Solvent controlled divergent syntheses of polysubstituted pyrroles and pyrrolo[2,3-b]-1,4-thiazines

Article abstract of DOI:10.1016/j.tet.2008.05.044

The reaction of 2-imidazolyl carbene-derived 2-arylthiocarbamoyl imidazolium salts with ethyl propiolate proceeded via the solvent dependent tandem [3+2] cycloaddition and subsequent ring transformation processes. While the reaction in butanone yielded 3-amino-2-vinylthiopyrroles as the major products, use of benzene as the solvent led to the predominant formation of pyrrolo[2,3-b][1,4]thiazines. This work disclosed a unique ring transformation of imidazoline-spiro-pyrrolines to pyrrolo[2,3-b][1,4]thiazines, which provides a simple route to both multifunctional pyrroles and pyrrolo[2,3-b][1,4]thiazines that are otherwise difficult to synthesize.

Full text of DOI:10.1016/j.tet.2008.05.044

Tetrahedron 64 (2008) 7362–7368
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Solvent controlled divergent syntheses of polysubstituted pyrroles and
pyrrolo[2,3-b]-1,4-thiazines
*
Ying Cheng , Zhi-Mei Kang, Yang-Guang Ma, Jiang-Hua Peng, Mei-Fang Liu
Chemistry Department, Beijing Normal University, Beijing 100875, China
a r t i c l e i n f o
a b s t r a c t
Article history:
The reaction of 2-imidazolyl carbene-derived 2-arylthiocarbamoyl imidazolium salts with ethyl pro-
piolate proceeded via the solvent dependent tandem [3þ2] cycloaddition and subsequent ring trans-
formation processes. While the reaction in butanone yielded 3-amino-2-vinylthiopyrroles as the major
products, use of benzene as the solvent led to the predominant formation of pyrrolo[2,3-b][1,4]thiazines.
This work disclosed a unique ring transformation of imidazoline-spiro-pyrrolines to pyrrolo[2,3-
b][1,4]thiazines, which provides a simple route to both multifunctional pyrroles and pyrrolo[2,3-
b][1,4]thiazines that are otherwise difficult to synthesize.
Received 9 March 2008
Received in revised form 6 May 2008
Accepted 9 May 2008
Available online 14 May 2008
Keywords:
2-Imidazolyl carbene
2-Arylthiocarbamoyl imidazolium salt
Ethyl propiolate
Ó 2008 Elsevier Ltd. All rights reserved.
Pyrrolo[2,3-b][1,4]thiazine
Pyrrole
1. Introduction
benzimidazolium 1 or imidazolinium salts 2 reacted with DMAD to
produce the expected [3þ2] cycloaddition products, spiro-thio-
Nucleophilic N-heterocyclic carbenes including 2-benzimid-
azolyl, 2-imidazolinyl, 2-imidazolyl, 3-triazolyl, and 2-thiazolyl
carbenes are known to react with aryl isothiocyanates to form
stable zwitterions, 2-thiocarbamoyl benzimidazolium,1 -imidazo-
linium,2,3 -imidazolium,4 -triazolium,5 and -thiazolium inner
salts,6,7 respectively. Recently, we found that these N-heterocyclic
carbene-derived inner salts are unique ambident bis-dipolar com-
pounds.8,9 These zwitterions can act as either Cþ–C–Sꢀor Cþ–C–Nꢀ
1,3-dipoles toward different dipolarophiles, and the site selectivity
of reaction is controlled by the nature of dipolarophiles. For ex-
ample, 2-arylthiocarbamoyl benzimidazolium 1 and imidazolinium
salts 2 reacted with dimethyl acetylenedicarboxylate (DMAD) or
dibenzoylacetylene to give spiro-thiophene derivatives 4–7 via the
Cþ–C–Sꢀ cycloaddition pathway,8a,b whereas in the reaction with
ethyl propiolate, methyl acrylate, acrylonitrile or ketenes, they
behaved as Cþ–C–Nꢀ dipolar species and produced spiro-pyrroles
8–14 predominantly (Scheme 1).8a–c
phenes 4 or 5.8a,b However, the same reaction of 2-arylthio-
carbamoyl imidazolium salts 15 or thiazolium salts 18 with DMAD
afforded imidazoline substituted olefins 179a or thieno[2,3-b]pyr-
azines 20,9b respectively (Scheme 2). Although both the mono-
heterocycle 17 and the fused heterocycle 20 can be derived,
Ar
R
N
N
R
N
S
X
S
Y
C C Y
C+-C-S-
cycloaddition
N
R
NAr
Y
N
R
Y
1, 2: X = C
3: X = N
4 or 5: Y = CO2Me
C+-C-N-
cycloaddition
6 or 7: Y = COPh
R12C C O
H2C CHZ
HC CCO2Et
S
S
S
R
N
R
N
R
N
Ar
Ar
Ar
Our studies have also revealed that the outcome of the [3þ2]
cycloaddition reactions of N-heterocyclic carbene-derived dipoles
was also regulated by the structures of carbenes, exemplified by the
reactions between different carbene-derived 1,3-dipoles with
DMAD. As described in Scheme 1, 2-arylthiocarbamoyl
N
N
N
X
O
N
R
N
R
N
R
8 or 9
1 R1
R
Z
CO2Et
10: Z = CO2Me
12, 13: X = C
11: Z = CN
1,4,6,8,12: benzimidazole derivatives
2,5,7,9,10,11,13: imidazoline derivatives
3, 14: triazoline derivatives
14: X = N
* Corresponding author.
E-mail address: ycheng2@bnu.edu.cn (Y. Cheng).
Scheme 1. The reaction of 2-arylthiocarbamoyl benzimidazolium 1, imidazolinium 2
or triazolium salts 3 with electron-deficient alkynes, alkenes or ketenes.
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.05.044

Y. Cheng et al. / Tetrahedron 64 (2008) 7362–7368
7363
Table 1
Ar
S
R
N
R
N
Reaction of N,N0-dibenzyl-2-phenylthiocarbamoyl imidazolium inner salt 15a with
N
S
R
N
NAr
S
DMAD
ethyl propiolate under different conditions
CO2Me
CO2Me
N
R
Entry Reaction conditions
Yield of product (%)
N
R
CO2Me
CO2Me
16
N
R
15a/21 R¼Bn Sol.
Tempa (ꢁC) T (h) 22a
23a
24a
15
17
1
2
3
4
5
6
7
8
9
10
1:3
1:5
1:3
1:1
1:3
1:5
1:3
1:3
1:5
1:5
DCEb
70–80
70–80
60–70
60–70
60–70
80–90
50–60
5
4
5
18
5
3
14
19
16
6
12
15
35
41
50
21
9
8
6
3
6
6
18
6
6
18
7
12
41
26
46
35
7
Ar
N
S
NAr
S
DCE
THF
S
S
MeO2C
CO2Me
DMAD
MeO2C
N
R
Benzene
Benzene
Benzene
Acetone
Butanone 70–80
Butanone 70–80
Me
Me
N
R
CO2Me
18
20
Ar
S
5
N
5
5
5
d
S
CH3CN
70–80
3
7
CO2Me
N
R
Me
a
CO2Me
19
Oil bath temperature.
DCE¼1,2-dichloroethane.
b
Scheme 2. The reaction of 2-arylthiocarbamoyl imidazolium salts 15 or thiazolium
salts 18 with DMAD.
pyrrolo[2,3-b][1,4]thiazine 24a (entries 3–6). On the contrary, the
more polar solvents including acetone and butanone favored the
formation of pyrrole 22a (entries 7–9). Other conditions, such as
reaction temperature and ratio of starting materials, did affect the
yields of products, but no reversal of the selectivity of the reaction
was observed. It should be pointed out that the product 24a was
somewhat unstable on silica gel and in solvents, probably due to its
water sensitive imino group. Thus, the isolation of 24a has to be
performed quickly using flash chromatography.
The scope of the reaction was then studied by using dipoles 15
bearing different substituents. In order to allow selective prepara-
tion of 3-amino-2-vinylthiopyrroles 22, the reactions of imidazo-
lium salts 15 with ethyl propiolate were performed in butanone
under refluxing condition. As compiled in Table 2, as for the for-
mation of 3-amino-2-vinylthiopyrroles, the nature of the sub-
stituents on the imidazolium salts has a marginal effect on the
reaction. All dipoles 15a–15i bearing either alkyl or benzyl groups
reacted with ethyl propiolate smoothly to produce (Z)-2-vinyl-
thiopyrroles 22 in 44–53% yields, along with (E)-isomer 23 (6–15%),
and sometimes pyrrolothiazines 24 (5–8%) was produced in these
reactions.
respectively, from the expected spiro-intermediates 16 and 19, it
was surprising that the two structurally similar intermediates,
imidazoline-spiro-dihydrothiophene 16 and thiazoline-spiro-
dihydrothiophene 19, followed dramatically different ring trans-
formation pathways. The imidazoline substituted olefin 17 was
apparently derived from fragmentation of the thiophene ring of 16.
On the contrary, the thieno[2,3-b]pyrazine 20 was formed by ex-
pansion of the thiazole ring of spiro-intermediate 19.
In order to gain a better understanding of the chemistry of
N-heterocyclic carbene-derived ambident dipolar compounds and
to further explore their synthetic applications, we undertook the
current study of the reaction of 2-thiocarbamoyl imidazolium inner
salts with ethyl propiolate. Interestingly, the reaction produced,
predominantly, novel 3-amino-2-vinylthiopyrrole or pyrrolo[2,3-
b]-1,4-thiazine derivatives in different solvents. We herein report
our observations.
2. Results and discussion
Multifunctional pyrroles constitute the key structural feature of
In this work, 2-arylthiocarbamoyl imidazolium salts 15 were
prepared from the reaction of aryl isothiocyanates with imidazole
carbenes generated in situ from the imidazolium salts with sodium
hydride.9a We started our investigation with the reaction between
N,N0-dibenzyl-2-phenylthiocarbamoyl imidazolium salt 15a and
ethyl propiolate. Initially, the reaction with 15a was examined in
dichloroethane. Under refluxing condition, interestingly, two iso-
meric substituted pyrroles 22a and 23a, and pyrrolo[2,3-
b][1,4]thiazine 24a were isolated, albeit in very low yields (Scheme
3, R¼Bn; Table 1, entries 1 and 2).
many natural products10 and bioactive synthetic compounds.11
Table 2
Reaction of 2-phenylthiocarbamoyl imidazolium salts 15 with ethyl propiolate in
butanone
Entry
15
R, Ar
Yield of producta (%)
1
2
3
4
5
6
7
8
9
15a
15b
15c
15d
15e
15f
15g
15h
15i
Bn, Ph
p-ClBn, Ph
22a, 50
22b, 44
22c, 53
22d, 48
22e, 52
22f, 53
22g, 51
22h, 48
22i, 49
23a, 6
24a, dc
24b, dc
24c, 8
23b, 12
23c, 15
23d, db
23e, db
23f, db
23g, db
23h db
23i, db
3,4-Cl2Bn, Ph
Bn, p-CH3OPh
Bn, p-ClPh
p-ClBn, p-ClPh
3,4-Cl2Bn, p-CH3Ph
i-Pr, Ph
24d, dc
24e, 6
To optimize the reaction conditions, the reaction was then car-
ried out by varying solvent, temperature, and the ratio of starting
materials. The outcome of the reaction was found to be strongly
dependent upon the solvent employed. To our delight, by using
different solvents, not only the yield of major product can be sig-
nificantly improved, but also the selectivity of the reaction can be
reversed. For example, as shown in Table 1, the less polar solvents
such as benzene and THF allowed selective formation of
24f, 6
24g, 5
24h, dc
24i, dc
n-Bu, Ph
a
Reaction conditions: 15/21¼1:5, butanone, 80–85 ꢁC, 3–8 h.
E-isomer 23 was isolated in 10–15% yields without characterization.
Pyrrolothiazine 24 was not isolated.
b
c
RHN
S
CO2Et
+
R
N
R
N
CO2Et
RHN
CO2Et
S
HC CCO2Et
+
N
Ar
S
N
Ar
NAr
N
Ar
N
R
N
R
S
21
EtO2C
CO2Et
15
23
24
22
Scheme 3. The reaction of 2-arylthiocarbamoyl imidazolium inner salts 15 with ethyl propiolate.

7364
Y. Cheng et al. / Tetrahedron 64 (2008) 7362–7368
They are also important synthetic intermediates in construction of
more complicated heterocycles.12 Our current study provides
a simple route to 3-amino-2-vinylthiopyrrole-4-carboxylates 22,
which are valuable intermediates for further elaborations.
Our second intention was to optimize the formation of the
pyrrolo[2,3-b][1,4]thiazines 24 by use of benzene as solvent. As il-
lustrated in Table 3, when reacted with ethyl propiolate in dry
benzene at 60–70 ꢁC, different benzyl-substituted dipoles 15 pro-
duced pyrrolothiazines 24 in 37–49% yields, along with small
amounts of pyrroles 22 and 23. On the other hand, it was observed
that the alkyl group substituted pyrrolothiazines, such as 24h and
24i (R¼iso-propyl and n-butyl), were less stable than the benzyl-
substituted analogs. They partially decomposed during the iso-
lation and purification process, and the pure products 24h and 24i
were not isolated.
The structures of all products were elucidated on the basis of
spectroscopic data and microanalysis. The NMR spectra, mass
spectral data, and elemental analyses indicated that the products
22 and 23 were isomers derived from one dipole and two ethyl
propiolate molecules, while the products 24 were the [1þ1] ad-
ducts of dipoles 15 with ethyl propiolate. Since spectroscopic data
did not allow full verification of the structures, X-ray diffraction
analyses were carried out to unambiguously assign that the product
22a was (Z) ethyl 3-benzylamino-2-(2-ethoxycarbonylvinylthio)-1-
phenylpyrrole-4-carboxylate and 24a was ethyl 1-benzyl-3-ben-
zylimino-5-phenyl-2,3-dihydropyrrolo[2,3-b][1,4]thiazine-7-car-
boxylate (Fig. 1).13 The Z and E isomers, 22 and 23, can be easily
differentiated by the J value of two vinyl protons in the 1H NMR
spectra.
The formation of the fused pyrrolo[2,3-b][1,4]thiazine 24 from
the 2-thiocarbamoyl imidazolium salt 15 with ethyl propiolate was
unexpected, although the ethoxycarbonyl-substituted pyrrole sub-
structure was conceivable based on the [3þ2] cycloaddition be-
tween the Cþ–C–N dipolar moiety of 15 and ethyl propiolate. The
proposed mechanism for the formation of substituted pyrroles 22,
23 and pyrrolo[2,3-b][1,4]thiazines 24 is indicated in Scheme 4.
[3þ2] Cycloaddition of the Cþ–C–Nꢀ dipole of 15 with ethyl pro-
piolate forms imidazoline-spiro-pyrroline intermediate 25. Selec-
tive C–N bond cleavage of the imidazoline ring of 25 gives rise to
a zwitterion 26A, which is tautomerized with 26B. Electro-
cyclization reaction of 26A results in the formation of the fused-ring
intermediate 27, which isomerizes into the pyrrolo[2,3-b][1,4]thia-
zine derivative 24. S-Nucleophilic addition of zwitterion 26B to ethyl
Comparison of the current reactions with those between dif-
ferent heterocyclic carbene-derived 1,3-dipoles and various dipo-
larophiles described in our earlier publications8,9 reveals some
significant observations. Firstly, different ambident dipoles derived
from various N-heterocyclic carbenes and aryl isothiocyanates have
the same chemo-selectivity between their C–C–S or C–C–N species
toward the same dipolarophile. Secondly, among the [3þ2] cyclo-
addition reactions that we have examined, those of 2-thio-
carbamoyl benzimidazolium, -imidazolinium, and -triazolium
inner salts with various dipolarophiles always produce the expec-
ted cycloadducts, spiro-thiophenes or spiro-pyrroles.8 On the other
hand, the reaction of 2-thiocarbamoyl imidazolium9a and -thiazo-
lium inner salts9b with different dipolarophiles generally afford
mono- or fused-heterocycles via ring transformation of the spiro-
intermediates. Finally, on the basis of the transformation products
of the spiro-intermediates, thiazoline-spiro-dihydrothiophene 19,
imidazoline-spiro-dihydrothiophene 16, and imidazoline-spiro-
pyrroline 25, the ring-opening aptitude in these spiro-heterocycles
is thiazoline>dihydrothiophene>imidazoline>pyrroline.
In summary, we have shown that the 2-imidazolyl carbene-
derived 2-thiocarbamoyl imidazolium salts are able to undergo
different tandem reactions with ethyl propiolate. The reaction was
highly solvent dependent. In non-polar solvent such as benzene,
the reaction proceeded via a [3þ2] cycloaddition followed by
a novel ring transformation of imidazoline-spiro-pyrroline to pro-
duce fused-ring pyrrolo[2,3-b][1,4]thiazine as the major product.
When reaction was performed in butanone, however, the reaction
yielded predominantly 3-amino-2-vinylthiopyrrole derivatives.
This work not only enriches the chemistry of 1,3-dipolar cycload-
dition and ring transformation reactions, but also provides a very
simple synthetic route to pyrrolo[2,3-b][1,4]thiazine and poly-
functionalized pyrrole derivatives, which are not readily prepared
by other methods and are potentially amenable to further
transformations.
3. Experiment section
3.1. General
Melting points are uncorrected. 1H NMR (500 or 300 MHz) and
13C NMR (125 or 75 MHz) were recorded in the solvent as indicated.
Benzene was dried by distilling from sodium benzophenone ketyl,
while the commercial butanone was used directly. The 2-arylth-
iocarbamoyl imidazolium inner salts 15 were prepared according to
our earlier publication.9a
propiolate forms
a pair of 2-vinylthio-3-pyrryl iminium in-
termediates 30 and 31. Hydrolysis of iminium salts 30 and 31 with
a trace amount of water in the solvent and/or in the chromato-
graphic elution leads tothe formation of pyrroles 22 and 23 (Scheme
4). The fact that the polar solvents favored the formation of pyrroles
22 supported this mechanism, since polar solvents should stabilize
the zwitterion intermediates 26A and 26B, and therefore should
slow down the electrocyclization.
3.2. General procedure for the reaction of 2-arylthio-
carbamoyl imidazolium inner salts 15 with ethyl
propiolate in butanone
At ambient temperature, the 2-arylthiocarbamoyl imidazolium
inner salts 15 (1 mmol) were mixed with ethyl propiolate (5 mmol)
in butanone (30 mL). The mixture was stirred at 80–85 ꢁC for 3–8 h.
After removal of the solvent under vacuum, the products 22–24
were isolated by chromatography on silica gel eluting with petro-
leum ether and ethyl acetate (8:1).
Table 3
Reaction of 2-phenylthiocarbamoyl imidazolium salts 15 with ethyl propiolate in
benzene
Entry
15
R, Ar
Yield of producta (%)
1
2
3
4
5
6
7
8
9
15a
15b
15c
15d
15e
15f
15g
15j
Bn, Ph
p-ClBn, Ph
22a, 12
22b, 10
22c, 10
22d, 14
22e, 11
22f, 10
22g, 8
23a, 6
23b, 6
23c, 7
24a, 46
24b, 49
24c, 37
24d, 43
24e, 44
24f, 49
24g, 46
22j, 42
24k, 37
3.3. General procedure for the reaction of 2-arylthio-
carbamoyl imidazolium inner salts 15 with ethyl
propiolate in benzene
3,4-Cl2Bn, Ph
Bn, p-CH3OPh
Bn, p-ClPh
p-ClBn, p-ClPh
3,4-Cl2Bn, p-CH3Ph
p-ClBn, p-CH3Ph
3,4-Cl2Bn, p-CH3OPh
23d, db
23e, db
23f, db
23g, db
23j, db
23k, 8
At ambient temperature, the 2-arylthiocarbamoyl imidazolium
inner salts 15 (1 mmol) were mixed with ethyl propiolate (3 mmol)
in dry benzene (30 mL). The mixture was stirred at 60–65 ꢁC for 5–
8 h under nitrogen atmosphere. After removal of the solvent under
vacuum, the products 24 and the mixture of by-products 22 and 23
22j, 10
22k, 12
15k
a
Reaction conditions: 15/21¼1:3, 60–70 ꢁC, 5–8 h.
b
By-products 23 were isolated in 5–8% yields without full characterization.

Y. Cheng et al. / Tetrahedron 64 (2008) 7362–7368
7365
Figure 1. The ORTEP drawing of single-crystal structures of compounds 22a and 24a.
were isolated by flash chromatography on a silica gel column
eluting with a mixture of petroleum ether (30–60 ꢁC) and ethyl
acetate (5:1 to 3:1). The two isomers 22 and 23 were further sep-
arated by chromatography a silica gel column (petroleum ether/
ethyl acetate¼8:1).
NMR (75 MHz, CDCl3) d (ppm): 165.3, 165.1, 147.7, 144.5, 140.2,
138.2, 129.7, 128.9,128.4,128.3, 127.4, 126.9, 126.3, 116.0, 104.7, 95.5,
60.3, 59.7, 48.6, 14.5, 14.3; MS (ESI): 451 (Mþ1). Anal. Calcd for
C25H26N2O4S: C, 66.64; H, 5.82; N, 6.22. Found: C, 66.69; H, 5.83; N,
6.14.
3.3.1. (Z) Ethyl 4-benzylamino-5-(2-ethoxycarbonylvinylthio)-1-
3.3.3. Ethyl 1-benzyl-3-(benzylimino)-5-phenyl-1,2,3,5-
phenyl-1H-pyrrole-3-carboxylate (22a)
tetrahydropyrrolo[2,3-b][1,4]thiazine-7-carboxylate (24a)
Yield 50% (butanone), 12% (benzene), mp 83–84 ꢁC; IR
n
(cmꢀ1):
(ppm): 7.36–
Yield 46% (benzene), mp 141–142 ꢁC; IR (cmꢀ1): 1708, 1612; 1H
n
3334, 3116, 1698, 1681; 1H NMR (300 MHz, CDCl3)
d
NMR (500 MHz, C6D6)
d
(ppm): 7.91 (d, J¼7.2 Hz, 2H), 7.55 (s, 1H),
7.44 (m, 6H), 7.21–7.33 (m, 5H), 6.67 (d, J¼10.1 Hz,1H), 6.00 (br,1H),
5.59 (d, J¼10.1 Hz, 1H), 4.71 (s, 2H), 4.30 (q, J¼7.1 Hz, 2H), 4.16 (q,
J¼7.1 Hz, 2H), 1.33 (t, J¼7.1 Hz, 3H), 1.27 (t, J¼7.1 Hz, 3H); 13C NMR
7.47 (d, J¼7.5 Hz, 2H), 7.33 (d, J¼7.6 Hz, 2H), 7.29 (d, J¼8.2 Hz, 2H),
7.19–7.24 (m, 2H), 7.02–7.13 (m, 5H), 4.63 (s, 2H), 4.52 (s, 2H), 4.37
(q, J¼7.1 Hz, 2H), 4.07 (s, 2H), 1.23 (t, J¼7.1 Hz, 3H); 13C NMR
(75 MHz, CDCl3)
d
(ppm): 166.2, 165.3, 153.5, 143.0, 140.2, 138.4,
(125 MHz, CDCl3) d (ppm): 163.3, 154.5, 138.8, 137.9, 137.6, 132.3,
129.1, 128.4, 127.9, 127.6, 126.9, 126.6, 113.1, 105.0, 104.2, 60.2, 59.7,
49.5, 14.5, 14.3; MS (ESI): 451 (Mþ1). Anal. Calcd for C25H26N2O4S:
C, 66.64; H, 5.82; N, 6.22. Found: C, 66.72; H, 5.79; N, 6.15.
129.74, 129.67, 128.5, 128.2, 127.8, 127.3, 127.0, 126.8, 124.4, 112.2,
111.1, 59.9, 57.7, 57.5, 56.5,14.6; MS (ESI): 482 (Mþ1). Anal. Calcd for
C29H27N3O2S: C, 72.32; H, 5.65; N, 8.73. Found: C, 72.02; H, 5.71; N,
8.75.
3.3.2. (E) 4-Benzylamino-5-(2-ethoxycarbonylvinylthio)-1-phenyl-
1H-pyrrole-3-carboxylate (23a)
3.3.4. (Z) Ethyl 4-(4-chlorobenzyl)amino-5-(2-ethoxycarbonyl
vinylthio)-1-phenyl-1H-pyrrole-3-carboxylate (22b)
Yield 6% (benzene or butanone), mp 64–65 ꢁC; IR
n
(cmꢀ1):
(ppm): 7.39 (s, 1H),
3396, 1704, 1683; 1H NMR (300 MHz, CDCl3)
d
Yield 44% (butanone), 10% (benzene), mp 100–101 ꢁC; IR
n
7.29–7.31 (m, 3H), 7.22–7.26 (m, 3H), 7.14–7.19 (m, 5H), 6.09 (br,
1H), 5.31 (d, J¼14.6 Hz, 1H), 4.59 (s, 2H), 4.22 (q, J¼7.1 Hz, 2H), 4.05
(q, J¼7.1 Hz, 2H), 1.26 (t, J¼7.1 Hz, 3H), 1.18 (t, J¼7.1 Hz, 3H); 13C
(cmꢀ1): 3382, 1697; 1H NMR (500 MHz, CDCl3)
d (ppm): 7.42 (s, 1H),
7.41–7.44 (m, 2H), 7.38 (t, J¼7.2 Hz, 1H), 7.23–7.32 (m, 6H), 6.64 (d,
J¼10.1 Hz, 1H), 5.60 (d, J¼10.1 Hz, 1H), 4.68 (s, 2H), 4.31 (q, J¼7.1 Hz,
R
N
R
N
R
N
S
CO2Et
CO2Et
R
N
Ar
S
CCO2Et
N
HC
N
Ar
N
R
21
NAr
N
Ar
N
R
S
N
R
N
R
S
CO2Et
25
26B
15
26A
electrocyclization
R
HC CCO2Et
R
N
R
N
R
N
CO2Et
CO2Et
CO2Et
CO2Et
N
N
Ar
N
Ar
N
Ar
N
Ar
RN
EtO2C
S
N
R
S
RN
N
R
S
S
H
27
28
30
31
CO2Et
H2O
H2O
CO2Et
CO2Et
R
N
R
N
CO2Et
RHN
S
CO2Et
RHN
N
Ar
N
Ar
S
N
Ar
N
Ar
N
R
S
N
R
S
EtO2C
22
23
24
CO2Et
29
Scheme 4. The proposed mechanism for the formation of pyrroles 22, 23 and pyrrolo[2,3-b][1,4]thiazines 24.

7366
Y. Cheng et al. / Tetrahedron 64 (2008) 7362–7368
2H), 4.17 (q, J¼7.1 Hz, 2H), 1.36 (t, J¼7.1 Hz, 3H), 1.28 (t, J¼7.1 Hz,
3H); 13C NMR (125 MHz, CDCl3)
(ppm): 166.2, 165.3, 153.0, 142.2,
138.7, 138.3, 132.6, 129.1, 129.0, 128.5, 128.0, 126.7, 113.2, 105.1,
104.8, 60.2, 59.8, 48.8, 14.5, 14.3; MS (EI): 125 (100), 215 (54), 261
(53), 313 (55), 333 (54), 451 (45), 484 (Mþ, 50%). Anal. Calcd for
7.12 (m, 4H), 7.06–7.08 (m, 1H), 6.93 (d, J¼8.0 Hz, 1H), 4.34 (s, 2H),
4.33 (q, J¼7.2 Hz, 2H), 4.10 (s, 2H), 3.84 (s, 2H), 1.22 (t, J¼7.1 Hz, 3H);
d
13C NMR (75 MHz, CDCl3)
d (ppm): 163.2, 155.5, 138.9, 138.0, 137.6,
132.6, 132.2, 131.8, 131.4, 130.4, 130.2, 129.8, 129.7, 128.9, 128.5,
127.0, 127.03, 124.5, 111.7, 110.9, 60.6, 56.7, 56.6, 55.9, 14.5; MS (EI):
159 (75), 161 (55), 227 (98), 273 (100), 617 (Mþ, 1.5%), 619 (Mþ2, 2).
Anal. Calcd for C29H23Cl4N3O2S: C, 56.23; H, 3.74; N, 6.78. Found: C,
56.48; H, 4.05; N, 6.63.
C
25H25ClN2O4S: C, 61.91; H, 5.20; N, 5.78. Found: C, 61.76; H, 5.30;
N, 5.71.
3.3.5. (E) Ethyl 4-(4-chlorobenzyl)amino-5-(2-ethoxycarbonyl-
vinylthio)-1-phenyl-1H-pyrrole-3-carboxylate (23b)
3.3.10. (Z) Ethyl 4-benzylamino-5-(2-ethoxycarbonylvinylthio)-1-
Yield 12% (butanone), 6% (benzene), mp 68–69 ꢁC; IR
n
(cmꢀ1):
(ppm): 7.49 (s, 1H), 7.41–
(4-methoxyphenyl)-1H-pyrrole-3-carboxylate (22d)
3373, 1701; 1H NMR (500 MHz, CDCl3)
d
Yield 48% (butanone), 14% (benzene), mp 94–95 ꢁC; IR
n
(cmꢀ1):
7.42 (m, 3H), 7.29 (s, 4H), 7.25 (d, J¼7.1 Hz, 2H), 7.21 (d, J¼14.6 Hz,
1H), 6.27 (br s, 1H), 5.35 (d, J¼14.6 Hz, 1H), 4.66 (s, 2H), 4.33 (q,
J¼7.0 Hz, 2H), 4.17 (q, J¼7.0 Hz, 2H), 1.37 (t, J¼7.0 Hz, 3H), 1.29 (t,
3359, 3333, 1688, 1570; 1H NMR (500 MHz, CDCl3)
d (ppm): 7.37 (d,
J¼6.9 Hz, 2H), 7.37 (s, 1H), 7.32 (t, J¼7.7 Hz, 2H), 7.24 (t, J¼7.3 Hz,
1H), 7.17 (d, J¼8.8 Hz, 2H), 6.92 (d, J¼8.8 Hz, 2H), 6.68 (d, J¼10.1 Hz,
1H), 6.10 (br, 1H), 5.59 (d, J¼10.1 Hz, 1H), 4.71 (s, 2H), 4.30 (q,
J¼7.1 Hz, 2H), 4.17 (q, J¼7.1 Hz, 2H), 3.85 (s, 3H), 1.34 (t, J¼7.1 Hz,
J¼7.0 Hz, 3H); 13C NMR (125 MHz, CDCl3)
d (ppm): 165.3, 165.0,
147.3, 144.1, 138.9, 138.2, 132.5, 129.7, 128.9, 128.6, 128.5, 128.3,
126.3, 116.1, 104.7, 95.6, 60.4, 59.8, 47.7, 14.5, 14.3; HRMS (TOF-EI):
484.1228 (Mþ1), C25H25ClN2O4S required 484.1224.
3H), 1.28 (t, J¼7.1 Hz, 3H); 13C NMR (125 MHz, CDCl3)
d (ppm):
166.2, 165.3, 159.2, 153.5, 142.4, 140.2, 131.4, 128.5, 128.4, 127.9,
127.6, 126.9, 114.2, 113.0, 104.7, 60.2, 59.6, 55.5, 49.6, 14.5, 14.3; MS
(MALDI-TOF): 480 (Mþ). Anal. Calcd for C26H28N2O5S: C, 64.98; H,
5.87; N, 5.83. Found: C, 64.61; H, 6.02; N, 5.80.
3.3.6. Ethyl 1-(4-chlorobenzyl)-3-(4-chlorobenzylimino)-5-phenyl-
1,2,3,5-tetrahydropyrrolo[2,3-b][1,4]thiazine-7-carboxylate (24b)
Yield 49% (benzene), mp 151–152 ꢁC; IR
n
(cmꢀ1): 1704, 1631,
1623; 1H NMR (500 MHz, C6D6)
d
(ppm): 7.60 (d, J¼8.1 Hz, 2H), 7.52
3.3.11. Ethyl 1-benzyl-3-(benzylimino)-5-(4-methoxyphenyl)-
(s, 1H), 7.24–7.26 (m, 3H), 7.15 (d, J¼8.2 Hz, 2H), 7.05–7.13 (m, 5H),
1,2,3,5-tetrahydropyrrolo[2,3-b][1,4]thiazine-7-carboxylate (24d)
4.46 (s, 2H), 4.35 (q, J¼7.1 Hz, 2H), 4.28 (s, 2H), 3.95 (s, 2H), 1.21 (t,
Yield 43% (benzene), mp 105–106 ꢁC; IR
n
(cmꢀ1): 1702, 1627,
J¼7.0 Hz, 3H); 13C NMR (125 MHz, C6D6)
d
(ppm): 162.7, 153.5,
1618; 1H NMR (500 MHz, CDCl3)
d (ppm): 7.47 (s, 1H), 7.45 (d,
138.0, 137.6, 136.8, 133.4, 133.1, 132.8, 131.2, 129.5, 129.1, 128.6,
128.5, 126.9, 124.3, 111.7, 111.6, 59.6, 56.73, 56.68, 56.1, 14.4; MS (EI):
125 (100), 549 (Mþ, 1.5%). Anal. Calcd for C29H25Cl2N3O2S: C, 63.27;
H, 4.58; N, 7.63. Found: C, 63.45; H, 4.96; N, 7.58.
J¼7.7 Hz, 1H), 7.25–7.39 (m, 10H), 7.02 (d, J¼8.8 Hz, 2H), 4.41 (s, 2H),
4.37 (q, J¼7.1 Hz, 2H), 4.32 (s, 2H), 3.96 (br s, 2H), 3.89 (s, 3H), 1.37
(t, J¼7.1 Hz, 3H); 13C NMR (125 MHz, CDCl3)
d (ppm): 163.4, 159.5,
154.7,138.9,137.6,131.8,130.8,129.8,128.5,128.2,127.8,127.3,127.0,
126.9, 126.1, 114.7, 112.7, 110.6, 59.9, 57.7, 57.5, 56.6, 55.6, 14.6; MS
(MALDI-TOF): 510 (Mꢀ1). Anal. Calcd for C30H29N3O3S: C, 70.43; H,
5.71; N, 8.21. Found: C, 70.15; H, 6.01; N, 8.00.
3.3.7. (Z) Ethyl 4-(3,4-dichlorobenzyl)amino-5-(2-ethoxycarbonyl-
vinylthio)-1-phenyl-1H-pyrrole-3-carboxylate (22c)
Yield 53% (butanone), 10% (benzene), mp 123–125 ꢁC; IR
n
(cmꢀ1): 3378, 1697, 1684; 1H NMR (500 MHz, CDCl3)
d
(ppm): 7.41–
3.3.12. (Z) Ethyl 4-benzylamino-5-(2-ethoxycarbonylvinylthio)-1-
7.45 (m, 3H), 7.38 (d, J¼5.9 Hz, 1H), 7.35 (d, J¼8.2 Hz, 1H), 7.26 (d,
J¼7.5 Hz, 2H), 7.20 (dd, J¼8.3, 1.6 Hz, 1H), 6.56 (d, J¼10.0 Hz, 1H),
5.56 (d, J¼10.0 Hz, 1H), 4.67 (s, 3H), 4.32 (q, J¼7.1 Hz, 2H), 4.16 (q,
J¼7.1 Hz, 2H), 1.36 (t, J¼7.1 Hz, 3H), 1.28 (t, J¼7.1 Hz, 3H); 13C NMR
(4-chlorophenyl)-1H-pyrrole-3-carboxylate (22e)
Yield 52% (butanone), 11% (benzene), mp 79–80 ꢁC; IR
n
(cmꢀ1):
d (ppm): 7.40 (d,
3399, 1701, 1679; 1H NMR (500 MHz, CDCl3)
J¼6.8 Hz, 2H), 7.39 (s, 1H), 7.37 (d, J¼7.5 Hz, 2H), 7.32 (t, J¼7.5 Hz,
2H), 7.25 (d, J¼7.0 Hz, 1H), 7.21 (d, J¼8.5 Hz, 2H), 6.65 (d, J¼10.0 Hz,
1H), 5.61 (d, J¼10.0 Hz, 1H), 4.71 (s, 2H), 4.31 (q, J¼7.1 Hz, 2H), 4.18
(q, J¼7.1 Hz, 2H), 1.34 (t, J¼7.1 Hz, 3H), 1.29 (t, J¼7.1 Hz, 3H); 13C
(125 MHz, CDCl3)
d (ppm): 166.1, 165.4, 152.8, 142.2, 141.0, 138.3,
132.3, 130.5, 130.2, 129.4, 129.1, 128.5, 128.3, 128.1, 126.74, 126.68,
113.2, 105.0, 60.2, 59.8, 48.2, 14.5, 14.3; MS (EI): 104 (70), 159 (78),
215 (95), 261 (100), 313 (80), 518 (Mþ, 33%). Anal. Calcd for
C25H24Cl2N2O4S: C, 57.81; H, 4.66; N, 5.39. Found: C, 58.32; H, 4.76;
N, 5.24.
NMR (125 MHz, CDCl3)
d (ppm): 166.2, 165.1, 153.0, 143.1, 140.1,
137.0, 133.8, 129.3, 128.4, 128.3, 127.8, 127.6, 126.9, 113.4, 105.4,
104.1, 60.2, 59.8, 49.4,14.5,14.3; MS (MALDI-TOF): 485 (Mþ1). Anal.
Calcd for C25H25ClN2O4S: C, 61.91; H, 5.20; N, 5.78. Found: C, 61.86;
H, 5.75; N, 5.47.
3.3.8. (E) Ethyl 4-(3,4-dichlorobenzyl)amino-5-(2-ethoxycarbonyl-
vinylthio)-1-phenyl-1H-pyrrole-3-carboxylate (23c)
Yield 15% (butanone), 7% (benzene), mp 77–79 ꢁC; IR
n
(cmꢀ1):
(ppm): 7.50 (s, 1H),
3.3.13. Ethyl 1-benzyl-3-(benzylimino)-5-(4-chlorophenyl)-1,2,3,5-
3381, 1701, 1679; 1H NMR (500 MHz, CDCl3)
d
tetrahydropyrrolo[2,3-b][1,4]thiazine-7-carboxylate (24e)
7.45 (d, J¼1.5 Hz,1H), 7.41–7.42 (m, 3H), 7.38 (d, J¼8.2 Hz,1H), 7.24–
7.26 (m, 2H), 7.20 (dd, J¼8.2, 1.0 Hz, 1H), 7.16 (d, J¼14.6 Hz, 1H), 5.31
(d, J¼14.6 Hz, 1H), 4.65 (s, 2H), 4.34 (q, J¼7.1 Hz, 2H), 4.15 (q,
J¼7.1 Hz, 2H), 1.38 (t, J¼7.1 Hz, 3H), 1.28 (t, J¼7.1 Hz, 3H); 13C NMR
Yield 44% (benzene), mp 133–134 ꢁC; IR (cmꢀ1): 1707, 1636; 1H
n
NMR (500 MHz, CDCl3)
d
(ppm): 7.50 (d, J¼6.6 Hz, 2H), 7.49 (s, 1H),
7.45 (d, J¼7.1 Hz, 2H), 7.36–7.39 (m, 6H), 7.27–7.31 (m, 4H), 4.42 (s,
2H), 4.37 (q, J¼7.1 Hz, 2H), 4.32 (s, 2H), 3.95 (s, 2H), 1.37 (t, J¼7.1 Hz,
(125 MHz, CDCl3)
d
(ppm): 165.3, 164.9, 146.9, 142.8, 140.5, 138.0,
3H); 13C NMR (125 MHz, CDCl3)
d (ppm): 163.2, 154.0, 138.7, 137.5,
132.5, 130.7, 130.4, 129.8, 129.3, 128.9, 128.5, 126.6, 126.3, 116.2,
104.9, 60.5, 60.0, 47.5, 14.5, 14.3; HRMS (TOF-EI): 518.0840,
136.3, 134.1, 132.6, 129.9, 129.7, 128.5, 128.2, 127.8, 127.4, 127.0,
126.6, 125.7, 112.2, 111.5, 60.0, 57.6, 56.4, 14.6; MS (MALDI-TOF): 515
(Mþ). Anal. Calcd for C29H26ClN3O2S: C, 67.49; H, 5.08; N, 8.14.
Found: C, 67.36; H, 5.23; N, 8.05.
C
25H24Cl2N2O4S required 518.0834.
3.3.9. Ethyl 1-(3,4-dichlorobenzyl)-3-(3,4-dichlorobenzylimino)-5-
phenyl-1,2,3,5-tetrahydropyrrolo[2,3-b][1,4]thiazine-7-
carboxylate (24c)
3.3.14. (Z) Ethyl 4-(4-chlorobenzyl)amino-5-(2-ethoxycarbonyl-
vinylthio)-1-(4-chlorophenyl)-1H-pyrrole-3-carboxylate (22f)
Yield 37% (benzene), mp 173–174 ꢁC; IR
NMR (500 MHz, C6D6)
7.25–7.27 (m, 1H), 7.19 (d, J¼8.2 Hz, 1H), 7.15 (d, J¼8.2 Hz, 1H), 7.11–
n
(cmꢀ1): 1698, 1635; 1H
Yield 53% (butanone),10% (benzene), mp 116–117 ꢁC; IR
n
(cmꢀ1):
(ppm): 7.40 (d,
J¼8.7 Hz, 2H), 7.39 (s, 1H), 7.26–7.31 (m, 4H), 7.20 (d, J¼9.0 Hz, 2H),
d
(ppm): 7.88 (s, 1H), 7.50 (s, 1H), 7.42 (s, 1H),
3390, 1699, 1678; 1H NMR (500 MHz, CDCl3)
d

Y. Cheng et al. / Tetrahedron 64 (2008) 7362–7368
7367
6.61 (dd, J¼10.0, 3.2 Hz,1H), 5.62 (dd, J¼10.0,1.5 Hz,1H), 4.68 (s, 2H),
4.31 (q, J¼7.1 Hz, 2H), 4.18 (q, J¼7.1 Hz, 2H),1.35 (t, J¼7.1 Hz, 3H),1.30
7.29 (dd, J¼6.8, 2.0 Hz, 2H), 6.77 (d, J¼10.0 Hz, 1H), 5.62 (d, J¼
10.0 Hz, 1H), 4.21 (q, J¼7.1 Hz, 2H), 4.08 (q, J¼7.1 Hz, 2H), 3.39 (t,
J¼6.9 Hz, 2H), 1.52 (qt, J¼7.6 Hz, 2H), 1.30–1.40 (m, 2H), 1.26 (t,
J¼7.1 Hz, 3H), 1.18 (t, J¼7.1 Hz, 3H), 0.85 (t, J¼7.3 Hz, 3H); 13C NMR
(t, J¼7.1 Hz, 3H); 13C NMR (125 MHz, CDCl3)
d (ppm): 166.1, 165.2,
152.7,142.7,138.8,136.8,133.9,132.5,129.3,128.9,128.5,128.3,127.8,
113.6, 105.3, 104.2, 60.3, 59.8, 48.6, 14.5, 14.3; MS (MALDI-TOF): 519
(Mþ1), 541 (MþNaþ). Anal. Calcd for C25H24Cl2N2O4S: C, 57.81; H,
4.66; N, 5.39. Found: C, 57.67; H, 4.79; N, 5.39.
(125 MHz, CDCl3)
d (ppm): 166.3, 165.4, 154.2, 143.9, 138.5, 129.1,
128.4, 127.9, 126.6, 113.1, 104.7, 103.5, 60.2, 59.6, 45.6, 32.4, 20.1,
14.5, 14.3, 14.0; HRMS (TOF-EI): 416.1775, C22H28N2O4S required
416.1770.
3.3.15. Ethyl 1-(4-chlorobenzyl)-3-(4-chlorobenzylimino)-5-
(4-chlorophenyl)-1,2,3,5-tetrahydropyrrolo[2,3-b][1,4]thiazine-
7-carboxylate (24f)
3.3.20. (E) Ethyl 4-(4-chlorobenzyl)amino-5-(2-ethoxycarbonyl-
vinylthio)-1-(p-tolyl)-1H-pyrrole-3-carboxylate (22j)
Yield 49% (benzene), mp 149–150 ꢁC; IR
NMR (500 MHz, CDCl3)
n
(cmꢀ1): 1711, 1637; 1H
Yield 10% (benzene), mp 103–104 ꢁC; IR (cmꢀ1): 3359, 1697,
n
d
(ppm): 7.51 (d, J¼8.7 Hz, 2H), 7.49 (s, 1H),
1683; 1H NMR (500 MHz, CDCl3)
d (ppm): 7.38 (s, 1H), 7.30 (d,
7.34–7.38 (m, 6H), 7.25–7.28 (m, 4H), 4.36 (q, J¼7.4 Hz, 2H), 4.36 (s,
J¼8.5 Hz, 2H), 7.26 (d, J¼8.5 Hz, 2H), 7.21 (d, J¼8.1 Hz, 2H), 7.13
(d, J¼8.2 Hz, 2H), 6.64 (d, J¼10.0 Hz, 1H), 6.11 (br, 1H), 5.59 (d,
J¼10.0 Hz, 1H), 4.67 (s, 3H), 4.30 (q, J¼7.1 Hz, 2H), 4.17 (q,
J¼7.1 Hz, 2H), 2.39 (s, 3H), 1.34 (t, J¼7.1 Hz, 3H), 1.29 (t, J¼7.1 Hz,
2H), 4.27 (s, 2H), 3.91 (br s, 2H), 1.37 (t, J¼7.1 Hz, 3H); 13C NMR
(125 MHz, CDCl3)
d (ppm): 163.1, 154.3, 137.1, 136.2, 136.1, 134.3,
133.2,132.9,132.4,131.0,129.9,129.1,128.7,128.4,126.7,125.8,111.9,
111.3, 60.0, 56.9, 56.8, 56.4,14.5; MS (MALDI-TOF): 582 (Mꢀ1). Anal.
Calcd for C29H24Cl3N3O2S: C, 59.55; H, 4.14; N, 7.18. Found: C, 59.48;
H, 4.41; N, 6.82.
3H); 13C NMR (125 MHz, CDCl3)
d (ppm): 166.1, 165.3, 153.1,
142.6, 139.0, 138.0, 135.9, 132.5, 129.6, 128.9, 128.5, 128.4, 126.4,
113.2, 104.9, 104.6, 60.1, 59.6, 48.8, 21.0, 14.4, 14.3; MS (MALDI-
TOF): 499 (Mþ1), 521 (MþNaþ). Anal. Calcd for C26H27
ClN2O4S: C, 62.58; H, 5.45; N, 5.61. Found: C, 62.31; H, 5.27; N,
5.39.
3.3.16. (Z) Ethyl 4-(3,4-dichlorobenzyl)amino-5-(2-ethoxycar-
bonylvinylthio)-1-(p-tolyl)-1H-pyrrole-4-carboxylate (22g)
Yield 51% (butanone), 8% (benzene), mp 111–112 ꢁC; IR
n
(cmꢀ1):
(ppm): 7.45 (s, 1H),
3339, 1697, 1685; 1H NMR (500 MHz, CDCl3)
d
3.3.21. Ethyl 1-(4-chlorobenzyl)-3-(4-chlorobenzylimino)-5-
(p-tolyl)-1,2,3,5-tetrahydropyrrolo[2,3-b][1,4]thiazine-7-
carboxylate (24j)
7.39 (s, 1H), 7.35 (d, J¼8.3 Hz, 1H), 7.19–7.22 (m, 3H), 7.12 (d,
J¼7.8 Hz, 2H), 6.56 (d, J¼10.0 Hz, 1H), 6.20 (br, 1H), 5.56 (d,
J¼10.0 Hz, 1H), 4.66 (s, 2H), 4.31 (q, J¼7.1 Hz, 2H), 4.16 (q, J¼7.0 Hz,
2H), 2.39 (s, 3H), 1.36 (t, J¼7.1 Hz, 3H), 1.28 (t, J¼7.0 Hz, 3H); 13C
Yield 42% (benzene), mp 159–160 ꢁC; IR
NMR (500 MHz, CDCl3)
n
(cmꢀ1): 1708, 1614; 1H
(ppm): 7.49 (s, 1H), 7.37 (d, J¼8.2 Hz, 2H),
d
NMR (125 MHz, CDCl3)
d
(ppm): 166.1, 165.4, 153.0, 142.0, 141.0,
7.34 (d, J¼8.4 Hz, 2H), 7.31 (d, J¼6.0 Hz, 4H), 7.27 (d, J¼9.4 Hz, 2H),
7.25 (d, J¼8.7 Hz, 2H), 4.36 (q, J¼7.1 Hz, 2H), 4.35 (s, 2H), 4.27 (s,
2H), 3.92 (br s, 2H), 2.45 (s, 3H), 1.37 (t, J¼7.1 Hz, 3H); 13C NMR
138.1, 135.8, 132.3, 130.5, 130.2, 129.7, 129.4, 128.5, 126.7, 126.5,
113.2, 104.8, 60.2, 59.7, 48.2, 21.1, 14.5, 14.3; MS (MALDI-TOF): 531
(Mꢀ1), 555 (MþNaþ). Anal. Calcd for C26H26Cl2N2O4S: C, 58.54; H,
4.91; N, 5.25. Found: C, 58.37; H, 5.25; N, 5.57.
(125 MHz, CDCl3)
d (ppm): 163.3, 154.9, 138.5, 137.3, 136.2, 135.3,
133.2,132.8,131.9,131.0,130.2,129.1,128.6,128.3,126.9,124.4,112.1,
110.7, 59.9, 56.9, 56.7, 56.6, 21.1, 14.6, 14.2; MS (MALDI-TOF): 562
(Mꢀ1). Anal. Calcd for C30H27Cl2N3O2S: C, 63.83; H, 4.82; N, 7.44.
Found: C, 63.49; H, 5.05; N, 7.33.
3.3.17. Ethyl 1-(3,4-dichlorobenzyl)-3-(3,4-dichlorobenzylimino)-
5-(p-tolyl)-1,2,3,5-tetrahydropyrrolo[2,3-b][1,4]thiazine-7-
carboxylate (24g)
Yield 46% (benzene), mp 147–148 ꢁC; IR
NMR (500 MHz, CDCl3)
n
(cmꢀ1): 1707, 1632; 1H
(ppm): 7.53 (s, 1H), 7.50 (s, 1H), 7.47 (s,
3.3.22. (Z) Ethyl 4-(2,4-dichlorobenzyl)amino-5-(2-ethoxycar-
bonylvinylthio)-1-(4-methoxyphenyl)-1H-pyrrole-3-
carboxylate (22k)
d
1H), 7.44 (d, J¼8.2 Hz, 1H), 7.26–7.37 (m, 6H), 7.18 (d, J¼8.2 Hz, 1H),
4.36 (q, J¼7.1 Hz, 2H), 4.32 (s, 2H), 4.27 (s, 2H), 3.92 (s, 2H), 2.46 (s,
Yield 12% (benzene), mp 99–100 ꢁC; IR
n
(cmꢀ1): 3394, 1707,
d (ppm): 7.45 (s, 1H), 7.37 (s, 1H),
3H), 1.37 (t, J¼7.1 Hz, 3H); 13C NMR (125 MHz, CDCl3)
d
(ppm):
1676; 1H NMR (500 MHz, CDCl3)
161.3, 153.5, 137.1, 136.7, 136.1, 133.2, 130.6, 130.3, 129.6, 129.5, 129.1,
128.5, 128.4, 128.2, 127.7, 127.0, 125.1, 122.5, 110.2, 108.7, 58.1, 54.9,
54.7, 54.0, 19.2, 12.6; MS (MALDI-TOF): 630 (Mꢀ1). Anal. Calcd for
7.35 (d, J¼8.4 Hz, 1H), 7.21 (d, J¼8.1 Hz, 1H), 7.16 (d, J¼8.3 Hz, 2H),
6.92 (d, J¼8.7 Hz, 2H), 6.56 (d, J¼9.9 Hz, 1H), 5.56 (d, J¼9.9 Hz, 1H),
4.67 (s, 2H), 4.31 (q, J¼7.0 Hz, 2H), 4.17 (q, J¼7.1 Hz, 2H), 3.85 (s, 3H),
1.36 (t, J¼7.1 Hz, 3H), 1.29 (t, J¼7.0 Hz, 3H); 13C NMR (125 MHz,
C
30H25Cl4N3O2S: C, 56.89; H, 3.98; N, 6.63. Found: C, 56.63; H, 4.24;
N, 6.28.
CDCl3) d (ppm): 166.1, 165.4, 159.3, 153.0, 141.9, 141.1, 132.3, 131.3,
130.5,130.2,129.4,128.6, 128.0,126.7, 114.2, 113.2,104.9,104.6, 60.2,
59.7, 55.5, 48.2, 14.5, 14.3; MS (MALDI-TOF): 548 (Mþ), 571
(MþNaþ). Anal. Calcd for C26H26Cl2N2O5S: C, 56.83; H, 4.77; N, 5.10.
Found: C, 56.89; H, 4.84; N, 5.20.
3.3.18. (Z) Ethyl 4-(iso-propyl)amino-5-(2-ethoxycarbonyl-
vinylthio)-1-phenyl-1H-pyrrole-3-carboxylate (22h)
Yield 48% (butanone), mp 107–108 ꢁC; IR
n
(cmꢀ1): 3370, 1688;
1H NMR (500 MHz, CDCl3)
d
(ppm): 7.44 (t, J¼7.3 Hz, 2H), 7.43 (s,
1H), 7.38 (t, J¼7.4 Hz, 1H), 7.30 (d, J¼7.6 Hz, 2H), 6.84 (d, J¼10.0 Hz,
1H), 5.73 (d, J¼10.1 Hz, 1H), 5.32 (br, 1H), 4.30 (q, J¼7.1 Hz, 2H), 4.18
(q, J¼7.1 Hz, 2H), 4.16–4.26 (m, 1H), 1.36 (t, J¼7.1 Hz, 3H), 1.28 (t,
J¼7.1 Hz, 3H), 1.21 (d, J¼6.2 Hz, 6H); 13C NMR (125 MHz, CDCl3)
3.3.23. (E) Ethyl 4-(2,4-dichlorobenzyl)amino-5-(2-ethoxycar-
bonylvinylthio)-1-(4-methoxyphenyl)-1H-pyrrole-3-
carboxylate (23k)
Yield 8% (benzene), mp 79–80 ꢁC; IR
n
(cmꢀ1): 3390, 1707, 1681;
d
(ppm): 166.3, 165.3, 153.4, 142.5, 138.6, 129.1, 128.5, 127.9, 126.6,
1H NMR (500 MHz, CDCl3)
d
(ppm): 7.45 (s, 2H), 7.37 (d, J¼8.2 Hz,
113.5,105.5,104.2, 60.2, 59.6, 45.4, 23.6,14.5,14.3; MS (EI): 215 (50),
341 (50), 369 (45), 402 (Mþ, 100%). Anal. Calcd for C21H26N2O4S: C,
62.66; H, 6.51; N, 6.96. Found: C, 62.62; H, 6.84; N, 6.95.
1H), 7.15–7.20 (m, 4H), 6.91 (d, J¼8.9 Hz, 2H), 5.30 (d, J¼14.6 Hz,
1H), 4.64 (s, 2H), 4.34 (q, J¼7.1 Hz, 2H), 4.15 (q, J¼7.1 Hz, 2H), 3.85 (s,
3H), 1.38 (t, J¼7.1 Hz, 3H), 1.29 (t, J¼7.1 Hz, 3H); 13C NMR (125 MHz,
CDCl3)
d (ppm): 165.3, 164.9, 159.5, 147.1, 142.8, 140.7, 132.4, 130.9,
3.3.19. (Z) Ethyl 4-(n-butyl)amino-5-(2-ethoxycarbonylvinylthio)-
130.7, 130.4, 129.9, 129.3, 127.6, 126.6, 116.2, 114.0, 104.6, 60.4, 59.9,
55.5, 47.5, 14.5, 14.3; MS (MALDI-TOF): 549 (Mþ1), 571 (MþNaþ).
Anal. Calcd for C26H26Cl2N2O5S: C, 56.83; H, 4.77; N, 5.10. Found: C,
56.76; H, 4.66; N, 4.80.
1-phenyl-1H-pyrrole-3-carboxylate (22i)
Yield 49% (butanone), mp 40–42 ꢁC; IR (cmꢀ1): 3375, 1698; 1H
n
NMR (300 MHz, CDCl3)
d (ppm): 7.28–7.37 (m, 3H), 7.31 (s, 1H),

7368
Y. Cheng et al. / Tetrahedron 64 (2008) 7362–7368
3. Regitz, M.; Hocker, J.; Scho¨ssler, W.; Weber, B.; Liedhegener, A. Liebigs Ann.
Chem. 1971, 748, 1.
3.3.24. Ethyl 1-(3,4-dichlorobenzyl)-3-(3,4-dichlorobenzylimino)-
5-(4-methoxyphenyl)-1,2,3,5-tetrahydropyrrolo[2,3-b][1,4]thiazine-
7-carboxylate (24k)
4. Schoenherr, H. J.; Wanzlick, H. W. Chem. Ber. 1970, 103, 1037.
5. Enders, D.; Breuer, K.; Runsink, J.; Teles, J. H. Liebigs Ann. 1996, 2019.
6. Takamizawa, A.; Hirai, K.; Matsumoto, S. Tetrahedron Lett. 1968, 4027.
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8. (a) Liu, M.-F.; Wang, B.; Cheng, Y. Chem. Commun. 2006, 1215; (b) Cheng, Y.; Liu,
M.-F.; Fang, D.-C.; Lei, X.-M. Chem.dEur. J. 2007, 13, 4282; (c) Li, J.-Q.; Liao, R.-Z.;
Ding, W.-J.; Cheng, Y. J. Org. Chem. 2007, 72, 6266; (d) Wang, B.; Li, J.-Q.; Cheng,
Y. Tetrahedron Lett. 2008, 49, 485.
Yield 37% (benzene), mp 144–145 ꢁC; IR
NMR (500 MHz, CDCl3)
n
(cmꢀ1): 1702, 1633; 1H
d
(ppm): 7.51 (s, 1H), 7.47 (d, J¼5.0 Hz, 2H),
7.44 (d, J¼8.2 Hz, 1H), 7.26–7.36 (m, 4H), 7.18 (d, J¼8.0 Hz, 1H), 7.03
(d, J¼8.0 Hz, 2H), 4.36 (q, J¼7.1 Hz, 2H), 4.31 (s, 2H), 4.28 (s, 2H),
3.97 (s, 2H), 3.90 (s, 3H), 1.37 (t, J¼7.1 Hz, 3H); 13C NMR (125 MHz,
9. (a) Zhu, Q.; Liu, M.-F.; Wang, B.; Cheng, Y. Org. Biomol. Chem. 2007, 5, 1282; (b)
Ma, Y.-G.; Cheng, Y. Chem. Commun. 2007, 5087.
CDCl3)
d (ppm): 163.3, 159.6, 155.5, 139.0, 138.0, 132.6, 132.2, 131.4,
131.2, 131.0, 130.5, 130.4, 130.1, 129.7, 129.0, 127.1, 127.0, 126.1, 114.8,
112.5, 110.5, 60.0, 56.8, 56.6, 55.9, 55.6, 14.6; HRMS (TOF-EI):
647.0367, C30H25Cl4N3O3S required 647.0371.
10. (a) Aiello, A.; D’Esposito, M.; Fattorusso, E.; Menna, M.; Mueller, W. E. G.; Per-
ovic-Ottstadt, S.; Tsuruta, H.; Gulder, T. A. M.; Bringmann, G. Tetrahedron 2005,
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Soest, R. W. M. J. Nat. Prod. 2001, 64, 1576; (c) El Sayed, K. A.; Hamann, M. T.;
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Costi, R.; Artico, M.; Ragno, R.; Massa, S.; La Colla, M.; Loddo, R.; La Colla, P.;
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Acknowledgements
This work was supported by the National Natural Science
Foundation of China for Distinguished Young Scholars (No.
20525207) and National Natural Science Foundation of China (No.
20672013).
12. (a) Diana, P.; Passannanti, A.; Barraja, P.; Lauria, A.; Cirrincione, G. Heterocycles
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References and notes
13. CCDC 680483 and 680482 [22a and 24a] contain the supplementary crystal-
lographic data for this paper. These data can be obtained free of charge from
The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_
request/cif.
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