'Higher-order' azomethine ylides in the synthesis of functionalized pyrroles and 5-oxo-5H-pyrrolizines

Article abstract of DOI:10.1016/j.tet.2006.12.025

Azafulvenium methides generated by the thermal extrusion of SO₂ from 1-methyl- and 1,1-dimethyl-1H,3H-pyrrolo[1,2-c]thiazole-2,2-dioxides undergo [1,8]H sigmatropic shifts to give vinylpyrroles. Flash vacuum pyrolysis of the C-vinylpyrroles affords 5-oxo-5H-pyrrolizines or C-allyl-1H-pyrroles.

Full text of DOI:10.1016/j.tet.2006.12.025

Tetrahedron 63 (2007) 1833–1841
‘Higher-order’ azomethine ylides in the synthesis of functionalized
pyrroles and 5-oxo-5H-pyrrolizines
*
Teresa M. V. D. Pinho e Melo, Maria I. L. Soares and Claudio M. Nunes
ꢀ
Department of Chemistry, University of Coimbra, 3004-535 Coimbra, Portugal
Received 13 September 2006; revised 18 October 2006; accepted 12 December 2006
Available online 10 January 2007
Abstract—Azafulvenium methides generated by the thermal extrusion of SO2 from 1-methyl- and 1,1-dimethyl-1H,3H-pyrrolo[1,2-c]thi-
azole-2,2-dioxides undergo [1,8]H sigmatropic shifts to give vinylpyrroles. Flash vacuum pyrolysis of the C-vinylpyrroles affords 5-oxo-5H-
pyrrolizines or C-allyl-1H-pyrroles.
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
We also intended to evaluate the scope of their use as inter-
mediates in the synthesis of heterocycles.
Storr and co-workers found that the generation of 1-azaful-
venium methides by the thermal extrusion of sulfur dioxide
from 1H,3H-pyrrolo[1,2-c]thiazole-2,2-dioxides could be
achieved under flash vacuum pyrolysis (FVP) reaction con-
ditions. They described the first evidence for the trapping of
these ‘higher-order’ azomethine ylides in pericyclic reac-
tions. The extended dipolar systems having a methyl group
at C-1 or C-7 undergo sigmatropic [1,8]H shifts giving vinyl-
pyrroles and the 1-acyl derivatives electrocyclise to give
pyrrolo[1,2-c]-[1,3]oxazines.1 We have further studied the
reactivity of azafulvenium methides including the reactivity
of a range of new systems derived from 1-unsubstitued-
1H,3H-pyrrolo[1,2-c]thiazole-2,2-dioxides and showed that
these transient 8p 1,7-dipole systems are interesting inter-
mediates for the synthesis of functionalized heterocyclic
compounds. The intramolecular trapping of these transient
8p 1,7-dipoles in pericyclic reaction, namely sigmatropic
[1,8]Hshiftsand1,7-electrocyclization, allowedthesynthesis
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
by FVP of 1H,3H-pyrrolo[1,2-c]thiazole-2,2-dioxides
(Scheme 1).2
2. Results and discussion
1,1-Dimethyl-1H,3H-pyrrolo[1,2-c]thiazole-2,2-dioxides 3a–
3d were prepared from penicillamine as outlined in Scheme
2. Heating a solution of 5,5-dimethyl-1,3-thiazolidine-4-
carboxylic acids 1a–1d in acetic anhydride in the presence
of dimethyl acetylenedicarboxylate the corresponding 1,1-
dimethyl-1H,3H-pyrrolo[1,2-c]thiazoles 2a–2d are obtained
in good yield (60–93%) via the intermolecular dipolar cyclo-
addition of the in situ generated 7,7-dimethyl-3-methyl-
5H,7H-thiazolo[3,4-c]oxazol-4-ium-1-olates. Oxidation of
1,1-dimethyl-1H,3H-pyrrolo[1,2-c]thiazoles 2a–2d with
MCPBA afforded sulfones 3a–3d with yields ranging from
41% to 78%. 1,1-Dimethyl-pyrrolo[1,2-c]thiazole-2,2-diox-
ide 3a has been prepared before using a less straightforward
approach.1b
This alkylation procedure1b was applied in the synthesis of
1-methyl-pyrrolo[1,2-c]thiazole-2,2-dioxide 5 (Scheme 2).
The metallation of sulfone 41b with LiHMDS and subse-
quent reaction with iodomethane give heterocyclic com-
pound 5 in 82% yield.
Here, we report our study on the azafulvenium methides
generated from 1-methyl- and 1,1-dimethyl-1H,3H-pyr-
rolo[1,2-c]thiazole-2,2-dioxides, aiming to get knowledge
on the reactivity pattern of these extended dipolar systems.
Storr and co-workers described that under FVP 1,1-di-
methyl-1H,3H-pyrrolo[1,2-c]thiazole-2,2-dioxide 3a un-
dergoes cheletropic extrusion of sulfur dioxide giving
azafulvenium methide 6, which leads to 2-isopropenylpyr-
role 7 via an allowed suprafacial [1,8]H shift in the 8p 1,7-
dipolar system.1b We observed that the same azafulvenium
methide intermediate 6 can also be generated by carrying
out thermolysis in a sealed tube and the corresponding peri-
cyclic reaction allows the synthesis of C-vinylpyrrole 7. The
Keywords: Azafulvenium methides; Azomethine ylides; Pyrrolo[1,2-c]thi-
azoles; Pyrroles; 5-Oxo-5H-pyrrolizines; Flash vacuum pyrolysis.
* Corresponding author. Tel.: +351 239 854475; fax: +351 239 826068;
e-mail: tmelo@ci.uc.pt
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.12.025

1834
T. M. V. D. Pinho e Melo et al. / Tetrahedron 63 (2007) 1833–1841
CO2Me
CO2Me
CO2Me
CO2Me
N
- SO2
R1
R2
R1
R2
1-azafulvenium methides
N
O2S
Me
Me
R3
N
R3
CO2Me
Me
MeO2C
Me
CO2Me
CO2Me
R1 = H
R2
H
MeO2C
N
Me
R1
N
Sigmatropic [1,8]H
R2
Me
O
R1
Me
R2
O
CO2Me
R1
R2 = Ph
CO2Me
R1
MeO2C
CO2Me
R1
CO2Me
N
H
N
N
via Electrocyclization
H
R1 = Me
R2
MeO2C
R2
N
R2 = t-Bu or H
O
Me
Scheme 1.
CO2Me
CO2Me
CO2Me
Me
Me
Me
Me
CO2H
NH
Me
CO2Me
Me
DMAD
Ac2O,
MCPBA
S
S
N
O2S
N
Me
Me
R
R
R
2a R = H
2b R = Me
2c R = CH2Ph 60%
2d R = Ph
81%
93%
3a R = H
3b R = Me
3c R = CH2Ph 67%
3d R = Ph 41%
78%
45%
1a R = H
1b R = Me
1c R = CH2Ph
1d R = Ph
89%
CO2Me
CO2Me
CO2Me
CO2Me
Me
O2S
i) LiHMDS
ii) MeI
N
O2S
N
Me
Me
Me
5, 82%
Me
4
Scheme 2.
bestresultwas obtained byheatingat260 ꢀC for1 h asolution
of 3a in sulfolane, which gave pyrrole 7 in 40% yield. The
FVPofsulfone3aunderourreactionconditionsledtoadiffer-
ent outcome than the previously reported result. By carrying
out the FVP at 700 ꢀC/2ꢁ10ꢂ2 mbar, the pyrrole 7 was ob-
tained as the major product in 70% yield together with the for-
mation of5-oxo-5H-pyrrolizine8 in5% yield. Performing the
flash vacuum pyrolysis at 750 ꢀC/2.7ꢁ10ꢂ2 mbar revealed
that the pyrrole 7 is again the major product (54%) but 5-
oxo-5H-pyrrolizine 8 is now obtained in 21% yield. At higher
temperature (850 ꢀC/5.3ꢁ10ꢂ2 mbar) only 5-oxo-5H-pyrrol-
izine 8 is obtained although in low yield (Scheme 3).
C-3, was also studied (Scheme 4). In this particular case,
the SO2 extrusion leads to azafulvenium methide 9 where
two potential [1,8]H sigmatropic shifts could occur. In
fact, it is known that thermolysis of dimethyl 3,5-di-
methyl-pyrrolo[1,2-c]thiazole-6,7-dicarboxylate-2,2-dioxide
can lead to dimethyl 2,5-dimethyl-N-vinyl-1H-pyrrole-3,4-
dicarboxylate via azafulvenium methide 9.1,2 However, the
flash vacuum pyrolysis of compound 3b did not afford
N-vinyl derivatives. Instead, C-vinylpyrrole 10 and 5-oxo-
5H-pyrrolizines 11a and 11b were obtained. The FVP
conditions determine the outcome of this reaction: at
600 ꢀC/2ꢁ10ꢂ2 mbar the C-vinylpyrrole 10 is obtained in
moderate yield (39%) whereas at 750 ꢀC/2.7ꢁ10ꢂ2 mbar
the FVP affords a mixture of 5-oxo-5H-pyrrolizines 11a
and 11b in 20% yield. These 5-oxo-5H-pyrrolizines could
also be prepared by the FVP of C-vinylpyrrole 10
(Scheme 4). Attempts to carry out the thermolysis of pyr-
rolo[1,2-c]thiazole-2,2-dioxide 3b in a sealed tube were
not successful.
5-Oxo-5H-pyrrolizine 8 can also be obtained by the flash
vacuum pyrolysis of 2-isopropenylpyrrole 7 (850 ꢀC/4ꢁ
10ꢂ2 mbar). This result allowed us to conclude that the
2-isopropenylpyrrole 7 is an intermediate in the synthesis
of 5-oxo-5H-pyrrolizine 8 from 1,1-dimethyl-pyrrolo[1,2-c]-
thiazole-2,2-dioxide 3a (Scheme 3).
The reactivity of 1,1-dimethyl-1H,3H-pyrrolo[1,2-c]thi-
azole-2,2-dioxide 3b, bearing an extra methyl group at
The flash vacuum pyrolysis of 1,1-dimethyl-3-benzyl-
1H,3H-pyrrolo[1,2-c]thiazole-2,2-dioxide 3c leads to the

T. M. V. D. Pinho e Melo et al. / Tetrahedron 63 (2007) 1833–1841
1835
CO2Me
Me
Sealed Tube
MeO2C
Me
CO2Me
Me
CO2Me
260 ºC, 1h
- SO2
40%
N
H
H2C
N
Me
CO2Me
CO2Me
Me
Me
6
Me
O2S
7
FVP (850 ºC, 5.3x10-2 mbar)
N
Me
15%
Me
3a
Me
O
MeO2C
Me
CO2Me
Me
FVP
- SO2
MeO2C
N
N
Me
Me
7
8
FVP
700 ºC, 2x10-2 mbar
70%
54%
----
5%
21%
17%
750 ºC, 2.7x10-2 mbar
850 ºC, 5.3x10-2 mbar
Scheme 3.
CO2Me
CO2Me
CO2Me
CO2Me
Me
Me
Me
O2S
FVP
- SO2
N
H
N
Me
Me
Me
3b
Me
9
FVP (750 °C, 2.7x10-2 mbar )
11a:11b 27% (62:38)
R1
Me
O
MeO2C
Me
CO2Me
MeO2C
Me
11a R1 = Et; R2 = Me
11b R1 = Me; R2 = Et
N
N
Et
R2
FVP
600 °C, 2x10-2 mbar
700 °C, 4x10-2
10
11a:11b
39%
13%
----
----
3%
20% (54:46)
6%
mbar
750 °C, 2.7x10-2 mbbar
-2 mbar
----
850 °C, 5.3x10
Scheme 4.
synthesis of C-vinylpyrrole 13 via the [1,8]H shift of aza-
fulvenium methide intermediate 12 (Scheme 5). The best
result was obtained by carrying out the FVP at 650 ꢀC/
3ꢁ10ꢂ2 mbar giving pyrrole 13 in 53% yield.
out the thermolysis of 1,1-dimethyl-3-benzyl-1H,3H-pyrrolo-
[1,2-c]thiazole-2,2-dioxide 3c in a sealed tube led to the
recovery of the starting material (250 ꢀC, 1.5 h) or to com-
plex mixtures when using more drastic reaction conditions
(265 ꢀC, 2.5 h). 5-Oxo-5H-pyrrolizines could not be ob-
tained from pyrrole 13 since the volatilization of the starting
material, required to perform the FVP, led to significant
decomposition of 1,1-dimethyl-3-benzyl-1H,3H-pyrrolo-
[1,2-c]thiazole-2,2-dioxide 3c.
We observed that the presence of two methyl groups at
C-1 in 1,1-dimethyl-3-benzyl-1H,3H-pyrrolo[1,2-c]thiazole-
2,2-dioxide 3c leads to only one reaction channel with the
exclusive formation of C-vinylpyrrole 13. Attempts to carry
CO2Me
Me
CO2Me
Me
MeO2C
Me
CO2Me
Me
Me
O2S
CO2Me
CO2Me
FVP
- SO2
N
N
H
N
Me
Me
CH2Ph
CH2Ph
Bn
3c
FVP
12
13
600°C, 2.0x10-2 mbar
650°C, 3.0x10-2 mbar
700°C, 2.5x10-2 mbar
750°C, 2.5x10-2 mbar
800°C, 2.0x10-2 mbar
22%
53%
24%
15 %
--
Scheme 5.

1836
T. M. V. D. Pinho e Melo et al. / Tetrahedron 63 (2007) 1833–1841
1-Benzyl-2-isopropenyl-5-methyl-1H-pyrrole-3,4-dicarboxy-
late 15 was prepared by the thermolysis of sulfone 3d. This
heterocyclic compound is obtained in low yield (14%) by
heating a solution of 3d in sulfolane in a sealed tube at
260 ꢀC for 1 h. The FVP of sulfone 3d led to the same
C-vinylpyrrole 15 but an unexpected product 16 was also
formed with an overall yield between 66–69%. In this
case, it was observed that by carrying out the FVP at higher
temperature (700 ꢀC or 850 ꢀC) only traces of the products
could be detected. On the other hand, by performing the
FVPatlowertemperature(450 ꢀC, 2ꢁ10ꢂ2 mbar)noreaction
occurs. The FVP of 1-benzyl-2-isopropenyl-5-methyl-1H-
pyrrole-3,4-dicarboxylate 15 affords 5-(2-methyl-1-phenyl-
allyl)-1H-pyrrole 16 (20%) proving that pyrrole 15 is an
intermediate in the synthesis of compound 16 from sulfone
3d (Scheme 6).
The FVP of 1-methyl-1H,3H-pyrrolo[1,2-c]thiazole-2,2-
dioxide 17 to give C-vinylpyrrole 19 has been reported
although this compound was not obtained pure.1b We decided
to look again into the chemical behaviour of compound 17.
1-Methyl-1H,3H-pyrrolo[1,2-c]thiazole-2,2-dioxide 17 was
prepared following the synthetic procedure described in the
literature.1b The SO2 extrusion of sulfone 17 can be accom-
plished by sealed tube thermolysis giving pure C-vinyl-
pyrrole 19 in 32% yield. The sealed tube thermal reaction
carried out at higher temperature (260 ꢀC, 0.75 h) led only
to the decomposition of the starting material. The flash vac-
uum pyrolysis of 1-methyl-1H,3H-pyrrolo[1,2-c]thiazole-
2,2-dioxide 17 at 700 ꢀC/4ꢁ10ꢂ2 mbar gave C-vinylpyrrole
19 in 11% yield whereas at 850 ꢀC/2.7ꢁ10ꢂ2 mbar methyl
1,3-dimethyl-5-oxo-5H-pyrrolizine-2-carboxylate 20 was
the sole product (Scheme 7).
The structural assignment of 1H-pyrrole 16 was achieved us-
ing two-dimensional NMR techniques. The COSY spectrum
showed cross-peaks between H-6 and H-8a, H-8b, H-9 and
with the ortho-protons of the phenyl group. The spectrum
shows also cross-peaks between H-9 and H-8a and H-8b.
The HMQC spectrum allowed the assignment of signals cor-
responding to the side chain carbons with chemical shifts of
22.1 (C-9), 48.8 (C-6) and 113.2 (C-8).
Finally, the reactivity of 1,3-dimethyl-1H,3H-pyrrolo[1,2-c]-
thiazole-2,2-dioxide 5 was studied (Scheme 8). This is a case
where the SO2 extrusion leads to an azafulvenium methide,
which can undergo two potential [1,8]H sigmatropic shifts.
In fact, on FVP the heterocycle 5 participates in both
[1,8]H shifts giving the corresponding C-vinylpyrrole 23
and N-vinylpyrrole 24. However, these were not the only
products and pyrrole 22 was obtained as the major product.
CO2Me
CO2Me
Me
Me
Sealed Tube
260 ºC, 1h
MeO2C
Me
CO2Me
Me
Me
O2S
CO2Me
CO2Me
N
14%
- SO2
N
H
N
Me
Me
Ph
3d
Bn
14
20%
Ph
FVP
15
MeO2C
CO2Me
4
MeO2C
Me
CO2Me
Me
3
FVP
- SO2
2
5
Ph
Me
N
N
Bn
6
1H
10
7
H8a
Me
8
9
H8b
FVP
15
40%
33%
16
29%
33%
550 ºC, 2.7x10-2 mbar
550 ºC, 2x10-2 mbar
Scheme 6.
CO2Me
CO2Me
Sealed Tube
245 ºC, 1h
MeO2C
Me
CO2Me
32%
- SO2
N
H
H2C
N
Me
19
Me
CO2Me
CO2Me
18
Me
O2S
N
Me
17
Me
MeO2C
Me
CO2Me
FVP
- SO2
MeO2C
N
N
Me
O
Me
FVP
19
20
700 ºC, 4x10-2 mbar
11%
----
----
4%
850 ºC, 2.7x10-2 mbar
Scheme 7.

T. M. V. D. Pinho e Melo et al. / Tetrahedron 63 (2007) 1833–1841
1837
CO2Me
CO2Me
CO2Me
CO2Me
Me
FVP
-SO2
Me
O2S
N
N
Me
Me
Me
Me
21
5
MeO2C
MeO2C
Me
CO2Me
Me
CO2Me
Me
MeO2C
Et
CO2Me
Me
+
+
N
Et
N
H
N
22
23
24
FVP
550 °C, 2.0x10-2 mbar*
600 °C, 2.5x10-2 mbar
650 °C, 3.0x10-2 mbar
700 °C, 3.5x10-2 mbar
46%
58%
39%
10%
traces
5%
10%
5%
10%
14%
13%
traces
* 5 = 12%
Scheme 8.
The 2-(but-3-en-2-yl) side chain of pyrrole 22 is easily iden-
tified by its H NMR spectrum. Three vinylic protons are
A clear reactivity pattern of the studied azafulvenium
methides can be defined (Scheme 9). Azafulvenium methi-
des generated from 1,1-dimethyl-1H,3H-pyrrolo[1,2-c]thi-
azole-2,2-dioxides undergo [1,8]H sigmatropic shifts to
give C-vinylpyrroles even in the cases where an alternative
pericyclic reactions could in principle occur. Azafulvenium
methides generated from a 1-methyl-1H,3H-pyrrolo[1,2-c]-
thiazole-2,2-dioxide unsubstituted at C-3 can only un-
dergo the same type of [1,8]H shift to the corresponding
1
observed (at 5.12, 5.17 and 5.93–6.04 ppm) together with
a multiplet at 4.05–4.10 ppm corresponding to H-2 and
a multiplet assigned to the methyl group at 1.33 ppm. On
the other hand, the spectrum shows a broad singlet at
8.22 ppm proving that 22 is a N-unsubstituted 1H-pyrrole.
This functionalized pyrrole 22 has a similar substitution pat-
tern to the one of pyrrole 16 (see Scheme 6).
R2
MeO2C
R1
R
R
R
1 = Me; R2 = H, Me
1 = R2 = Me
CO2Me
R1
1 = R2 = H
MeO2C
CO2Me
R1
N
CO2Me
O
Me
Sigmatropic [1,8]H
N
H
Me
N
Me
R1 = Me; R2 = Ph
R1 = H; R2 = Me
R2
R2
MeO2C
Me
CO2Me
R2
R1 = Me; R2 = H, Me, CH2Ph, Ph
R1 = R2 = Me
N
H
R
R
1 = R2 = H
R1
1 = H; R2 = Me
R2
MeO2C
Me
CO2Me
MeO2C
MeO2C
Me
CO2Me
R1
CO2Me
R1
R2
R1
[1,5] shift
R2
[1,5] shift
R1
1. [1,7] shift
2. [1,7]H
Me
N
N
N
R2
R1
R2
R2
MeO2C
R1
CO2Me
MeO2C
MeO2C
N
NH
N
O
- MeOH
O
Me
Me
25
Me
MeO2C
Me
CO2Me
R1
MeO2C
MeO2C
Me
CO2Me
R1
R1
H
MeO2C
[1,5] shift
[1,5] shift
N
N
Me
N
R2
R2
R2
MeO2C
MeO2C
MeO2C
Me
CO2Me
MeO2C
Me
CO2Me
R1
R2
[1,3]H
[1,6] shift
[1,5]H
H
R2
R2
R1
Me
N
H
N
N
H
R1
Scheme 9.

1838
T. M. V. D. Pinho e Melo et al. / Tetrahedron 63 (2007) 1833–1841
C-vinylpyrrole. However, the reaction of 1,3-dimethyl-
1H,3H-pyrrolo[1,2-c]thiazole-2,2-dioxide derivative leads
to the azafulvenium methide intermediate, which undergoes
two possible [1,8]H sigmatropic shifts.
at 75.5 MHz or on an instrument operating at 125 MHz. The
solvent is deuteriochloroform except where indicated other-
wise; chemical shifts are expressed in parts per million
related to internal TMS, and coupling constants (J) are in
hertz. Mass spectra were recorded under electron impact
(EI) at 70 eV.
The formation of 5-oxo-5H-pyrrolizines from C-vinylpyr-
roles can be rationalized as outlined in Scheme 9. The
pyrrol-2-ylpropionates 25 must be intermediates in the syn-
thesis of the 5-oxo-5H-pyrrolizines, formed from the
C-vinylpyrroles through a sequence of sigmatropic shifts.
The pyrrol-2-ylpropionates undergo concerted elimination
of methanol giving pyrrol-2-ylideneketenes, which are
converted into 5-oxo-5H-pyrrolizines by electrocyclization.
This is in agreement with the reported rearrangement to
5-oxo-5H-pyrrolizines.2,3 The synthesis of 11b involves an
initial methyl migration followed by a sequence of sigma-
tropic shifts to give the corresponding pyrrol-2-ylpropio-
nates, which is converted to the final product.
4.2. General procedure for the synthesis of 5,5-dimethyl-
1,3-thiazolidine-4-carboxylic acid
DL-Penicillamine (2.98 g, 20 mmol) was dissolved in meth-
anol (400 mL) followed by the dropwise addition of the
aldehyde (22 mmol). The reaction mixture was stirred over-
night at room temperature. The solvent was evaporated off
and the product crystallized.
4.2.1. 5,5-Dimethyl-1,3-thiazolidine-4-carboxylic acid 1a.
Yield 84%, mp 200–202 ꢀC (from ethanol) (lit.6 mp 200–
201 ꢀC). IR (KBr) 3010 (br s), 1628, 1382, 1334,
1
The mechanism for the new rearrangement of C-vinylpyr-
roles to give functionalized C-allyl-1H-pyrroles is shown
in Scheme 9.
1126 cmꢂ1. H NMR (CD3OD) 1.44 (3H, s), 1.71 (3H, s),
3.77 (1H, s), 4.30 (1H, d, J¼9.8), 4.38 (1H, d, J¼9.8).
4.2.2. 2,5,5-Trimethyl-1,3-thiazolidine-4-carboxylic acid
1b. Compound 1b was obtained as a white solid in 83%
yield, mp 192.3–193.2 ꢀC (from ethanol) (lit.7 mp 186–
3. Conclusion
1
188 ꢀC). The H NMR spectrum showed the presence of
We reported the reactivity of azafulvenium methides gener-
ated by thethermal extrusionof sulfurdioxide from 1-methyl-
and 1,1-dimethyl-1H,3H-pyrrolo[1,2-c]thiazole-2,2-dioxides
as well as the chemical behaviour of C-vinylpyrroles to-
wards thermolysis.
1
two diastereoisomers (ratio 51:49). Major component: H
NMR (CD3OD) 1.46 (3H, s), 1.58 (3H, d, J¼6.3), 1.69
(3H, s), 3.81 (1H, s), 4.76 (1H, q, J¼6.3). Minor component:
1H NMR (CD3OD) 1.41 (3H, s), 1.62 (3H, d, J¼6.4), 1.70
(3H, s), 3.98 (1H, s), 4.96 (1H, q, J¼6.4). MS (ES+) m/z
176 (MH+, 25%), 159 (100), 130 (46) and 84 (10).
Azafulvenium methides generated by thermolysis of 1,1-di-
methyl-1H,3H-pyrrolo[1,2-c]thiazole-2,2-dioxides and C-3
unsubstituted 1-methyl-1H,3H-pyrrolo[1,2-c]thiazole-2,
2-dioxide undergo [1,8]H sigmatropic shifts to give C-vinyl-
pyrroles. However, the thermal reaction of 1-methyl-1H,3H-
pyrrolo[1,2-c]thiazole-2,2-dioxide bearing a methyl group at
C-3 affords the corresponding C-vinylpyrrole and N-vinyl-
pyrrole via two competitive [1,8]H sigmatropic shifts. Vinyl-
pyrroles are valuable building blocks for the synthesis of
functionalized pyrroles including condensed pyrrole-annu-
lated heterocycles.3c,4 Moreover, 2-vinylpyrroles are found
in many biologically active molecules and they are also of
interest as vinyl monomers and as ligands for new photocata-
lysts and biologically active complexes.3c,4,5
4.2.3. 2-Benzyl-5,5-dimethyl-1,3-thiazolidine-4-carboxy-
lic acid 1c. Compound 1c was obtained as a white in 70%
yield, mp 114–115 ꢀC (from diethyl ether/hexane). IR
(KBr) 1638, 1414, 1386, 1117 cmꢂ1. The 1H NMR spectrum
showed the presence of two diastereoisomers (ratio 71:29).
1
Major component: H NMR 1.22 (3H, s), 1.60 (3H, s),
3.07 (1H, d, J¼7.5), 3.25 (1H, d, J¼5.2), 3.81 (1H, s),
4.87 (1H, dd, J¼5.2 and 7.5), 7.1–7.4 (5H, m, Ar–H). Minor
component: 1H NMR 1.35 (3H, s), 1.63 (3H, s), 3.03 (1H, d,
J¼7.5), 3.28 (1H, d, J¼5.2), 4.12 (1H, s), 5.06 (1H, dd,
J¼5.2 and 7.5), 7.1–7.3 (5H, m, Ar–H). 13C NMR (major
component) 28.8, 29.8, 41.9, 56.9, 66.3, 73.8, 127.5,
129.0, 129.7, 136.9, 171.5. Anal. Calcd for C13H17NO2S:
C, 62.12; H, 6.82; N, 5.57; S, 12.76%. Found: C, 62.52; H,
7.13; N, 5.93; S, 12.89%.
Taking advantage of the particular reaction conditions that
FVP offers, an important technique for carrying out intra-
molecular reactions, new C-vinylpyrrole rearrangements to
afford 5-oxo-5H-pyrrolizines or functionalized C-allyl-1H-
pyrroles are also reported. 5-Oxo-5H-pyrrolizines are het-
erocycles with an interesting chemistry, which has been
applied to the synthesis of the pyrrolizine alkaloid, 3,8-dide-
hydroheliotridin-5-one.3b
4.2.4. 5,5-Dimethyl-2-phenyl-1,3-thiazolidine-4-carboxy-
lic acid 1d. Yield 48%, mp 136.7–138.8 ꢀC (from diethyl
ether) (lit.8 mp 145–146 ꢀC, for the thiazolidine obtained
1
from D-penicillamine). The H NMR spectrum showed the
presence of two diastereoisomers. H NMR 1.59 and 1.61
1
(3H, 2ꢁs), 1.81 and 1.84 (3H, 2ꢁs), 4.08 (1H, s), 6.04
(1H, s), 7.40–7.49 (3H, m, Ar–H), 7.67–7.69 (2H, m, Ar–H).
4. Experimental
4.1. General
4.3. General procedure for the synthesis of dimethyl
1,1,5-trimethyl-1H,3H-pyrrolo[1,2-c]thiazole-6,7-di-
carboxylates
1H NMR spectra were recorded on an instrument operating
at 300 MHz or on an instrument operating at 500 MHz.
13C NMR spectra were recorded on an instrument operating
The appropriate 5,5-dimethyl-1,3-thiazolidine-4-carboxylic
acid (5 mmol), dimethyl acetylenedicarboxylate (0.9 mL,

T. M. V. D. Pinho e Melo et al. / Tetrahedron 63 (2007) 1833–1841
1839
7.5 mmol) and acetic anhydride (20 mL) were heated at
110–120 ꢀC for 4 h. The reaction mixture was cooled to
room temperature and was diluted with CH2Cl2 (50 mL).
The organic phase was washed with a saturated aqueous
solution of NaHCO3 and with water, dried (MgSO4) and
the solvent was evaporated off. The crude product was puri-
fied by flash chromatography (hexane/ethyl acetate).
was washed twice with 10% (w/v) aqueous sodium bisulfite
solution (2ꢁ20 mL) and twice with 10% (w/v) aqueous so-
dium bicarbonate solution (2ꢁ20 mL). The organic fraction
was then dried over anhydrous MgSO4 and the solvent was
evaporated off. The crude product was purified by flash chro-
matography (hexane/ethyl acetate).
4.4.1. Dimethyl 1,1,5-trimethyl-1H,3H-pyrrolo[1,2-c]thi-
azole-6,7-dicarboxylate-2,2-dioxide 3a. Yield 78%, mp
150.2–151.6 ꢀC (from diethyl ether) (lit.2b mp 149–150 ꢀC).
MS (EI) m/z 315 (M+, 7%), 284 (12), 251 (23), 219 (100),
187 (40), 161 (20) and 133 (48).
4.3.1. Dimethyl 1,1,5-trimethyl-1H,3H-pyrrolo[1,2-c]thi-
azole-6,7-dicarboxylate 2a. Compound 2a was obtained as
a white solid in 81% yield, mp 106.0–107.4 ꢀC (from diethyl
ether/hexane). IR (KBr) 1708, 1692, 1530, 1235,
1
1207 cmꢂ1. H NMR 1.80 (6H, s), 2.34 (3H, s), 3.79 (6H,
s), 4.91 (2H, s). 13C NMR 11.0, 30.0, 46.1, 51.4, 51.5,
52.7, 106.4, 116.4, 128.8, 144.3, 164.9, 165.3. MS (EI) m/z
283 (M+, 27%), 268 (23), 252 (11) and 236 (100). Anal.
Calcd for C13H17NO4S: C, 55.11; H, 6.05; N, 4.94. Found:
C, 55.25; H, 6.26; N, 4.54.
4.4.2. Dimethyl 1,1,3,5-tetramethyl-1H,3H-pyrrolo[1,2-
c]thiazole-6,7-dicarboxylate-2,2-dioxide 3b. Compound
3b was obtained as a white solid in 45% yield, mp 92.7–
94.3 ꢀC (from diethyl ether/hexane). IR (KBr) 1689, 1531,
1
1322, 1235, 1213, 1119 cmꢂ1. H NMR 1.73 (3H, s), 1.76
(3H, s), 1.77 (3H, d, J¼6.8), 2.43 (3H, s), 3.83 (3H, s),
3.84 (3H, s), 4.97 (1H, q, J¼6.8). MS (EI) m/z 329 (M+,
21%), 298 (20), 265 (23), 233 (64), 201 (39) and 147
(100). Anal. Calcd for C14H19NO6S: C, 51.05; H, 5.81; N,
4.25. Found: C, 50.82; H, 5.70; N, 3.78.
4.3.2. Dimethyl 1,1,3,5-tetramethyl-1H,3H-pyrrolo[1,2-c]-
thiazole-6,7-dicarboxylate 2b. Compound 2b was obtained
as a white solid in 93% yield, mp 71.1–72.5 ꢀC (from diethyl
1
ether/hexane). IR (KBr) 1694, 1529, 1232, 1202 cmꢂ1. H
NMR 1.72 (3H, s), 1.73 (3H, d, J¼6.2), 1.88 (3H, s), 2.35
(3H, s), 3.77 (3H, s), 3.79 (3H, s), 5.35 (1H, q, J¼6.2).
MS (EI) m/z 297 (M+, 31%), 282 (28), 266 (9) and 250
(100). Anal. Calcd for C14H19NO4S: C, 56.55; H, 6.44; N,
4.71. Found: C, 56.73; H, 6.63; N, 4.38.
4.4.3. 1,1-Dimethyl-3-benzyl-1H,3H-pyrrolo[1,2-c]thi-
azole-2,2-dioxide 3c. Compound 3c was obtained as a white
solid in 67% yield, mp 104.0–105.8 ꢀC (from ethyl acetate/
hexane). IR (KBr) 1712, 1704, 1323, 1219, 1114 cmꢂ1. 1H
NMR 1.66 (3H, s), 1.71 (3H, s), 1.97 (3H, s), 3.10 (1H,
dd, J¼6.4 and 15.0), 3.65 (1H, dd, J¼6.4 and 15.0), 3.81
(3H, s), 3.84 (3H, s), 5.09 (1H, t, J¼6.4), 7.13–7.34 (5H,
m, Ar–H). 13C NMR 11.6, 19.9, 25.8, 40.0, 52.1, 52.4,
62.2, 74.2, 112.8, 115.9, 128.5, 129.7, 130.1, 132.9, 134.2,
135.3, 164.8, 165.2. MS (EI) m/z 405 (M+, 23%), 345
(38), 332 (68), 294 (100), 223 (49) and 173 (29). HRMS
(EI) m/z 405.1255 (C20H23NO6S [M+], 405.1246).
4.3.3. Dimethyl 1,1,5-trimethyl-3-benzyl-1H,3H-pyr-
rolo[1,2-c]thiazole-6,7-dicarboxylate 2c. Compound 2c
was obtained as a white solid in 60% yield, mp 104–
106 ꢀC (from ethyl acetate/hexane). IR (KBr) 1706, 1525,
1228, 1200 cmꢂ1. 1H NMR 1.63 (3H, s), 1.71 (3H, s), 2.45
(3H, s), 3.16 (1H, dd, J¼8.7 and 13.8), 3.35 (1H, dd,
J¼3.6 and 13.8), 3.78 (3H, s), 3.82 (3H, s), 5.47 (1H, dd,
J¼3.6 and 8.7), 7.11–7.31 (5H, m, Ar–H). 13C NMR 11.9,
30.6, 32.9, 45.3, 51.9, 52.0, 52.3, 64.2, 106.8, 117.9,
127.8, 129.0, 130.4, 135.4, 145.5, 165.3, 166.0. MS (EI)
m/z 373 (M+, 13%), 326 (15), 282 (100), 250 (89) and 206
(27). Anal. Calcd for C20H23NO4S: C, 64.32; H, 6.21; N,
3.75; S, 8.59. Found: C, 64.15; H, 6.17; N, 3.96; S, 8.41.
4.4.4. Dimethyl 1,1,5-trimethyl-3-phenyl-1H,3H-pyr-
rolo[1,2-c]thiazole-6,7-dicarboxylate-2,2-dioxide 3d.
Compound 3d was obtained as a white solid in 41% yield,
mp 161.2–162.3 ꢀC (from diethyl ether). IR (KBr) 1707,
1
1533, 1327, 1227, 1217, 1117 cmꢂ1. H NMR 1.64 (3H,
s), 1.79 (3H, s), 2.14 (3H, s), 3.85 (3H, s), 3.88 (3H, s),
5.94 (1H, s), 7.03–7.06 (2H, m, Ar–H), 7.44–7.46 (3H, m,
Ar–H). 13C NMR 11.5, 20.4, 25.2, 51.8, 52.0, 62.2, 76.2,
112.0, 115.7, 126.9, 129.4, 130.4, 130.5, 132.4, 135.7,
164.4, 164.7. MS (EI) m/z 391 (M+, 13%), 360 (15), 327
(50), 275 (100), 263 (36) and 71 (82). Anal. Calcd for
C19H21NO6S: C, 58.30; H, 5.41; N, 3.58. Found: C, 58.65;
H, 5.67; N, 3.26.
4.3.4. Dimethyl 1,1,5-trimethyl-3-phenyl-1H,3H-pyr-
rolo[1,2-c]thiazole-6,7-dicarboxylate 2d. Compound 2d
was obtained as a pale yellow solid in 89% yield, mp
118.6–119.7 ꢀC (from diethyl ether/hexane). IR (KBr)
1
1705, 1698, 1527, 1227, 1217 cmꢂ1. H NMR 1.84 (3H,
s), 1.90 (3H, s), 1.95 (3H, s), 3.81 (3H, s), 3.84 (3H, s),
6.34 (1H, s), 7.06–7.10 (2H, m, Ar–H), 7.33–7.35 (3H, m,
Ar–H). MS (EI) m/z 359 (M+, 59%), 344 (64), 312 (100)
and 206 (67). Anal. Calcd for C19H21NO4S: C, 63.49; H,
5.89; N, 3.90. Found: C, 63.67; H, 6.30; N, 3.65.
4.4.5. Dimethyl 1,3,5-trimethyl-1H,3H-pyrrolo[1,2-c]thi-
azole-6,7-dicarboxylate-2,2-dioxide 5. LiHMDS (2.4 mL,
1.0 M in hexanes, 2.4 mmol) was slowly added to a solution
of dimethyl 3,5-methyl-1H,3H-pyrrolo[1,2-c][1,3]thiazole-
6,7-dicarboxylate-2,2-dioxide 11 (0.5 g, 1.6 mol) in anhy-
drous THF (30 mL) at ꢂ78 ꢀC and the mixture was stirred
for 1 h. A solution of iodomethane (175 mL, 2.8 mmol,
1.7 equiv) was added slowly and the reaction mixture was
stirred for 1 h. The reaction mixture was then allowed to
warm to room temperature and quenched with saturated
aqueous ammonium chloride solution (100 mL). The organic
fractions were extracted with ethyl acetate (2ꢁ50 mL),
4.4. General procedure for the synthesis of sulfones
To a stirred ice-cold solution of the appropriate dimethyl
1H,3H-pyrrolo[1,2-c]thiazole-6,7-dicarboxylate (1 mmol)
in dry dichloromethane (7 mL) was added portionwise 3-
chloroperoxybenzoic acid (3 equiv, 3 mmol) under N2 atmo-
sphere. The cooling bath was removed and the reaction
mixture was allowed to warm to room temperature. After
stirring at room temperature for 3 h, the reaction mixture

1840
T. M. V. D. Pinho e Melo et al. / Tetrahedron 63 (2007) 1833–1841
washed with water (50 mL), brine (50 mL) and dried over
anhydrous NaSO4. The solvent was removed in vacuo and
the crude product was purified by flash chromatography
(hexane/ethyl acetate) to give dimethyl 1,3,5-trimethyl-
1H,3H-pyrrolo[1,2-c]thiazole-6,7-dicarboxylate-2,2-dioxide
(0.414 g, 82%) as a white foam, together with 15% (0.076 g)
of the starting material. IR (KBr) 1707, 1525, 1138 cmꢂ1. 1H
NMR 1.68 (3H, d, J¼7.4), 1.74 (3H, d, J¼7.1), 2.42 (3H, s),
3.83 (3H, s), 3.87 (3H, s), 4.58 (1H, q, J¼7.4), 4.94 (1H, q,
J¼7.1). 13C NMR 11.1, 17.6, 18.9, 51.6, 51.8, 57.2, 70.2,
111.4, 115.8, 131.9, 132.8, 163.1, 164.9. MS (EI) m/z 315
(M+, 20%), 326 (30), 284 (15), 251 (39), 219 (74), 161
(27), 133 (100), 91 (11). HRMS (EI) m/z 315.0789
(C13H17NO6S [M+], 315.0777).
the pyrolysate was removed from the cold finger with di-
chloromethane and the solvent was removed in vacuo.
4.6.1. Dimethyl 2-isopropenyl-1,5-dimethyl-1H-pyrrole-
3,4-dicarboxylate 7 (70%)1b and 5-oxo-5H-pyrrolizine 8
(5%) from 3a [700 ꢀC/2310L2 mbar]. Product 7 was iden-
tified by comparison with the specimen previously prepared.
5-Oxo-5H-pyrrolizine 8 was an oil with an intense orange
1
colour. IR (KBr) 1740, 1711, 1241, 1124 cmꢂ1. H NMR
2.04 (3H, s), 2.25 (3H, s), 2.26 (3H, s), 3.83 (3H, s), 5.50
(1H, s). 13C NMR 9.8, 10.1, 16.2, 51.2, 115.8, 118.9,
121.4, 128.8, 138.2, 153.2, 164.4, 166.7. MS (EI) m/z 219
(M+, 100%), 204 (17), 188 (17), 176 (38), 160 (24) and
148 (22). HRMS (EI) m/z 219.0894 (C12H13NO3 [M+],
219.0895).
4.5. General procedure for the sealed tube reactions
4.6.2. 5-Oxo-5H-pyrrolizine 8 (15%) from 7 [850 ꢀC/
4310L2 mbar]. Product 7 was identified by comparison
with the specimen previously prepared.
The appropriate 1H,3H-pyrrolo[1,2-c]thiazole-6,7-dicar-
boxylate-2,2-dioxide (0.35 mmol) was dissolved in sulfo-
lane (1 mL) in a glass pyrolysis tube, which was cooled in
liquid nitrogen, evacuated, sealed and heated. After cooling
to room temperature the tube was opened, the reaction
mixture was diluted with dichloromethane and washed
with water. The mixture was purified by flash chromato-
graphy [ethyl acetate/hexane (1:2) and then ethyl acetate/
hexane (1:1)].
4.6.3. Dimethyl 2-isopropenyl-1-ethyl-5-methyl-1H-pyr-
role-3,4-dicarboxylate 10 (39%) from 3b [600 ꢀC/
2.0310L2 mbar]. Product 10 was obtained as a yellow oil
in 39% yield. 1H NMR 1.24 (3H, t, J¼7.2), 2.05 (3H,
br s), 2.43 (3H, s), 3.78 (3H, s), 3.80 (3H, s), 3.84 (2H, q,
J¼7.2), 5.05 (1H, br s), 5.45 (1H, br s). 13C NMR 10.9,
16.2, 24.2, 39.1, 51.3, 51.5, 111.8, 112.5, 120.3, 133.5,
136.0, 137.0, 165.7 and 165.8. MS (EI) m/z 265 (M+,
40%), 233 (46), 218 (26), 201 (24), 173 (14) and 147
(100). HRMS (EI) m/z 265.1311 (C14H19NO4 [M+],
265.1314).
4.5.1. Dimethyl 2-isopropenyl-1,5-dimethyl-1H-pyrrole-
3,4-dicarboxylate 7.1b Compound 7 was obtained from 3a
as a colourless solid in 40% yield, mp 68.0–69.4 ꢀC (from
1
ethyl acetate/hexane). H NMR 2.02 (3H, br s), 2.42 (3H,
s), 3.41 (3H, s), 3.78 (3H, s), 3.80 (3H, s), 5.03–5.04 (1H,
m), 5.42–5.44 (1H, m).
4.6.4. Methyl 1-ethyl-3,7-dimethyl-5-oxo-5H-pyrrol-
izine-2-carboxylate 11a and methyl 3-ethyl-1,7-di-
methyl-5-oxo-5H-pyrrolizine-2-carboxylate 11b from
3b [750 ꢀC/2.7310L2 mbar]. Compounds 11a and 11b
were obtained as a 54:46 mixture in 20% yield. IR (KBr)
1746, 1711, 1528, 1237, 1128 cmꢂ1. Major component: 1H
NMR 1.06 (3H, t, J¼7.4), 2.25 (3H, s), 2.26 (3H, s), 2.51
(2H, q, J¼7.4), 5.48–5.49 (1H, m). 13C NMR 9.6, 15.3,
16.2, 17.6, 51.1, 115.1, 118.8, 128.1, 135.0, 138.2, 153.2,
164.2, 166.6. Minor component: 1H NMR 1.15 (3H, t,
J¼7.4), 2.04 (3H, s), 2.25 (3H, s), 2.67 (2H, q, J¼7.4),
5.48–5.49 (1H, m). 13C NMR 9.9, 12.6, 16.2, 17.4, 51.1,
115.8, 119.0, 128.7, 132.2, 138.4, 153.2, 164.4, 166.3.
MS (EI) m/z 233 (M+, 72%), 218 (100), 202 (10) and 186
(12). HRMS (EI) m/z 233.1050 (C13H15NO3 [M+],
233.1052).
4.5.2. Dimethyl 1-benzyl-2-isopropenyl-5-methyl-1H-
pyrrole-3,4-dicarboxylate 15. Compound 15 was obtained
from 3d in 14% yield as an oil. IR (KBr) 1709, 1443,
1
1210 cmꢂ1. H NMR 1.90 (3H, br s), 228 (3H, s), 3.80
(3H, s), 3.82 (3H, s), 4.98–4.99 (1H, m), 5.07 (2H, s),
5.32–5.34 (1H, m), 6.89–6.91 (2H, m, Ar–H), 7.25–7.34
(3H, m, Ar–H). 13C NMR 11.2, 24.0, 47.5, 51.4, 51.6,
112.2, 113.0, 120.4, 125.5, 127.5, 128.9, 134.5, 135.7,
136.8, 137.7, 165.6, 165.8. MS (EI) m/z 327 (M+, 35%),
295 (58), 263 (27), 259 (59) and 91 (100). HRMS (EI) m/z
327.1473 (C19H21NO4 [M+], 327.1471).
4.5.3. Dimethyl 1,2-dimethyl-5-vinyl-1H-pyrrole-3,4-di-
carboxylate 19.1b Compound 19 was obtained from 17 as
a colourless solid in 32% yield, mp 79.2–80.7 ꢀC (from ethyl
ether). 1H NMR 2.45 (3H, s), 3.51 (3H, s), 3.80 (3H, s), 3.82
(3H, s), 5.42 (1H, dd, J¼1.1 and 11.8), 5.54 (1H, dd, J¼1.1
and 17.7), 6.66 (1H, dd, J¼11.8 and 17.7).
4.6.5. Methyl 1-ethyl-3,7-dimethyl-5-oxo-5H-pyrrol-
izine-2-carboxylate 11a and methyl 3-ethyl-1,7-di-
methyl-5-oxo-5H-pyrrolizine-2-carboxylate 11b from 10
[750 ꢀC/2.7310L2 mbar]. Compounds 11a and 11b were
obtained as a 62:38 mixture in 27% yield and were identified
by comparison with the specimen previously prepared.
4.6. General procedure for the flash vacuum pyrolysis
Pyrolysis of the appropriate 1H,3H-pyrrolo[1,2-c]thiazole-
2,2-dioxide (0.30–0.90 mmol) or vinyl-1H-pyrrole (0.20–
0.35 mmol) at 700–850 ꢀC/2ꢁ10ꢂ2–5ꢁ10ꢂ2 mbar onto a
surface cooled at ꢂ196 ꢀC over a period of 1.5–5 h gave a
yellowish pyrolysate (or red pyrolysate where indicated).
(The rate of volatilization of the starting material was con-
trolled by the use of a Kugelrohr oven, which heated the
sample at 100–250 ꢀC.) After cooling to room temperature
4.6.6. Dimethyl 1-phenylethyl-2-methyl-5-(1-isopropenyl-
2-methyl)-1H-pyrrole-3,4-dicarboxylate 13 from 3c
[650 ꢀC/2.5310L2 mbar]. Product 13 was obtained in
53% yield, mp 96 ꢀC (from ethyl acetate/hexane). IR
1
(KBr) 1721, 1705, 1227, 1330, 1123 cmꢂ1. H NMR 2.02
(3H, d, J¼0.9), 2.37 (3H, s), 2.87 (2H, approx. t, J¼7.9),
3.78 (3H, s), 3.81 (3H, s), 3.99 (2H, approx. t, J¼7.9),

T. M. V. D. Pinho e Melo et al. / Tetrahedron 63 (2007) 1833–1841
1841
5.03–5.04 (1H, m), 5.35–5.45 (1H, m), 7.05–7.33 (5H, m).
13C NMR 11.0, 25.1, 37.4, 45.8, 51.4, 51.5, 111.8, 112.9,
120.5, 127.0, 128.6, 128.9, 133.8, 137.0, 137.6, 165.7 and
165.8. MS (EI) m/z 341 (M+, 54%), 326 (30), 309 (49),
294 (100), 223 (53), 173 (42), 105 (40), 77 (19). HRMS
(EI) m/z 341.1627 (C20H23NO4 [M+], 341.1627).
(1H, m), 8.22 (1H, br s, NH). 13C NMR 12.5, 18.6, 33.8,
51.3, 51.4, 111.7, 112.2, 115.1, 132.6, 138.0, 139.6, 165.7
and 165.8. MS (EI) m/z 251 (M+, 12%), 220 (21), 204
(13), 187 (100), 177 (12), 159 (33), 132 (16), 118 (11).
HRMS (EI) m/z 251.1164 (C13H17NO4 [M+], 251.1158).
Dimethyl 1-ethyl-2-methyl-5-vinyl-1H-pyrrole-3,4-dicar-
boxylate 23 was obtained in 5% yield. H NMR 1.28 (3H,
1
4.6.7. Dimethyl 1-benzyl-2-isopropenyl-5-methyl-1H-
pyrrole-3,4-dicarboxylate 15 (33%) and dimethyl
2-methyl-5-(2-methyl-1-phenylallyl)-1H-pyrrole-3,4-di-
carboxylate 16 (33%) from 3d [550 ꢀC/2310L2 mbar].
Product 15 was identified by comparison with the specimen
previously prepared. Dimethyl 2-methyl-5-(2-methyl-1-phe-
nylallyl)-1H-pyrrole-3,4-dicarboxylate 16: IR (KBr) 1703,
t, J¼7.3), 2.47 (3H, s), 3.79 (3H, s), 3.83 (3H, s), 3.94
(2H, q, J¼7.3), 5.38 (1H, dd, J¼11.7 and 1.2), 5.58 (1H,
dd, J¼17.7 and 1.2), 6.59 (1H, dd, J¼17.7 and 11.7). 13C
NMR 10.9, 15.5, 40.0, 51.3, 52.1, 111.4, 112.2, 118.6,
124.1, 130.3, 135.1, 165.7 and 165.8. MS (EI) m/z 251
(M+, 35%), 220 (45), 190 (9), 161 (16), 133 (100), 118
(6). HRMS (EI) m/z 251.1146 (C13H17NO4 [M+], 251.1158).
1
1682, 1445, 1220, 1103 cmꢂ1. H NMR 1.71 (3H, br s, H-
9), 2.26 (3H, s, H-10), 3.68 (3H, s), 3.73 (3H, s), 4.45 (1H,
br s, H-8a), 4.99 (1H, br s, H-8a), 5.20 (1H, br s, H-6),
7.10–7.12 (2H, m, Ar–H, o-H), 7.18–7.21 (1H, m, Ar–H,
p-H), 7.25–7.28 (2H, m, Ar–H, m-H), 7.69 (1H, br s, NH).
13C NMR 11.6 (C-10), 22.1 (C-9), 48.8 (C-6), 50.3
(CO2CH3), 50.4 (CO2CH3), 111.5 (C-3), 111.9 (C-4),
113.2 (C-8), 126.2 (p-C, Ar), 127.6 (o-C, Ar), 127.9 (m-C,
Ar), 131.2 (C-7), 134.5 (ipso-C, Ar), 138.7 (C-2), 145.2
(C-5), 164.2 (CO), 164.7 (CO). MS (EI) m/z 327 (M+, 8%),
295 (49), 263 (100), 235 (56) and 77 (4). HRMS (CI) m/z
327.1470 (C19H21NO4 [M+], 327.1471).
Dimethyl 2-ethyl-5-methyl-1-vinyl-1H-pyrrole-3,4-dicar-
boxylate 24 was obtained in 14% yield. IR (KBr) 1708,
1
1443, 1214 cmꢂ1. H NMR 1.14 (3H, t, J¼7.5), 2.36 (3H,
s), 2.79 (2H, q, J¼7.5), 3.81 (6H, s), 5.32 (1H, d, J¼15.7),
5.47 (1H, d, J¼8.4), 6.63 (1H, dd, J¼8.4 and 15.7). 13C
NMR 12.1, 14.0, 18.7, 51.4, 51.5, 111.9, 113.0, 115.8,
129.7, 133.2, 139.3, 165.8 and 166.0. MS (EI) m/z 251
(M+, 42%), 236 (10), 219 (100), 204 (29), 187 (26), 161
(30), 133 (44), 118 (14). HRMS (EI) m/z 251.1161
(C13H17NO4 [M+], 251.1158).
4.6.8. Dimethyl 2-methyl-5-(2-methyl-1-phenylallyl)-1H-
pyrrole-3,4-dicarboxylate 16 from 15. Product 16 was
obtained in 20% yield and was identified by comparison
with the specimen previously prepared.
Acknowledgements
We thank Chymiotechnon, Fundac¸a~o para a Cie^ncia e a
Tecnologia (Project POCI/QUI/55584/2004 and Grant
SFRH/BD/9123/2002) and FEDER for financial support.
4.6.9. Dimethyl 1,2-dimethyl-5-vinyl-1H-pyrrole-3,4-di-
carboxylate 191b from 17 [700 ꢀC/4310L2 mbar]. Prod-
uct 19 was obtained in 11% yield and was identified by
comparison with the specimen previously prepared.
References and notes
4.6.10. Methyl 1,3-dimethyl-5-oxo-5H-pyrrolizine-2-car-
boxylate 20 from 17 [850 ꢀC/2.7310L2 mbar]. Product
20 was obtained in 4% yield, mp 116.0–118.0 ꢀC (from di-
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.
ethyl ether/hexane): IR (KBr) 1614, 1695 and 1729 cmꢂ1
.
1H NMR 2.11 (3H, s, H-8), 2.57 (3H, s, H-11), 3.73 (3H,
s, H-10), 5.58 (1H, d, J¼6.0, H-6), 7.12 (1H, d, J¼6, H-7).
13C NMR (off-resonance decoupling) 10.9 (q, J¼129.2,
C-8), 11.2 (q, J¼130.7, C-11), 49.9 (q, J¼147.4, C-10),
117.1 (s, C-2), 119.0 (d, J¼181.9, C-6), 123.7 (s, C-1),
131.4 (s, C-7a), 135.9 (d, J¼174.7, 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).
2. (a) 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;
(b) Pinho e Melo, T. M. V. D.; Soares, M. I. L.; Rocha Gonsalves,
~
A. M. d’A.; Paixao, J. A.; Matos Beja, A.; Ramos Silva, M.
J. Org. Chem. 2005, 70, 6629–6638.
3. (a) McNab, H.; Parson, S.; Stevenson, E. J. Chem. Soc., Perkin
Trans. 1 1999, 2047–2048; (b) McNab, H. Aldrichimica Acta
2004, 37, 19–26; (c) Trofimov, B. A.; Sobenina, L. N.;
Demenev, A. P.; Mikhaleva, A. I. Chem. Rev. 2004, 104,
2481–2506.
ꢁ
4. Sour, A.; Boillot, M.-L.; Riviere, E.; Lesot, P. Eur. J. Org. Chem.
4.6.11. Dimethyl 2-(but-3-en-2-yl)-5-methyl-1H-pyrrole-
3,4-dicarboxylate 22, dimethyl 1-ethyl-2-methyl-5-vinyl-
1H-pyrrole-3,4-dicarboxylate 23 and dimethyl 2-ethyl-
5-methyl-1-vinyl-1H-pyrrole-3,4-dicarboxylate 24 from
5 [600 ꢀC/2.5310L2 mbar]. Dimethyl 2-(but-3-en-2-yl)-5-
methyl-1H-pyrrole-3,4-dicarboxylate 22 was obtained as
a colourless oil in 58% yield. IR (KBr) 1707, 1692, 1447,
1999, 2117–2119.
5. Kim, T.; Ellsenbaumer, R. L. Macromolecules 2000, 33, 6407–
6411.
6. Cook, A. R.; Heilbron, L. M. The Chemistry of Penicillin;
Clarke, H. T., Johson, J. R., Robinson, R., Eds.; Princeton
University Press: Princeton, NJ, 1949.
7. Nagasawa, H. T.; Goon, D. J. W.; DeMaster, E. G. J. Med. Chem.
1978, 21, 1274–1279.
8. Bell, R. A.; Britten, J. F.; Howard-Lock, H. E.; Lock, C. J. L.;
Schimdt, M. Can. J. Chem. 1994, 72, 1621–1624.
1
1292, 1097 cmꢂ1. H NMR 1.33 (3H, d, J¼7.1), 2.38 (3H,
s), 3.80 (3H, s), 3.81 (3H, s), 4.05–4.10 (1H, m), 5.12 (1H,
approx. dt, J¼7.7 and 1.4), 5.17 (1H, d, J¼1.7), 5.93–6.04