Synthesis of novel tricyclic and tetracyclic sultone scaffolds via intramolecular 1,3-dipolar cycloaddition reactions

Article abstract of DOI:10.1016/j.tet.2012.02.053

The initially prepared 2-formylphenyl-(E)-2-phenylethenesulfonates from the condensation of (E)-2-phenylethenesulfonyl chloride with 2-hydroxybenzaldehyde derivatives underwent intramolecular [3+2] cycloaddition with methyl or phenylhydroxylamine, sarcosi

Full text of DOI:10.1016/j.tet.2012.02.053

Tetrahedron 68 (2012) 3641e3648
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Synthesis of novel tricyclic and tetracyclic sultone scaffolds via intramolecular 1,
3-dipolar cycloaddition reactions
,
a
a
a
b,c
Mehdi Ghandi a , Abuzar Taheri , Abolfazl Hasani Bozcheloei , Alireza Abbasi , Reza Kia
*
a School of Chemistry, College of Science, University of Tehran, Tehran, P.O. Box 14155 6455, Iran
b X-ray Crystallography Laboratory, Plasma Physics Research Center, Science and Research Branch, Islamic Azad University, Tehran, Iran
c Department of Chemistry, Science and Research Branch, Islamic Azad University, Tehran, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
The initially prepared 2-formylphenyl-(E)-2-phenylethenesulfonates from the condensation of (E)-2-
Received 30 November 2011
Received in revised form 29 January 2012
Accepted 21 February 2012
Available online 15 March 2012
phenylethenesulfonyl chloride with 2-hydroxybenzaldehyde derivatives underwent intramolecular
[3þ2] cycloaddition with methyl or phenylhydroxylamine, sarcosine, and
L
-proline, affording the cor-
responding novel isoxazolidine, pyrrolidine and pyrrolizidine-annulated
g
,d
-benzo- -sultones, re-
d
spectively, in good yields. Unambiguous assignment of the molecular structures was carried out by
single-crystal X-ray diffraction.
Keywords:
Pyrrolidine
Ó 2012 Elsevier Ltd. All rights reserved.
Pyrrolizidine
1,3-Dipoar cycloaddition
Sultone
1. Introduction
Cycloaddition is one of the most efficient and reliable synthetic
transformations for the rapid, predictable, and reliable assembly of
The internal esters of hydroxy sulfonic acids or sulfur analogues
of lactones, which are called sultones, constitute a class of hetero-
cyclic compounds whose chemistry continues to be of interest.1 The
biological activities of sultones consist of skin sensitization2 and
antiviral activities.3 A new family of non-nucleoside anti-HCMV
and anti-VZV agents has recently been discovered.4 Sultones are
considered as sulfoalkylating agents due to their easy reaction with
a variety of nucleophiles for the synthesis of alkylsulfonic acids.5
Traditionally, sultone syntheses have relied on classical cycliza-
tion protocols, such as the elimination reaction of the corre-
sponding hydroxy sulfonic acid derivatives,6 treatment of
diazotized amino sulfonic acids and esters with powdered copper,7
and intramolecular DielseAlder reaction of vinylsulfonic acid es-
ters.8 A number of transition metal-catalyzed processes and in-
direct methods to sultones have also recently been reported.9
Sultones are known as valuable heterocyclic intermediates that
offer novel possibilities for stereoselective transformations. For
molecular complexity. Among these processes, for example, 1,3-
dipolar cycloadditions of azomethine ylides11 and nitrones12 have
been developed for construction of pyrrolidine13 or pyrrolizidine14
and isoxazolidine.15 These scaffolds are specifically important for
the creation of diverse chemical libraries of drug-like molecules for
biological screening.16
Construction of five-membered pyrrolidines and pyrrolizine
rings via simple synthetic methods affords an important class of
substances with highly pronounced biological activities.17 The iso-
xazolidine cycloaddition products are also valuable precursors to
biologically active b-amino acids, b-lactams, amino sugars, and al-
kaloids.18 As such, synthesis of heterocyclic compounds containing
the benzo-sultone and five-membered isoxazolidine, pyrrolidines,
and pyrrolizine motifs seemed to be interesting due to their
individual widespread known biological activities and uses. As
a part of our own interest in cycloaddition reactions,19 herein, we
describe the synthesis of novel isoxazolidine, pyrrolidine, and
example,
d-sultones obtained via the rhodium-catalyzed reaction of
pyrrolizidine-annulated benzo-
d-sultones via condensation of
sulfonate ester derivatives have undergone reductive and oxidative
(E)-2-phenylethenesulfonyl chloride with
a
number of 2-
reactions that make excision of the eSO3e moiety possible.9a On
hydroxybenzaldehyde derivatives followed by intramolecular
[3þ2] cycloaddition of either nitrones or azomethine ylides derived
in situ from the reaction with N-methyl or N-phenylhydroxylamine
the other hand, the b-iodo-a,b-unsaturated g-sultones were found
to show dual behavior with soft or hard nucleophiles.10
and sarcosine or L-proline, respectively. To the best of our knowl-
edge, no reports on systems where the dipolarophile is tethered to
the dipole moiety by a sulfonate link are present in literature.
* Corresponding author. Tel.: þ98 21 61112250; fax: þ98 21 66495291; e-mail
address: ghandi@khayam.ut.ac.ir (M. Ghandi).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2012.02.053

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M. Ghandi et al. / Tetrahedron 68 (2012) 3641e3648
2. Results and discussion
The sulfonates 2aee were then treated with sarcosine in boiling
toluene for h. After evaporation of the solvent and re-
3
The synthesis of 2-formylphenyl-(E)-2-phenylethenesulfonates
2aee from (E)-2-phenylethenesulfonyl chloride and a number of
2-hydroxybenzaldehydes 1aee were carried out according to the
previously reported procedures (Scheme 1).20 Subsequent reaction
of sulfonates 2aee with N-methyl or N-phenylhydroxylamine in
boiling EtOH proceeded to completion over 10 h. After cooling the
solution to room temperature and filtration, 3aej were obtained in
moderate to high yields (Scheme 2, Table 1). All analytical data
including 1H and 13C NMR and MS were consistent with the pro-
posed structures. For example, the 1H NMR spectrum of 3e
exhibited characteristic signals at 2.83 (3H, s), 4.07 (1H, br s), 4.22
(1H, dd, J 7.3, 8.7 Hz), and 5.67 (d, 1H, J 7.3 Hz) due to MeN, ArCHN,
CHSO2, and PhCHO, respectively. The 13C NMR spectrum of 3e
crystallization of the crude products from MeOH, 4aee were
obtained in high yields (Scheme 3, Table 1). All analytical data in-
cluding 1H and 13C NMR and MS were consistent with the proposed
structures. For example, the 1H NMR spectrum of 4a demonstrated
characteristic signals at 2.37 (3H, s), 3.84 (1H, d, J 8.4 Hz), and 4.12
(1H, dd, J 8.5, 7.9 Hz) due to MeN, PhCHN, and CHSO2, respectively.
The 13C NMR spectrum of 4a showed five peaks at
aliphatic carbons and 10 peaks at 121.2e152.1 for aromatic car-
d 39.6e69.5 for
d
bons, in agreement with the structure. The MS (EI) spectrum
exhibited the molecular ion peak at m/z 315 corresponding to the
molecular weight of 4a. Unambiguous evidence for the proposed
structure of 4a was finally obtained by single-crystal X-ray-dif-
fraction analysis (Fig. 2).22
exhibited four peaks at
d
42.5e81.3 for aliphatic carbons and 10
Particularly significant is the crystal packing of compound 4a in
which pairs of intermolecular C/H/O hydrogen bonds link
neighboring molecules into centerosymmetric individual dimers,
which are arranged along the a-axis of the unit cell. Only the hy-
drogen atoms involved in the hydrogen bonding are shown.23
peaks at 120.1e151.0 due to the aromatic carbons. The MS (EI)
d
spectrum showed the molecular ion peak at m/z 396 corresponding
to the molecular weight of 3e. Unambiguous evidence for the
proposed structure of 3e was finally obtained by single-crystal X-
ray-diffraction analysis (Fig. 1).21
The sulfonates 2aee were also treated with L-proline in boiling
toluene for 3 h. After evaporation of the solvent, the crude mixture
was subjected to plate chromatography on silica gel, affording 5aee
and 6aee with all analytical data including 1H and 13C NMR and MS
consistent with the proposed structures (Scheme 4, Table 2). For
example, whereas the CHSO2 and ArCHN ring junction protons in
5b appear with the coupling constant of 8.0 Hz, the similar protons
in 6b resonate with the coupling of 9.2 Hz in the corresponding 1H
NMR spectra, respectively. Unambiguous evidence for the proposed
structure of 5b was finally obtained by single-crystal X-ray-dif-
fraction analysis (Fig. 3).24 Therefore, intramolecular 1,3-dippolar
reactions should have been proceeded to cycloadducts cis-fused
5b and trans-fused 6b, respectively.
Scheme 1. Synthesis of (E)-2-formylphenyl 2-phenylethenesulfonates 2aee.
The dipolar cycloaddition of a nitrone or azomethine ylide
generated from methyl or phenylhydroxylamine and sarcozine or L-
proline and an aldehyde with a dipolarophile could lead to a mix-
ture of stereoisomers. Since the trans stereochemistry of the alkene
dipolarophile has been maintained in the isoxazolidine, pyrrolidine
and pyrrolizidine rings (see Schemes 2e4), the cycloadditions have
proceeded concerted with both carbonecarbon
s-bonds being
formed at the same time, although not necessarily to the same
extent. On the other hand, the stereochemistry of the resultant
isoxazolidines 3aej or pyrrolidines 4aee and pyrrolizidines 5aee/
6aee at the annelation bonds emerges from the geometry of the
nitrone or azomethine ylides, respectively. Hence, either the E- or
Scheme 2. Synthesis of isoxazolidine-annulated benzo-d-sultones 3aej.
Table 1
Isolated yields of benzo-
d-sultones 3aej and 4aee obtained from reaction of 2aee with N-methyl or N-phenylhydroxylamine and sarcosine
Product structure
Yield (%)
Product structure
Yield (%)
Product structure
Yield (%)
75
85
90
3a
3b
4a
3f
77
90
87
4b
3g

M. Ghandi et al. / Tetrahedron 68 (2012) 3641e3648
3643
Table 1 (continued )
Product structure
Yield (%)
Product structure
Yield (%)
Product structure
Yield (%)
83
92
80
4c
4d
4e
3c
3h
80
87
80
3d
3i
85
85
85
3e
3j
3. Conclusion
In summary, novel isoxazolidine, pyrrolidine, and pyrrolizidine-
annulated benzo- -sultones were synthesized via condensation of
(E)-2-phenylethenesulfonyl chloride with 2-hydrox-
d
ybenzaldehydes followed by intramolecular [3þ2] cycloaddition of
the nitrone or azomethine ylides derived in situ from the reaction
with N-methyl or N-phenylhydroxylamine, and sarcosine or
L-
proline. These new structures broaden the benzo- -sultone scaf-
d
folds that are accessible through intramolecular [3þ2] cycloaddi-
tion and many of them may represent interesting pharmacophores.
An important aspect of the above reported syntheses, which de-
serves some consideration is the effect of the eOSO2e group in the
intramolecular cycloaddition process. To the best of our knowledge,
no reports of systems where the dipolarophile is tethered to the
dipole moiety by a sulfonate link are present in literature.
Fig. 1. X-ray crystal structure of compound 3e.
4. Experimental section
4.1. General information
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 sol-
vent and with the residual solvent signal as internal reference
(CDCl3, 7.24 and 77.0 ppm). Mass spectra of the products were
obtained with an HP (Agilent technologies) 5937 Mass Selective
Detector. Elemental analyses were carried out by a CHN-Rapid
Heraeus elemental analyzer (Wellesley, MA).
Scheme 3. Synthesis of pyrrolidine-annulated benzo-d-sultones 4aee.
Z-nitrone or azomethine ylides could have been implicated in the
formation of 3aej and 4aee. The Z-nitrone (Scheme 5) and E-ylide
(Scheme 6) seem to be more stable than the E and Z analouges,
respectively, since more steric hindrance between Ar and either C
or O atoms caring free negative charges are experienced if these
groups located cis to each others.
Notably, the dipolar cycloaddition reaction of an azomethine
ylide generated from
L
-proline and an aldehyde with a dienophile
4.2. Representative procedure for the synthesis of 3aej
could lead to a mixture of W- and S-shaped ylides.11c Inspection of
the results reveals that both ylides have been implicated in these
cycloadditions, leading to pyrrolizidines transetrans 5aee and
cisetrans 6aee as the major and minor products, respectively
(Scheme 6).
A mixture of N-phenylhydroxylamine (1.0 mmol) (or N-meth-
ylhydroxyammonium chloride plus an equimolar amount of Et3N),
2-formylphenyl-(E)-2-phenylethenesulfonates 2aee (1.0 mmol) in
EtOH (10 mL) was heated at reflux with stirring for 10 h. After

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M. Ghandi et al. / Tetrahedron 68 (2012) 3641e3648
Fig. 2. X-ray crystal structure of compound 4a.
cooling the mixture to room temperature, the crystals were filtered
to give the products.
4.2.1. 1-Methyl-3-phenyl-1,3,3a,9b-tetrahydrobenzo[e][1,2]-ox-
athiino[4,3-c]isoxazole-4,4-dioxide (3a). Colorless solid (238 mg,
75%); mp 173e174 ꢁC; [Found: C, 60.37; H, 4.84; N, 4.31. C16H15NO4S
requires C, 60.55; H 4.76; N 4.41%]. nmax (KBr): 1155, 1366
(eSO2) cmꢀ1
; dH (500 MHz, CDCl3): 2.82 (3H, s, MeN); 4.11 (1H, br s,
ArCHN), 4.23 (1H, dd, J 7.3, 8.6 Hz, CHSO2), 5.70 (1H, d, J 7.3 Hz,
CHO), 7.29e7.59 (9H, m, Ar); dC (125 MHz, CDCl3): 42.4, 70.7, 72.5,
Scheme 4. Synthesis of pyrrolizidine-annulated benzo-d-sultones 5aee and 6aee.
Table 2
Isolated yields of benzo-d-sultones 5aee and 6aee obtained from reaction of 2aee with L-proline
Transetrans stereoisomer
Cisetrans stereoisomer
Total yield (%)
Yield (%)
5
6
59
37
22
5a
6a
6b
6c
80
64
16
5b
58
48
10
5c

M. Ghandi et al. / Tetrahedron 68 (2012) 3641e3648
3645
Table 2 (continued )
Transetrans stereoisomer
Cisetrans stereoisomer
Total yield (%)
Yield (%)
5
6
56
32
24
6d
6e
5d
66
40
26
5e
Fig. 3. X-ray crystal structure of compound 6b.
Scheme 5. Transition state model evoked for the observed diastereoselectivities of
3aej.
Scheme 6. Transition state model evoked for the formation of 4b, 5b, and 6b.
81.4, 120.1, 122.8, 123.9, 127.4, 129.3, 129.6, 133.6, 134.6, 136.2, 151.0;
m/z (EI, 70 eV) 317 (32, Mþ), 207 (23), 178 (14), 134 (100), 105 (18%).
1363 (eSO2) cmꢀ1
; dH (500 MHz, CDCl3): 2.70 (3H, s, MeN), 3.83
4.2.2. 6-Methoxy-1-methyl-3-phenyl-1,3,3a,9b-tetrahydrobenzo[e]
[1,2]-oxathiino[4,3-c]isoxazole-4,4-dioxide (3b). Colorless solid
(269 mg, 77%); mp 185e186 ꢁC; [Found: C, 58.45; H, 4.48; N, 4.32.
C17H17NO5S requires 58.78; H, 4.93; N, 4.03%]. nmax (KBr): 1146,
(3H, s, MeO), 4.02 (1H, br s, ArCHN), 4.12 (1H, dd, J 7.4, 8.7 Hz,
CHSO2), 5.56 (1H, d, J 7.4 Hz, CHO), 6.87 (1H, d, J 7.5 Hz, Ar), 7.02 (1H,
d, J 8.0 Hz, Ar), 7.20 (1H, t, J 8.0 Hz, Ar), 7.29e7.47 (5H, m, Ar) ppm;
dC (125 MHz, CDCl3): 42.5, 56.7, 70.4, 72.5, 81.3, 114.8, 121.9, 122.9,

3646
M. Ghandi et al. / Tetrahedron 68 (2012) 3641e3648
127.4, 127.5, 129.2, 129.5, 136.5, 141.0, 151.0; m/z (EI, 70 eV) 347 (81,
69.9, 72.7, 81.3, 106.2, 112.7, 113.0, 121.8, 127.1, 127.4, 129.2, 129.4,
129.6, 132.3, 136.7, 147.0, 152.9, 162.2 ppm; m/z (EI, 70 eV) 409 (12,
Mþ), 301 (25), 196 (42), 105 (40), 91 (100%).
Mþ), 301 (7), 237 (12), 164 (100), 134 (11%).
4.2.3. 7-Methoxy-1-methyl-3-phenyl-1,3,3a,9b-tetrahydrobenzo[e]
[1,2]-oxathiino[4,3-c]isoxazole-4,4-dioxide
(3c). Colorless solid
4.2.9. 1,3-Diphenyl-8-nitro-1,3,3a,9b-tetrahydrobenzo[e][1,2]-ox-
athiino[4,3-c]isoxazole-4,4-dioxide (3i). Colorless solid (370 mg,
87%); mp 182e183 ꢁC; [Found: C, 59.64; H, 3.51; N, 6.84.
C21H16N2O6S requires C, 59.43; H, 3.80; N, 6.60%]. nmax (KBr): 1159,
(289 mg, 83%); mp 167e168 ꢁC; [Found: C, 58.65; H, 4.53; N, 4.23.
C17H17NO5S requires C, 58.78; H, 4.93; N, 4.03%]. nmax (KBr): 1160,
1363 (eSO2) cmꢀ1
; dH (500 MHz, CDCl3): 2.80 (3H, s, MeN), 3.87
(3H, s, MeO), 4.06 (1H, br s, ArNCH), 4.20 (1H, dd, J 7.2, 8.5 Hz,
CHSO2), 5.69 (1H, d, J 7.2 Hz, CHO), 6.83 (1H, s, Ar); 6.89 (1H, d, J
8.4 Hz, Ar), 7.28 (1H, t, J 8.4 Hz, Ar), 7.40e7.58 (5H, m, Ar); dC
(125 MHz, CDCl3): 42.3, 56.2, 70.7, 72.1, 81.3, 106.8, 113.5, 122.3,
127.4, 129.3, 129.6, 131.4, 136.7, 153.0, 162.3; m/z (EI, 70 eV) 347 (32,
Mþ), 301 (26), 237 (32), 164 (100), 134 (37%).
1383 (eSO2) cmꢀ1
; dH (500 MHz, CDCl3): 4.55 (1H, dd, J 7.7, 8.3 Hz,
CHSO2), 4.80 (1H, d, J 8.3 Hz, ArCHN), 5.85(1H, d, J 7.7 Hz, CHO),
7.00e8.28 (13H, m, Ar); dC (125 MHz, CDCl3) 68.7, 70.2, 81.4, 121.4,
121.7, 123.0, 126.8, 126.9, 127.4, 127.6, 129.4, 129.6, 129.8, 136.1,
145.5, 146.1, 155.9; m/z (EI, 70 eV) 424 (40, Mþ), 196 (33), 178 (31),
105 (44), 91 (95%).
4.2.4. 1-Methyl-8-nitro-3-phenyl-1,3,3a,9b-tetrahydrobenzo[e][1,2]-
oxathiino[4,3-c]isoxazole-4,4-dioxide (3d). Colorless solid (290 mg,
80%); mp 207e208 ꢁC; [Found: C, 53.48; H, 3.66; N, 7.52.
C16H14N2O6S requires C, 53.03; H, 3.89; N, 7.73%]. nmax (KBr): 1163,
4.2.10. 8-Bromo-1,3-diphenyl-1,3,3a,9b-tetrahydrobenzo[e][1,2]-ox-
athiino[4,3-c]isoxazole-4,4-dioxide (3j). Colorless solid (389 mg,
85%); mp 164e165 ꢁC; [Found: C, 55.31; H, 3.28; N, 3.24.
C21H16BrNO4S requires C, 55.03; H, 3.52; N, 3.06%]. nmax (KBr): 1156,
1378 (eSO2) cmꢀ1
;
dH (500 MHz, CDCl3): 2.76 (3H, s, MeN), 4.28
1371 (eSO2) cmꢀ1
; dH (500 MHz, CDCl3): 4.45 (1H, dd, J 7.6, 8.1 Hz,
(1H, br s, ArCHN), 4.32 (1H, dd, J 7.3, 8.6 Hz, CHSO2), 5.56 (1H, d, J
7.3 Hz, CHO), 7.29e7.49 (6H, m, Ar), 8.27 (1H, d, J 8.6 Hz, Ar),
8.31e8.34 (1H, dd, J 2.7, 8.6 Hz, Ar); dC (125 MHz, CDCl3): 42.7, 69.9,
71.5, 81.4, 122.3, 126.4, 127.1, 127.3, 129.4, 129.8, 133.3, 146.2, 156.2;
m/z (EI, 70 eV) 362 (25, Mþ), 179 (46), 167 (58), 149 (100), 103 (42%).
CHSO2), 4.83 (1H, d, J 8.1 Hz, ArCHN), 5.79 (1H, d, J 7.6 Hz, CHO),
6.99e7.62 (13H, m, Ar); dC (125 MHz, CDCl3): 69.1, 71.0, 81.5, 119.7,
121.3, 122.2, 123.4, 127.3, 127.5, 129.4, 129.5, 129.7, 134.2, 134.5,
136.3, 146.7, 150.8 ppm; m/z (EI, 70 eV) 457 (14, Mþ), 196 (29), 149
(27), 105 (39), 91 (100%).
4.2.5. 8-Bromo-1-methyl-3-phenyl-1,3,3a,9b-tetrahydrobenzo[e]
4.3. General procedure for the for the preparation of 4aee
[1,2]-oxathiino[4,3-c]isoxazole-4,4-dioxide
(3e). Colorless solid
(337 mg, 85%); mp 190e191 ꢁC; [Found: C, 48.85; H, 3.66; N 3.79.
C16H14BrNO4S requires C, 48.50; H, 3.56; N, 3.53%]. nmax (KBr):
A mixture of sarcosine (1.0 mmol), 2-formylphenyl (E)-2-
phenylethenesulfonate 2a(1.0 mmol) in dry toluene (30 mL) con-
1156,1369 (eSO2) cmꢀ1
;
dH (500 MHz, CDCl3): 2.83 (3H, s, MeN),
taining molecular sieves (500 mg, 4 A) was heated at reflux with
ꢀ
4.07 (1H, br s, ArCHN), 4.22 (1H, dd, J 7.3, 8.7 Hz, CHSO2), 5.67 (1H,
d, J 7.3 Hz, CHO), 7.33e7.49 (6H, m, Ar), 8.28 (1H, s, Ar), 8.32 (1H, d, J
8.8 Hz, Ar); dC (125 MHz, CDCl3): 42.5, 70.2, 71.7, 81.3, 120.1, 122.8,
123.9, 127.3, 129.3, 129.6, 133.6, 134.6, 136.2, 151.0 ppm; m/z (EI,
70 eV) 396 (11, Mþ), 212 (46), 164 (86), 77 (100%).
stirring for 3 h. The solvent was then removed under reduced
pressure and the residue was recrystallized from MeOH to give
4aee.
4.3.1. 1-Methyl-3-phenyl-1,2,3,3a,4,9b-hexahydrobenzo[e][1,2]ox-
athiino[4,3-b]pyrrole-4,4-dioxide (4a). Colorless solid (285 mg,
90%); mp 192e193 ꢁC; [Found: C, 64.47; H, 5.12; N, 4.62.
C17H17NO3S requires C, 64.74; H, 5.43; N, 4.44%]. nmax (KBr): 1359,
1150 cmꢀ1 (eSO2); dH (500 MHz, CDCl3): 2.37 (3H, s, MeN),
2.61e2.64 (1H, m, CHN), 3.56e3.59 (1H, m, CHPh), 3.84 (1H, d, J
8.4 Hz, ArCHN), 4.12 (1H, dd, J 8.5, 7.9 Hz, CHSO2), 4.23e4.26 (1H,
dd, J 9.4, 7.9 Hz, CHN), 7.25e7.47 (9H, m, Ar); dC (125 MHz, CDCl3):
39.6; 47.2, 63.4, 68.9, 69.5, 121.2, 124.8, 126.7, 128.1, 128.3, 129.4,
130.2, 131.0, 139.6, 152.1; m/z (EI, 70 eV) 315 (31, Mþ), 208 (100), 167
(22), 149 (43), 131 (36%).
4.2.6. 1,3-Diphenyl-1,3,3a,9b-tetrahydrobenzo[e][1,2]-oxathiino[4,3-
c]isoxazole-4,4-dioxide (3f). Colorless solid (391 mg, 85%); mp
166e167 ꢁC; [Found: C, 66.23; H, 4.61; N, 3.45. C21H17NO4S requires
C, 66.47; H, 4.52; N, 3.69%]. nmax (KBr): 1154, 1365 (eSO2) cmꢀ1
; dH
(500 MHz, CDCl3): 4.43 (1H, dd, J 7.3, 8.6 Hz, CHSO2), 4.80 (1H, d, J
8.6 Hz, ArCHN), 5.84 (1H, d, J 7.3 Hz, CHO), 6.82 (1H, d, J 7.7 Hz, Ar),
7.07e7.64 (13H, m, Ar); dC (125 MHz, CDCl3): 69.8, 71.9, 81.5, 120.7,
121.3, 121.8, 126.8, 127.2, 127.5, 129.3, 129.4, 129.6, 131.6, 131.7, 136.6,
146.9, 152.0 ppm; m/z (EI, 70 eV) 379 (100, Mþ), 207 (20), 196 (44),
105 (17), 91 (50%).
4.3.2. 6-Methoxy-1-methyl-3-phenyl-1,2,3,3a,4,9b-hexahydrobenzo
[e][1,2]oxathiino[4,3-b]pyrrole-4,4-dioxide (4b). Colorless solid
(300 mg, 87%); mp 196e197 ꢁC; [Found: C, 62.37; H, 5.33; N, 3.88.
C18H19NO4S requires C, 62.59; H, 5.54; N, 4.06%]. nmax (KBr): 1367,
1151 cmꢀ1 (eSO2); dH (500 MHz, CDCl3): 2.36 (3H, s, MeN), 2.60
(1H, t, J 9.9 Hz, CHN), 3.56 (1H, dd, J 9.9, 7.0 Hz, CHPh), 3.84 (1H, d, J
8.8 Hz, ArCHN), 3.92 (3H, s, MeO), 4.00 (1H, dd, J 8.8, 7.2 Hz, CHSO2),
4.23e4.28 (1H, m, CHN), 6.91(1H, d, J 8.9 Hz, Ar), 7.06 (1H, d, J
8.3 Hz, 1H, Ar), 7.24e7.42 (6H, m, Ar); dC (125 MHz, CDCl3): 39.7,
47.2, 56.8, 63.4, 68.7, 69.7, 114.2, 122.0, 126.1, 126.7, 128.0, 128.3,
129.4,139.6,141.1,151.2; m/z (EI, 70 eV) 345 (30, Mþ), 238 (100), 223
(10), 178 (14), 161 (14%).
4.2.7. 1,3-Diphenyl-6-methoxy-1,3,3a,9b-tetrahydrobenzo[e][1,2]-ox-
athiino[4,3-c]isoxazole-4,4-dioxide (3g). Colorless solid (348 mg,
86%); mp 197e198 ꢁC; [Found: C, 64.65; H, 4.47; N, 3.65.
C19H19Cl2NO requires C, 64.53; H, 4.68; N, 3.42%]. nmax (KBr): 1151,
1363 (eSO2) cmꢀ1
; dH (500 MHz, CDCl3): 3.97 (3H, s, MeO), 4.40
(1H, dd, J 7.4, 8.5 Hz, CHSO2), 4.80 (1H, d, J 8.5 Hz, ArCHN), 5.85(1H,
d, J 7.4 Hz, CHO), 6.82 (1H, d, J 7.3 Hz, Ar), 7.07e7.65 (12H, m, Ar); dC
(125 MHz, CDCl3): 56.8, 69.7, 72.1, 81.5, 106.8, 114.6, 121.6, 122.6,
124.6, 127.1, 127.5, 129.2, 129.4, 129.6, 136.6, 141.1, 147.1, 150.7 ppm;
m/z (EI, 70 eV) 409 (29, Mþ), 196 (33), 105 (45), 91 (95), 77 (100%).
4.2.8. 1,3-Diphenyl-7-methoxy-1,3,3a,9b-tetrahydrobenzo[e][1,2]-ox-
athiino[4,3-c]isoxazole-4,4-dioxide (3h). Colorless solid (348 mg,
4.3.3. 7-Methoxy-1-methyl-3-phenyl-1,2,3,3a,4,9b-hexahydrobenzo
85%); mp 167e168 ꢁC; [Found: C, 64.37; H, 4.32;
N
3.64.
C22H19NO5S requires C, 64.53; H 4.68, N, 3.42%]. nmax (KBr): 1154,
1372 (eSO2) cmꢀ1
dH (500 MHz, CDCl3): 3.87 (3H, s, MeO), 4.39
[e][1,2]oxathiino[4,3-b]pyrrole-4,4-dioxide
(4c). Colorless solid
(276 mg, 80%); mp 193e194 ꢁC; [Found: C, 62.30; H, 5.20; N, 4.44.
C18H19NO4S requires C, 62.59; H, 5.54; N, 4.06%]. nmax (KBr): 1359,
1166 cmꢀ1 (eSO2); dH (500 MHz, CDCl3): 2.35 (3H, s, MeN), 2.59
(1H, t, J 9.9 Hz, CHN), 3.56 (1H, dd, J 9.9, 7.0 Hz, CHPh), 3.78 (1H, d, J
;
(1H, dd, J 7.4, 8.5 Hz, CHSO2), 4.80 (1H, d, J 8.5 Hz, ArCHN), 5.85 (1H,
d, J 7.4 Hz, CHO), 6.69e7.65 (13H, m, Ar); dC (125 MHz, CDCl3): 56.1,

M. Ghandi et al. / Tetrahedron 68 (2012) 3641e3648
3647
8.9 Hz, ArCHN), 3.86 (3H, s, MeO), 4.09 (1H, dd, J 8.9, 7.2 Hz, CHSO2),
4.21e4.25 (1H, m, CHN), 6.80 (1H, s, Ar), 6.86 (1H, d, J 8.4 Hz, Ar),
7.23 (1H, d, J 8.4 Hz, Ar), 7.33e7.41(5H, m, Ar); dC (125 MHz, CDCl3):
39.5, 47.1, 56.1, 63.2, 68.9, 69.1, 106.8, 112.8, 116.4, 127.9, 128.3, 129.4,
131.3, 139.7, 152.9, 161.7; m/z (EI, 70 eV) 345 (30, Mþ) 345 (30, Mþ),
238 (100), 223 (8), 178 (15), 161 (36%).
26.3, 29.1, 49.7, 56.8, 57.2, 60.5, 67.6, 68.9, 112.7, 120.6, 126.8, 127.6,
128.0, 128.8, 129.0, 136.9, 138.4, 149.9; m/z (EI, 70 eV) 371 (1, Mþ),
247 (21), 119 (35), 91 (67), 77 (100%).
4.4.3. 6,6a,7,7a,8,9,10,11a,12-Nonahydro-3-methoxy-7-phenylbenzo
[e][1,2]oxathiino[3,4-b]pyrrolizine-6,6-dioxide (5c). Colorless solid
(178 mg, 48%); mp 89e91 ꢁC; [Found: C, 64.35; H, 5.37; N, 4.15.
C20H21NO4S requires C, 64.67; H, 5.70; N, 3.77%]. nmax (KBr): 1361,
1147 cmꢀ1 (eSO2); dH (500 MHz, CDCl3) 1.21e1.39 (2H, m,
CH2CH2CH2N), 1.77e1.88 (2H, m, CH2CH2CH2N), 2.86e2.87 (1H, m,
CHN), 3.47e3.48 (1H, m, CHN), 3.84 (3H, s, MeO), 3.89e3.91 (1H, m,
CHPh), 4.07 (1H, t, J 8.8 Hz, NCHCPh), 4.48 (1H, dd, J 11.2, 7.8 Hz,
CHSO2), 4.64 (1H, d, J 7.8 Hz, ArCHN), 6.65 (1H, d, J 2.2 Hz, Ar), 6.90
(1H, dd, J 8.6, 1.6 Hz, Ar), 7.29e7.42 (5H, m, Ar), 7.49e7.56 (1H, m,
Ar); dC (125 MHz, CDCl3): 24.0, 28.2, 48.0, 53.5, 56.1, 64.1, 70.4, 72.7,
1.5.2, 113.8, 115.2, 128.3, 129.1, 129.6, 131.5, 138.9, 152.0, 161.1; m/z
(EI, 70 eV) 371 (1, Mþ), 369 (51), 305 (100), 276 (51), 183 (38%).
4.3.4. 8-Nitro-1-methyl-3-phenyl-1,2,3,3a,4,9b-hexahydrobenzo[e]
[1,2]oxathiino[4,3-b]pyrrole-4,4-dioxide
(4d). Colorless
solid
(288 mg, 80%); mp 176e177 ꢁC; [Found: C, 56.35; H, 4.23; N, 7.47.
C17H16N2O5S requires C, 56.66; H, 4.47; N, 7.77%]. nmax (KBr): 1346,
1155 cmꢀ1 (eSO2); dH (500 MHz, CDCl3): 2.37 (3H, s, MeN), 2.71
(1H, br s, CHN), 3.58 (1H, br s, CHPh), 4.02 (1H, br s, ArCHN),
4.19e4.22 (2H, m, CHSO2, CHN), 7.29e7.54 (6H, m, Ar), 8.26 (s, 1H,
Ar), 8.36 (br s, 1H, Ar); dC (125 MHz, CDCl3): 39.7, 47.2, 63.1, 68.3,
68.6, 122.3, 126.0, 126.4, 126.6, 128.2, 128.4, 129.5, 138.7, 145.8,
156.8; m/z (EI, 70 eV) 360 (20, Mþ), 253 (100), 206 (11), 176 (17), 149
(36%).
4.4.4. 6,6a,7,7a,8,9,10,11a,12-Nonahydro-2-nitro-7-phenylbenzo[e]
[1,2]oxathiino[3,4-b]pyrrolizine-6,6-dioxide (5d). Colorless solid
(124 mg, 32%); mp 164e166 ꢁC; [Found: C, 58.91; H, 4.58; N, 7.08.
C19H18N2O5S requires C, 59.06, H, 4.70; N, 7.25%]. nmax (KBr): 1375,
1161 cmꢀ1 (eSO2); dH (500 MHz, CDCl3) 1.16e1.38 (2H, m,
CH2CH2CH2N), 1.74e1.88 (2H, m, CH2CH2CH2N), 2.83e2.87 (2H, m,
CH2N), 3.86e3.95 (2H, m, CHPh and NCHCPh), 4.58 (1H, dd, J¼11.6,
7.8 Hz, CHSO2), 4.70 (1H, d, J 7.8 Hz, ArCHN), 7.21e7.23 (3H, m, Ar),
7.27 (1H, t, J 7.3 Hz, Ar), 7.34 (2H, t, J 7.3 Hz, Ar), 8.20 (1H, dd, J 8.8,
2.6 Hz, Ar), 8.60 (1H, d, J 2.3 Hz, Ar); dC (125 MHz, CDCl3): 26.4, 29.3,
49.5, 57.5, 59.6, 67.1, 68.7, 120.7, 125.4, 126.2, 127.9, 129.0, 129.2,
135.9, 146.3, 153.1; m/z (EI, 70 eV) 386 (1, Mþ), 322 (30), 252 (100),
206 (32), 153 (33%).
4.3.5. 8-Bromo-1-methyl-3-phenyl-1,2,3,3a,4,9b-hexahydrobenzo[e]
[1,2]oxathiino[4,3-b]pyrrole-4,4-dioxide
(4e). Colorless
solid
(335 mg, 85%); mp 216e217 ꢁC; [Found: C, 51.59; H, 3.92; N, 3.37.
C17H16BrNO3S requires C, 51.79; H, 4.09; N, 3.55%]. nmax (KBr): 1365,
1152 cmꢀ1 (eSO2); dH (500 MHz, CDCl3): 2.22 (3H, s, MeN),
2.44e2049 (1H, m, CHN), 3.37 (1H, dd, J 9.5, 5.6 Hz, CHPh), 3.71 (1H,
d, J 8.8 Hz, ArCHN), 3.97e4.01 (2H, m, CHN, CHSO2), 6.98 (1H, d, J
8.6 Hz, Ar), 7.15e7.28 (5H, m, Ar), 7.34 (1H, s, Ar), 7.42 (1H, d, J
8.5 Hz, Ar); dC (125 MHz, CDCl3): 39.5, 47.1, 63.1, 68.2, 68.5, 119.5,
122.7, 127.0, 128.0, 128.2, 129.3, 133.4, 133.6, 139.0, 150.8; m/z (EI,
70 eV) 395 (Mþþ2, 26), 393 (24, Mþ), 393 (22), 288 (100), 286
(85%).
4.4. General procedure for the for the preparation of 5aee
and 6aee
4.4.5. 6,6a,7,7a,8,9,10,11a,12-Nonahydro-2-bromo-7-phenylbenzo[e]
[1,2]oxathiino[3,4-b]pyrrolizine-6,6-dioxide (5e). Colorless solid
(168 mg, 40%); mp 71e73 ꢁC; [Found: C, 54.01; H, 4.09; N, 3.17.
C19H18BrNSO3 requires: C, 54.28; H, 4.28; N, 3.33%]. nmax (KBr):
1377, 1161 cmꢀ1 (eSO2); dH (500 MHz, CDCl3): 1.18e1.39 (m, 2H,
CH2CH2CH2N), 1.78e1.89 (m, 2H, CH2CH2CH2N), 2.82e2.85 (m, 1H,
CHN), 3.52e3.54 (m, 1H, CHN), 3.91 (dd, 1H, J 15.5, 8.7 Hz, NCHCPh),
3.98 (dd,1H, J 11.3, 8.7 Hz, CHPh), 4.53 (dd,1H, J 11.3, 7.8 Hz, CHSO2),
4.66 (d, 1H, J 7.8 Hz, ArCHN), 7.01 (d, 1H, J 8.6 Hz, Ar), 7.24e7.41 (m,
5H, Ar), 7.48 (d, 1H, J 8.6 Hz, Ar), 7.86 (s, 1H, Ar); dC (125 MHz,
CDCl3): 26.4, 29.3, 49.6, 57.5, 60.0, 67.2, 68.7, 120.1, 121.4, 127.8,
127.9, 129.1, 129.6, 132.7, 133.0, 136.4, 148.0; m/z (EI, 70 eV) 420 (1,
Mþ), 419 (0.4), 288 (54), 286 (50), 149 (100%).
A mixture of
L-proline (1.0 mmol), 2-formyl-phenyl (E)-2-
phenylethenesulfonate 2a (1.0 mmol) in dry toluene (30 mL) con-
ꢀ
taining molecular sieves (500 mg, 4 A) was heated at reflux with
stirring for 3 h. The solvent was removed under reduced pressure
and the crude mixture was purified through silica gel chromatog-
raphy using hexane/ethyl acetate (1:1) to afford the products 5aee
and 6aee.
4.4.1. 6,6a,7,7a,8,9,10,11a,12-Nonahydro-7-phenylbenzo[e][1,2]ox-
athiino[3,4-b]pyrrolizine-6,6-dioxide (5a). Colorless solid (122 mg,
37%); mp 57e60 ꢁC; [Found: C, 66.67; H, 5.34; N, 3.92. C19H19NSO3
requires C, 66.86; H, 5.57; N, 4.10%]. nmax (KBr): 1371, 1161 cmꢀ1
(eSO2); dH (500 MHz, CDCl3): 1.21e1.39 (2H, m, CH2CH2CH2N),
1.64e1.89 (2H, m, CH2CH2CH2N), 2.86e2.93 (m, 1H, CHN),
3.51e3.53 (1H, m, CHN), 3.92e4.04 (1H, m, CHPh), 4.06e4.08 (1H,
m, NCHCPh), 4.54 (dd, 1H, J 7.8, 11.5 Hz, CHSO2); 4.70 (d, 1H, J 7.8 Hz,
ArCHN); 7.12 (d, 1H, J6.8 Hz, Ar); 7.26e7.39 (m, 7H, Ar); 7.69 (d, 1H, J
7.4 Hz, Ar); dC (125 MHz, CDCl3): 26.4, 29.2, 49.6, 57.3, 60.2, 67.4,
68.9, 119, 126.9, 127.0, 127.7, 128.0, 129.1, 129.9, 136.7, 149.2; m/z (EI,
70 eV) 341 (1, Mþ), 277 (38), 208 (100), 131 (34%).
4.4.6. 6,6a,7,7a,8,9,10,11a,12-Nonahydro-7-phenylbenzo[e][1,2]ox-
athiino[3,4-b]pyrrolizine-6,6-dioxide (6a). Colorless solid (75 mg,
22%); mp 154e155 ꢁC; [Found: C, 66.77; H, 5.48; N, 3.93.
C19H19NO3S requires C, 66.84; H, 5.61; N, 4.10%]. nmax (KBr): 1360,
1164 cmꢀ1 (eSO2); dH (500 MHz, CDCl3): 1.84e1.94 (2H, m,
CH2CH2CH2N), 2.01e2.10 (2H, m, CH2CH2CH2N), 2.63e2.77 (2H, m,
CH2N), 3.57e3.63 (1H, m, CHPh), 3.66 (1H, br s, NCHCPh), 4.16e4.28
(1H, m, CHSO2), 5.28 (1H, d, J 7.5 Hz, ArCHN); 7.12e7.16 (1H, m, Ar);
7.18e7.36 (7H, m, Ar); 7.46e7.56 (1H, m, Ar): dC (125 MHz, CDCl3):
24.2, 28.1, 48.1, 53.5, 65.0, 70.7, 73.2, 120.2, 124.0, 127.0, 128.0, 128.2,
129.2, 130.9, 131.3, 139.0, 151.3; m/z (EI, 70 eV) 341 (3, Mþ), 277 (67),
207 (100), 178 (39), 131 (86%).
4.4.2. 6,6a,7,7a,8,9,10,11a,12-Nonahydro-4-methoxy-7-phenylbenzo
[e][1,2]oxathiino[3,4-b]pyrrolizine-6,6-dioxide (5b). Colorless solid
(237 mg, 64%); mp 89e90 ꢁC; [Found: C, 64.53; H, 5.51; N, 3.59.
C20H21NO4S requires C, 64.67; H, 5.70; N, 3.77%]. nmax (KBr):
1363,1146 cmꢀ1 (eSO2); dH (500 MHz, CDCl3) 1.19e1.41 (2H, m,
CH2CH2CH2N), 1.73e1.89 (2H, m, CH2CH2CH2N), 2.84e2.89 (1H, m,
CHN), 3.47e350 (1H, m, CHN), 3.90 (3H, s, MeO), 3.91e3.93 (1H, m,
CHPh), 4.07 (1H, br t, J 8.8 Hz, NCHCPh), 4.55 (1H, dd, J 11.4, 8.0 Hz,
CHSO2), 4.68 (1H, d, J 8.0 Hz, ArCHN), 6.96 (1H, t, J 4.5 Hz, Ar),
7.25e7.30 (5H, m, Ar), 7.36 (2H, t, J 7.3 Hz, Ar); dC (125 MHz, CDCl3):
4.4.7. 6,6a,7,7a,8,9,10,11a,12-Nonahydro-4-methoxy-7-phenylbenzo
[e][1,2]oxathiino[3,4-b]pyrrolizine-6,6-dioxide (6b). Colorless solid
(59 mg, 16%); mp 200e201 ꢁC; [Found: C, 64.37; H, 5.43; N, 3.58.
C20H21NO4S requires C, 64.67; H, 5.70; N, 3.77%]. nmax (KBr):
1357,1140 cmꢀ1 (eSO2); dH (500 MHz, CDCl3) 1.71e1.79 (2H, m,
CH2CH2CH2N), 1.95e1.99 (2H, m, CH2CH2CH2N), 2.48e2.65 (2H, m,
CH2N), 3.48 (1H, t, J 8.7 Hz, CHPh), 3. 54 (1H, m, NCHCPh), 3.78 (3H,

3648
M. Ghandi et al. / Tetrahedron 68 (2012) 3641e3648
2. (a) Meschkat, E.; Barratt, M. D.; Lepoittevin, M. D. Chem. Res. Toxicol. 2001, 14,
110e117; (b) Roberts, D. W.; Williams, D. L.; Bethell, D. Chem. Res. Toxicol. 2007,
20, 61e71.
3. Perez-Perez, M. J.; Balzarini, J.; Hosoya, M.; Clercq, E. D.; Camarasa, M. J. Bioorg.
Med. Chem. Lett. 1992, 2, 647e648.
4. De Castro, S.; García-Aparicio, C.; Andrei, G.; Snoeck, R.; Balzarini, J.; Camarasa,
M. J.; Velízquez, S. J. Med. Chem. 2009, 52, 1582e1591.
5. Roberts, D. W.; Williams, D. L. Tetrahedron 1987, 43, 1027e1062.
6. (a) Kaiser’, E. T.; Lo, K. W. J. Am. Chem. Soc. 1969, 91, 4912e4918; (b) Wolinsky, J.;
Dimmel, D. R.; Gibson, T. J. Am. Chem. Soc. 1967, 89, 2087e2097; (c) Mustafa, A.;
Hilmy, M. K. J. Chem. Soc. 1952, 1339e1342.
s, MeO), 4.15(1H, dd, J 9.2, 8.7 Hz, CHSO2), 5.19 (1H, d, J 9.2 Hz,
ArCHN), 6.89 (1H, d, J 8.07 Hz, Ar), 7.03 (1H, d, J 7.63 Hz, Ar),
7.12e7.30 (6H, m, Ar); dC (125 MHz, CDCl3): 24.0, 27.9, 48.1, 53.4,
56.6, 65.0, 70.3, 73.0, 112.9, 121.8, 126.9, 127.9, 128.2, 128.9, 129.4,
138.9, 140.5, 150.1; m/z (EI, 70 eV) 371 (1, Mþ), 307 (20), 238 (100),
2088 (10), 161 (15%).
ꢁ
ꢁ
4.4.8. 6,6a,7,7a,8,9,10,11a,12-Nonahydro-3-methoxy-7-phenylbenzo
[e][1,2]oxathiino[3,4-b]pyrrolizine-6,6-dioxide (6c). Colorless solid
(37 mg, 10%); mp 218e220 ꢁC; [Found: C, 64.48; H, 5.58; N, 3.63.
C20H21NO4S requires C, 64.67; H, 5.70; N, 3.77%]. nmax (KBr): 1359,
1152 cmꢀ1 (eSO2); dH (500 MHz, CDCl3) 1.85e1.97 (2H, m,
CH2CH2CH2N), 2.05e2.19 (2H, m, CH2CH2CH2N), 2.74e2.86 (1H, m,
CHN), 3.65 (1H, t, J 6.3 Hz, CHN), 3.84 (3H, s, MeO), 3.88e3.91 (1H,
m, NCHCPh), 4.05e4.09 (1H, m, CHPh), 4.25 (1H, t, J 8.7 Hz, CHSO2),
5.40 (1H, d, J 8.7 Hz, PhCHN), 6.70 (1H, d, J 2.2 Hz, Ar), 6.90 (1H, dd, J
8.6, 1.6 Hz, Ar), 7.29e7.42 (5H, m, Ar), 7.49e7.56 (1H, m, Ar); dC
(125 MHz, CDCl3): 26.3, 29.1, 49.6, 56.1, 56.9, 60.2, 67.0, 68.2, 104.4,
113.7, 118.5, 127.7, 128.1, 129.1, 130.6, 136.9, 149.8, 160.9; m/z (EI,
70 eV) 371 (1, Mþ), 307 (32), 238 (100), 161 (41), 149 (74%).
7. (a) Schetty, G. Helv. Chim. Acta 1949, 32, 24e30; (b) Schetty, G. Helv. Chim. Acta
1947, 30, 1650e1660.
8. (a) Metz, P.; Fleischer, M.; Frohlich, R. Tetrahedron 1995, 51, 711e732; (b) Metz,
€
P.; Fleischer, M. Synlett 1993, 399e400; (c) Bovenschult, E.; Metz, P.; Henkel, G.
Angew. Chem., Int. Ed. Engl. 1989, 28, 202e203.
9. (a) Wolckenhauer, S. A.; Devlin, A. S.; Bois, J. D. Org. Lett. 2007, 9, 4363e4366;
(b) Flohic, A. L.; Meyer, C.; Cossy, J. Tetrahedron 2006, 62, 9017e9037; (c) Flohic,
A. L.; Meyer, C.; Cossy, J. Org. Lett. 2005, 7, 339e342; (d) Cossy, J.; Desmurs, J.-R.;
Galland, J.-C. Synlett 2003, 667e670; (e) Karsch, S.; Schwab, P.; Metz, P. Synlett
2002, 2015e2022; (f) Okuma, K.; Koda, M.; Maekawa, S.; Shioji, K.; Inoue, T.;
Kurisaki, T.; Wakita, H.; Yokomorib, Y. Org. Biomol. Chem. 2006, 4, 2745e2752;
(g) Boeckman, R. K., Jr.; Hanson, S. M.; Cody, J. A. Heterocycles 2006, 70,
519e530.
10. Braverman, S.; Pechenick-Azizi, T.; Major, D. T.; Sprecher, M. J. Org. Chem. 2007,
72, 6824e6831.
11. (a) Yu, U.; Shi, F.; Gong, L. Z. Acc. Chem. Res. 2011, 44, 1156e1171; (b) Pandey, G.;
Banerjee, P.; Gadre, S. R. Chem. Rev. 2006, 106, 4484e4517; (c) Coldham, I.;
Hufton, R. Chem. Rev. 2005, 105, 2765e2809.
4.4.9. 6,6a,7,7a,8,9,10,11a,12-Nonahydro-2-nitro-7-phenylbenzo[e]
[1,2]oxathiino[3,4-b]pyrrolizine-6,6-dioxide (6d). Colorless solid
(93 mg, 24%); mp 209e210 ꢁC; [Found: C, 58.87; H, 4.48; N, 7.12.
C19H18N2O5S requires C, 59.06, H, 4.70; N, 7.25%]. nmax (KBr): 1347,
1155 cmꢀ1 (eSO2); dH (500 MHz, CDCl3) 1.86e2.02 (2H, m,
CH2CH2CH2N), 2.08e2.18 (2H, m, CH2CH2CH2N), 2.75e2.79 (2H, m,
CH2N), 3.63e3.67 (1H, m, CHPh), 3.71e3.74 (1H, m, NCHCPh), 4.29
(1H, t, J 9.2 Hz, CHSO2), 5.35 (1H, d, J 9.2 Hz, ArCHN), 7.32e7.45 (6H,
m, Ar), 8.30 (1H, d, J 8.6 Hz, Ar), 8.54 (1H, s, Ar); dC (125 MHz,
CDCl3): 24.2, 28.0, 48.2, 53.3, 64.6, 70.3, 73.3, 121.5, 125.8, 126.7,
128.1, 128.4, 129.7, 138.3, 148.0, 157.2; m/z (EI, 70 eV) 386 (2, Mþ),
322 (50), 253 (100), 176 (27), 149 (40%).
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4.4.10. 6,6a,7,7a,8,9,10,11a,12-Nonahydro-2-bromo-7-phenylbenzo
[e][1,2]oxathiino[3,4-b]pyrrolizine-6,6-dioxide (6e). Colorless solid
(109 mg, 26%); mp 190e191 ꢁC; [Found: C, 54.13; H, 4.17; N, 3.19.
C19H18BrNSO3 requires : C, 54.28; H, 4.28; N, 3.33%]. nmax (KBr):
1359, 1156 cmꢀ1 (eSO2); dH (500 MHz, CDCl3): 1.65e1.88 (2H, m,
CH2CH2CH2N), 2.04e2.10 (2H, m, CH2CH2CH2N), 2.70e2.77 (2H, m,
CH2N), 3.58 (1H, t, J 8.8 Hz, CHPh), 3.64e3.68 (1H, m, NCHCPh), 4.08
(1H, dd, J 9.8,11.3 Hz, CHSO2), 5.22 (1H, d, J 9.8 Hz, ArCHN), 7.04 (1H,
d, J 8.6 Hz, Ar), 7.28e7.40 (5H, m, Ar), 7.49 (1H, d, J 8.7 Hz, Ar), 7.72
(1H, s, Ar); dC (125 MHz, CDCl3): 24.1, 28.0, 48.2, 53.3, 64.6, 70.4,
73.2, 119.9, 121.9, 126.1, 128.2, 129.1, 129.6, 133.4, 133.6, 138.7, 150.2;
m/z (EI, 70 eV) 420 (1, Mþ), 357 (19), 288 (100), 178 (48), 149 (44%).
Acknowledgements
The authors acknowledge the University of Tehran for financial
support of this research.
20. Ghandi, M.; Hasani Bozcheloei, A.; Nazari, S. A.; Sadeghzadeh, M. J. Org. Chem.
2011, 76, 9975e9982.
Supplementary data
21. Crystallographic data for 3e have been deposited at the Cambridge Crystallo-
graphic Data Centre with the deposition number CCDC-750346. Copies of these
data can be obtained free of charge via www.ccdc.ca-m.ac.uk/conts/retrieving.
html (or from the Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge, CB2 1EZ, UK; fax: þ44 1223 336 033; or e-mail: deposit@ccdc.cam.
ac.uk).
22. Crystallographic data for 4a have been deposited at the Cambridge Crystallo-
graphic Data Centre with the deposition number CCDC-853726.
23. The crystal packing Figure of compound 4a is available in Supplementary data,
page 52.
Supplementary data associated with this article can be found in
the online version, at doi:10.1016/j.tet.2012.02.053. These data in-
clude MOL files and InChiKeys of the most important compounds
described in this article.
References and notes
24. Crystallographic data for 5b have been deposited at the Cambridge Crystallo-
graphic Data Centre with the deposition number CCDC-748453.
1. Majumdar, K. C.; Mondal, S.; Ghosh, D. Tetrahedron Lett. 2009, 50, 4781e4784.