N-vinyl- and C-vinylpyrroles from azafulvenium methides. Flash vacuum pyrolysis route to 5-oxo-5H-pyrrolizines and 1-azabenzo[f]azulenes

Article abstract of DOI:10.1021/jo050480i

1-Azafulvenium methides, generated from pyrrolo[1,2-c]thiazole-2,2- dioxides' thermal extrusion of sulfur dioxide, led to the synthesis of functionalized pyrroles. The intramolecular trapping of these transient 8π 1,7-dipoles in pericyclic reactions, name

Full text of DOI:10.1021/jo050480i

N-Vinyl- and C-Vinylpyrroles from Azafulvenium Methides.
Flash Vacuum Pyrolysis Route to 5-Oxo-5H-pyrrolizines and
1-Azabenzo[f]azulenes
Teresa M. V. D. Pinho e Melo,*,† Maria I. L. Soares,† Anto´nio M. d’A. Rocha Gonsalves,†
Jose´ A. Paixa˜o,‡ Ana Matos Beja,‡ and Manuela Ramos Silva‡
Departamento de Quı´mica, Universidade de Coimbra, 3004-535 Coimbra, Portugal, and Departamento de
Fı´sica, Universidade de Coimbra, 3004-516 Coimbra, Portugal
tmelo@ci.uc.pt
Received March 10, 2005
1-Azafulvenium methides, generated from pyrrolo[1,2-c]thiazole-2,2-dioxides’ thermal extrusion of
sulfur dioxide, led to the synthesis of functionalized pyrroles. The intramolecular trapping of these
transient 8π 1,7-dipoles in pericyclic reactions, namely sigmatropic [1,8]H shifts and 1,7-
electrocyclization, allowed the synthesis of N-vinylpyrroles and C-vinylpyrroles which, under flash
vacuum pyrolysis conditions, are converted into 5-oxo-5H-pyrrolizines or 4-oxo-1,4-dihydro-1-aza-
benzo[f]azulenes, respectively. These heterocycles can also be obtained directly from FVP of pyrrolo-
[1,2-c]thiazole 2,2-dioxides. The synthesis and X-ray structure of a new 6-oxocyclopenta[b]pyrrole
derivative is also reported.
Introduction
The generation of 1-azafulvenium methides (1a-d) by
the thermal extrusion of sulfur dioxide from pyrrolo[1,2-
c]thiazole-2,2-dioxides under flash vacuum pyrolysis
(FVP) conditions has been reported.1 These extended
dipolar systems 1a-c undergo sigmatropic [1,8]H shifts
giving vinylpyrroles, and the acyl derivatives 1d electro-
cyclize to give pyrrolo[1,2-c][1,3]oxazines.
In relation with our ongoing research,2 we became
interested in exploring the generation of azafulvenium
methides in order to get further knowledge on the
reactivity of these transient 8π 1,7-dipoles. In a prelimi-
nary communication, we have shown that 1-azafulve-
nium methides (1), generated by the thermal extrusion
of sulfur dioxide from pyrrolo[1,2-c]thiazole-2,2-dioxides
(2a, 2b, and 2j), are valuable intermediates for the
synthesis of heterocylic compounds (Scheme 1).3 Sealed
tube reaction conditions allow the synthesis of N- (3a)
(2) (a) Pinho e Melo, T. M. V. D.; Barbosa, D. M.; Ramos, P. J. R. S.;
Rocha Gonsalves, A. M. d’A.; Gilchrist, T. L.; Beja, A. M.; Paixa˜o, J.
A.; Silva, M. R.; Alte da Veiga, L. J. Chem. Soc., Perkin Trans. 1 1999,
1219-1223. (b) Pinho e Melo, T. M. V. D.; Soares, M. I. L.; Barbosa,
D. M.; Rocha Gonsalves, A. M. d’A.; Paixa˜o, J. A.; Beja, A. M.; Silva,
M. R.; Alte da Veiga, L. Tetrahedron 2000, 56, 3419-3424. (c) Pinho
e Melo, T. M. V. D.; Soares, M. I. L.; Rocha Gonsalves, A. M. d’A.;
Paixa˜o, J. A.; Beja, A. M.; Silva, M. R.; Alte da Veiga, L.; Costa Pessoa,
J. J. Org. Chem. 2002, 67, 4045-4054. (d) Pinho e Melo, T. M. V. D.;
Gomes, C. S. B.; Rocha Gonsalves, A. M. d’A.; Paixa˜o, J. A.; Beja, A.
M.; Ramos Silva, M.; Alte da Veiga, L. Tetrahedron 2002, 58, 5093-
5102.
† Departamento de Qu´ımica, Universidade de Coimbra.
‡ Departamento de F´ısica, Universidade de Coimbra.
(1) (a) Sutcliffe, O. B.; Storr, R. C.; Gilchrist, T. L.; Rafferty, P.; Crew,
A. P. A. Chem. Commun. 2000, 675-676. (b) Sutcliffe, O. B.; Storr, R.
C.; Gilchrist, T. L.; Rafferty, P. J. Chem. Soc., Perkin Trans. 1 2001,
1795-1806.
(3) Pinho e Melo, T. M. V. D.; Soares, M. I. L.; Rocha Gonsalves, A.
M. d’A.; McNab, H. Tetrahedron Lett. 2004, 45, 3889-3893.
10.1021/jo050480i CCC: $30.25 © 2005 American Chemical Society
Published on Web 07/19/2005
J. Org. Chem. 2005, 70, 6629-6638
6629

Pinho e Melo et al.
SCHEME 1
SCHEME 2
and C-vinylpyrroles (4) whereas FVP conditions lead to
heterocycles where another ring system is annulated to
pyrrole, namely 1,3-dimethyl-5-oxo-5H-pyrrolizine-2-car-
boxylate (5a) and 2-methyl-4-oxo-1,4-dihydro-1-azabenzo-
[f]azulene-3-carboxylate (6). It was demonstrated that N-
(3a) and C-vinylpyrroles (4) were intermediates in the
formation of 1,3-dimethyl-5-oxo-5H-pyrrolizine-2-carbox-
ylate (5a) and 2-methyl-4-oxo-1,4-dihydro-1-azabenzo[f]-
azulene-3-carboxylate (6), respectively, starting from the
pyrrolo[1,2-c]thiazole 2,2-dioxides. Thus, the correspond-
ing pyrrolo-annulated heterocycles were obtained by
carrying out the FVP of N-vinylpyrrole 3a and the FVP
of styryl-1H-pyrroles 4.
Results and Discussion
The 5-methyl-1H-pyrrolo[1,2-c]thiazole-2,2-dioxides
2a-h were prepared from L-cysteine as outlined in
Scheme 2. Heating a solution of the thiazolidine (7a-7h)
in acetic anhydride in the presence of dimethyl acetyl-
enedicarboxylate, the corresponding 5-methylpyrrolo[1,2-
c]thiazoles (8a-c and 8e-h) were obtained in good yield
(48-94%). The 3-ethyl-5-methyl-1H-pyrrolo[1,2-c]thiazole
8d could only be obtained in low yield (9%). An attempt
was made to improve the synthesis of compound 8d. The
acylation of thiazolidine 7d was carried out with acetic
anhydride to give the N-acyl derivative in 52% yield.
When this N-acetyl-2-ethylthiazolidine was heated in
acetic anhydride in the presence of dimethyl acetylene-
dicarboxylate, pyrrolo[1,2-c]thiazole 8d was again ob-
tained in low yield (15%). Oxidation of the heterocycles
8a-h with m-CPBA gave sulfones 2a-h with yields
ranging from 33% to 94%. In the oxidation of 8f, the
In this paper, we describe full details of an extensive
study on the generation and reactivity of azafulvenium
methides as well as the study of the thermolysis of
N-vinyl- and C-vinylpyrroles.
6630 J. Org. Chem., Vol. 70, No. 17, 2005

N-Vinyl- and C-Vinylpyrroles from Azafulvenium Methides
SCHEME 3
corresponding sulfoxide was also obtained in 8% yield.
The synthesis of the pyrrolo[1,2-c]thiazole 2,2-dioxides
bearing a phenyl at C-5 (2i-j) required, as the first step,
the N-acylation of the starting thiazolidine with benzoyl
chloride following a general procedure previously report-
ed.2d The cyclodehydration of the N-benzoylthiazolidines
led to the generation of 5-phenyl-5H,7H-thiazolo[3,4-c]-
oxazol-4-ium-1-olates which participate in the 1,3-dipolar
cycloaddition with dimethyl acetylenedicarboxylate to
give pyrrolo[1,2-c]thiazoles 8i and 8j, respectively. Sul-
fones 2i and 2j are obtained by oxidation with m-CPBA.
Scheme 2 shows also the route used to prepare the
pyrrolo[1,2-c]thiazole 2,2-dioxide derivatives unsubsti-
tuted at C-5. Formylation of thiazolidines 7a and 7b was
carried out by reaction with formic acid and acetic
anhydride following a known procedure.4 Treatment of
the N-formylthiazolidines (10a and 10b) with triethyl-
amine and tosyl chloride in the presence of dimethyl
acetylenedicarboxylate afforded the pyrrolo[1,2-c]thiaz-
oles 8k and 8l.5 The oxidation of 8k with m-CPBA leads
to the sulfone 2k in low yield (17%) together with the
formation of the corresponding sulfoxide in 11% yield.
However, when hydrogen peroxide was used as the
oxidant, sulfone 2k was obtained in 72% yield. The
reaction of 8l with m-CPBA gave sulfone 2l as the major
product (53%) with the formation of the sulfoxide in 13%
yield.
As a first objective we decided to look more carefully
into the generation of azafulvenium methide 1a (Scheme
3). It has been reported that on FVP (700 °C/1.3 × 10-3
mbar) sulfone 2a leads to vinylpyrrole 3a via an allowed,
suprafacial [1,8]H shift in the 8π 1,7-dipolar system 1a.1
We found that the same vinylpyrrole (3a) could be
obtained in 61% yield carrying out the reaction in a
sealed tube allowing us to conclude that sulfone 2a
extrudes sulfur dioxide without the need of FVP condi-
tions.
The flash vacuum pyrolysis of sulfone 2a was also
studied. Interestingly, our FVP conditions (700 °C/8 ×
10-2 mbar) led to a different outcome than the previously
reported result.1 One product was obtained in 46% yield
and identified as being methyl 1,3-dimethyl-5-oxo-5H-
pyrrolizine-2-carboxylate 5a.3 When the FVP of 2a was
carried out at 700 °C/4 × 10-2 mbar, a mixture of 5a
(44%) and 3a (27%) was obtained. This suggested that
the lower pressure reduces the period of time that the
substance to be pyrolyzed remains in the hot zone not
allowing the complete conversion of 2a into compound
5a. The result of the sulfone 2a FVP (700 °C/1.3 × 10-3
mbar) described by Storr et al.1 is also in agreement with
this observation. Thus, vinylpyrrole 3a must in fact be
an intermediate in the formation of methyl 1,3-dimethyl-
5-oxo-5H-pyrrolizine-2-carboxylate 5a from sulfone 2a.
To corroborate this mechanistic interpretation, we per-
formed the FVP of dimethyl 2,5-dimethyl-1-vinyl-1H-
pyrrole-3,4-dicarboxylate 3a. In fact, the flash vacuum
pyrolysis carried out at 700 °C/4 × 10-2 mbar led to the
efficient synthesis of compound 5a (79%). The FVP of
compound 3a was also performed using milder reaction
conditions (400 °C and 550 °C/4 × 10-2 mbar) in an
attempt to intercept intermediates of the synthesis of 5a.
However, only sublimation of N-vinylpyrrole 3a was
observed.
We set out to evaluate the scope of the approach to
N-vinylpyrroles and 5-oxo-5H-pyrrolizines from pyrrolo-
[1,2-c]thiazole 2,2-dioxides.
The reactivity of 3-benzyl-1H-pyrrolo[1,2-c]thiazole 2,2-
dioxide 2c was studied (Scheme 3). The thermolysis of
2c carried out in a sealed tube led to N-vinylpyrrole 3b
in 43% yield. On the other hand, compound 2c was
converted into 5-oxo-5H-pyrrolizine 5b on FVP (44%).
The same product was obtained from the FVP of 3b
confirming that the N-vinylpyrrole 3b is an intermediate
of the synthesis of 5-oxo-5H-pyrrolizine 5b from pyrrolo-
[1,2-c]thiazole 2c.
Starting from a pyrrolo[1,2-c]thiazole 2e bearing an
isopropyl group at C-3, pyrrole 13a was obtained in
moderate yield. The two substituents at the terminus of
the double bond of 13a preclude its conversion into a
pyrrolizine.3 Nevertheless, we hoped that this study
would give new information concerning the reactivity of
this type of pyrroles. Under FVP reaction conditions, two
products were obtained, the N-vinylpyrrole 13a and
6-oxocyclopenta[b]pyrrole 14. The 6-oxocyclopenta[b]pyr-
role 14 structure was determined by X-ray crystal-
lography (see the Supporting Information). We could also
conclude that the presence of a substituent (Me or Ph)
(4) Experimental procedure described for the formylation of 2-(py-
ridin-3-yl)-1,3-thiazolidine in: Fabre, J.-L.; Farge, D.; James, C.; Lave´,
D. US Patent 4,529,728.
(5) Experimental procedure described for the synthesis of 7-cyano-
3-(3-pyridyl)-1H,3H-pyrrolo[1,2-c]thazole in: Rajoharison, H. G., US
Patent 5,124,459.
J. Org. Chem, Vol. 70, No. 17, 2005 6631

Pinho e Melo et al.
SCHEME 4
TABLE 1.
suprafacial [1,8]H shift in the 8π 1,7-dipolar system
(Scheme 3).
The formation of 5-oxo-5H-pyrrolizines from N-vi-
nylpyrroles can be rationalized as outlined in Scheme 5.3
It is known that 2-substituted 3-(pyrrol-2-yl)propionate
methyl esters undergo concerted elimination of methanol
on FVP to give pyrrol-2-ylideneketene intermediates
which give pyrrolizinones by electrocyclization.6 Thus,
pyrrol-2-ylpropionates 17 must be intermediates in the
synthesis of the 5-oxo-5H-pyrrolizines, formed from the
N-vinylpyrroles through a sequence of sigmatropic shifts.
The pyrrol-2-ylpropionates undergo concerted elimination
of methanol giving pyrrol-2-ylideneketenes which are
converted into pyrrolizinones by electrocyclization. The
formation of 5-oxo-5H-pyrrolizines 16b and 16c followed
the general mechanism outlined in Scheme 5. However,
the synthesis of 16b involves a methyl migration as the
second mechanistic step whereas in the case of 5-oxo-
5H-pyrrolizine 16c it is a phenyl migration.
starting
material
reaction
conditions
products
2d
2d
15a
2i
2i
15b
sealed tube
FVP
FVP
sealed tube
FVP
FVP
16a (7%)
16a (39%)
16a (72%)
15a (41%)
15b (45%)
15b (3%)
15b (3%)
16b (8%)
16b (8%)
16c (13%)
16c (10%)
at C-5 of the starting pyrrolo[1,2-c]thiazole is important
in order to have an efficient process. In fact, the ther-
molysis of the unsubstituted derivative 2k led to N-
vinylpyrrole 13b in poor yield (Scheme 4).
The synthesis of N-vinylpyrrole 15a and 5-oxo-5H-
pyrrolizine 16a could also be achieved starting from
pyrrolo[1,2-c]thiazole 2d. When the reaction was carried
out in a sealed tube (260 °C, 1.5 h), a mixture of 15a
(41%) and 16a (7%) was obtained. The FVP (700 °C, 6 ×
10-2 mbar) of 2d allowed the synthesis of pyrrolizine 16a
in 39% yield. The same compound was obtained in 72%
yield from 15a through FVP (Table 1).
N-Vinylpyrrole 13a cannot be converted into a pyr-
rolizine of the type described in Scheme 5. Instead, this
compound is converted into 6-oxo-cyclopenta[b]pyrrole 14
via an alternative mechanistic pathway outlined in
Scheme 6.
The thermolysis of 3-phenyl-1H-pyrrolo[1,2-c]thiazole-
2,2-dioxides 2b and 2j was also studied (Scheme 7). We
found that the cheletropic extrusion of SO2 from these
sulfones could be carried out in a sealed tube leading to
styryl-1H-pyrroles (4a and 4b). The best results were
obtained by heating at 220 °C for 1.5 h a solution of 2j
in sulfolane giving 4b in 80% yield. A similar result was
obtained starting from 5-methyl-3-phenyl-1H-pyrrolo[1,2-
c]thiazole-2,2-dioxide 2b, and the corresponding styryl-
1H-pyrrole 4a could be obtained in 54% yield. Storr et
al.1b have described attempts of thermal extrusion of SO2
from 2b although no products of this reaction were
reported.
The formation of styryl-1H-pyrroles 4a and 4b can be
explained considering the generation of azafulvenium
methides (1e or 1f) followed by an 1,7-electrocyclic
reaction giving 26a and 26b, respectively, which rear-
range to the final products. Attempts were made to trap
1f by promoting the sealed tube thermolysis in the
In the case of pyrrolo[1,2-c]thiazole-2,2-dioxides 2i, the
sealed tube thermolysis leads to the expected N-vinylpyr-
role 15b. However, from the FVP of 2i two isomeric 5-oxo-
5H-pyrrolizines (16b and 16c) were obtained together
with the formation of some N-vinylpyrrole 15b. The same
compounds were obtained from the flash vacuum pyroly-
sis of N-vinylpyrrole 15b (Table 1). Based on a compari-
1
son of the H NMR spectra of 5-oxo-5H-pyrrolizines 5a,
5b, 16a, and 35 with those of derivatives 16b and 16c,
we could determine the structures of these last com-
pounds. Protons of methyl groups at the C-1 position of
5-oxo-5H-pyrrolizines are characterized by having reso-
nances at lower chemical shift then the ones observed
for methyl groups at C-3.
The mechanism of conversion of pyrrolo[1,2-c]thiazole
2,2-dioxides into N-vinylpyrroles was proposed by Storr
et al., who first reported the synthesis of N-vinylpyrrole
3a from the 1-azafulvenium methide 1a.1 It is an allowed,
(6) (a) McNab, H. J. Chem. Soc., Perkin Trans. 1 1987, 657-659.
(b) McNab, H.; Parson, S.; Stevenson, E. J. Chem. Soc., Perkin Trans.
1 1999, 2047-2048. (c) McNab, H. Aldrichim. Acta 2004, 37, 19-26.
(d) Trofimov, B. A.; Sobenina, L. N.; Demenev, A. P.; Mikhaleva, A. I.
Chem. Rev. 2004, 104, 2481-2506.
6632 J. Org. Chem., Vol. 70, No. 17, 2005

N-Vinyl- and C-Vinylpyrroles from Azafulvenium Methides
SCHEME 5
SCHEME 6
SCHEME 7
presence of DMAD and also in the presence of bis-
(trimethylsilyl)acetylene although no evidence was ob-
tained for the formation of adducts and the only product
was styryl-1H-pyrrole 4b. Nevertheless, the synthesis of
pyrroles 4a and 4b is a strong evidence of the generation
of the new azafulvenium methides 1e and 1f.
5-Methyl-3-phenyl-1H-pyrrolo[1,2-c]thiazole 2,2-diox-
ide 2b is converted into methyl 2-methyl-4-oxo-1,4-
dihydro-1-azabenzo[f]azulene-3-carboxylate 6a on flash
vacuum pyrolysis (Scheme 7). Under these reaction
conditions, styryl-1H-pyrrole 4a is formed and converted
into a pyrrole fused to a benzocyclohepten-5-one ring
J. Org. Chem, Vol. 70, No. 17, 2005 6633

Pinho e Melo et al.
SCHEME 8
SCHEME 9
attempted the flash vacuum pyrolysis (700 °C/1.3 ×
10-3 mbar).1 Although sulfur dioxide was eliminated
from sulfone 2g no identifiable products were detect-
ed.
We decided to evaluate if our FVP reaction conditions
(700 °C/4 × 10-2 mbar) applied to the thermolysis of 2g
would lead to a different outcome. In fact, under these
conditions, two products are obtained from pyrrolo[1,2-
c]thiazole 2,2-dioxide 2g, the C-vinylpyrrole 34 and 5-oxo-
5H-pyrrolizine 35, although in low yield. No product
could be isolated from the sealed tube thermolysis of 2g
(Scheme 9).
system. This was confirmed by promoting the FVP of
styryl-1H-pyrrole 4a, which also gave compound 6a
(31%). 3-Phenyl-1H-pyrrolo[1,2-c]thiazole 2,2-dioxide 2j
and styryl-1H-pyrrole 4b showed similar chemical be-
havior when compared with 2b and 4a, respectively, and
the corresponding 4-oxo-1,4-dihydro-1-aza-benzo[f]azu-
lene-3-carboxylate 6b could be obtained on FVP although
in low yield.
The reactivity of 3-phenyl-1H-pyrrolo[1,2-c]thiazole
2,2-dioxide unsubstituted at C-5 (2l) toward thermolysis
was also studied (Scheme 7). Sealed tube reaction condi-
tions allowed the conversion of 2l into C-vinylpyrrole 4c
in 24% yield. Interestingly, starting from sulfone 2l or
from C-vinylpyrrole 4c the FVP results in the synthesis
of two isomeric 4-oxo-1,4-dihydro-1-azabenzo[f]azulenes
6c and 27.
The most likely mechanism for the formation of 6 is
shown in Scheme 8. It has been reported that methyl
pyrrole-2-carboxylate undergoes elimination of methanol
to produce pyrrol-2-ylketene under FVP conditions.7 In
a similar manner, styryl-1H-pyrrole 4 generates pyrrol-
3-ylketene 28 on eliminating methanol. Electrocyclization
of 28 followed by two sigmatropic H-shifts gives com-
pounds 6.
Since 4-oxo-1,4-dihydro-1-azabenzo[f]azulene 27 can be
obtained from C-vinylpyrrole 4c, the rationalization of
its formation can also be done considering the initial
isomerization of 4c into 31 as outlined in Scheme 8. We
assume that the existence of unsubstituted position in
4c favors the rearrangement in comparison with 2-sub-
stituted pyrrole derivatives 4a and 4b. Pyrrole 33 gener-
ates the corresponding pyrrol-3-ylketene on eliminating
methanol, and this intermediate can lead to the final
product 27.
Evidence for the formation of 1-azafulvenium methide
36, the intermediate involved in the synthesis of C-
vinylpyrrole 34, was observed for the first time (Scheme
10). This 8π 1,7-dipolar system (36) does not have a
proton in the appropriate position to allow the suprafacial
[1,8]H shift of the type described in Scheme 3 for the
synthesis of N-vinylpyrroles. Therefore, the process oc-
curs via an alternative route; an 1,7-electrocyclic reaction
gives 37 which undergoes a rearrangement to pyrrole 34.
This is in fact, a mechanism pathway similar to the one
described for the phenyl derivatives 1e, 1f, and 1l.
The mechanistic interpretation for the synthesis of
5-oxo-5H-pyrrolizine 35 from 34 is outlined in Scheme
10. We could conclude that C-vinylpyrroles can also be
converted into the corresponding 5-oxo-5H-pyrroli-
zines.
We looked also into the thermolysis of 1H-pyrrolo[1,2-
c]thiazole 2,2-dioxide 2f (Scheme 11). The FVP (700 °C,
4 × 10-2 mbar) of this sulfone led to an unexpected
result: 5-oxo-5H-pyrrolizine 35 was isolated in 24% yield,
the same compound previously obtained from the FVP
of 2g. When the FVP was carried out at 700 °C/6 × 10-2
mbar two products were isolated, 5-oxo-5H-pyrrolizine
35 and dimethyl 2-(3,3-dimethylbut-1-enyl)-5-methyl-1H-
pyrrole-3,4-dicarboxylate 42. This result indicates this
pyrrole is an intermediate in the synthesis of 5-oxo-5H-
pyrrolizine 35. No product could be isolated from the
sealed tube thermolysis of 2f.
We could conclude that 1H-pyrrolo[1,2-c]thiazole 2,2-
dioxide 2f shows a similar chemical behavior to the one
described for sulfone 2g giving a C-vinylpyrrole. The
synthesis of 35 from 42 can be explained considering an
initial rearrangement followed by isobutene elimination
to give 3-(pyrrol-2-yl)propionate 40, which is converted
into the final product (Scheme 12).
Padwa et al. reported unsuccessful attempts to extrude
sulfur dioxide from pyrrolo[1,2-c]thiazole 2,2-dioxide 2g
by solution-phase thermolysis (300 °C).8 Storr et al.,
considering that this unsuccessful result was due to the
high thermal stability of this sulfone, characterized by
the low bond order of the 3,4-bond of the sulfolene moiety,
Storr et al. reported that azafulvenium methides 1d
electrocyclize to give pyrrolooxazines.1 Attempts were
made to generate azafulvenium methide 44 in order to
explore the same type of chemistry. However, from the
FVP at 700 °C/ 4 × 10-2 mbar of dimethyl 3-benzoyl-5-
methyl-1H,3H-pyrrolo[1,2-c]thiazole-6,7-dicarboxylate 2,2-
(7) Gross, G.; Wentrup, C. J. Chem. Soc., Perkin Trans. 1 1982, 360-
361.
(8) Padwa, A.; Fryxell, G. E.; Gasdaska, J. R.; Venkatramanan, M.
K.; Wong, G. S. K. J. Org. Chem. 1989, 54, 644-652.
6634 J. Org. Chem., Vol. 70, No. 17, 2005

N-Vinyl- and C-Vinylpyrroles from Azafulvenium Methides
SCHEME 10
the reaction mixture diluted with dichloromethane and washed
with water. The mixture was purified by flash chromatography
[ethyl acetate-hexane (1:2) then ethyl acetate-hexane (1:1)].
Dimethyl 2,5-Dimethyl-1-vinyl-1H-pyrrole-3,4-dicar-
boxylate 3a. Compound 3a was isolated as a white solid
(61%): mp 67.5-68.2 °C9 (from diethyl ether-hexane); 1H
NMR 2.37 (6H, s), 3.81 (6H, s), 5.27 (1H, dd, J ) 0.7 and 15.7
Hz), 5.44 (1H, dd, J ) 0.7 and 8.5 Hz), 6.60 (1H, dd, J ) 8.5
and 15.7 Hz); MS (EI) m/z 237 (M+, 30), 205 (87), 147 (41),
119 (100), 77 (28), 68 (40), and 42 (53).
SCHEME 11
Dimethyl 2,5-Dimethyl-1-styryl-1H-pyrrole-3,4-dicar-
boxylate 3b. Compound 3b was isolated as a white solid
(43%): mp 149.6-151.0 °C (from diethyl ether); IR (KBr) 1225,
1443, 1548, and 1694 cm-1; 1H NMR 2.41 (6H, s), 3.82 (6H, s),
6.61 (1H, dd, J ) 14.4 Hz), 6.97 (1H, dd, J ) 14.4 Hz), 7.35-
7.47 (5H, m, Ar-H); 13C NMR 12.1, 51.5, 112.9, 122.1, 126.6,
128.8, 128.9, 131.5, 133.8, 133.9, 165.9; HRMS (CI) m/z
313.1315 (C18H19NO4 [MH+], 313.1314).
dioxide 2h no evidence for the formation of the desired
product was observed.
Dimethyl 2,5-Dimethyl-1-(2-methylpropenyl)-1H-pyr-
role-3,4-dicarboxylate 13a. Compound 13a was isolated as
a solid (36%): mp 54.5-55.8 °C (from diethyl ether-hexane);
IR (KBr) 1091, 1182, 1219, 1443, 1694, and 1715 cm-1 1H
;
NMR 1.47 (3H, d, J ) 1.3 Hz), 1.91 (3H, d, J ) 1.4 Hz), 2.23
(6H, s), 3.81 (6H, s), 6.03-6.04 (1H, m); 13C NMR 11.4, 17.5,
21.8, 51.3, 111.7, 118.0, 134.3, 140.7, 166.1; MS (EI) m/z 265
(M+, 28), 234 (39), 218 (100), and 147 (18); HRMS (CI) m/z
265.1319 (C14H19NO4 [M+], 265.1314).
Conclusion
We described new chemistry of 1-azafulvenium me-
thides, generated by the thermal extrusion of sulfur
dioxide from pyrrolo[1,2-c]thiazole-2,2-dioxides. The in-
tramolecular trapping of these transient 8π 1,7-dipoles
in pericyclic reaction, namely sigmatropic [1,8]H shifts
and 1,7-electrocyclization, leads to the synthesis of N-
vinylpyrroles and C-vinylpyrroles. Under FVP conditions
the vinylpyrroles are converted into heterocycles where
another ring system is annulated to pyrrole, namely
5-oxo-5H-pyrrolizines and 4-oxo-1,4-dihydro-1-azabenzo-
[f]azulenes. The synthesis of these heterocycles can also
be achieved directly from the flash vacuum pyrolysis of
pyrrolo[1,2-c]thiazole-2,2-dioxides. The synthesis of a new
6-oxocyclopenta[b]pyrrole derivative is also reported.
Dimethyl 2-Methyl-1-vinyl-1H-pyrrole-3,4-dicarboxyl-
ate 13b. Compound 13b was isolated as an oil (8%): IR (film)
1
1208, 1284, 1444, and 1706 cm-1; H NMR 2.42 (3H, s), 3.81
(3H, s), 3.84 (3H, s), 4.99 (1H, dd, J ) 1.7 and 8.8 Hz), 5.32
(1H, dd, J ) 1.7 and 15.5 Hz), 6.84 (1H, dd, J ) 8.8 and 15.5
Hz), 7.43 (1H, s); 13C NMR 10.7, 51.5, 51.6, 104.2, 106.8, 122.1,
122.5, 129.3, 134.6, 164.1, 165.3; HRMS (CI) m/z 224.0925
(C11H14NO4 [MH+], 224.0923).
Methyl 1,3,6-Trimethyl-5-oxo-5H-pyrrolizine-2-carbox-
ylate 16a and Dimethyl 2,5-Dimethyl-1-propenyl-1H-
pyrrole-3,4-dicarboxylate 15a. The purification of the crude
product by flash chromatography gave, in order of elution,
methyl 1,3,6-trimethyl-5-oxo-5H-pyrrolizine-2-carboxylate 16a
as solid with an intense orange color (7%) and dimethyl 2,5-
dimethyl-1-propenyl-1H-pyrrole-3,4-dicarboxylate 15a as a
mixture of the trans/cis (86:14) stereoisomers, obtained as an
oil (41%).
Experimental Section
Methyl 1,3,6-trimethyl-5-oxo-5H-pyrrolizine-2-carbox-
ylate 16a: mp 138.0-140.0 °C (from diethyl ether); IR (KBr)
General Procedure for the Sealed Tube Reactions. The
appropriate 1H,3H-pyrrolo[1,2-c]thiazole-6,7-dicarboxylate 2,2-
dioxide (0.36 mmol) was dissolved in sulfolane (1 mL) in a glass
pyrolysis tube which was cooled in liquid nitrogen, evacuated,
sealed, and heated (see the Supporting Information). After
being cooled to room temperature, the tube was opened and
1
1129, 1385, 1695, and 1721 cm-1; H NMR 1.88 (3H, d, J )
1.6 Hz), 2.13 (3H, s), 2.63 (3H, s), 3.79 (3H, s), 6.83 (1H, d, J
) 1.6 Hz); 13C NMR 10.8, 11.7, 12.1, 50.8, 121.7, 128.6, 130.1,
(9) Compound previously described in ref 1 as a yellowish oil.
J. Org. Chem, Vol. 70, No. 17, 2005 6635

Pinho e Melo et al.
SCHEME 12
130.6, 131.6, 141.6, 165.4, 167.5; MS (EI) m/z 219 (M+, 100),
204 (28), 188 (48), 159 (37), and 130 (11); HRMS (CI) m/z
219.0892 (C12H13NO3 [M+], 219.0895).
× 10-2 mbar onto a surface cooled at -196 °C over a period of
1.5-5h gave a yellowish pyrolysate (or red pyrolysate where
indicated) [The rate of volatilization of the starting material
was controlled by the use of a Kugelrohr oven which heated
the sample at 100-250 °C] (see the Supporting Information).
After being cooled to room temperature, the pyrolysate was
removed from the coldfinger with dichloromethane and the
solvent was removed in vacuo.
Methyl 1,3-Dimethyl-5-oxo-5H-pyrrolizine-2-carboxyl-
ate 5a3 from 2a. The crude product was purified by flash
chromatography [ethyl acetate-hexane (1:2), then ethyl ac-
etate-hexane (1:1)] to give 5a as a solid with an intense orange
color (46%): mp 116.0-118.0 °C (from diethyl ether-hexane);
IR (KBr) 1614, 1695 and 1729 cm-1; 1H NMR 2.11 (3H, s, H-8),
2.57 (3H, s, H-11), 3.73 (3H, s, H-10), 5.58 (1H, d, J ) 6.0 Hz,
H-6), 7.12 (1H, d, J ) 6 Hz, H-7); 13C NMR (off-resonance
decoupling) 10.9 (q, J ) 129.2 Hz, C-8), 11.2 (q, J ) 130.7 Hz,
C-11), 49.9 (q, J ) 147.4 Hz, C-10), 117.1 (s, C-2), 119.0 (d, J
) 181.9 Hz, C-6), 123.7 (s, C-1), 131.4 (s, C-7a), 135.9 (d, J )
174.7 Hz, C-7), 141.3 (s, C-3), 164.3 (s, C-9), 165.6 (s, C-5);
MS (EI) m/z 205 (M+, 100), 190 (24), 174 (69), 162 (16), 145
(45) ,and 117 (16); HRMS (CI) m/z 205.0746 (C11H11NO3 [M+],
205.0739).
Dimethyl 2,5-dimethyl-1-propenyl-1H-pyrrole-3,4-di-
carboxylate 15a: IR (film) 1175, 1217, 1279, 1443, and 1706
cm-1 1H NMR (trans-isomer) 1.89 (3H, dd, J ) 1.7 and 6.8
;
Hz), 2.31 (6H, s), 3.80 (6H, s), 5.77 (1H, approx sext, J ) 6.9
and 13.8 Hz), 6.23-6.27 (1H, m); (cis-isomer) 1.51 (3H, dd, J
) 1.8 and 6.9 Hz), 2.26 (6H, s), 3.81 (6H, s), 5.97-6.06 (1H,
m), 6.30-6.31 (1H, m); MS (EI) (trans-isomer) m/z 251 (M+,
27), 219 (30), 204 (100), 190 (8), 146 (11), and 133 (10); (EI)
(cis-isomer) m/z 251 (M+, 28), 219 (49), 204 (100), 190 (9), 146
(13), and 133 (16); HRMS (CI) m/z 252.1230 (C13H18NO4 [MH+],
252.1236).
Dimethyl 2-Methyl-5-phenyl-1-vinyl-1H-pyrrole-3,4-di-
carboxylate 15b. Compound 15b was isolated as a solid
(45%): mp 97.5-98.5 °C (from diethyl ether); IR (KBr) 1202,
1
1233, 1439, 1705, and 1722 cm-1; H NMR 2.54 (3H, s), 3.67
(3H, s), 3.83 (3H, s), 5.03 (1H, dd, J ) 0.9 and 15.8 Hz), 5.18
(1H, dd, J ) 0.9 and 8.7 Hz), 6.48 (1H, dd, J ) 8.7 and 15.8
Hz), 7.36 (5H, bs); 13C NMR 12.4, 51.5, 51.8, 112.7, 113.6,
115.7, 123.6, 128.0. 128.4, 128.8, 130.2, 130.6, 135.1, 165.2,
166.1; MS (EI) m/z 299 (M+, 89), 267 (100), 207 (75), 180 (44),
117 (22), and 104 (19). Anal. Calcd for C17H17NO4: C, 68.21;
H, 5.72; N, 4.68. Found: C, 68.28; H, 6.07; N, 4.37.
Methyl 1,3-Dimethyl-5-oxo-5H-pyrrolizine-2-carboxyl-
ate 5a from 3a. The crude product was purified by flash
chromatography [ethyl acetate-hexane (1:2), then ethyl ac-
etate-hexane (1:1)] to give 5a in 79% yield. The product was
identified by comparison with the specimen previously pre-
pared.
Dimethyl 2-Methyl-5-styryl-1H-pyrrole-3,4-dicarboxyl-
ate 4a. Compound 4a was isolated as a solid (54%): mp 151.9-
153.6 °C (from diethyl ether); IR (KBr) 1218, 1259, 1448, 1672,
1
1717, and 3268 cm-1; H NMR 2.40 (3H, s), 3.80 (3H, s), 3.85
(3H, s), 6.77 (1H, d, J ) 16.8 Hz), 7.32 (1H, d, J ) 16.8 Hz),
7.19-7.38 (5H, m); 13C NMR 12.6, 51.5, 51.8, 113.0, 114.2,
116.3, 126.4, 127.8, 127.9, 128.6, 132.3, 135.7, 136.5, 165.7,
165.9; MS (EI) m/z 299 (M+, 100), 267 (53), 236 (39), 209 (25),
and 180 (51). Anal. Calcd for C17H17NO4: C, 68.22; H, 5.72;
N, 4.68. Found: C, 68.60; H, 6.07; N, 4.79.
Dimethyl 2-Phenyl-5-styryl-1H-pyrrole-3,4-dicarboxyl-
ate 4b. Compound 4b was isolated as a white solid (80%): mp
198.2-199.8 °C (from diethyl ether); IR (KBr) 1220, 1260,
1445, 1693, and 3239 cm-1; 1H NMR 3.81 (3H, s), 3.87 (3H, s),
6.87 (1H, d, J ) 16.9 Hz), 7.28-7.55 (10H, m), 7.64 (1H, d, J
) 16.9 Hz); 13C NMR 51.6, 52.2, 113.8, 115.3, 116.6, 126.6,
127.4, 128.1, 128.5, 128.7, 128.7, 129.0, 130.4, 133.4, 134.4,
136.3, 164.7, 166.8; MS (EI) m/z 361 (M+, 100), 298 (47), 270
(35), 254 (19), 120 (23), and 96 (23); HRMS (CI) m/z 361.1302
(C22H19NO4 [M+], 361.1314).
Methyl 1,3-Dimethyl-5-oxo-6-phenyl-5H-pyrrolizine-2-
carboxylate 5b from 2c. The crude product (red pyrolysate)
was purified by flash chromatography [ethyl acetate-hexane
(1:2)] to give 5b as a solid with an intense dark red color
(44%): mp 126.8-127.9 °C (washed with diethyl ether); IR
1
(KBr) 1132, 1688, and 1730 cm-1; H NMR 2.22 (3H, s), 2.70
(3H, s), 3.81 (3H, s), 7.27-7.41 (3H, m, Ar-H), 7.32 (1H, s),
7.74-7.78 (2H, m); 13C NMR 12.0, 12.3, 50.9, 118.3, 124.1,
126.2, 128.1, 128.6, 128.7, 130.8, 131.2, 131.3, 142.3, 165.2,
165.6; MS (EI) m/z 281 (M+, 100%), 266 (12), 258 (18), 221
(26), and 152 (10); HRMS (CI) m/z 282.1126 (C17H16NO3 [MH+],
282.1130).
Methyl 1,3-Dimethyl-5-oxo-6-phenyl-5H-pyrrolizine-2-
carboxylate 5b from 3b. The crude product (red pyrolysate)
was purified by preparative thin-layer chromatography [ethyl-
acetate-hexane (1:2)] to give 5b in 56% yield. The product
was identified by comparison with the specimen previously
prepared.
Dimethyl 2,5-Dimethyl-1-(2-methylpropenyl)-1H-pyr-
role-3,4-dicarboxylate 13a and Methyl 5-Isopropenyl-2-
methyl-6-oxo-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-3-
carboxylate 14 from 2e. The crude product was purified by
flash chromatography [ethyl acetate-hexane (1:2), then ethyl
acetate-hexane (1:1)] to give 13a (13%) and 14 (7%) both as
solids. The pyrrole 13a was identified by comparison with the
specimen previously prepared.
Dimethyl 2-Styryl-1H-pyrrole-3,4-dicarboxylate 4c. Pu-
rification by flash chromatography [ethyl acetate-hexane (1:
2), ethyl acetate-hexane (1:1), then ethyl acetate-hexane (2:
1)] gave 4c as a solid (24%): mp 162.0-164.1 °C (from diethyl
ether); IR (KBr) 1065, 1288, 1445, 1704, 1728, and 3292 cm-1
;
1H NMR 3.83 (3H, s), 3.91 (3H, s), 6.81 (1H, d, J ) 16.8), 7.28-
7.38 (4H, m), 7.44-7.49 (2H, m), 7.46 (1H, d, J ) 16.8), 8.87
(1H, bs); 13C NMR 51.6, 51.9, 113.5, 116.5, 116.6, 125.2, 126.5,
128.1, 128.7, 129.0, 135.0, 136.3, 164.5, 165.6; MS (EI) m/z 285
(M+, 100), 252 (28), 222 (49), 194 (35), 167 (25), and 139 (19);
HRMS (CI) m/z 285.0995 (C16H15NO4 [M+], 285.1001).
Methyl 5-isopropenyl-2-methyl-6-oxo-1,4,5,6-tetrahy-
drocyclopenta[b]pyrrole-3-carboxylate 14: mp 156.4-
158.2 °C (from diethyl ether); IR (KBr) 1086, 1119, 1277, 1460,
General Procedure for the Flash Vacuum Pyrolysis.
Pyrolysis of the appropriate 1H,3H-pyrrolo[1,2-c]thiazole 2,2-
dioxide or vinyl-1H-pyrrole (0.8 mmol) at 700 °C/2 × 10-2-8
1
1661, 1717, and 3163 cm-1; H NMR 1.68-1.69 (3H, m), 2.66
6636 J. Org. Chem., Vol. 70, No. 17, 2005

N-Vinyl- and C-Vinylpyrroles from Azafulvenium Methides
1
(3H, s), 2.89 (1H, dd, J ) 2.3 and 18.1 Hz), 3.26 (1H, dd, J )
6.6 and 18.1 Hz), 3.61 (1H, dd, J ) 2.3 and 6.6 Hz), 3.83 (3H,
s), 4.94-4.97 (2H, m), 10.85 (1H, s); 13C NMR 14.3, 19,2, 28.6,
51.0, 59.8, 110.3, 114.0, 131.9, 142.9, 150.8, 155.7, 164.9, 191.7;
MS (EI) m/z 233 (M+, 100), 218 (46), 190 (26), 174 (45), 146
(22), 131 (14), and 77 (8); HRMS (CI) m/z 233.1055 (C13H15-
NO3 [M+], 233.1052).
Methyl 1,3,6-Trimethyl-5-oxo-5H-pyrrolizine-2-carbox-
ylate 16a from 2d. The crude product was purified by flash
chromatography [ethyl acetate-hexane (1:2)] to give 16a as a
solid with an intense orange color (39%). The product was
identified by comparison with the specimen previously pre-
pared.
Methyl 1,3,6-Trimethyl-5-oxo-5H-pyrrolizine-2-carbox-
ylate 16a from 15a. Compound 16a was isolated as a solid
with an intense orange color (72%). The product was identified
by comparison with the specimen previously prepared.
Methyl 3-Methyl-5-oxo-1-phenyl-5H-pyrrolizine-2-car-
boxylate 16c and Methyl 1-Methyl-5-oxo-3-phenyl-5H-
pyrrolizine-2-carboxylate 16b from 2i. The crude product
was purified by preparative thin-layer chromatography [ethyl
acetate-hexane (1:3)] to give, in order of elution, 16c (13%),
16b (8%), both as solids with an intense orange color, and 15b
(3%).
1702, and 3224 cm-1; H NMR 3.71 (3H, s), 6.93 (1H, d, J )
2.9 Hz), 7.32-7.84 (6H, m), 7.72 (1H, d, J ) 9.3 Hz), 8,40 (1H,
d, J ) 9.3 Hz), 8.97-9.01 (2H, m), 9.44 (1H, bs); MS (EI) m/z
329 (M+, 100), 301 (26), 270 (84), 241 (52) and 120 (27); HRMS
(CI) m/z 330.1139 (C21H16NO3 [MH+], 330.1130).
Methyl 4-Oxo-1,4-dihydro-1-azabenzo[f]azulene-2-car-
boxylate 27 and Methyl 4-Oxo-1,4-dihydro-1-azabenzo-
[f]azulene-3-carboxylate 6c from 2l. The crude product was
purified by flash chromatography [ethyl -acetate-hexane (1:
3), ethyl acetate-hexane (1:2) and then ethyl acetate-hexane
(1:1)] to give, in order of elution, 27 (11%) and 6c (10%), both
as orange solids.
Methyl 4-oxo-1,4-dihydro-1-azabenzo[f]azulene-2-car-
boxylate 27: mp 141.6-143.5 °C (from diethyl ether); IR (KBr)
1083, 1236, 1442, 1672, and 1711 cm-1; 1H NMR 3.96 (3H, s),
7.53-7.58 (1H, m), 7.72 (1H, dd, J ) 1.6 and 8.7 Hz), 7.74
(1H, d, J ) 9.1 Hz), 7.81 (1H, dd, J ) 1.5 and 7.9 Hz), 8.04
(1H, s), 8.35 (1H, d, J ) 9.1 Hz), 9.40 (1H, d, J ) 8.7 Hz), 9.76
(1H, bs); 13C NMR 51.5, 108.9, 117.4, 121.0, 125.0, 126.0, 128.5,
129.2, 129.7, 130.0, 134.3, 134.8, 141.4, 163.9, 176.8; HRMS
(CI) m/z 254.0817 (C15H12NO3 [MH+], 254.0810). Anal. Calcd
for C15H11NO3: C, 71.14; H, 4.38; N, 5.53. Found: C, 71.40;
H, 4.84; N, 5.15.
Methyl 4-oxo-1,4-dihydro-1-azabenzo[f]azulene-3-car-
boxylate 6c: mp 229.0-231.0 °C (from diethyl ether); IR (KBr)
1155, 1441, 1575, 1714, and 3343 cm-1; 1H NMR 3.92 (3H, s),
7.38 (1H, d, J ) 11.8 Hz), 7.53-7.86 (3H, m), 8.01 (1H, d, J )
3.3 Hz), 8.29 (1H, d, J ) 11.8 Hz), 8.95 (1H, dd, J ) 1.5 and
8.1 Hz); 13C NMR 51.4, 119.2, 123.8, 127.7, 127.8, 128.4, 128.8,
130.5, 131.0, 132.4, 132.5, 134.8, 137.0, 164.6, 176.9; MS (EI)
m/z 253 (M+, 100), 222 (53), 207 (25), 139 (18) and 73 (27);
HRMS (CI) m/z 253.0734 (C15H11NO3 [M+], 253.0739).
Methyl 4-Oxo-1,4-dihydro-1-azabenzo[f]azulene-2-car-
boxylate 27 and Methyl 4-Oxo-1,4-dihydro-1-azabenzo-
[f]azulene-3-carboxylate 6c from 4c. The crude product was
purified by flash chromatography [ethyl acetate-hexane (1:
3) and then ethyl acetate-hexane (1:2)] to give 27 (37%) and
6c (14%), both as orange solids. The products were identified
by comparison with the specimens previously prepared.
Methyl 3-Methyl-5-oxo-5H-pyrrolizine-2-carboxylate
35 and Dimethyl 2-Methyl-5-vinyl-1H-pyrrole-3,4-dicar-
boxylate 34 from 2g. The crude product was purified by flash
chromatography [ethyl acetate-hexane (1:3), ethyl acetate-
hexane (1:2), and then ethyl acetate-hexane (1:1)] to give 35
(8%) as a solid with an intense orange color and 34 (10%) as
a white solid.
Methyl 3-methyl-5-oxo-1-phenyl-5H-pyrrolizine-2-car-
boxylate 16c: mp 128.7-130.5 °C (from diethyl ether); IR
1
(KBr) 1079, 1154, 1195, 1387, 1699, and 1731 cm-1; H NMR
2.71 (3H, s), 3.69 (3H, s), 5.78 (1H, d, J ) 5.8 Hz), 7.15 (1H, d,
J ) 5.8 Hz), 7.34-7.38 (5H, m); 13C NMR 12.2, 51.0, 121.5,
127.9, 128.0, 128.1, 129.2, 132.4, 132.5, 137.9, 142.0, 164.7,
166.5; MS (EI) m/z 267 (M+, 100), 236 (46), 207 (16), 179 (23),
152 (14), and 76 (7); HRMS (CI) m/z 267.0902 (C16H13NO3 [M+],
267.0895).
Methyl 1-methyl-5-oxo-3-phenyl-5H-pyrrolizine-2-car-
boxylate 16b: mp 128.4-129.2 °C (from diethyl ether); IR
1
(KBr) 1076, 1139, 1195, 1370, 1705, and 1742 cm-1; H NMR
2.24 (3H, s), 3.62 (3H, s), 5.68 (1H, d, J ) 5.9 Hz), 7.24 (1H, d,
J ) 5.9 Hz), 7.40-7.44 (3H, m), 7.52-7.55 (2H, m); 13C NMR
11.7, 50.9, 118.9, 121.1, 124.3, 127.6, 128.4, 129.7, 134.0, 136.7,
141.6, 164.6, 165.6; MS (EI) m/z 267 (M+, 100), 236 (46), 208
(10), 180 (19), and 77 (10). Anal. Calcd for C16H15NO3: C, 71.90;
H, 4.90; N, 5.24. Found: C, 71.69; H, 5.13; N, 5.26.
Methyl 3-Methyl-5-oxo-1-phenyl-5H-pyrrolizine-2-car-
boxylate 16c and Methyl 1-Methyl-5-oxo-3-phenyl-5H-
pyrrolizine-2-carboxylate 16b from 15b. The crude product
was purified by preparative thin-layer chromatography [ethyl
acetate-hexane (1:3)] to give 16c (6%) and 16b (10%), both
as solids with an intense orange color. The products were
identified by comparison with the specimens previously pre-
pared.
Methyl 3-methyl-5-oxo-5H-pyrrolizine-2-carboxylate
35 was identified by comparison with the specimen previously
prepared (see below).
Dimethyl 2-methyl-5-vinyl-1H-pyrrole-3,4-dicarboxyl-
ate 34: mp 115.9-117.7 °C (from diethyl ether); IR (KBr) 1100,
Methyl 2-Methyl-4-oxo-1,4-dihydro-1-azabenzo[f]azu-
lene-3-carboxylate 6a from 2b. The crude product was
purified by flash chromatography [ethyl acetate-hexane (1:
2) and then ethyl acetate-hexane (1:1)] to give 6a as a yellow
solid (22%): mp 261.0-263.0 °C (from diethyl ether-hexane);
1210, 1295, 1450, 1694, 1709, and 3307 cm-1; H NMR 2.41
1
(3H, s), 3.80 (3H, s), 3.83 (3H, s), 5.21 (1H, d, J ) 11.5 Hz),
5.43 (1H, d, J ) 18.0 Hz), 6.91 (1H, dd, J ) 11.4 and 18.0 Hz),
8.92 (1H, bs); 13C NMR 12.7, 51.4, 51.8, 112.6, 112.7, 114.2,
125.0, 131.6, 135.2, 165.4, 165.6; MS (EI) 223 (M+, 43), 191
(100), 162 (19), 133 (36), and 105 (34); HRMS (CI) m/z 223.0843
(C11H13NO4 [M+], 223.0845).
1
IR (KBr) 1492, 1545, 1697, 3238 cm-1; H NMR 2.77 (3H, s),
3.95 (3H, s), 7.36 (1H, d, J ) 12.0 Hz), 7.67-7.75 (1H, m),
7.77-7.80 (1H, m), 7.84 (1H, dd, J ) 1.4 and 7.8 Hz), 8.27
(1H, d, J ) 12.0 Hz), 9.96 (1H, dd, J ) 1.5 and 8.0 Hz), 10.64
(1H, bs); MS (EI) m/z 267 (M+, 100), 252 (11), 236 (64), 178
(12), 152 (37) and 76 (16); HRMS (CI) m/z 267.0903 (C16H13-
NO3 [M+], 267.0895).
Methyl 3-Methyl-5-oxo-5H-pyrrolizine-2-carboxylate
35 from 2f. The crude product was purified by flash chroma-
tography [ethyl acetate-hexane (1:3)] to give methyl 3-methyl-
5-oxo-5H-pyrrolizine-2-carboxylate 35 as a solid with an
intense orange color (24%): mp 91.8-93.9 °C (from hexane);
IR (KBr) 1179, 1199, 1702, and 1734 cm-1; 1H NMR 2.68 (3H,
s), 3.80 (3H, s), 5.75 (1H, d, J ) 5.9 Hz), 6.38 (1H, s), 7.17
(1H, d, J ) 5.9 Hz); 13C NMR 11.6, 51.2, 111.8, 118.4, 121.9,
134.0, 138.2, 141.1, 164.6, 166.6; MS (EI) m/z 191 (M+, 92),
176 (34), 160 (100), 132 (24), 104 (9), and 77 (10); HRMS (CI)
m/z 191.0577 (C10H9NO3 [M+], 191.0582).
Methyl 2-Methyl-4-oxo-1,4-dihydro-1-azabenzo[f]azu-
lene-3-carboxylate 6a from 4a. The crude product was
purified by preparative thin-layer chromatography [ethyl
acetate-hexane (1:2)] to give 6a as a yellow solid (31%). The
product was identified by comparison with the specimen
previously prepared.
Methyl 4-Oxo-2-phenyl-1,4-dihydro-1-azabenzo[f]azu-
lene-3-carboxylate 6b from 2j. The crude product was
purified by flash chromatography [ethyl-acetate-hexane (1:
3)] to give 6b as a yellow oil (2%): IR (film) 1443, 1559, 1653,
Carrying out the pyrolysis of 2f at 700 °C/ 6 × 10-2 mbar
,two products are obtained: methyl 3-methyl-5-oxo-5H-pyr-
J. Org. Chem, Vol. 70, No. 17, 2005 6637

Pinho e Melo et al.
rolizine-2-carboxylate 35 (17%) and dimethyl 2-(3,3-dimeth-
ylbut-1-enyl)-5-methyl-1H-pyrrole-3,4-dicarboxylate 42 (6%).
Dimethyl 2-(3,3-dimethylbut-1-enyl)-5-methyl-1H-pyrrole-
3,4-dicarboxylate 42 was obtained as an oil: IR (film) 1097,
Acknowledgment. We thank Chymiotechnon and
Fundac¸a˜o para a Cieˆncia e a Tecnologia (POCTI/QUI/
55584/2004 and SFRH/BD/9123/2002) for financial sup-
port.
1
1216, 1448, 1707, and 3309 cm-1; H NMR 1.08 (9H, s), 2.41
(3H, s), 3.80 (3H, s), 3.83 (3H, s), 5.95 (1H, d, J ) 16.6 Hz),
6.59 (1H, d, J ) 16.6 Hz); MS (EI) m/z 279 (M+, 61), 248 (31),
232 (100), 222 (90), 200 (84), and 160 (30); HRMS (CI) m/z
279.1475 (C15H21NO4 [M+], 279.1471).
X-ray crystal data for methyl 5-isopropenyl-2-methyl-
6-oxo-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-3-carbox-
ylate 14: C13H15NO3, Mr ) 233.26 amu, triclinic, space group
P1h with unit cell a ) 5.160(2) Å, b ) 10.5619(7) Å, c ) 11.939-
(2) Å, a ) 108.097(8)°, b ) 99.00(3)°, γ ) 94.537(17)°, and V )
605.2(3) Å3. It contains two molecules/unit cell. Dcalc ) 1.280
g cm-3, Z ) 2, T ) 293 K, m(Cu KR) ) 0.748 mm-1. R(I >
2σ(I)) ) 0.0445 and Rw ) 0.1188 for 2406 independent
reflections. The hydrogen atoms were placed at calculated
positions and refined as riding on their parent atoms.
Supporting Information Available: Experimental pro-
cedures and characterization data for the synthesis of N-formyl-
1,3-thiazolidines, 1H,3H-pyrrolo[1,2-c]thiazoles, and 1H,3H-
pyrrolo[1,2-c]thiazole-2,2-dioxides. 1H NMR and 13C NMR
spectra for selected compounds. Crystallographic data for
methyl 5-isopropenyl-2-methyl-6-oxo-1,4,5,6-tetrahydrocyclo-
penta[b]pyrrole-3-carboxylate 14. Reaction conditions for the
sealed tube reactions and for the flash vacuum pyrolysis. This
material is available free of charge via the Internet at
http://pubs.acs.org.
JO050480I
6638 J. Org. Chem., Vol. 70, No. 17, 2005