Efficient access to novel hexahydro-chromene and tetrahydro-pyrano[2,3-d] pyrimidine-annulated benzo-δ-sultones via a domino Kno?evenagel- hetero-Diels-Alder reaction in water

Article abstract of DOI:10.1016/j.tet.2011.09.010

An efficient catalyst-free, diastereosective synthesis of novel hexahydro-chromene and tetrahydro-pyrano[2,3-d]pyrimidine-annulated benzo-δ-sultones is described. A number of 2-formyl-4-phenyl (E)-2-phenylethenesulfonates were synthesized and underwent a one-pot domino Kno?evenagel-hetero-Diels-Alder reaction, respectively, with dimedone and N,N-dimethylbarbituric acid in water, affording the desired products in moderate to excellent yields.

Full text of DOI:10.1016/j.tet.2011.09.010

Tetrahedron 67 (2011) 8484e8491
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Efficient access to novel hexahydro-chromene and tetrahydro-pyrano[2,3-d]
€
pyrimidine-annulated benzo-
d
-sultones via a domino Knoevenagel-hetero-
DielseAlder reaction in water
*
Mehdi Ghandi , Elham Mohammadimehr, Masoud Sadeghzadeh, Abolfazl Hasani Bozcheloei
School of Chemistry, College of Science, University of Tehran, PO Box 14155 6455, Tehran, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 12 June 2011
Received in revised form 26 August 2011
Accepted 6 September 2011
Available online 12 September 2011
An efficient catalyst-free, diastereosective synthesis of novel hexahydro-chromene and tetrahydro-pyr-
ano[2,3-d]pyrimidine-annulated benzo-
d
-sultones is described. A number of 2-formyl-4-phenyl (E)-2-
€
phenylethenesulfonates were synthesized and underwent a one-pot domino Knoevenagel-hetero-Diel-
seAlder reaction, respectively, with dimedone and N,N-dimethylbarbituric acid in water, affording the
desired products in moderate to excellent yields.
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Domino reactions
€
Knoevenagel-hetero-DielseAlder(E)-2-
Formylphenyl-2-phenylethenesulfonates
Hexahydrochromenes
Tetrahydropyranopyrimidines
Benzo-d-sultones
1. Introduction
properties. However, the b-keto-g-sultones and their enol ethers,
as well as the analogous sultams, are claimed in a 1976 patent to
have cellular immunosuppressive properties, which could make
them useful therapeutic agents for inhibiting transplant rejection
and in treating autoimmune disorders.5 The biological activities of
sultones consist of skin sensitization,6 and antiviral activities.7
However, in 1992, Camarasa and co-workers discovered a new
class of specific human immunodeficiency virus type 1 (HIV-1)
inhibitors, called TSAO derivatives containing a sultone moiety.8
Sultones are considered as sulfoalkylating agents due to their eas-
ily reaction with a variety of nucleophiles for the synthesis of
alkylsulfonic acids.9
The synthesis of complex organic molecules needs to rely on
methods that provide maximum efficiency in modern research in
organic chemistry. Combinatorial chemistry has emerged as
a powerful synthetic procedure in this area. Obtaining scaffolds
from the combination of multiple transformations in a single-pot
designated as domino reactions, is a highly efficient means for im-
provement of the reaction efficiency.1 The domino Knoevenagel-
€
hetero-DielseAlder reaction, which was developed widely by Tietze
and Rackelman, is an efficient process in organic synthesis, espe-
cially in the area of heterocycles and natural products.2 Trans-
formation of the precursors into the desired products including two
or more rings at once, avoiding sequential chemical steps is the main
advantage of this reaction. However, such processes could be
implemented efficiently provided that activating groups are to be
built up into dienophiles to achieve the desired reactivity.3
To the best of our knowledge, there has been no report in the
literature on the intramolecular hetero-DielseAlder reaction of
a dienophile tethered to a diene moiety by a sulfonate link. As a part
of our own interest in cycloaddition reactions,10 herein we report
our one-pot synthetic approach for the preparation of benzo-d-
The internal esters of hydroxy sulfonic acids or sulfur analogues
of lactones, sultones, constitute a class of heterocyclic compounds
whose chemistry continues to be of interest.4 Most of the literature
on biological properties of sultones is concerned with toxicological
sultones bearing hexahydro-chromene and tetrahydro-pyrano[2,3-
d]pyrimidine motifs. Since water is an easily available and envi-
ronmentally friendly matter in nature, a number of processes in-
cluding DielseAlder reactions have been carried out in aqueous
media.3f,11 Therefore, we decided to use it as a safe solvent in our
new procedure. We were also intended to work under catalyst-free
conditions in order to develop an eco-friendly benign synthetic
method.
* Corresponding author. Tel.: þ9821 61112250; fax: þ9821 66495291; e-mail
address: ghandi@khayam.ut.ac.ir (M. Ghandi).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.09.010

M. Ghandi et al. / Tetrahedron 67 (2011) 8484e8491
8485
2. Results and discussion
solvent (entry 5). Finally, changing the ratio of 3a/4 from 1/1 to 1/
1.2 and 1/1.4 was also found to have a determining effect on the
product yields (entries 6 and 7). An inseparable mixture of 6a
(cisetrans) and 7a (transetrans) was obtained when the crude
product was subjected to column chromatography on silica gel
(Table 1). Attempts to separate the diastereoisomers were un-
successful due to the similar polarities of 6a and 7a. The diaster-
eoselectivity of 6a and 7a was determined as 89/11 from the
corresponding 1H NMR spectrum and comparison of the relevant
characteristic signals. All analytical data including IR, 1H and 13C
NMR of 6a and 7a were in agreement with the proposed structures.
For example, the cisetrans and transetrans annealation of 6a and 7a
were determined by coupling patterns for H6a, which showed
medium-small and large/large coupling constants, respectively.
2.1. Preparation of 2-formylphenyl-(E)-2-
phenylethenesulfonates 3aef
Compounds 3aef were prepared by condensation of (E)-2-
phenylethenesulfonyl chloride 2aec with 2-hydroxybenzal-
dehydes 1aed (Scheme 1). The structures of 3aef were con-
firmed from analytical data. For example, appearing of two dou-
blets at
and a singlet at
d
7.00 and 7.63 with J¼15.5 Hz for SO2CH]C and PheCH]C
d
10.37 in the 1H NMR spectrum of 2a is consistent
with the (E)-configuration of the olefin protons and the presence of
an aldehyde group.
Thus, though the H6a of 6a resonates at
d 4.21 as a doublet of
a doublet with J¼10.8 and 5.5 Hz, the H6a of 7a appears at
d 3.63 as
a doublet of doublet with J¼12.0 and 10.2 Hz (Fig. 1).
(a)
Scheme 1. Synthesis of 3aef from condensation of 1aed with 2aec.
(b)
€
2.2. Preparation of domino Knoevenagel-hetero-DielseAlder
cycloadducts of 6aef and 7aef
To optimize the reaction conditions, we screened several sol-
vents and catalysts. Changing the ratio of aldehyde to 1,3-dione
counterpart (3a/4) was also found to have a considerable effect
on the reaction yield (Table 1). The hetero-DielseAlder reaction was
sluggish and inefficient in the presence of ethylenediamine N,N0-
diacetic acid (EDDA)12 as catalyst in toluene (entry 1). Interestingly,
piperidine,12 a commonly used base in Knoevenagel condensations
€
(c)
in ethanol, afforded the corresponding cycloadduct in 48e60%
yields (entries 2, 3, and 4). Surprisingly, 62% of the product was
obtained under catalyst-free condition when we used water as
Table 1
€
Results obtained for the domino Knoevenagel-hetero-DielseAlder reaction of 3a
with 4
O
O
H
Fig. 1. Structures of (a) 6a and 7a, (b) 8d and 9d, (c) characteristic NOE of 8d.
O
O
H
O
S
O
H
H
H
O
O
O
H
4
O
We next examined the substrate scope under optimal condi-
tions with a variety of sulfonates 3aef and dimedone 4 (Scheme 2,
Table 2). Inseparable mixtures of 6aef and 7aef were obtained
with all analytical data including IR, 1H and 13C NMR consistent
with the proposed structures.
+
SO2
SO2
H2O/reflux/12 h
O
O
3a
6a
7a
Entry
Solvent
Catalyst
EDDA
3a/4 Ratio
Time (h)
Yield (%)
1
2
3
4
5
6
7
Toluene
EtOH
EtOH
EtOH
H2O
1.0/1.0
1.0/1.0
1.0/1.2
1.0/1.4
1.0/1.0
1.0/1.2
1.0/1.4
46
12
12
12
12
12
12
23
48
60
60
62
78
78
€
2.3. Preparation of domino Knoevenagel-hetero-DielseAlder
Piperidine
Piperidine
Piperidine
d
cycloadducts of 8aef and 9aef
€
Sulfonates 3aef smoothly underwent domino Knoevenagel-
H2O
H2O
d
hetero-DielseAlder reactions with N,N-dimethylbarbituric acid (5)
under optimal conditions affording a mixture of 8aef and 9aef
d

8486
M. Ghandi et al. / Tetrahedron 67 (2011) 8484e8491
Scheme 2. Synthesis of hexahydro-chromene-annulated benzo-
d
-sultones 6aef and 7aef.
Table 2
€
Results obtained for the domino Knoevenagel-hetero-DielseAlder reaction of 3aef with 4
Entry
R1
R2
Products
Yield (%)
Ratio of 6/7
6
7
O
H
O
H
O
O
H
H
H
1
eH
eH
78
89/11
H
SO2
S
O2
O
O
H
7a
6a
O
O
H
O
O
H
H
H
Br
2
4-Br
eH
60
84/16
Br
H
SO2
S
O2
O
O
7b
6b
O
O
H
O
O
H
H
H
H
O2N
3
4
4-NO2
eH
56
75
85/15
88/12
O2N
H
S
O2
SO2
O
O
7c
6c
O
O
O
O
H
H
H
H
6-OMe
eH
H
H
SO2
SO2
O
O
OMe
OMe
6d
7d
O
O
H
O
O
H
H
H
5
6
eH
-4-Cl
-4-Br
46
42
87/13
H
H
SO2
S
O2
O
Cl
O
Cl
6e
7e
O
O
O
O
H
H
H
H
H
eH
91/9
H
SO2
S
O2
O
Br
O
Br
6f
7f
after column chromatography with silica gel (Scheme 3, Table 3).
All analytical data including IR, 1H and 13C NMR of 8aef and 9aef
were in agreement with the proposed structures. For example, the
cisetrans and transetrans annealations of 8d and 9d were
determined by coupling patterns for H6a, which showed medium/
small and large/large coupling constants with H12b and H6, re-
spectively. Thus, though the H6a of 8a resonates at
d 4.34 as a dou-
blet of a doublet with J¼10.8 and 5.8 Hz, the H6a of 9a appears at

M. Ghandi et al. / Tetrahedron 67 (2011) 8484e8491
8487
d
3.68 as a doublet of doublet with J¼11.9 and 10.3 Hz (Fig. 1b). The
Overall, the hexahydro-chromene and tetrahydro-pyrano[2,3-d]
pyrimidine-annulated benzo- -sultones 6aef/8aef were obtained
via highly diastreoselective processes in good yields. When benz-
aldehyde bearing an electron-donating group, such as methoxyl
1H NMR data agreed with their assignment and were further sup-
ported by 1H NMR NOESY experiment, which confirmed that the
ring junction stereochemistry is cis (Fig. 1c).
d
Scheme 3. Synthesis of tetrahydro-pyrano[2,3-d]pyrimidine-annulated benzo-
d
-sultones 8aef and 9aef.
Table 3
Results obtained for the domino Knoevenagel-hetero-DielseAlder reaction of 3aef with 5
€
Entry
R1
R2
Product
Yield (%)
Ratio of 8/9
8
9
O
O
O
O
N
N
N
H
N
O
H
O
H
O
O
H
H
H
1
eH
eH
93
64
90/10
SO2
SO2
8a
9a
O
N
N
H
N
N
H
O
O
H
H
O
O
H
H
Br
2
4-Br
eH
90/10
Br
SO2
O
SO2
O
8b
9b
O
O
N
N
N
N
O
O
O
O
H
H
H
O2N
3
4-NO2
eH
H
75
75/25
O2N
H
H
S
O2
S
O2
O
O
8c
O
9c
O
N
N
N
H
N
O
O
H
O
O
H
H
4
5
6-OMe
eH
86
48
93/7
91/9
H
H
S
O2
S
O2
O
OMe
O
OMe
8d
9d
O
O
N
H
N
N
H
O
N
O
O
O
O
H
H
H
eH
-4-Cl
H
S
O2
SO2
O
9e
O
Cl
Cl
8e
O
N
H
N
O
N
H
N
O
O
O
H
H
6
eH
-4-Br
46
85/15
H
H
SO2
S
O2
O
Br
O
Br
9f
8f

8488
M. Ghandi et al. / Tetrahedron 67 (2011) 8484e8491
was used, modest yields of the corresponding benzo-
were obtained (entry 4, Tables 2 and 3). Aldehydes bearing
electron-withdrawing groups, such as bromine or nitro also pro-
d
-sultones
according to similar intramolecular processes.16 The high stereo-
€
control in all cases has been attributed to the Knoevenagel products
containing a trisubstituted double bond with a geminal substitution
at the sp2 terminus.17 The endo-E-syn transition state leading to the
cisetrans annulated cycloadducts must have been more favorable
than the exo-E-anti transition state due to an sp2-geminal effect
based on the phenomenon of 1,3-allylic strain.18
vided benzo-
d
-sultones in lower yields (entries 2e3, Tables 2 and
€
3). The domino Knoevenagel-hetero-DielseAlder reactions affor-
ded the corresponding benzo-d-sultones in lowest yields when the
condensed products of unsubstituted aldehydes with (E)-2-
phenylethenesulfonyl chlorides bearing electron-withdrawing
groups were used as the starting materials (entries 5 and 6, Tables 2
and 3). Rationalization of the obtained results may not be an easy
task. Changing the substituents on either phenyl ring has simul-
taneous effects on the diene HOMO and the dienophile LUMO en-
ergies since these moieties are directly tethered to the phenyl
group. Therefore, one may not expect to observe the results in
agreement either with normal or inverse electron demand behav-
ior, which has been extensively reviewed in frontier molecular or-
bital theory.13
Comparison of the results depicted in Table 3 with those of Table
2 shows that the domino-hetero-DielseAlder of 3aef with N,N-
dimethylbarbituric acid (5) has afforded the corresponding cyclo-
adducts in higher product yields. The lower Pka of 5 (4.40)14 than
that of dimedone (4), which is 5.23,15 seems to be responsible for
the higher efficiency of 5 in the formation of the corresponding
3. Conclusion
In conclusion, a number of synthesized bifunctional starting
materials containing an aldehyde and an unsaturated sulfonate
€
groups underwent a one-pot domino Knoevenagel-hetero-Diel-
seAlder reaction, respectively, with dimedone and N,N-dime-
thylbarbituric acid in water, affording novel hexahydro-chromene
and -pyrano[2,3-d]pyrimidine-annulated benzo-d-sultones in
moderate to high yields. These new structures broaden the scaffolds
that are accessible through domino-hetero-DielseAlder reactions
and many of them may represent interesting pharmacophores.
4. Experimental section
4.1. General information
€
Knoevenagel products.
It is generally accepted that the cycloaddition is concerted with
both carbonecarbon s-bonds being formed at the same time, al-
though not necessarily to the same extent. The cycloaddition of
All commercially available chemicals and reagents were pur-
chased from Merck Chemical Company and used without further
purification. Melting points were determined with an Electrother-
mal model 9100 apparatus and are uncorrected. IR spectra were
recorded on a Shimadzu 4300 spectrophotometer, in cmꢀ1. 1H and
13C NMR spectra were recorded on a Bruker DRX-500-AVANCE
spectrometer at 500 (1H) and 125 MHz (13C) using CDCl3 as solvent
and with the residual solvent signal as internal reference (CDCl3,
7.24 and 77.0 ppm). Mass spectra of the products were obtained
with a HP (Agilent technologies) 5937 Mass Selective Detector.
Elemental analyses were carried out by a CHN-Rapid Heraeus
elemental analyzer (Wellesley, MA).
€
a heterodiene generated from Knoevenagel condensation of an al-
dehyde either with dimedone or N,N-dimethylbarbituric acid and
an (E)-2-phenylethenesulfonate as a dienophile could lead to
a mixture of stereoisomers. The stereochemical outcome of the
cycloaddition is dependent on the geometries of the diene as well as
the dipolarophile. For example, while the trans stereochemistry of
the resultant pyran C6aeC7 bond emerges from the trans geometry
of the dipolarophile, the stereochemistry of the sultone C6aeC12b
bond depends on the transition state structure of the cycloadditions.
It seems justified that the cisetrans and transetrans annulated
products are formed via endo-E-syn transition state I and exo-E-anti
4.2. General procedure for the preparation of 3aef
transition state II (Fig. 2), respectively, if aromatic a,b-unsaturated
1b
€
aldehydes are used in the Knoevenagel step. The investigated
To a solution of a 2-hydroxybenzaldehyde (610 mg, 5 mmol) and
hetero-DielseAlder reactions showed high diastereoselectivity,
(E)-2-phenylethenesulfonyl chloride (1010 mg, 5 mmol) in acetone
Fig. 2. Transition state model evoked for the formation of 6a and 7a.

M. Ghandi et al. / Tetrahedron 67 (2011) 8484e8491
8489
(30 mL) was added K2CO3 (690 mg, 5 mmol) and the mixture was
stirred for 2 h at room temperature. After evaporation of the sol-
vent at reduced pressure, 30 mL of H2O was added and the organic
compound was extracted with CH2Cl2 (30 mL). The solvent was
then evaporated under reduced pressure and the crude products
were recrystallized from C2H5OH to afford 3aef.
(500 MHz, CDCl3) 6.98 (1H, d, J 15.5 Hz, SO2CH]CH), 7.39 (2H, d, J
8.4 Hz, Ar), 7.45 (1H, d, J 8.2 Hz, Ar), 7.48 (1H, t, J 7.5 Hz, Ar), 7.55
(1H, d, J 15.5 Hz, ArCH]CH), 7.61 (2H, d, J 8.4 Hz, Ar), 7.68 (1H, t, J
7.7 Hz, Ar), 7.97 (1H, t, J 7.7 Hz, Ar), 10.35 (1H, s, CHO); dC (125 MHz,
CDCl3): 121.1, 124.3, 127.3, 128.2, 129.7, 130.1, 130.5, 130.7, 133.1,
135.9, 146.3, 150.9, 188.3 (C]O); m/z (EI, 70 eV) 369 (2, Mþþ2), 367
(3, Mþ), 247 (54), 183 (94), 120 (60), 102 (100%).
4.2.1. 2-Formylphenyl-(E)-2-phenylethenesulfonate (3a). Colorless
solid; (276 mg, 96%); mp: 59e62 ꢁC; Found: C, 62.32; H, 4.12.
C15H12O4S requires C, 62.49; H, 4.20%. nmax (KBr): 3059; 2885; 1690
4.3. General procedure for domino Knoevenagel-hetero-
DielseAlder reaction
(C]O); 1604, 1361 (OSO2), 1147 (OSO2) cmꢀ1
. dH (500 MHz, CDCl3)
7.00 (1H, d, J 15.5 Hz, SO2CH]CH); 7.44e7.53 (7H, m, Ar); 7.63 (1H,
d, J 15.5 Hz, ArCH]CH); 7.66 (1H, t, J 7.6 Hz, Ar); 7.96 (1H, d, J 7.6 Hz,
Ar); 10.37 (1H, s, CHO); dC (125 MHz, CDCl3): 120.3, 124.2, 128.1,
129.2, 129.6, 129.7, 129.8, 130.0, 132.6, 135.9, 147.8, 151.1, 188.3 (C]
O); m/z (EI, 70 eV) 287 (10, Mþꢀ1), 167 (88), 120 (25), 103 (100), 77
(36%).
A mixture of (E)-2-formylphenyl-2-phenylethenesulfonate 3
(1 mmol) and active methylene compounds 4 or 5 (1.2 mmol) in
water (15 mL) was heated to reflux whilst stirring. The progress of
the reaction was monitored by TLC. After completion (See Tables 2
and 3), the solid precipitate was filtered, washed with hot water
(5 mL), and dried in air. The products were separated by column
chromatography (ethyl acetate/hexane, 1:3). A mixture of two di-
astereomers was obtained in each case. All attempts to separate
these two isomers were unsuccessful due to their similar polarities.
The diastereomeric ratios were determined based on their 1H NMR
using the characteristic signals.
4.2.2. 2-Formyl-4-bromophenyl-(E)-2-phenylethenesulfonate
(3b). Colorless solid; (351 mg, 96%); mp: 69e70 ꢁC; Found: C,
49.01; H, 3.00. C15H11BrO4S requires C, 49.06; H, 3.02%. nmax (KBr):
3064, 2877, 1693 (C]O), 1607, 1380 (OSO2), 1165 (OSO2) cmꢀ1
; dH
(500 MHz, CDCl3) 6.94 (1H, d, J 15.5 Hz, SO2CH]CH), 7.33 (1H, d, J
8.7 Hz, Ar), 7.46e7.54 (5H, m, Ar), 7.63 (1H, d, J 15.5 Hz, ArCH]CH),
7.75 (1H, d, J 8.7 Hz, Ar), 8.07 (1H, s, Ar), 10.37 (1H, s, CHO); dC
(125 MHz, CDCl3): 119.8, 121.8, 126.0, 129.3, 129.8, 131.0, 131.6,
132.5, 132.8, 138.6, 148.4, 149.9, 186.9 (C]O); m/z (EI, 70 eV) 367 (1,
Mþþ1), 200 (8), 167 (90), 103 (100), 77 (29%).
4.3.1. 10,10-Dimethyl-7-phenyl-6a,7,9,10,11,12b-hexahydro-5,8-dioxa-
6-thia-benzo[c]phenanthren-12-one-6,6-dioxide (6a, 7a). White solid
(89:11 dr 320 mg, 78%), mp 174e177 ꢁC. Found: C, 67.23; H, 5.37.
C23H22O5S requires C, 67.30; H, 5.40%. nmax (KBr): 1653, 1629, 1384,
1162 cmꢀ1
; dH (500 MHz, CDCl3) 1.18 (s, 3H, Me) {for 7a, 1.20 (3H, s,
Me)}, 1.22 (s, 3H, Me) {for 7a, 1.23 (3H, s, Me)}, 2.46 (s, 2H, CH2C]C)
{for 7a, 2.45 (s, 2H, CH2C]C)}, 2.43 (1H, d, J 16.3 Hz, CHHC]O), part
of ABq, 2.54 (1H, d, J 16.3 Hz, CHHC]O) part of ABq {for 7a, 2.45e2.50
(2H, m, CH2C]O)}, 4.21 (1H, dd, J 10.8, 5.5 Hz, H6a) {for 7a, 3.63 (1H,
dd, J 12.0, 10.2 Hz, H6a)}, 4.97 (1H, d, J 10.8 Hz, PhCHO) {for 7a, 4.60
(1H, d, J 12.0 Hz, PhCHO)}, 5.02 (1H, d, J 5.5 Hz, H12b) {for 7a, 5.19 (1H,
d, J 10.2 Hz, H12b)}, 7.13 (1H, d, J 7.8 Hz, Ar), 7.18 (1H, d, J 8.0 Hz, Ar),
7.24e7.49 (7H, m, Ar); dC (125 MHz, CDCl3): 28.8 (Me), 28.9 (Me),
32.6 (CMe2), 33.6 (C12b), 42.7 (CC]C), 51.0 (CC]O), 60.4 (C6a), 76.5
(PhCeO), 108.7 (C12a), 120.1, 126.4, 127.4, 128.6, 129.3, 129.8, 129.9,
130.4, 136.0, 149.8 (CeAr), 171.1 (C8a), 196.9 (C]O); m/z (EI, 70 eV)
410 (3, Mþ), 346 (100, MþꢀSO2), 330 (63, MþꢀSO3), 239 (28), 207
(30%).
4.2.3. 2-Formyl-4-nitrophenyl (E)-2-phenylethenesulfonate
(3c). Cream solid; (316 mg, 95%); mp: 104e107 ꢁC; Found: C,
54.00; H, 3.29; N, 4.14. C15H11NO6S requires C, 54.05; H, 3.33; N,
4.20%. nmax (KBr): 3062, 2896, 1693 (C]O), 1609, 1344 (OSO2), 1162
(OSO2) cmꢀ1
; dH (500 MHz, CDCl3) 7.02 (1H, d, J 15.4 Hz, SO2CH]
CH), 7.48e7.67 (6H, m, Ar), 7.71 (1H, d, J 15.4 Hz, ArCH]CH), 8.50
(1H, d, J 7.9 Hz, Ar), 8.79 (1H, s, Ar), 10.37 (1H, s, CHO); dC (125 MHz,
CDCl3): 119.5, 125.4, 125.6, 129.5, 129.9, 130.1, 130.3, 131.3, 133.2,
146.9, 149.2,154.7, 186.1 (C]O); m/z (EI, 70 eV) 334 (10, Mþþ1), 316
(53), 273 (100), 183 (27), 151 (49%).
4.2.4. 2-Formyl-6-methoxyphenyl-(E)-2-phenylethenesulfonate
(3d). Colorless solid; (302 mg, 95%); mp: 96e98 ꢁC; Found: C,
60.29; H, 4.38. C16H14O5S requires C, 60.37; H, 4.43%. nmax (KBr):
3065, 2898, 1690 (C]O), 1614, 1576, 1362 (OSO2), 1144 (OSO2)
4.3.2. 2-Bromo-10,10-dimethyl-7-phenyl-6a,7,9,10,11,12b-hexahy-
dro-5,8-dioxa-6-thia-benzo[c]phenanthren-12-one-6,6-dioxide
(6b,7b). White solid (84:16 dr 293 mg, 60%); mp: 218e220 ꢁC.
Found: C, 56.35; H, 4.23. C23H21BrO5S requires C, 56.45; H, 4.33%.
cmꢀ1
; dH (500 MHz, CDCl3) 3.82 (3H, s, MeO), 7.07 (1H, d, J 15.6 Hz,
SO2CH]CH), 7.21 (1H, d, J 8.2 Hz, Ar), 7.37 (1H, t, J 7.9 Hz, Ar),
7.45e7.56 (6H, m, Ar), 7.55 (1H, d, J 15.6 Hz, ArCH]CH),10.41 (1H, s,
CHO); dC (125 MHz, CDCl3): 56.9, 118.6, 120.4, 121.6, 128.1, 128.4,
129.7, 129.9, 131.8, 132.2, 140.8, 146.0, 152.0, 188.7 (C]O); m/z (EI,
70 eV) 301 (1, Mþꢀ1), 167 (83), 151 (53), 103 (100), 77 (42%).
nmax (KBr): 1658, 1628, 1380, 1162 cmꢀ1
; dH (500 MHz, CDCl3): 1.18
(3H, s, Me) {for 7b, 1.22 (3H, S, Me)}, 1.24 (3H, s, Me) {for 7b, 1.33
(3H, s, Me)}, 2.48 (2H, s, CH2C]C) {for 7b, 2.47 (s, 2H, CH2C]C)},
2.43 (1H, d, J 16.3 Hz, CH2C]O), part of ABq, 2.57 (1H, d, J 16.3 Hz,
CH2C]O), part of ABq, {for 7b, 2.43e2.52 (2H, m, CH2C]O)}, 4.21
(1H, dd, J 10.8, 5.5 Hz, H6a) {for 7b, 3.61 (1H, dd, J 12.3,10.1 Hz, H6a)},
4.94 (1H, d, J 10.8 Hz, PhCHO) {for 7b, 4.57 (1H, d, J 12.3 Hz,
PhCHO)}, 4.99 (1H, d, J 5.5 Hz, H12b) {for 7b, 5.17 (1H, d, J 10.1 Hz,
H12b)}, 7.07 (1H, d, J 8.6 Hz, Ar), 7.21 (1H, s, Ar), 7.38e7.53 (6H, m,
Ar); dC (125 MHz, CDCl3): 28.7 (Me), 28.9 (Me), 32.7 (CMe2), 33.5
(C12b), 42.7 (CC]C), 51.0 (CC]O), 60.4 (C6a), 76.4 (PhCeO), 107.9
(C12a), 118.8, 121.8, 128.6, 128.8, 129.3, 130.5, 132.9, 133.1, 136.5,
148.5 (CeAr), 171.5 (C8a), 197.0 (C]O); m/z (EI, 70 eV) 489 (2, Mþ),
425 (16, MþꢀSO2), 409 (33, MþꢀSO3), 256 (100), 144 (93%).
4.2.5. (E)-2-Formylphenyl 2-(4-chlorophenyl)ethenesulfonate (3e).
Yellow solid; (305 mg, 95%); mp: 113e116 ꢁC; Found: C, 55.76; H,
3.38. C15H11ClO4S requires C, 55.82; H, 3.44%. nmax (KBr): 3058,
2887, 1691 (C]O), 1595, 1350 (OSO2), 1176 (OSO2) cmꢀ1
; dH
(500 MHz, CDCl3) 6.96 (1H, d, J 15.5 Hz, SO2CH]CH), 7.44e7.48
(6H, m, Ar), 7.57 (1H, d, J 15.5 Hz, ArCH]CH), 7.96 (1H, t, J 6.6 Hz,
Ar), 7.97 (1H, d, J 6.7 Hz, Ar), 10.35 (1H, s, CHO); dC (125 MHz,
CDCl3): 120.9, 124.3, 128.2, 129.8, 130.1, 130.2, 130.3, 130.4, 135.9,
138.8, 146.3, 150.9, 188.3 (C]O); m/z (EI, 70 eV) 324 (1, Mþþ2), 322
(3, Mþ), 201 (74), 137 (100), 120 (41), 102 (54%).
4.3.3. 2-Nitro-10,10-dimethyl-7-phenyl-6a,7,9,10,11,12b-hexahydro-
5,8-dioxa-6-thia-benzo[c]phenanthren-12-one-6,6-dioxide
(6c,7c). Yellow solid (85:15 dr 255 mg, 56%); mp: 202e205 ꢁC.
Found: C, 60.65; H, 4.59. C23H21NO7S requires C, 60.65; H, 4.65%.
4.2.6. (E)-2-Formylphenyl 2-(4-bromophenyl)ethenesulfonate (3f).
White solid; (348 mg, 95%); mp: 101e104 ꢁC; Found: C, 48.98; H,
3.03. C15H11BrO4S requires C, 49.06; H, 3.02%. nmax (KBr): 3054,
2894, 1690 (CO), 1676, 1601, 1341 (OSO2), 1161 (OSO2) cmꢀ1
;
dH
nmax (KBr): 1662, 1627, 1383, 1165 cmꢀ1
; dH (500 MHz, CDCl3): 1.20

8490
M. Ghandi et al. / Tetrahedron 67 (2011) 8484e8491
(3H, s, Me) {for 7c,1.24 (3H, s, Me)},1.26 (3H, s, Me) {for 7c,1.38 (3H,
s, Me)}, 2.50 (2H, s, CH2C]C) {for 7c, 2.49 (2H, s, CH2C]C)}, 2.46
(1H, d, J 16.4 Hz, CH2C]O), part of ABq, 2.60 (1H, d, J 16.4 Hz,
CH2C]O), part of ABq {for 7c, 2.44e2.57 (2H, m, CH2C]O)}, 4.30
(1H, dd, J 10.7, 5.7 Hz, H6a) {for 7c, 3.68 (1H, dd, J 12.0,10.1 Hz, H6a)},
4.96 (1H, d, J 10.7 Hz, PhCHO) {for 7c, 4.65 (1H, d, J 12.0 Hz,
PhCHO)}, 5.05 (1H, d, J 5.7 Hz, H12b) {for 7c, 5.22 (1H, d, J 10.1 Hz,
H12b)}, 7.33 (1H, d, J 8.9 Hz, Ar), 7.36e7.49 (5H, m, Ar), 8.04 (1H, s,
Ar), 8.28 (1H, dd, J 8.6, 2.4 Hz, Ar); dC (125 MHz, CDCl3): 28.7 (Me),
28.8 (Me),32.7 (CMe2), 33.8 (C12b), 42.7 (CC]C), 50.9 (CC]O), 60.2
(C6a), 76.4 (PhCeO), 107.8 (C12b), 121.2, 125.6, 126.1, 128.2, 128.5,
129.4, 130.7, 135.3,146.6, 153.8 (CeAr),171.8 (C8a), 196.8 (C]O); m/z
(EI, 70 eV) 455 (9, Mþ), 391 (43, MþꢀSO2), 375 (100, MþꢀSO3), 344
(24), 103 (28%).
J 5.5 Hz, H12b) {for 7f, 5.15 (1H, d, J 10.1 Hz, H12b)}, 7.11 (1H, d, J
7.7 Hz, Ar), 7.18 (1H, d, J 8.1 Hz, Ar), 7.27 (2H, d, J 8.1 Hz, Ar), 7.39
(2H, t, J 7.7 Hz, Ar), 7.58 (2H, d, J 8.1 Hz, Ar); dC (125 MHz, CDCl3):
28.8 (Me), 28.9 (Me), 32.6 (CMe2), 33.5 (C12b), 42.6 (CC]C), 51.0
(CC]O), 60.0 (C6a), 75.8 (PhCHO), 108.8 (C12a), 120.1, 124.7, 126.3,
127.5, 129.8, 130.0, 130.3, 132.5, 135.1149.7 (CeAr), 170.8 (C8a), 196.8
(C]O); m/z (EI, 70 eV) 489 (5, Mþ), 425 (100, MþꢀSO2), 409 (69,
MþꢀSO3), 227 (80), 171 (33%).
4.3.7. 2,4-Dimethyl-6-phenyl-2,4,6,6a,12b-pentahydro-5,8-dioxa-7-
thia-2,4-diaza-benzo[c]phenanthrene-1,3-dione-7,7-dioxide
(8a,
9a). White solid (90:10 dr 396 mg, 93%); mp: 225e227 ꢁC. Found:
C, 59.34; H, 4.37; N, 6.24. C21H18N2O6S requires: C, 59.15; H, 4.25; N,
6.57%. nmax (KBr): 1699, 1635, 1380, 1156 cmꢀ1
, dH (500 MHz,
CDCl3): 3.31 (3H, s, Me) {for 9a, 3.39 (3H, s, Me)}, 3.47 (3H, s, Me)
{for 9a, 3.46 (3H, s, Me)}, 4.29 (1H, dd, J 10.7, 5.5 Hz, H6a) {for 9a,
3.68 (1H, dd, J 12.0, 10.2 Hz, H6a)}, 5.12 (1H, d, J 5.5 Hz, H12b) {for 9a,
5.42 (1H, d, J 10.2 Hz, H12b)}, 5.19 (1H, d, J 10.7 Hz, PhCHO) {for 9a,
5.43 (1H, d, J 12.0 Hz, PhCHO)}, 7.19 (1H, d, J 8.0 Hz, Ar), 7.32e7.51
(8H, m, Ar); dC (125 MHz, CDCl3): 28.9 (Me), 29.5 (Me), 34.5 (C12b),
60.0 (C6a), 78.8 (PhCeO), 85.5 (C12c), 120.1, 125.8, 127.7, 128.6, 129.5,
130.0, 130.3, 130.9, 134.8, 149.6 (CeAr), 151.1 (C]O), 156.7 (C4a),
162.7 (C]O); m/z (EI, 70 eV) 426 (2, Mþ), 362 (43, MþꢀSO2), 346
(33, MþꢀSO3), 243 (100), 207 (53%).
4.3.4. 4-Methoxy-10,10-dimethyl-7-phenyl-6a,7,9,10,11,12b-hexahy-
dro-5,8-dioxa-6-thia-benzo[c]phenanthren-12-one-6,6-dioxide (6d,
7d). White solid (88:12 dr 330 mg, 75%); mp: 222e225 ꢁC. Found:
C, 65.40; H, 5.48. C24H24O6S requires C, 65.44; H, 5.49%. nmax (KBr):
1650, 1635, 1378, 1162 cmꢀ1
; dH (500 MHz, CDCl3): 1.18 (3H, s, Me)
{for 7d, 1.20 (3H, s, Me)}, 1.24 (3H, s, Me) {for 7d, 1.32 (3H, s, Me)},
2.46 (2H, s, CH2C]C) {for 7d, 2.45 (2H, s, CH2C]C)}, 2.42 (1H, d, J
16.3 Hz, CH2C]O), part of ABq, 2.53 (1H, d, J 16.3 Hz, CH2C]O) part
of ABq {for 7d, 2.40e2.47 (2H, m, CH2C]O)}, 3.91 (3H, s, OMe) {for
7d, 3.90 (3H, s, OMe)}, 4.25 (1H, dd, J 10.8, 5.7 Hz, H6a) {for 7d, 3.64
(1H, dd, J 12.0, 10.1 Hz, H6a)}, 4.92 (1H, d, J 10.8 Hz, PhCHO) {for 7d,
4.58 (1H,d, J 12.0 Hz, PhCHO)}, 4.99 (1H, d, J 5.7 Hz, H12b) {for 7d,
5.18 (1H, d, J 10.2 Hz, H12b)}, 6.65 (1H, d, J 7.8 Hz, Ar), 6.99 (1H, d, J
8.3 Hz, Ar), 7.23 (1H, t, J 8.1 Hz, Ar), 7.39e7.50 (5H, m, Ar); dC
(125 MHz, CDCl3): 28.8 (Me), 29.0 (Me), 32.6 (CMe2), 33.7 (C12b),
42.7 (CC]C), 51.0 (CC]O), 56.8 (MeO), 61.0 (C6a), 76.4 (PhCeO),
108.2 (C12a),113.1,120.6, 127.4,128.4, 128.7,129.2, 130.3, 136.1,138.8,
150.6 (CeAr), 170.9 (C8a), 196.7 (C]O); m/z (EI, 70 eV) 440 (6, Mþ),
376 (15, MþꢀSO2), 360 (100, MþꢀSO3), 269 (65), 178 (20%).
4.3.8. 11-Bromo-2,4-dimethyl-6-phenyl-2,4,6,6a,12b-pentahydro-
5,8-dioxa-7-thia-2,4-diaza-benzo[c]phenanthrene-1,3-dione-7,7-
dioxide (8b, 9b). White solid (90:10 dr 323 mg, 64%); mp:
234e237 ꢁC. Found: C, 49.59; H, 3.26; N, 5.50. C21H17BrN2O6S re-
quires C, 49.91; H, 3.39; N, 5.54%. nmax (KBr): 1709, 1638, 1380,
1163 cmꢀ1
, dH (500 MHz, CDCl3): 3.33 (3H, s, Me) {for 9b, 3.39 (3H,
s, Me)}, 3.48 (3H,s, Me) {for 9b, 3.49 (3H, s, Me)}, 4.29 (1H, dd, J 10.7,
5.7 Hz, H6a) {for 9b, 3.65 (1H, dd, J 12.0, 10.3 Hz, H6a)}, 5.10 (1H, d, J
5.7 Hz, H12b) {for 9b, 5.41 (1H, d, J 10.3 Hz, H12b)}, 5.15 (1H, d, J
10.7 Hz, PhCHO) {for 9b, 5.41 (1H, d, J 12.0 Hz, PhCHO)}, 7.09 (1H, d,
J 8.6 Hz, Ar), 7.42e7.52 (6H, m, Ar), 7.56 (1H, dd, J 8.5, 1.8 Hz, Ar); dC
(125 MHz, CDCl3): 29.0 (Me), 29.5 (Me), 34.6 (C12b), 60.0 (C6a), 78.6
(PhCeO), 84.6 (C12c), 121.0, 121.8, 128.2, 128.6, 129.5, 130.1, 132.8,
133.5,134.5,148.6 (CeAr),151.0 (C]O),156.8 (C4a),162.4 (C]O); m/
z (EI, 70 eV) 506 (4, Mþþ2), 441(50, MþꢀSO2), 425 (90, MþꢀSO3),
323 (90), 103 (100%).
4.3.5. 10,10-Dimethyl-7-(4-chloro)-phenyl-6a,7,9,10,11,12b-hexahy-
dro-5,8-dioxa-6-thia-benzo[c]phenanthren-12-one-6,6-dioxide
(6e,7e). White solid (87:13 dr 204 mg, 46%); mp: 202e205 ꢁC.
Found: C, 62.01; H, 4.74. C23H21ClO5S requires C, 62.09; H, 4.76%.
nmax (KBr): 1663, 1625, 1383, 1162 cmꢀ1
, dH (500 MHz, CDCl3): 1.19
(3H, s, Me) {for 7e, 1.22 (3H, s, Me)},1.23 (3H, s, Me) {for 7e, 1.29 (3H,
s, Me)}, 2.45 (2H, s, CH2C]C) {for 7e, 2.44 (2H, s, CH2C]C)}, 2.43
(1H, d, J 11.6 Hz, CH2C]O) part of ABq, 2.58 (1H, d, J 11.6 Hz, CH2C]
O) part of ABq, {for 7e, 2.43e2.50 (2H, m, CH2C]O)}, 4.14 (1H, dd, J
10.8, 5.5 Hz, H6a) {for 7e, 3.57 (1H, dd, J 12.0, 10.2 Hz, H6a)}, 4.93
(1H, d, J 10.8 Hz, PhCHO){for 7e, 4.58 (1H, d, J 12.0 Hz, PhCHO)},
5.02 (1H, d, J 5.5 Hz, H12b) {for 7e, 5.17 (1H, d, J 10.2 Hz, H12b)},
7.11(1H, d, J 7.7 Hz, Ar), 7.18 (1H, d, J 8.0 Hz, Ar), 7.35e7.43 (6H, m,
Ar); dC (125 MHz, CDCl3): 28.8 (Me), 28.9 (Me), 32.6 (CMe2), 33.5
(C12b), 42.6 (CC]C), 51.0 (CC]O), 60.5 (C6a), 75.7 (PhCeO), 107.0
(C12a), 120.1, 126.3, 127.5, 129.5, 129.8, 130.0, 130.0, 130.3,
136.0.149.7 (CeAr), 170.7 (C8a), 196.0 (C]O); m/z (EI, 70 eV) 446
(10, Mþþ1), 381 (100, MþꢀSO2), 365 (63, MþꢀSO3), 256 (79), 296
(19%).
4.3.9. 11-Nitro-2,4-dimethyl-6-phenyl-2,4,6,6a,12b-pentahydro-5,8-
dioxa-7-thia-2,4-diaza-benzo[c]phenanthrene-1,3-dione-7,7-dioxide
(8c, 9c). Yellow solid (75:25 dr 353 mg, 75%); mp: 162e163 ꢁC.
Found: C, 53.52; H, 3.60; N, 8.88. C21H17N3O8S requires C, 53.50; H,
3.63; N, 8.91%. nmax (KBr): 1704,1651,1394,1165 cmꢀ1
, dH (500 MHz,
CDCl3): 3.25 (3H, s, Me) {for 9c, 3.32 (3H, s, Me)}, 3.40 (3H, s, Me)
{for 9c, 3.37 (3H, s, Me)}, 4.48 (1H, dd, J 10.7, 6.0 Hz, H6a) {for 9c,
3.74 (1H, dd, J 12.0, 10.2 Hz, H6a)}, 5.07 (1H, d, J 6.0 Hz, H12b) {for 9c,
5.41 (1H, d, J 10.2 Hz, H12b)}, 5.09 (1H, d, J 10.7 Hz, PhCHO) {for 9c,
4.75 (1H, d, J 12.0 Hz, PhCHO)}, 7.33e7.47 (6H, m, Ar), 8.20 (1H, s,
Ar), 8.23 (1H, dd, J 8.8, 2.4 Hz, Ar); dC (125 MHz, CDCl3): 28.9 (Me),
29.5 (Me), 35.4 (CH12b), 59.3 (CH6a), 78.5 (PhCeO), 84.5 (C12b),121.2,
125.8, 126.3, 127.6, 128.6, 129.5, 131.4, 134.1, 146.7 (CeAr), 150.8 (C]
O), 153.5 (CeAr), 157.1 (C4a), 162.6 (C]O); m/z (EI, 70 eV) 471 (3,
Mþ), 407 (16, MþꢀSO2), 391 (39, MþꢀSO3), 103 (58), 66 (100%).
4.3.6. 10,10-Dimethyl-7-(4-boromo)-phenyl-6a,7,9,10,11,12b-hexahy-
dro-5,8-dioxa-6-thia-benzo[c]phenanthren-12-one-6,6-dioxide (6f,
7f). White solid (91:9 dr 205 mg, 42%); mp: 196e200 ꢁC. Found: C,
56.70; H, 4.23. C23H21BrO5S requires C, 56.54; H, 4.33%. nmax (KBr):
4.3.10. 9-Methoxy-2,4-dimethyl-6-phenyl-2,4,6,6a,12b-pentahydro-
5,8-dioxa-7-thia-2,4-diaza-benzo[c]phenanthrene-1,3-dione-7,7-
dioxide (8d, 9d). White solid (93:7 dr 392 mg, 86%); mp:
240e243 ꢁC. Found: C, 57.91; H, 4.45; N, 5.96. C22H20N2O7S requires
1655, 1625, 1373, 1158 cmꢀ1
, dH (500 MHz, CDCl3): 1.18 (3H, s, Me)
{for 7f, 1.21 (3H, s, Me)}, 1.23 (3H, s, Me) {for 7f, 1.27 (3H, s, Me)},
2.45 (2H, s, CH2C]C) {for 7f, 2.44 (s, 2H, CH2C]C) }, 2.43 (1H, d, J
16.2 Hz, CH2C]O), part of ABq, 2.54 (1H, d, J 16.2 Hz, CH2C]O), part
of ABq, {for 7f, 2.41e2.56 (2H, m, CH2C]O)}, 4.16 (1H, dd, J 10.8,
5.5 Hz, H6a) {for 7f, 3.48 (1H, dd, J 12.0, 10.1 Hz, H6a)}, 4.91 (1H, d, J
10.8 Hz, PhCHO) {for 7f, 4.58 (1H, d, J 12.0 Hz, PhCHO)}, 5.01 (1H, d,
C, 57.89; H, 4.42; N, 5.95%. nmax (KBr): 1703, 1655, 1380, 1148 cmꢀ1
,
dH (500 MHz, CDCl3): 3.32 (3H, s, Me) {for 9d, 3.38 (3H, s, Me)}, 3.45
(3H, s, Me) {for 9d, 3.46 (3H, s, Me)}, 3.92 (3H, s, OMe) {for 9d, 3.90
(3H, s, OMe)}, 4.34 (1H, dd, J 10.8, 5.8 Hz, H6a) {for 9d, 3.68 (1H, dd, J

M. Ghandi et al. / Tetrahedron 67 (2011) 8484e8491
8491
11.9, 10.3 Hz, H6a)}, 5.08 (1H, d, J 5.8 Hz, H12b) {for 9d, 5.41 (1H, d, J
Supplementary data
10.3 Hz, H12b)}, 5.14 (1H, d, J 10.8 Hz, PhCHO) {for 9d, 4.75 (1H, d, J
11.9 Hz, PhCHO)}, 6.83 (1H, d, J 7.8 Hz, Ar), 7.01 (1H, d, J 8.3 Hz, Ar),
7.26 (1H, t, J 8.1 Hz, Ar), 7.41e7.51 (5H, m, Ar); dC (125 MHz, CDCl3):
28.8 (Me), 29.5 (Me), 34.6 (C12b), 56.8 (MeO), 60.6 (C6a), 78.6
(PhCeO), 84.9 (C12c), 113.4, 120.5, 127.6, 127.8, 128.7, 129.5, 130.9,
134.8, 138.6 (CeAr), 150.6 (C]O), 151.1 (CeAr), 156.7 (C4a), 162.5
(C]O); m/z (EI, 70 eV) 456 (1, Mþ), 392 (12, MþꢀSO2), 376 (40,
MþꢀSO3), 268 (53), 255 (28), 253 (100%).
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tet.2011.09.010. These data in-
clude MOL files and InChiKeys of the most important compounds
described in this article.
References and notes
1. (a) Tietze, L. F. Domino Reaction in Organic Synthesis; Wiley-VCH: 2006; (b)
Tietze, L. F. Chem. Rev. 1996, 96, 115e136; (c) Khoshkholgh, M. J.; Saeed Balalaie,
S.; Bijanzadeh, H. R.; Rominger, F.; Gross, J. H. Tetrahedron Lett. 2008, 49,
6965e6968.
4.3.11. 2,4-Dimethyl-6-(4-chloro)-phenyl-2,4,6,6a,12b-pentahydro-
5,8-dioxa-7-thia-2,4-diaza-benzo[c]phenanthrene-1,3-dione,7,7-
dioxide (8e, 9e). White solid (91:9 dr 221 mg, 48%); mp:
232e235 ꢁC. Found: C, 54.69; H, 3.76; N, 6.06. C21H17ClN2O6S re-
quires C, 54.73; H, 3.72; N, 6.08%. nmax (KBr): 1701, 1651, 1377,
2. (a) Tietze, L. F.; Rackelman, N. In Multicomponent Reaction; Zhu, J., Bienayme, H.,
Eds.; Wiely-VCH: Weinheim, 2005; pp 121e167; (b) Tietze, L. F.; Rackelmann,
N. Pure Appl. Chem. 2004, 76, 1967e1983; (c) Tietze, L. F. J. Heterocycl. Chem.
€
1990, 27, 47e69; (d) Tietze, L. F.; Rackelmann, N.; Muller, I. Chem.Eur. J. 2004, 10,
1152 cmꢀ1
, dH (500 MHz, CDCl3): 3.25 (3H, s, Me) {for 9e, 3.32 (3H,
2722e2731; (e) Tietze, L. F.; Modi, A. Med. Res. Rev. 2000, 20, 304e322.
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s, Me)}, 3.40 (3H, s, Me) {for 9e, 3.90 (3H, s, Me)}, 4.30 (1H, dd, J
10.8, 5.7 Hz, H6a) {for 9e, 3.68 (1H, dd, J 11.7, 10.3 Hz, H6a)}, 5.06
(1H, d, J 5.7 Hz, H12b) {for 9e, 5.37 (1H, d, J 10.3 Hz, H12b)}, 5.09 (1H,
d, J 10.8 Hz, PhCHO) {for 9e, 4.73 (1H, d, J 11.7 Hz, PhCHO)}, 7.14
(1H, d, J 8.1 Hz, Ar), 7.28 (2H, d, J 4.5 Hz, Ar), 7.34 (2H, d, J 8.5 Hz,
Ar), 7.35e7.39 (1H, m, Ar), 7.40 (2H, d, J 8.5 Hz, Ar); dC (125 MHz,
CDCl3): 28.8 (Me), 29.5 (Me),34.5 (C12b), 59.7 (C6a), 77.9 (PhCeO),
85.5 (C12c), 119.9, 125.6, 127.7, 129.7, 130.0, 130.1, 130.3, 133.3, 136.9,
149.4 (CeAr), 152.0 (C]O), 156.5 (C4a), 162.6 (C]O); m/z (EI,
70 eV) 460 (2, Mþ), 396 (19, MþꢀSO2), 380 (8, MþꢀSO3), 299 (63),
243 (100%).
4. Majumdar, K. C.; Mondal, S.; Ghosh, D. Tetrahedron Lett. 2009, 50, 4781e4784.
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(b) Roberts, D. W.; Williams, D. L.; Bethell, D. Chem. Res. Toxicol. 2007, 20, 61e71.
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7. Perez-Perez, M. J.; Balzarini, J.; Hosoya, M.; Clercq, E. D.; Camarasa, M. J. Bioorg.
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8. Camarasa, M. J.; Perez-Perez, M. J.; San-Felix, A.; Balzarini, J.; Clercq, E. D. J. Med.
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1991; Chapter 19, pp 789e878; (d) Metz, P. J. Prakt. Chem. 1998, 340, 1e10.
10. (a) Ghandi, M.; Tabatabaei Rezaei, S. J.; Yari, A.; Taheri, A. Tetrahedron Lett. 2008,
49, 5899e5901; (b) Ghandi, M.; Yari, A.; Tabatabaei Rezaei, S. J.; Taheri, A.
Tetrahedron Lett. 2009, 50, 4724e4726; (c) Ghandi, M.; Taheri, A.; Abbasi, A.
Tetrahedron 2010, 66, 6744e6748.
11. (a) Grieco, P. A. Organic Synthesis in Water; Blacky Academic & Professional:
London, 1998; p 82; (b) Lindstrom, U. M. Chem. Rev. 2002, 102, 2751e2772; (c)
Li, C.-J. Chem. Rev. 2005, 105, 3095e3166; (d) Li, C.-J.; Chan, T.-H. Comprehensive
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4.3.12. 2,4-Dimethyl-6-(4-boromo)-phenyl-2,4,6,6a,12b-pentahydro-
5,8-dioxa-7-thia-2,4-diaza-benzo[c]phenanthrene-1,3-dione,7,7-
dioxide (8f, 9f). White solid (85:15 dr 231 mg, 46%); mp:
212e215 ꢁC. Found: C, 49.90; H, 3.37; N, 5.49. C21H17BrN2O6S re-
quires C, 49.91; H, 3.39; N, 5.54%. nmax (KBr): 1701, 1616, 1378,
1158 cmꢀ1
, dH (500 MHz, CDCl3): 3.32 (3H, s, Me) {for 9f, 3.39 (3H, s,
Me)}, 3.48 (3H, s, Me) {for 9f, 3.52 (3H, s, Me)}, 4.24 (1H, dd, J 10.8,
5.7 Hz, H6a) {for 9f, 3.63 (1H, dd, J 12.1, 10.3 Hz, H6a)}, 5.13 (1H, d, J
5.7 Hz, H12b) {for 9f, 5.39 (1H, d, J 10.3 Hz, H12b)}, 5.14 (1H, d, J
10.8 Hz, PhCHO) {for 9f, 4.78 (1H,d, J 12.1 Hz, PhCHO)}, 7.21 (1H, d, J
8.3 Hz, Ar), 7.30e7.45 (5H, m, Ar), 7.63 (2H, d, J 8.5 Hz, Ar); dC
(125 MHz, CDCl3): 28.8 (Me), 29.4 (Me), 34.5 (C12b), 59.4 (C6a), 75.2
(PhCeO), 85.5 (C12b), 119.8, 125.0, 125.5, 127.6, 130.0, 130.2, 130.3,
132.5,133.9,149.4 (CeAr),151.0 (C]O),156.5 (C4a),162.6 (C]O); m/
z (EI, 70 eV) 505 (13, Mþþ1), 441 (8, MþꢀSO2), 425 (83, MþꢀSO3),
285 (63), 243 (100%).
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17. Tietze, L. F.; Geissler, H.; Fennen, J.; Brumby, T.; Brand, S.; Schulz, G. J. Org. Chem.
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The authors acknowledge the University of Tehran for financial
€
Ruther, M.; Ruhlmann, A.; Antel, J.; Sheldrick, G. M. Angew. Chem., Int. Ed. Engl.
support of this research.
1988, 27, 1186e1187.