 6 (path b). The re-
action does not occur via ‘path a’ to afford the product 10. Here only
the products 5aeh and 6aeh were isolated, which shows that the
reaction precedes via ‘path b’. However, in contrast to the homol-
The structures and the ratio of the products 5aeh and 6aeh
were established on the basis of their spectroscopic data (1H, 13
C
NMR, and DEPT) and elemental analyses. The relative configu-
rations were determined from the coupling constants of the
relevant H-atoms, NOE experiments and also by direct compar-
ison with the reported data in the literature.19 In the 1H NMR
spectra, there are two distinct groups of peaks with different
intensities proportional to the ratio of products. For instance, the
characteristic peaks for 5a and 6a in the 1H NMR spectra are
a doublet of doublet (5a, J¼13.6, 11.0 Hz and 6a, J¼11.7, 3.8 Hz) for
the Hb followed closely by two doublets for Ha (5a, J¼11.0 Hz and
6a, J¼11.7 Hz, both in trans-relation with Hb) and Hc (for 5a, the
J¼13.6 Hz in trans-relation with Hb and for 6a, J¼3.8 Hz in cis-
relation with Hb). Also, NOE measurements on compound 6g
confirmed the cis-orientation of Hb and Hc and trans-orientation
of Ha and Hb (Fig. 1).
ogous oxygenated substrates, a,b-unsaturated thiocarbonyls gen-
erally present very low stability.20 Indeed, except for conveniently
substituted thiocarbonyl compounds, the polymerization or di-
merization of these products have been observed.21 In most cases,
these highly reactive thiocompounds are not isolated, but are
generated and trapped in situ.22
The stereochemistry of the final products depends on the endo-
and exo-orientation of the dienophile in the transition state. We could
assume that the trans-cycloadducts 5aeh were formed via an exo-
transition state (path b, intermediates 7), whereas the cis-isomers
6aeh resulted from an endo-transition state (path b, intermediates
8), as represented in Scheme 3. In the case of compounds with
a cinnamoyl moiety 3aed we observed exo-transition states with the
predominance of the trans-isomers. In crotonoyl derivatives 3eeh,
due to secondary orbital interactions, endo-transition states occurred
and the cis-isomers were in predominance.
S
The results can be understood in terms of frontier molecular
orbital (FMO) theory. According to FMO theory, the reactions hav-
ing small HOMOeLUMO gaps manifest faster rates. It seems that
the effective interaction takes place between the LUMO of the
acryloyl moiety and the HOMO of the diene and thus we are dealing
with a normal DielseAlder reaction. Similarly, chemoselectivity
observed in this reaction can be explained in frontier orbital terms.
It seems that two important factors control the synthesis of prod-
ucts 5 and 6 that could be classified as (a) a more efficient
O
S
Hc
Ha
Br
CH3
Hb
O
O
6g
Fig. 1. Selected NOE enhancements on 6g.

F.M. Moghaddam et al. / Tetrahedron 66 (2010) 8615e8622
8619
S
S
path a
S
O
S
O
O
R3
R2
R2
R3
OH
S
R2
CHO
O
O
O
R1
R1
+
9
10
S
R1
O
R3
3a-h
4
S
S
O
O
S
R3
O
S
path b
R3
R2
O
R1
O
R1
O
R2
7
8
S
S
O
S
O
S
R3
H
H
H
R3
H
R2
R2
H
O
H
O
O
6a-h
O
R1
R1
5a-h
Scheme 3. A plausible mechanism for the formation of compounds 5and 6.
HOMOeLUMO interaction for
a
,
b
-unsaturated thioester as diene
NMR) and 125 (13C NMR and DEPT) MHz, in CDCl3 and DMSO-d6 as
solvents. Chemical shift have been expressed in parts per million rel
to Me4Si as internal standard. Signals of the 13C NMR spectra cor-
responding to CH, CH2, or CH3 groups are assigned from DEPT (135
and 90). Elemental analysis was obtained using a PerkineElmer
2004 (II) CHN analyzer.
and acryloyl moiety as dienophile in the intermediate 7 and 8 than
compared to intermediate 9. The reactivity could be explained by
considering the presence of a soft sulfur atom in the diene moiety
of the substrates. (b) More steric hinderance in the intermediate 8
compared to 7. The steric hinderance is much more when the cin-
namoyl moiety acts as the dienophile compared to the crotonoyl
group and so 7 is favored.
4.2. General procedure for preparation of the O-acrylated
salicylaldehyde derivatives 3aej
3. Conclusion
To a stirred solution of salicylaldehyde derivative (5 mmol) and
acryloyl chloride or its derivative (6 mmol) in acetone (10 mL) was
added K2CO3 (0.69 g, 6 mmol). After stirring for 8e10 h at room
temperature, ice-cold water (50 mL) was added to the mixture with
vigorous stirring to afford a light precipitate that was filtered,
washed with water, and air-dried.
We have reported a highly efficient and catalyst-free method for
the synthesis of novel heteropolycyclic compounds through
a domino Knoevenagel-hetero-DielseAlder reaction of O-acrylated
salicylaldehydes 3aeh with 4-hydroxy dithiocoumarin in aqueous
medium. Using H2O as a solvent has advantages, such as safety,
environmentally friendly, and low cost. This reaction also offers
other advantages such as high yields of products, short reaction
time, clean reactions, ease of workup, and no need of a catalyst,
which make it a useful and attractive procedure for the synthesis of
pentacyclic 3,4-dihydrocoumarine derivatives.
4.2.1. 2-Formylphenyl (2E)-3-phenylacrylate (3a). White solid, yield
95% (1.20 g), mp: 74e76 ꢀC; IR (KBr): 1743, 1707, 1640, 1599, 1202,
1125, 759 cmꢁ1 1H NMR (500 MHz, CDCl3):
; d 6.70 (1H, d,
J¼16.0 Hz), 7.28 (1H, d, J¼8.1 Hz, AreH), 7.39 (1H, t, J¼7.5 Hz, AreH),
7.41e7.46 (3H, m, AreH), 7.59e7.61 (2H, m, AreH), 7.64 (1H, t,
J¼7.8 Hz, AreH), 7.93 (2H, m), 10.01 (1H, s, HC]O); 13C NMR
4. Experimental section
4.1. General
(125 MHz, CDCl3):
d 116.7 (CH), 123.9 (CH), 126.8 (CH), 128.7 (C),
128.9 (CH), 129.5 (CH), 130.5 (CH), 131.5 (CH), 134.4 (C), 135.7 (CH),
148.2 (CH), 152.6 (C), 165.5 (C, OeC]O), 188.9 (CH, HC]O). Anal.
Calcd for C16H12O3: C, 76.18; H, 4.79%. Found: C, 76.04; H, 4.76%.
Commercially available materials were used without any addi-
tional purification. 4-Hydroxy dithiocoumarin 4 was prepared
according to the previously reported procedure.23 Melting points
were determined on a Büchi melting point B-540 apparatus and
were uncorrected. IR spectra were taken films KBr pellets on
a Nicolet spectrometer (Magna 550). 1H NMR and 13C NMR Spectra
were run on Bruker (DRX-500 Avance) spectrometer at 500 (1H
4.2.2. 2-Formyl-6-methoxyphenyl (2E)-3-phenylacrylate (3b). Pale
white solid, yield 93% (1.32 g), mp: 106e108 ꢀC; IR (KBr): 1732,
1696, 1630, 1583, 1480, 1006, 769 cmꢁ1; 1H NMR (500 MHz, CDCl3):
d
3.87 (3H, s, OCH3), 6.73 (1H, d, J¼16.0 Hz), 7.25 (1H, d, J¼7.7 Hz,
AreH), 7.34 (1H, t, J¼7.6 Hz, AreH), 7.43e7.44 (3H, m, AreH), 7.51

8620
F.M. Moghaddam et al. / Tetrahedron 66 (2010) 8615e8622
(1H, d, J¼7.8 Hz, AreH), 7.60e7.62 (2H, m, AreH), 7.94 (1H, d,
(1H, d, J¼2.8 Hz, AreH), 10.25 (1H, s, HC]O); 13C NMR (125 MHz,
J¼16.0 Hz), 10.21 (1H, s, HC]O); 13C NMR (125 MHz, CDCl3):
d
56.8
CDCl3): d 19.0 (CH3), 120.8 (CH), 125.3 (CH), 125.5 (CH), 129.1 (C),
(OCH3), 116.5 (CH), 118.3 (CH), 120.9 (CH), 127.2 (CH), 128.9 (CH),
129.5 (CH), 129.9 (C), 131.4 (CH), 134.5 (C), 142.5 (C), 148.1 (CH),
152.3 (C), 165.0 (C, OeC]O), 189.0 (CH, HC]O). Anal. Calcd for
C17H14O4: C, 72.33; H, 5.00%. Found: C, 72.22; H, 5.05%.
129.9 (CH), 150.8 (CH), 152.7 (C), 156.8 (C), 163.8 (C, OeC]O), 186.6
(CH, HC]O). Anal. Calcd for C11H9NO5: C, 56.17; H, 3.86; N, 5.96%.
Found: C, 56.12; H, 3.82; N, 5.93%.
4.2.9. 2-Formyl-6-methoxyphenyl acrylate (3i). White solid, yield
85% (0.88 g), mp: 67e69 ꢀC; IR (KBr): 1748, 1692, 1486, 1274, 1135,
4.2.3. 4-Bromo-2-formylphenyl (2E)-3-phenylacrylate (3c). White
solid, yield 90% (1.49 g), mp: 135e137 ꢀC; IR (KBr): 1738, 1681, 1238,
790 cmꢁ1; 1H NMR (500 MHz, CDCl3):
d 3.90 (3H, s, OCH3), 6.13 (1H,
1197 cmꢁ1; 1H NMR (500 MHz, CDCl3):
d
6.67 (1H, d, J¼16.0 Hz), 7.20
d, J¼10.5 Hz), 6.44 (1H, dd, J¼17.3, 10.5 Hz), 6.71 (1H, d, J¼17.3 Hz),
7.26 (1H, d, J¼8.0 Hz, AreH), 7.38 (1H, t, J¼8.0 Hz, AreH), 7.52 (1H,
d, J¼7.6 Hz, AreH), 10.19 (1H, s, HC]O); 13C NMR (125 MHz, CDCl3):
(1H, d, J¼8.6 Hz, AreH), 7.44e7.46 (3H, m, AreH), 7.60e7.62 (2H, m,
AreH), 7.75 (1H, dd, J¼8.6, 2.5 Hz, AreH), 7.93 (1H, d, J¼16.0 Hz), 8.04
(1H, d, J¼2.5 Hz, AreH), 10.14 (1H, s, HC]O); 13C NMR (125 MHz,
d
56.8 (OCH3), 118.3 (CH), 121.1 (CH), 127.2 (CH), 127.3 (CH), 129.7
CDCl3):
d
116.2 (CH), 120.2 (C), 125.8 (CH), 129.0 (CH), 129.5 (CH),
(C), 134.0 (CH2), 142.2 (C), 152.2 (C), 164.1 (C, OeC]O), 188.9 (CH,
HC]O). Anal. Calcd for C11H10O4: C, 64.07; H, 4.89%. Found: C,
64.10; H, 4.83%.
129.9 (C), 131.7 (CH), 132.8 (CH), 134.2 (C), 138.4 (CH), 148.8 (CH),
151.7 (C), 165.2 (C, OeC]O), 187.4 (CH, HC]O). Anal. Calcd for
C16H11BrO3: C, 58.03; H, 3.35%. Found: C, 57.94; H, 3.31%.
4.2.10. 4-Bromo-2-formylphenyl acrylate (3j). White solid, yield
83% (1.06 g), mp: 70e72ꢀC; IR (KBr): 1753, 1686, 1470, 1398, 1207,
4.2.4. 2-Formyl-4-nitrophenyl (2E)-3-phenylacrylate (3d). Light
yellow solid, yield 95% (1.41 g), mp: 152e154 ꢀC; IR (KBr): 1738,
1161, 1109, 883 cmꢁ1 1H NMR (500 MHz, CDCl3):
; d 6.17 (1H, d,
1686,1614,1527,1351,1182 cmꢁ1; 1H NMR (500 MHz, CDCl3):
d
6.76
J¼10.4 Hz), 6.41 (1H, dd, J¼17.3, 10.5 Hz), 6.72 (1H, d, J¼17.3 Hz),
(1H, d, J¼16.0 Hz), 7.47e7.55 (3H, m, AreH), 7.60 (1H, d, J¼8.9 Hz,
AreH), 7.66e7.68 (2H, m, AreH), 8.03 (1H, d, J¼16.0 Hz), 8.55 (1H,
dd, J¼8.9, 2.7 Hz, AreH), 8.84 (1H, d, J¼2.8 Hz, AreH), 10.31 (1H, s,
7.20 (1H, d, J¼8.6 Hz, AreH), 7.78 (1H, d, J¼8.5 Hz, AreH), 8.06 (1H,
s, AreH), 10.12 (1H, s, HC]O); 13C NMR (125 MHz, CDCl3):
d 120.3
(C), 125.6 (CH), 127.2 (CH), 129.8 (C), 133.1 (CH), 134.7 (CH2), 138.4
(CH), 151.3 (C), 164.3 (C, OeC]O), 187.3 (CH, HC]O). Anal. Calcd for
C10H7BrO3: C, 47.09; H, 2.77%. Found: C, 47.00; H, 2.74%.
HC]O); 13C NMR (125 MHz, CDCl3):
d 115.5 (CH), 125.3 (CH), 125.7
(CH), 129.0 (C), 129.1 (CH), 129.5 (C), 129.6 (CH), 129.9 (CH), 132.0
(CH), 134.0 (C), 149.8 (CH), 156.8 (C), 164.5 (C, OeC]O), 186.6 (CH,
HC]O). Anal. Calcd for C16H11NO5: C, 64.65; H, 3.73; N, 4.71%.
Found: C, 64.60; H, 3.70; N, 4.68%.
4.3. General procedure for domino Knoevenagel-hetero-
DielseAlder reaction
4.2.5. 2-Formylphenyl (2E)-but-2-enoate (3e). Colorless oil, yield
A mixture of an O-acrylated salicylaldehyde derivative 3
75% (0.71 g); IR (KBr): 1748, 1707, 1666, 1599, 1398, 1213, 1165, 1104,
(0.5 mmol) and 4-hydroxy dithiocoumarin 4 (0.6 mmol) in water
(7 mL) was stirred at reflux temperature. The progress of the re-
action was monitored by TLC (mini-extraction with CH2Cl2 carried
out for TLC) using petroleum ethereethyl acetate mixture (2:1) as
eluent. After completion (3 h), the solid precipitate was filtered,
washed with hot water, dried, and recrystallized from EtOH.
Compounds 5 and 6 have the same polarity; therefore our attempt
to separate these compounds using different solid supports and
solvents was not successful.
976, 764 cmꢁ1; 1H NMR (500 MHz, CDCl3):
d
2.05 (3H, d, J¼6.9 Hz,
CH3), 6.16 (1H, d, J¼15.4 Hz), 7.25e7.34 (2H, m), 7.41 (1H, t, J¼7.6 Hz,
AreH), 7.67 (1H, t, J¼7.8 Hz, AreH), 7.95 (1H, d, J¼7.7 Hz, AreH),
10.20 (1H, s, HC]O); 13C NMR (125 MHz, CDCl3):
d 18.8 (CH3), 121.6
(CH), 123.9 (CH), 126.7 (CH), 128.6 (C), 130.4 (CH), 135.7 (CH), 148.9
(CH), 152.6 (C), 164.9 (C, OeC]O), 189.0 (CH, HC]O). Anal. Calcd
for C11H10O3: C, 69.46; H, 5.30%. Found: C, 69.39; H, 5.27%.
4.2.6. 2-Formyl-6-methoxyophenyl (2E)-but-2-enoate (3f). Pale
white, yield 90% (0. 99 g), mp: 77e79 ꢀC; IR (KBr): 1748, 1692, 1651,
1584, 1480, 1274, 1090, 1063, 769 cmꢁ1; 1H NMR (500 MHz, CDCl3):
4.3.1. Mixture of 5a and 6a. Following the general procedure the
reaction afforded a mixture of 5a and 6a (59:41, 193 mg, 90%) as
a yellow solid; Rf: 0.64; mp: 282e284 ꢀC; IR (KBr): 1759, 1625, 1527,
1223, 1105, 759 cmꢁ1. Anal. Calcd for C25H16O3S2: C, 70.07; H, 3.76%.
Found: C, 69.95; H, 3.71%.
d
2.04 (3H, d, J¼6.9 Hz, CH3), 3.89 (3H, s, OCH3), 6.18 (1H, d,
J¼15.5 Hz), 7.24e7.37 (3H, m), 7.51 (1H, d, J¼7.7 Hz, AreH), 10.19
(1H, s, HC]O); 13C NMR (125 MHz, CDCl3):
18.8 (CH3), 56.8
d
(OCH3),118.3 (CH),120.8 (CH),121.4 (CH),127.1 (CH),129.9 (C),142.5
(C), 148.7 (CH), 152.3 (C), 164.3 (C, OeC]O), 189.1 (CH, HC]O).
Anal. Calcd for C12H12O4: C, 65.45; H, 5.49%. Found: C, 65.38; H,
5.45%.
4.3.1.1. (6aR
chromeno [30,20:5,6]thiopyrano[3,4-c]chromene-6,14-dione (5a). 1H
NMR (500 MHz, CDCl3):
*
,7S
*
,14bR
*
)-7-Phenyl-6a,14b-dihydro-6H,7H,14H-thio-
d
3.75 (1H, dd, J¼13.6, 11.0 Hz, Hb), 4.73
(1H, d, J¼11.0 Hz, Ha), 4.59 (1H, d, J¼13.6 Hz, Hc), 6.74 (1H, d,
J¼7.8 Hz, AreH), 7.06 (1H, t, J¼7.6 Hz, AreH), 7.12e7.16 (1H, m,
AreH), 7.31e7.45 (6H, m, AreH), 7.54e7.71 (3H, m, AreH), 8.51 (1H,
4.2.7. 4-Bromo-2-formylphenyl (2E)-but-2-enoate (3g). Pale white
solid, yield 88% (1.18 g), mp: 79e81 ꢀC; IR (KBr): 1743, 1681, 1650,
1470, 1295, 1207, 1140, 965 cmꢁ1; 1H NMR (500 MHz, CDCl3):
d
2.05
d, J¼7.8 Hz, AreH); 13C NMR (125 MHz, CDCl3):
d 38.9 (CH), 47.5
(3H, d, J¼6.6 Hz, CH3), 6.14 (1H, d, J¼15.5 Hz), 7.17 (1H, d, J¼8.6 Hz,
(CH), 50.4 (CH), 117.5 (CH), 124.4 (C), 124.7 (CH), 125.5 (CH), 125.6
(CH), 128.2 (C), 128.3 (CH), 128.5 (CH), 129.0 (CH), 129.4 (CH), 129.7
(CH), 130.2 (CH), 131.5 (C), 132.3 (CH), 136.2 (C), 136.3 (C), 151.3 (C),
151.7 (C), 167.7 (C, OeC]O), 178.1 (C, C]O).
AreH), 7.28e7.33 (1H, m), 7.76 (1H, d, J¼8.5 Hz, AreH), 8.04 (1H, s,
AreH),10.12 (1H, s, HC]O); 13C NMR (125 MHz, CDCl3):
d 18.9 (CH3),
120.0 (C), 121.3 (CH), 125.8 (CH), 129.9 (C), 132.6 (CH), 138.3 (CH),
149.5 (CH), 151.7 (C), 164.5 (C, OeC]O), 187.4 (CH, HC]O). Anal.
Calcd for C11H9BrO3: C, 49.10; H, 3.37%. Found: C, 48.98; H, 3.42%.
4.3.1.2. (6aS
chromeno [30,20:5,6]thiopyrano[3,4-c]chromene-6,14-dione (6a). 1H
NMR (500 MHz, CDCl3):
*
,7R
*
,14bR )-7-Phenyl-6a,14b-dihydro-6H,7H,14H-thio-
*
4.2.8. 2-Formyl-4-nitrophenyl (2E)-but-2-enoate (3h). Pale white
solid, yield 85% (1.00 g), mp: 102e104 ꢀC; IR (KBr): 1738, 1697, 1650,
d
3.55 (1H, dd, J¼11.7, 3.8 Hz, Hb), 4.47 (1H,
d, J¼11.7 Hz, Ha), 5.49 (1H, d, J¼3.8 Hz, Hc), 6.86 (1H, d, J¼7.6 Hz,
AreH), 7.12e7.16 (2H, m, AreH), 7.31e7.45 (6H, m, AreH), 7.54e7.71
(3H, m, AreH), 8.61 (1H, d, J¼7.9 Hz, AreH); 13C NMR (125 MHz,
1527, 1352, 1146, 1094, 970 cmꢁ1; 1H NMR (500 MHz, CDCl3):
d 2.10
(3H, d, J¼6.9 Hz, CH3), 6.18 (1H, d, J¼15.6 Hz), 7.36e7.40 (1H, m),
7.53 (1H, d, J¼8.9 Hz, AreH), 8.52 (1H, dd, J¼8.9, 2.8 Hz, AreH), 8.81
CDCl3): d 35.1 (CH), 44.6 (CH), 46.1 (CH), 117.3 (CH), 122.9 (C), 124.7

F.M. Moghaddam et al. / Tetrahedron 66 (2010) 8615e8622
8621
(CH), 125.5 (CH), 125.9 (CH), 128.5 (CH), 128.7 (CH), 128.8 (CH),
129.3 (CH), 129.4 (CH), 129.8 (CH), 130.3 (C), 132.4 (CH), 134.5 (C),
136.2 (C), 136.3 (C), 150.4 (C), 152.3 (C), 166.0 (C, OeC]O), 176.8 (C,
C]O).
J¼8.0 Hz, AreH); 13C NMR (125 MHz, CDCl3):
d
38.9 (CH), 47.3 (CH),
49.8 (CH), 118.3 (CH), 122.3 (CH), 122.9 (C), 124.7 (CH), 125.6 (CH),
128.4 (CH), 129.0 (CH), 129.5 (C), 129.6 (CH), 129.8 (CH), 129.9 (CH),
131.3 (C), 132.8 (CH), 135.6 (C), 136.1 (C), 144.6 (C), 152.9 (C), 156.0
(C), 165.9 (C, OeC]O), 177.0 (C, C]O). Anal. Calcd for C25H15NO5S2:
C, 63.41; H, 3.19; N, 2.96%. Found: C, 63.49; H, 3.22; N, 2.92%.
4.3.2. Mixture of 5b and 6b. Following the general procedure the
reaction afforded a mixture of 5b and 6b (63:37, 198 mg, 86%) as
a yellow solid; Rf: 0.53; mp: 244e246 ꢀC; IR (KBr): 1753, 1614, 1589,
1480, 1440, 1346, 1202, 1175, 1065, 759 cmꢁ1. Anal. Calcd for
C26H18O4S2: C, 68.10; H, 3.96%. Found: C, 67.99; H, 3.91%.
4.3.5. (6aS
*
,7S
*
,14bR )-7-Methyl-6a,14b-dihydro-6H,7H,14H-thio-
*
chromeno [30,20:5,6]thiopyrano[3,4-c]chromene-6,14-dione (6e). Follo-
wing the general procedure the reaction afforded a mixture of 5e and
6e (07:93, 134 mg, 73%) as a yellow solid; Rf: 0.66; mp: 227e229 ꢀC;
IR (KBr): 1759, 1609, 1527, 1449, 1187, 735 cmꢁ1; 1H NMR (500 MHz,
4.3.2.1. (6aR
6H,7H,14H-thiochromeno[30,20:5,6]thiopyrano[3,4-c]chromene-6,14-
dione (5b). 1H NMR (500 MHz, CDCl3):
*
,7S
*
,14bR )-4-Methoxy-7-phenyl-6a,14b-dihydro-
*
CDCl3):
d
1.49 (3H, d, J¼6.7 Hz, CH3) {for 5e, 1.75 (3H, d, J¼6.5 Hz,
d
3.76 (1H, dd, J¼13.6,
CH3)}, 3.01 (1H, dd, J¼11.4, 3.9 Hz, Hb), 3.40e3.47 (1H, m, Ha) {for 5e,
3.72e3.76 (1H, m, Ha)}, 5.37 (1H, d, J¼3.9 Hz, Hc) {for 5e, 4.79 (1H, d,
J¼13.6 Hz, Hc)}, 6.76 (1H, d, J¼7.6 Hz, AreH), 7.07 (1H, t, J¼7.5 Hz,
AreH), 7.11 (1H, d, J¼8.0 Hz, AreH), 7.27 (1H, t, J¼9.2 Hz, AreH), 7.52
(1H, d, J¼8.0 Hz, AreH), 7.57 (1H, t, J¼7.4 Hz, AreH), 7.64 (1H, t,
J¼7.1 Hz, AreH), 8.56 (1H, d, J¼7.9 Hz, AreH); 13C NMR (125 MHz,
11.0 Hz, Hb), 3.91 (3H, s, OCH3), 4.70 (1H, d, J¼11.0 Hz, Ha), 4.99 (1H,
d, J¼13.6 Hz, Hc), 6.33 (1H, d, J¼7.8 Hz, AreH), 6.91 (1H, d, J¼8.2 Hz,
AreH), 6.99 (1H, t, J¼8.1 Hz, AreH), 7.34e7.43 (5H, m, AreH),
7.52e7.68 (3H, m, AreH), 8.49 (1H, d, J¼7.2 Hz, AreH); 13C NMR
(125 MHz, CDCl3):
d 39.0 (CH), 47.5 (CH), 50.2 (CH), 56.6 (OCH3),
111.9 (CH), 117.3 (CH), 124.5 (C), 124.8 (CH), 125.5 (CH), 128.4 (CH),
129.1 (CH), 129.4 (CH), 129.6 (CH), 129.7 (C), 129.8 (CH), 131.5 (C),
132.4 (CH), 136.2 (2C), 140.9 (C), 148.3 (C), 151.1 (C), 167.2 (C, OeC]
O), 178.1 (C, C]O).
CDCl3): d 18.9 (CH3), 34.4 (CH), 34.6 (CH), 46.4 (CH), 117.2 (CH), 123.1
(C), 124.4 (C), 125.4 (CH), 125.7 (CH), 128.2 (CH), 128.5 (CH), 129.1
(CH), 130.2 (CH), 130.3 (C), 132.1 (CH), 136.3 (C), 150.4 (C), 151.8 (C),
166.7 (C, OeC]O), 176.5 (C, C]O). Anal. Calcd for C20H14O3S2: C,
65.55; H, 3.85%. Found: C, 65.43; H, 3.81%.
4.3.2.2. (6aS
6H,7H,14H-thiochromeno[30,20:5,6]thiopyrano[3,4-c]chromene-6,14-
dione (6b). 1H NMR (500 MHz, CDCl3):
*
,7R
*
,14bR )-4-Methoxy-7-phenyl-6a,14b-dihydro-
*
4.3.6. (6aS
*
,7S
*
,14bR )-4-Methoxy-7-methyl-6a,14b-dihydro-
*
d
3.53 (1H, dd, J¼11.7, 3.9 Hz,
6H,7H,14H-thiochromeno[30,20:5,6]thiopyrano[3,4-c]chromene-6,14-
dione (6f). Following the general procedure the reaction afforded
a mixture of 5f and 6f (06:94,159 mg, 80%) as a Pale yellow solid; Rf:
0.47; mp: 263e265 ꢀC; IR (KBr): 1764, 1624, 1485, 1459, 1274,
Hb), 3.93 (3H, s, OCH3), 4.52 (1H, d, J¼11.7 Hz, Ha), 5.48 (1H, d,
J¼3.8 Hz, Hc), 6.44 (1H, d, J¼7.7 Hz, AreH), 6.96 (1H, d, J¼8.3 Hz,
AreH), 7.07 (1H, t, J¼8.0 Hz, AreH), 7.34e7.43 (5H, m, AreH),
7.52e7.68 (3H, m, AreH), 8.59 (1H, d, J¼7.1 Hz, AreH); 13C NMR
744 cmꢁ1; 1H NMR (500 MHz, CDCl3):
d
1.48 (3H, d, J¼6.6 Hz, CH3)
(125 MHz, CDCl3):
d
35.1 (CH), 44.5 (CH), 45.8 (CH), 56.8 (OCH3),
{for 5f, 1.71 (3H, d, J¼6.5 Hz, CH3)}, 2.99 (1H, dd, J¼11.4, 4.0 Hz, Hb),
3.44e3.50 (1H, m, Ha) {for 5f, 3.86e3.91 (1H, m, Ha)}, 3.91 (3H, s,
OCH3), 5.37 (1H, d, J¼3.7, Hc) {for 5f, 4.80 (1H, d, J¼13.8 Hz, Hc)}, 6.34
(1H, d, J¼7.7 Hz, AreH), 6.89 (1H, d, J¼8.1 Hz, AreH), 6.99 (1H, t,
J¼7.9 Hz, AreH), 7.51 (1H, d, J¼8.0 Hz, AreH), 7.56 (1H, t, J¼7.5 Hz,
AreH), 7.63 (1H, t, J¼6.9 Hz, AreH), 8.55 (1H, d, J¼7.9 Hz, AreH); 13C
112.5 (CH), 120.0 (CH), 123.0 (C), 125.4 (C), 125.5 (CH), 125.7 (CH),
128.3 (CH), 128.5 (CH), 129.2 (CH), 130.1 (CH), 130.2 (CH), 130.3 (C),
132.2 (CH), 134.6 (C), 136.3 (C), 139.5 (C), 148.1 (C), 152.2 (C), 165.3
(C, OeC]O), 176.6 (C, C]O).
4.3.3. (6aR
*
,7S
*
,14bR
*
)-2-Bromo-7-phenyl-6a,14b-dihydro-
NMR (125 MHz, CDCl3): d 19.1 (CH3), 34.4 (CH), 34.7 (CH), 46.1 (CH),
6H,7H,14H-thiochromeno[30,20:5,6]thiopyrano[3,4-c]chromene-6,14-
dione (5c). Following the general procedure the reaction afforded
a mixture of 5c and 6c (97:03,153 mg, 60%) as a yellow solid; Rf: 0.69;
mp: 279e281 ꢀC; IR (KBr): 1779, 1615, 749 cmꢁ1; 1H NMR (500 MHz,
56.6 (OCH3), 112.1 (CH), 119.7 (CH), 123.0 (C), 125.4 (C), 125.5 (CH),
125.6 (CH), 128.2 (CH), 130.1 (CH), 130.2 (C), 132.1 (CH), 136.3 (C),
139.5 (C),147.9 (C),152.0 (C),166.4 (C, OeC]O),176.6 (C, C]O). Anal.
Calcd for C21H16O4S2: C, 63.62; H, 4.07%. Found: C, 63.74; H, 4.12%.
CDCl3):
d
3.70 (1H, dd, J¼13.6, 11.0 Hz, Hb) {for 6c, 3.53 (1H, dd,
J¼11.8, 3.9 Hz, Hb)}, 4.71 (1H, d, J¼11.0 Hz, Ha) {for 6c, 4.45 (1H, d,
J¼11.8 Hz, Ha)}, 4.96 (1H, d, J¼13.7 Hz, Hc) {for 6c, 5.52 (1H, d,
J¼3.9 Hz, Hc)}, 6.82 (1H, s, AreH), 7.03 (1H, d, J¼8.6 Hz, AreH),
7.38e7.47 (6H, m, AreH), 7.58 (1H, d, J¼7.9 Hz, AreH), 7.64 (1H, t,
J¼7.5 Hz, AreH), 7.70 (1H, t, J¼7.2 Hz, AreH), 8.51 (1H, d, J¼7.9 Hz,
4.3.7. (6aS
*
,7S
*
,14bR )-2-Bromo-7-methyl-6a,14b-dihydro-
*
6H,7H,14H-thiochromeno[30,20:5,6]thiopyrano[3,4-c]chromene-6,14-
dione (6g). Following the general procedure the reaction afforded
a mixture of 5g and 6g (04:96, 182 mg, 82%) as a Pale yellow solid;
Rf: 0.69; mp: 275e278 ꢀC; IR (KBr): 1764,1612, 1527, 1475, 1192,
AreH); 13C NMR (125 MHz, CDCl3):
d
38.9 (CH), 47.4 (CH), 50.1 (CH),
1171, 738 cmꢁ1; 1H NMR (500 MHz, CDCl3):
d
1.48 (3H, d, J¼6.5 Hz,
117.7 (C), 119.2 (CH), 123.7 (C), 125.5 (CH), 128.4 (CH), 128.7 (CH),
128.8 (CH), 129.4 (CH), 129.5 (CH), 129.8 (CH), 130.4 (C), 131.4 (C),
131.7 (CH), 132.5 (CH), 136.0 (C), 136.1 (C), 150.7 (C), 152.0 (C), 167.0
(C, OeC]O), 177.8 (C, C]O). Anal. Calcd for C25H15BrO3S2: C, 59.18;
H, 2.98%. Found: C, 59.09; H, 2.93%.
CH3) {for 5g,1.73 (3H, d, J¼6.5 Hz, CH3)}, 3.01 (1H, dd, J¼11.4, 3.9 Hz,
Hb), 3.37e3.42 (1H, m, Ha) {for 5g, 3.74e3.79 (1H, m, Ha)}, 5.35 (1H,
d, J¼3.7, Hc) {for 5g, 4.76 (1H, d, J¼13.7 Hz, Hc)}, 6.83 (1H, s, AreH),
7.00 (1H, d, J¼8.5 Hz, AreH), 7.41 (1H, d, J¼8.0 Hz, AreH), 7.54 (1H,
d, J¼8.0 Hz, AreH), 7.59 (1H, t, J¼7.6 Hz, AreH), 7.66 (1H, t, J¼7.5 Hz,
AreH), 8.56 (1H, d, J¼8.0 Hz, AreH); 13C NMR (125 MHz, CDCl3):
4.3.4. (6aR
*
,7S
*
,14bR
*
)-2-Nitro-7-phenyl-6a,14b-dihydro-
d 19.0 (CH3), 34.4 (CH), 34.6 (CH), 46.0 (CH), 118.6 (C), 119.0 (CH),
6H,7H,14H-thiochromeno [30,20:5,6]thiopyrano[3,4-c]chromene-6,14-
dione (5d). Following the general procedure the reaction afforded
a mixture of 5d and 6d (92:08, 173 mg, 73%) as a yellow solid; Rf:
0.61; mp: 252e254 ꢀC; IR (KBr): 1779, 1619, 1522, 1346, 1073,
122.2 (C), 125.5 (CH), 126.7 (C), 128.3 (CH), 130.1 (C), 130.2 (CH),
131.3 (CH), 132.2 (CH), 132.3 (CH), 136.3 (C), 149.5 (C), 152.6 (C),
166.3 (C, OeC]O), 176.5 (C, C]O). Anal. Calcd for C20H13BrO3S2: C,
53.94; H, 2.94%. Found: C, 53.82; H, 2.89%.
749 cmꢁ1; 1H NMR (500 MHz, CDCl3):
d
3.73 (1H, dd, J¼13.8,11.1 Hz,
Hb) {for 6d, 3.64 (1H, dd, J¼11.7, 3.7 Hz, Hb)}, 4.75 (1H, d, J¼11.0 Hz,
Ha) {for 6d, 4.40 (1H, d, J¼11.7 Hz, Ha)}, 5.01 (1H, d, J¼13.8 Hz, Hc)
{for 6d, 5.51 (1H, d, J¼3.7 Hz, Hc)}, 7.27 (1H, d, J¼8.8 Hz, AreH),
7.40e7.44 (5H, m, AreH), 7.58e7.67 (3H, m, AreH), 7.73 (1H, t,
J¼7.6 Hz, AreH), 8.22 (1H, dd, J¼8.8, 2.5 Hz, AreH), 8.51 (1H, d,
4.3.8. (6aS
*
,7S
*
,14bR )-7-Methyl-2-nitro-6a,14b-dihydro-6H,7H,14H-
*
thiochromeno [30,20:5,6]thiopyrano[3,4-c]chromene-6,14-dione (6h).
Following the general procedure the reaction afforded a mixture of 5h
and 6h (05:95, 155 mg, 75%) as an orange solid; Rf: 0.63; mp:
271e273 ꢀC; IR (KBr): 1779,1588,1522,1346,1187, 749 cmꢁ1; 1H NMR

8622
F.M. Moghaddam et al. / Tetrahedron 66 (2010) 8615e8622
2005, 127, 15644; (g) Palacios, F.; Herrán, E.; Rubiales, G.; Ezpeleta, J. M. J. Org.
(500 MHz, DMSO-d6):
d
1.34 (3H, d, J¼6.4 Hz, CH3) {for 5h,1.77 (3H, d,
Chem. 2002, 67, 2131; (h) Osborn, H. M. I.; Coisson, D. Mini-Rev. Org. Chem. 2004,1,
41; (i) Behforouz, M.; Ahmadian, M. Tetrahedron 2000, 56, 5259.
J¼6.6 Hz, CH3)}, 3.26 (1H, dd, J¼11.4, 4.1 Hz, Hb) {for 5h, 3.05 (1H, dd,
J¼13.9, 11.0 Hz, Hb)}, 3.42e3.50 (1H, m, Ha) {for 5h, 3.72e3.76 (1H, m,
Ha)}, 5.41 (1H, d, J¼3.7 Hz, Hc) {for 5h, 4.84 (1H, d, J¼13.9 Hz, Hc)}, 7.42
(1H, d, J¼8.9 Hz, AreH), 7.46 (1H, s, AreH), 7.64 (1H, t, J¼7.2Hz, AreH),
7.76 (1H, t, J¼7.2 Hz, AreH), 7.81 (1H, d, J¼8.0 Hz, AreH), 8.21 (1H, d,
J¼7.2 Hz, AreH), 8.38 (1H, d, J¼7.8 Hz, AreH); 13C NMR (125 MHz,
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thesis; Wiley-VCH: Weinheim, 2006; (b) Chapman, C. J.; Frost, C. G. Synthesis
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DMSO-d6):
d 19.2 (CH3), 34.6 (CH), 34.8 (CH), 45.0 (CH), 119.2 (CH),
122.5 (C), 124.4 (CH), 125.3 (C), 125.6 (CH),126.3 (C), 126.7 (CH), 129.2
(CH), 129.5 (CH), 133.2 (CH), 136.1 (C), 154.0 (C), 152.4 (C), 155.3 (C),
165.6 (C, OeC]O), 176.3 (C, C]O). Anal. Calcd for C20H13NO5S2: C,
58.38; H, 3.18; N, 3.40%. Found: C, 58.46; H, 3.21; N, 3.36%.
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Acknowledgements
14. (a) Matiychuk, V. S.; Lesyk, R. B.; Obushak, M. D.; Gzella, A.; Atamanyuk, D. V.;
Ostapiuk, Y. V.; Kryshchyshyn, A. P. Tetrahedron Lett. 2008, 49, 4648; (b) Yadav,
J. S.; Reddy, B. V. S.; Gopal, A. V. H.; Rao, R. N.; Somaiah, R.; Reddy, P. P.; Kunwar,
A. C. Tetrahedron Lett. 2010, 51, 2305.
We gratefully acknowledge partial financial support from the
Research Council of Sharif University of Technology.
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Rackelmann, N.; Müller, I. Chem.dEur. J. 2004, 10, 2722; (c) Tietze, L. F.; Modi, A.
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