New regioselective synthesis of polyfunctionalized 3-ferrocenyl-1H-pyrroles under microwave irradiation

Article abstract of DOI:10.1016/j.tetlet.2016.08.088

A facile and regioselective synthesis of a series of new methyl 3-ferrocenyl-1H-pyrrole-2-carboxylates obtained from methyl ferrocenyl azido acrylate and symmetrical or non-symmetrical 1,3-dicarbonyl compounds under microwave-assisted conditions is report

Full text of DOI:10.1016/j.tetlet.2016.08.088

Tetrahedron Letters 57 (2016) 4568–4573
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Tetrahedron Letters
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New regioselective synthesis of polyfunctionalized 3-ferrocenyl-1H-
pyrroles under microwave irradiation
a,
⇑
a
a
a
b
Helio G. Bonacorso , Francieli M. Libero , Gean M. Dal Forno , Everton P. Pittaluga , Davi F. Back ,
c
a
a
Manfredo Hörner , Marcos A. P. Martins , Nilo Zanatta
a
Núcleo de Química de Heterociclos—NUQUIMHE, Departamento de Química, Universidade Federal de Santa Maria, 97105-900, Santa Maria, RS, Brazil
Laboratório de Materiais Inorgânicos—LMI, Departamento de Química, Universidade Federal de Santa Maria, 97105-900, Santa Maria, RS, Brazil
Núcleo de Investigação de Triazenos e Complexos—NITRICO, Depto. de Química, Universidade Federal de Santa Maria, 97105-900, Santa Maria, RS, Brazil
b
c
a r t i c l e i n f o
a b s t r a c t
Article history:
A facile and regioselective synthesis of a series of new methyl 3-ferrocenyl-1H-pyrrole-2-carboxylates
obtained from methyl ferrocenyl azido acrylate and symmetrical or non-symmetrical 1,3-dicarbonyl
compounds under microwave-assisted conditions is reported. 3-Ferrocenyl substituted pyrroles, which
are normally difficult to obtain via the known reported methods, can now be regioselectively prepared
by this protocol. Compared to already known acidic, basic, or metal-catalyzed methodologies for polysub-
stituted pyrrole synthesis, the present synthetic route is mild, quick, simple, and it furnishes new func-
tionalized tetrasubstituted-pyrroles in short reaction times (30 min) and at satisfactory to good yields
Received 11 August 2016
Accepted 29 August 2016
Available online 31 August 2016
Keywords:
Ferrocene
Tetrasubstituted pyrroles
Regioselective synthesis
Azido vinylesters
Microwave irradiation
(32–75%).
Ó 2016 Elsevier Ltd. All rights reserved.
Introduction
On the other hand, pyrroles can be obtained by the use of classic
2
1
22
methodologies, or recent elegant approaches; however, many
of these methods suffer from disadvantages, thus, there is a need
for alternative methods like microwave irradiation, which nowa-
Ferrocene has always attracted the interest of the scientific
community. Many are its applications1 and compounds contain-
ing this metallocene could be used as sensitive probes, chro-
mophores, biological markers, redox-active sites, catalytic sites,
–3
2
3–25
days are exploited in material sciences
and biochemical
2
6
processes, enabling modifications in selectivity and solvent-
4
27,28
etc. (Fig. 1).
and catalyst-free conditions.
The association of ferrocene to an organic compound could
result in unexpected biological activity because of its membrane-
permeation properties and anomalous metabolism.5 Also, com-
pounds containing ferrocene presented effects against diseases
which has resistance to commercial drugs (Fig. 1).6
Recently, we have also been interested in the use of vinyl azides
2
9
to synthesize functionalized pyrroles. This reaction was first
22h
reported by Chiba et al.,
regioisomer; however, only
who provided one 1H-pyrrole
few literature reports have
a
–11
described pyrroles with a reverse regioselectivity starting from
alkenyl azides, and most of the protocols have disadvantages as
the use of toxic/expensive catalysts or reagents such as
Five-membered heterocycles such as pyrroles are part of the
structural unit of many natural compounds,12 essential drugs,
13
14–17
30
31
32
33
and pharmacologically valuable synthetic substances
and are
manganese, gold, copper, photoredox catalysts, or haz-
18
34
widely used in the pharmaceutical industry (Fig. 2) and in func-
ardous bases.
1
9
35
tional materials. The assembling with a ferrocene unit is an
attractive way to entitle new functions to a bioactive molecule
such as pyrrole. Nevertheless, studies related to the obtainment
of pyrroles bonded to a ferrocenyl moiety are scarce in the litera-
ture and, as far as we know, no study addresses the direct synthe-
sis of pyrroles from building blocks containing the ferrocenyl
substituent has been reported.
The possibility of vinyl azides acting as a nitrene source,
together with the fact that ferrocene can inject an electron36 into
the starting material (Fig. 3)—has lead our research group to favor-
ing studies employing ferrocenyl vinyl azides for the synthesis of
ferrocenyl-substituted pyrroles with a reverse regioselectivity pat-
tern, through conventional heating or microwave irradiation pro-
tocols. In particular, we are interested in developing a new, fast,
and regioselective strategy to synthesize polyfunctionalized non-
symmetric tetrasubstituted pyrroles, which would be very difficult
to obtain by traditional methods.
2
0
⇑
Corresponding author. Tel.: +55 55 3220 8867; fax: +55 55 3220 8031.
E-mail address: heliog.bonacorso@ufsm.br (H.G. Bonacorso).
http://dx.doi.org/10.1016/j.tetlet.2016.08.088
040-4039/Ó 2016 Elsevier Ltd. All rights reserved.
0

H. G. Bonacorso et al. / Tetrahedron Letters 57 (2016) 4568–4573
4569
Cl
R
OH
Fe
-e-
Fe
O
N
N
Figure 3. One-electron oxidation from the two electrons located in the hybridized
iron orbital must result in the cation radical.
HN
N
Fe
N
N
Fe
Fe
O
O
R
R
1
Ferroquine
Anti-malarial)
1,1'-Bis(oxazolinyl)ferrocenes
O
O
N
N
Ferrocifen
(
(Assymmetric catalyst)
CO Me
MeO
Me
O
Me
Me
(
Anti-cancer drug)
2
O
O
NH
2
NHR1
R
N
3
Me
Me
Δ
R
Me
3a'
Figure 1. Organic compounds ferrocenyl substituted.
N
H
R
N
H
1
2a
4
0
Scheme 1. Pyrrolo[3,4-d]pyridazinones synthesis from pyrrole 3 .
Results and discussion
We recently developed a new methodology to obtain pyrrolo
O
O
[
3,4-d]pyridazinones, by employing vinyl azides 1 and 1,3-dike-
MeO
Fe
Me
2
CO Me
0
tone 2a as starting materials. The pyrrole intermediate 3a was
β
α
Fe
O
2
a
2a
N
3
Me
obtained by introducing two carbonyl functions at the 3- and
-positions, which in a subsequent step undergo a cyclization reac-
Me
a'
0
%
N
H
β
MeO
4
Fe
1a
3
α
Me
3a
N
H
tion with dinucleophiles in order to furnish the desired fused hete-
O
rocyclic system 4 (Scheme 1).29
Thus, based on previous results, initially we tried to obtain a
Scheme 2. Unexpected pyrrole 3a formation.
0
29
similar pyrrole 3a by our reported reaction conditions, but when
the reaction was carried out employing the ferrocenylazide 1a, the
unexpected new pyrrole 3a was isolated with a reverse substitu-
Since the best yield obtained through conventional heating was
low (Table 1, entry 9), the same solvents were tested under ultra-
sound and microwave irradiation (Table 2). To our surprise, DCE
under MW irradiation greatly improved the product conversion
in only 30 min, furnishing compound 3a at a 70% yield (Table 2,
entry 11). The ultrasound cavitation process was less efficient,
resulting only in traces of 3a (entries 14 and 15). Other solvents
or a solvent-free system did not result in yield improvements
tion pattern (a-methoxycarbonyl, b-ferrocenyl—Scheme 2). The
observed regioselectivity at the 2- and 3-positions for the synthesis
of a pyrrole ring encouraged us to explore the scope of this reaction
using six examples of non-symmetrical 1,3-dicarbonyl compounds.
Starting from the synthesis of pyrroles, the preliminary investi-
gation employed methyl 2-azido-3-ferrocenyl acrylate (1a), previ-
3
8
3
7
ously prepared, and 2,4-pentanedione (2a) as substrates. We
investigated different temperatures, times, solvents, and conven-
tional or alternative heating sources—representative results are
summarized in Table 1. In our first tests, no desired cyclization pro-
duct 3a was obtained when the reaction was performed in polar
solvents like MeOH or EtOH (entries 3 and 4), or apolar solvents
like toluene or THF (entries 1, 2, 5, and 6).
(
Table 2, entries 1–7 and 13). The difficulty of obtaining the regios-
elective pyrrole 3a from diketones, even with the use of catalysts,
2
2h,31
has been described in the literature.
The synthetic scope of the reaction was expanded to some non-
symmetrical 1,3-dicarbonyl compounds (2b–h) and methyl 2-
azido-3-ferrocenyl acrylate (1a), which led to the formation of pyr-
roles 3b–g, as shown in Table 3. Upon employing trifluoromethyl
However, when dichloroethane was used as solvent, under
reflux for 8 h, compound 3a was obtained at a yield of only 8%
entry 8). Further investigation revealed that the yield of 3a could
be improved to a maximum of 40% when DCE is used under reflux
for 16 h (entry 9), but longer reaction times showed us significantly
decrease the yield due to the decomposition of the possible
products.
(
2b) or phenyl (2c) substituted 1,3-diketones, poor yields were
obtained for the respective pyrroles 3b and 3c (entries 2 and 3).
These non-symmetrical 1,3-diketones only furnish the product of
a C–N bond formation at reasonable yields with a less hindered
acetyl group. When b-keto esters such as ethyl acetoacetate (2d)
(
were employed,
a slight yield improvement was observed,
although a small amount of the starting materials was recovered.
Precursor compounds like thioester (2e), amide (2f), and 4 -chlor-
oanilide (2g) have been successfully inserted at the C-4 position of
the pyrrole, and provide the substituted products 3e, 3f, and 3g,
respectively, at moderate to good yields (entries 5, 6, and 7). Only
for ethyl 3-oxohexanoate (2h) the formation of the pyrrole 3h was
The X-ray diffraction of the structure of 3a is shown in Figure 4,
which illustrates and confirms the structure of the pyrrole ring
with the presence of a ester function, the ferrocenyl substituent,
a ketone function and the methyl group at the 2-, 3-, 4-, and
0
-position, respectively.39
5
O
Me
N
H
NH
OH
F
Me
O
O
N
S
N
F
O
O
N
O
2
CO H
Me
N
N
Me
HO
HO
2
C
O
Me
2
CO H
Vonoprazan
Acid blocker)
HO
Atorvastatin
Cholesterol lowering drug)
Tolmetin
(Anti-inflammatory)
(
Bhimamycin D
(
(Antibiotic)
Figure 2. Examples of pyrrole-based commercial drugs.

4
570
H. G. Bonacorso et al. / Tetrahedron Letters 57 (2016) 4568–4573
Table 1
Optimization of reaction conditions via conventional heating for 3a
CO
2
Me
+
Fe
C
O
O
O
Me
Me
N
3
i
Me
Me
Fe
MeO
2
N
H
1a
2a
3
a
Entrya
Solvent
Temperature (°C)
Time
Yieldb (%)
c
1
2
3
4
5
6
7
8
9
Toluene
Toluene
Methanol
Ethanol
THF
THF
DCE
DCE
DCE
50
110
65
78
25
66
40
84
84
84
8 h
5 h
c
d
d
e
d
d
24 h
24 h
24 h
24 h
24 h
8 h
8
40
Traces
16 h
24 h
1
0
DCE
a
b
c
Tests performed using (i) = 0.5 equiv of 1a and 0.55 equiv of pentane-2,4-dione (2a), in 5 mL of the respective solvent. The product conversion was followed by TLC.
Isolated yield.
Decomposition of the starting materials.
Formation of a complex mixture.
Recovery of the starting materials.
d
e
Figure 4. ORTEP obtained from the crystal structure of methyl 4-acetyl-3-ferrocenyl-5-methyl-1H-pyrrole-2-carboxylate 3a (CCDC 1442034).39 Displacement ellipsoids are
drawn at the 50% probability level.
not observed—a complex dark mixture was generated. In all cases
entries 1–7), the reaction was regioselective for the formation of a
new series of 2-methoxycarbonyl-3-ferrocenyl substituted pyr-
roles 3, with the most hindered portion of the dicarbonyl starting
material remaining at the 4-position of the pyrrole.
traces of the pyrrole 3a were observed, which suggests that the
reaction should follow a radical path in the cyclization process.
Since no catalyst was used in this work, we assumed that the
ferrocene linked to vinyl azide plays an important role in this
regioselectivity inversion. The ability of ferrocene to undergo
reversible one-electron oxidation to the ferrocenium cation, under
(
The regioinversion of substituents from the expected
-position obtained in these molecules had only been described
in the literature with the aid of catalysts and through a radical
a,b- to the
36
b,a
air or photo-oxidation, is known and has been widely explored.
2
2h,30,32,36
Based on similar reports,
we presume that, in this
2
2h,30,32
pathway.
control experiment was performed, adding the radical scavenger
2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO) to the standard
synthetic conditions (Scheme 3). From this experiment, only
Thus, in order to support this initial idea, a
catalytic reaction, the ferrocenyl vinyl azide can act as both
reactant and catalyst.
(
All new structures obtained for pyrroles 3 were also unequivo-
1
13
cally elucidated by H-, C NMR and GC–MS. The compound 3a

H. G. Bonacorso et al. / Tetrahedron Letters 57 (2016) 4568–4573
4571
Table 2
Optimization of reaction conditions via alternative heating for 3a
CO
2
Me
+
Fe
C
O
O
O
Me
Me
N
3
i
Me
Me
Fe
MeO
2
N
H
1a
2a
3
a
Entrya
Solvent
Heating (°C)
Time
Yieldb (%)
c
1
2
3
4
5
6
7
8
9
Toluene
Methanol
Methanol
Methanol
Methanol
Ethanol
Ethanol
DCE
DCE
DCE
DCE
DCE
MW (110)
MW (65)
MW (100)
MW (120)
MW (120)
MW (100)
MW (130)
MW (130)
MW (120)
MW (100)
MW (100)
MW (84)
MW (100)
US (70)
30 min
30 min
15 min
5 min
e
d
27
d
15 min
30 min
15 min
15 min
30 min
40 min
30 min
30 min
30 min
30 min
30 min
8
Traces
c
24
30
70
32
34
Traces
6
1
1
1
1
1
1
0
1
2
3
4
5
-
DCE
DCE
US (80)
a
b
c
Tests performed using (i) = 0.5 equiv of 1a and 0.55 equiv of pentane-2,4-dione (2a), in 5 mL of the respective solvent. The reaction was followed by TLC.
Isolated yield.
Decomposition.
Formation of a complex mixture.
Recovery of the starting materials.
d
e
Table 3
Table 3 (continued)
Entrya
Precursor
Reactions of 1a with non-symmetrical dicarbonyl compounds 2a–h
Product
Yieldb (%)
O
O
CO
2
Me
Fe
O
Fe
O
O
R1
Me
SEt
NH
O
O
2
e
SEt
Me
N
3
+
DCE, MW,
MeO
5
58
R
R1
100 °C, 30 min.
MeO
O
R
Fe
N
H
N
H
e
O
1a
2a-h
3a-h
3
1
R: Me, (CH
2
)
2
CH
3 2 3
; R : Me, Ph, NH , SEt, CF , OEt, NH-4-PhCl
O
O
Entrya
Yieldb (%)
Fe
Precursor
Product
Me
2
NH
Me
2
2
f
O
O
O
O
O
6
7
8
62
75
0
MeO
O
Fe
O
N
H
f
Me
Me
Me
Me
Me
3
1
2a
70
MeO
O
Cl
Cl
N
H
a
O
O
3
Me
Me
N
H
Fe
O
O
NH
Me
Fe
O
O
O
2g
MeO
O
CF
3
N
H
2
b
CF
Me
3
2
3
4
32
38
43
MeO
O
3g
N
H
b
O
O
Fe
O
3
OEt
2
h
OEt
O
c
MeO
O
Fe
Me
Me
N
H
3h
2
d
MeO
O
Me
N
H
3
a
Experiments performed using 0.5 equiv of 1a and 0.55 equiv of dicarbonyl
compound (2a–h) in 5 mL of DCE, under MW irradiation for 30 min.
c
b
O
Isolated yield.
Fe
OEt
2
OEt
Me
(obtained via conventional thermal heating and by MW) and com-
pounds 3b–g (obtained via MW protocol) agreed structurally in
relation to the molecular substitution pattern (a-methoxycar-
bonyl, b-ferrocenyl). Also, an experiment was done employing
MeO
O
N
H
d
3
the new protocol via MW with methyl 2-azido-3-phenylacrylate

4
572
H. G. Bonacorso et al. / Tetrahedron Letters 57 (2016) 4568–4573
McDonagh, A. M.; Humphrefeyi, M. G. Adv. Organomet. Chem. 1998, 42, 291; (d)
CO
2
Me
Uno, M.; Dixneuf, P. H. Angew. Chem., Int. Ed. 1998, 37, 1714; (e)Ferrocene:
Homogeneous Catalysis, Organic Synthesis and Materials Science; Togni, A.,
Hayashi, T., Eds.; VCH: New York, 1995; (f) Balavoine, G. G. A.; Daran, J. C.;
Iftime, G.; Lacrolx, P. G.; Manoury, E.; Delaire, J. A.; Maltey-Fanton, I.; Natatani,
K.; Bella, S. D. Organometallics 1999, 18, 21; (g) Liu, J.; Castro, R.; Abboud, K. A.;
Kaifer, A. E. J. Org. Chem. 2000, 65, 6973; (h) Biernat, J. F.; Wilczewski, T.
Tetrahedron 1980, 36, 2521; (i) Akabori, S.; Habata, Y.; Sakamoto, Y.; Sato, M.;
Ebine, S. Bull. Chem. Soc. Jpn. 1983, 56, 537.
Torres, J. C.; Pilli, R. A.; Vargas, M. D.; Violante, F. A.; Garden, S. J.; Pinto, A. C.
Tetrahedron 2002, 58, 4487.
(a) Sarhan, A. A. O.; Izumi, T. J. Organomet. Chem. 2003, 675, 1; (b) Fang, J.; Jin,
Z.; Li, Z.; Liu, W. J. Organomet. Chem. 2003, 674, 1; (c) Porte, L. M. F.; Paim, G. R.;
Schwanz, T. G.; Meyer, A. R.; Bonacorso, H. G.; Martins, M. A. P.; Zanatta, N. J.
Het. Chem. 2014, 51, 1333.
Fe
O
O
O
Me
Me
N
3
+
+
Me
Me
Me
Me
i
N
O
Me
Me
MeO
Fe
N
H
1
a
2a
TEMPO
O
3
a
i: 1 mmol of 1a, 1 mmol of TEMPO, 1.1 mmol of 2a,
(only traces)
5
mL of DCE, MW, 100 °C, 30 min.
2
.
.
Scheme 3. Experiment with radical scavenger (TEMPO).
3
O
O
CO
2
Me
+
O
MeO
Me
Me
O
O
Me
Me
4. (a) Moriuchi, T.; Hirao, T. Top. Organomet. Chem. 2006, 17, 143; (b) Sutcliffe, O.
B.; Bryce, M. B. Tetrahedron Asymmetry 2003, 14, 2297.
DCE, MW,
N
3
100 °C,
Me
Me 30 min.
+ MeO
N
H
5. (a) Hanzlik, R. P.; Soine, P.; Soine, W. H. J. Med. Chem. 1979, 22, 424; (b)
Pansuriya, P. B.; Patel, M. N. Appl. Organomet. Chem. 2007, 21, 926 (and
references herein); (c) Zecri, O.; Hillard, E. A.; Top, S.; Vessiéres, A.; Pigeon, P.;
Plamont, M.; Huche, M.; Boutamine, S.; McGlinchey, M. J.; Muller-Bunz, H.;
Jaouen, G. Dalton Trans. 2009, 22, 4318; (d) Joksovic, M. D.; Markovic, V.;
Juranic, Z. D.; Stanojkovic, T.; Jovanovic, L. S.; Damljanovic, I. S.; Szeseyi, K. M.;
Todorovic, N.; Trifunovic, S.; Vukicevic, R. D. J. Organomet. Chem. 2009, 694,
N
H
1b
2a
O
7
2%
0%
Scheme 4. Reaction performed for methyl 2-azido-3-phenylacrylate 1b.
3
935; (e) Pan, X. H.; Liu, X.; Zhao, B. X.; Xie, Y. S.; Shin, D. S.; Zhang, S. L.; Zhao,
(
1b) and acetylacetone (2a). The pyrrole obtained was the same as
J.; Miao, J. Y. Bioorg. Med. Chem. 2008, 16, 9093; (f) Nguyenb, A.; Marsaud, V.;
Bouclier, C.; Top, S.; Vessieres, A.; Pigeon, P.; Gref, R.; Legrand, P.; Jaouen, G.;
Renoir, J. M. Int. J. Pharm. 2008, 347, 128; (g) Spencer, J.; Mendham, A. P.; Kotha,
A. K.; Richardson, S. C. W.; Elizabeth, A.; Hillard, E. A.; Jaouen, G.; Malec, L.;
Hursthouse, M. B. Dalton Trans. 2009, 6, 918; (h) Ferreira, A. P.; Silva, J. L. F.;
Duarte, M. T.; Piedade, M. F. M.; Robalo, P. M.; Harjivan, S. G.; Marzano, C.;
Gandin, V.; Marques, M. M. Organometallics 2009, 28, 5412.
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Wataya, Y. Bioorg. Med. Chem. Lett. 2000, 10, 1657; (b) Guillon, J.; Moreau, S.;
Mouray, E.; Sinou, V.; Forfar, I.; Fabre, S. B.; Desplat, V.; Millet, P.; Parzy, D.;
Jarry, C.; Grellier, P. Bioorg. Med. Chem. 2008, 16, 9133; (c) Wu, X.; Wilairatb, P.;
Go, M. L. Bioorg. Med. Chem. Lett. 2002, 12, 2299; (d) Biot, C.; Daher, W.;
Chavain, N.; Fandeur, T.; Khalife, J.; Dive, D.; Clercq, E. D. J. Med. Chem. 2006, 49,
2845; (e) Biot, C.; Dessolin, J.; Ricard, I.; Dive, D. J. Organomet. Chem. 2004, 689,
29
described in our previous work, showing no regioinversion in the
absence of ferrocene (Scheme 4). This fact corroborates with the
first idea that the regioinversion is a result of the influence from
the ferrocenyl substituent and not from the solvent, the heating
source, or temperature.
6
.
Conclusions
From pentane-2,4-dione or non-symmetrical 1,3-dicarbonyl
compounds and ferrocenyl vinyl azide we developed a simple
and regioselective synthesis of polysubstituted pyrroles containing
ferrocene. The cyclization reactions could be performed under
microwave-assisted conditions in a 30 min reaction, which fur-
nished, in a highly regioselective manner, a new class of 3-ferro-
4678; (f) Wu, X.; Tiekink, E. R. T.; Kostetski, I.; Kocherginsky, N.; Tan, A. L. C.;
Khoo, S. B.; Wilairat, P.; Go, M. L. Eur. J. Pharm. Sci. 2006, 27, 175; (g) Biot, C.;
Caron, S.; Maciejewski, L. A.; Brocard, J. S. J. Labelled Compd. Radiopharm. 1998,
XLI, 911.
(a) Long, B.; He, C.; Yang, Y.; Xiang, J. Eur. J. Med. Chem. 2010, 45, 1181; (b)
Damljanovic, I.; Vukicevic, M.; Radulovic, N.; Palic, R.; Ellmerer, E.; Ratkovic, Z.;
Joksovic, M. D.; Vukicevic, R. D. Bioorg. Med. Chem. Lett. 2009, 19, 1093; (c)
Joksovic, M. D.; Vukicevic, R. D.; Vukicevic, M.; Ratkovic, Z. Synlett 2006, 2581.
Jin, Z.; Huo, A.; Liu, T.; Hu, Y.; Liu, J.; Fang, J. J. Organomet. Chem. 2005, 690,
7.
cenyl
substituted
pyrroles
containing
also
different
functionalities at the C4-position. Compared with the acidic, basic,
or metal-catalyzed methodologies reported in the literature for
regio-controlled polysubstituted pyrrole synthesis, the present
reaction conditions are mild, quick, and simple. It was observed
that the ferrocenyl substituent plays an important role in the
inversion of the regioselectivity, in which b-ferrocenyl,
8
.
.
1226.
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Acknowledgments
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The authors thank: the Coordination for Improvement of Higher
Education Personnel (CAPES) for the fellowships; and the National
Council for Scientific and Technological Development (CNPq Proj.
nr 306.883/2015-5) and the Rio Grande do Sul Foundation for
Support of Research (FAPERGS) for financial support.
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38. Synthesis of methyl 3-ferrocenyl-1H-pyrrole-2-carboxylates (3a–h) General
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1 mmol, 0.341 g) and the respective 1,3-dicarbonyl compounds (2a–h,
1.1 mmol) were added to a reaction vessel equipped with a stir bar. The
mixture was irradiated in microwave at 100 W, 20–30 PSI, for 0.5 h. The
temperature was set to 100 °C, and the irradiation was automatically stopped
at this temperature. After concluded the reaction time, the mixture was cooled
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was purified by column chromatography on silica gel (AcOEt/hexane 15% as
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2
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(600 MHz, DMSO-d
6
): d (ppm) = 11.91 (s, 1H), 4.58 (s, 2H), 4.27 (s, 2H), 3.97 (s,
13
5H), 3.84 (s, 3H), 2.28 (s, 3H), 2.05 (s, 3H). C NMR (150 MHz, DMSO-d
6
): d
2
2
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9. (a) Bonacorso, H. G.; Libero, F. M.; Dal Forno, G. M.; Pittaluga, E. P.; Porte, L. M.
F.; Martins, M. A. P.; Zanatta, N. Tetrahedron Lett. 2015, 56, 5190; (b) Bonacorso,
H. G.; Libero, F. M.; Dal Forno, G. M.; Pittaluga, E. P.; Martins, M. A. P.; Zanatta,
N. BR Patent deposited on National Institute for Industrial Property—INPI (BR
(ppm) = 197.3, 160.2, 134.7, 127.5, 125.7, 117.1, 79.1, 71.1, 69.1, 67.3, 51.1,
31.1, 12.3. MS: m/z (%) 365 (M+, 8), 307 (26), 281 (23), 242 (44), 207 (100), 191
(10), 97 (30), 83 (36), 69 (47). HRMS: C19H19FeNO calcd for [M]: 365.0714,
3
found: 365.0717. Complete experimental data are available at Supplementary
material.
39. The crystallographic data for the structure of 3a have been deposited with the
Cambridge Crystallographic Data Centre and allocated the deposition number
CCDC 1442034. Copies of the data can be obtained free of charge, on
application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK. (fax: +44
1223336033 or deposit@ccdc.com.ac.uk).
1
020140199110) in agreement to Federal University of Santa Maria, 2014.
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