1,6-Conjugated addition of nitromethane to (E)-2-styrylchromones: A new synthesis of novel 2-substituted 4-arylpyrrole derivatives

Article abstract of DOI:10.1055/s-0031-1289525

The 1,6-conjugate addition of nitromethane to (E)-2-styrylchromones were achieved, in moderate to good yields, by using DBU as organocatalyst. Reduction studies on the 2-(2-aryl-3-nitropropyl)chromone adducts formed surprisingly led to novel 2-substituted

Full text of DOI:10.1055/s-0031-1289525

2740
LETTER
1,6-Conjugated Addition of Nitromethane to (E)-2-Styrylchromones:
A New Synthesis of Novel 2-Substituted 4-Arylpyrrole Derivatives
Synthesis of
N
o
d
vel 2-Substi
u
a
yrrole
D
eri
r
vatives da M. P. Silva, Artur M. S. Silva,* José A. S. Cavaleiro
Department of Chemistry, QOPNA, University of Aveiro, 3810-193 Aveiro, Portugal
Fax +351(234)370714; E-mail: artur.silva@ua.pt
Received 19 August 2011
culties in controlling the regioselectivity explain the
limited results in this area. Considering asymmetric 1,4-
conjugate additions, previous work within the group14 had
led to the development of a general and efficient asym-
Abstract: The 1,6-conjugate addition of nitromethane to (E)-2-
styrylchromones were achieved, in moderate to good yields, by us-
ing DBU as organocatalyst. Reduction studies on the 2-(2-aryl-3-ni-
tropropyl)chromone adducts formed surprisingly led to novel 2-
substituted 4-arylpyrrole derivatives. These new derivatives are metric organocatalytic addition of malononitrile and ni-
formed from nitro-group reduction, followed by a 1,4-Michael-type
addition of the primary amine intermediate to the a,b-unsaturated
carbonyl system of the chromone moiety and concomitant heterocy-
cellent enantioselectivities (up to 99%), high yields (up to
clic ring opening.
tromethane to 1,5-diarylpenta-2,4-dien-1-ones catalyzed
by cinchona organocatalysts. The reactions afforded ex-
97%), and exclusive 1,4-addition regioselectivity.14
Key words: (E)-2-styrylchromones, nitromethane, 1,6-conjugated
To the best of our knowledge no example of 1,6-conjugate
additions to (E)-2-styrylchromones has been described in
the literature. Therefore, the potential of this new reaction
led us to pursue the addition of nitromethane to (E)-2-
styrylchromones (Scheme 1).
addition, 1,4-Michael addition, 2-substituted 4-arylpyrroles, DBU
2-Styrylchromones constitute a group of oxygen hetero-
cyclic compounds which, although scarce in nature,1 have
been widely synthesized and studied for their biological
activities.2 (E)-2-Styrylchromones are easily prepared in
good overall yields according to a three-step sequence, by
using 2¢-hydroxyacetophenones and the appropriate cin-
namoyl chlorides as starting materials.3 Biological evalu-
ations of a number of synthesized 2-styrylchromone
derivatives revealed the significant anti-allergic,4 antitu-
mor,1a,b,5 antiviral,6 antioxidant,7 and anti-inflammatory8
activities of these compounds and also their use as antag-
onists of the A3 adenosine receptor.9 In view of the impor-
tant biological activities described in the literature for this
group of compounds, 2-styrylchromones represent a rath-
er important substrate for numerous transformations.
R
R
NO2
B
β
8
α
9
O
O
O
7
6
MeNO2
base
2
3
A
C
10
5
O
1a R = H
2a R = H
1b R = OMe
1c R = NO2
1d R = Cl
2b R = OMe
2c R = NO2
2d R = Cl
Scheme 1 1,6-Conjugate additions of nitromethane to (E)-2-styryl-
chromones 1a–d
The conjugate addition of carbon nucleophiles to elec-
tron-deficient alkenes is one of the most important meth-
ods available for carbon–carbon bond-forming
reactions.10 Furthermore, the asymmetric catalysis of this
reaction has become an efficient synthetic tool for the for-
mation of tertiary and quaternary carbon stereocenters,
important for the development of new potentially impor-
tant bioactive compounds.11 In addition, the use of chiral
metal-free organocatalysts has been the object of intense
studies due to their potential application to chemical trans-
formation in pharmaceutical industry.
To investigate the reactivity of compound 1a towards the
conjugate addition of nitromethane we first examined the
action of some typical poorly nucleophilic amine bases
(Scheme 1). trans-2,5-Dimethylpiperazine (DMP), pyri-
dine, N,N-diisopropylethylamine (Hünig’s base), imida-
zole, 4-dimethylaminopyridine (DMAP), 1,8-diaza-
bicyclo[5.4.0]undec-7-ene (DBU), 1,5-diazabicyclo-
[4.3.0]non-5-ene (DBN), and 1,5,7-triazabicyclo-
[4.4.0]dec-5-ene (TBD) were considered for the 1,6-con-
jugate addition at room temperature without the use of any
solvent (Table 1).
A large number of publications describing asymmetric
1,4-conjugate additions of carbon nucleophiles is avail-
able but the analogous asymmetric 1,6-addition methods
are underdeveloped.12,13 The presence of several electro-
philic sites in extended conjugated systems and the diffi-
DMP, Hünig’s base, pyridine, imidazole, and DMAP
were totally inefficient, and the starting material was re-
covered (67–100%). Similarly, the use of an inorganic
base, such as K2CO3, was inefficient in promoting the re-
action. However, the use of a stronger base such as DBU
under the same conditions afforded the desired 2-(3-nitro-
2-phenylpropyl)chromone (2a)15,16 in 84% yield after 6.5
hours of reaction time (Table 1, entry 1). The main fea-
SYNLETT 2011, No. 18, pp 2740–2744
x
x
.x
x
.2
0
1
1
Advanced online publication: 19.10.2011
DOI: 10.1055/s-0031-1289525; Art ID: D26611ST
© Georg Thieme Verlag Stuttgart · New York

LETTER
Synthesis of Novel 2-Substituted 4-Arylpyrrole Derivatives
2741
tures in the 1H NMR spectrum of 2a were the signals of
the diastereotopic a protons at d = 3.09 (3J = 6.5 Hz;
2J =14.5 Hz) and 3.00 ppm (3J = 8.8 Hz; 2J = 14.5 Hz; see
Scheme 1 for numbering). Additionally, the presence of a
multiplet at d = 4.11–4.01 ppm and a doublet at d = 4.72
ppm (3J = 7.6 Hz), corresponding to the b- and the a-CH2
protons, respectively, revealed the regioselective 1,6-ad-
dition of nitromethane to the a,b,g,d-unsaturated carbonyl
system.
Table 2 1,6-Conjugate Additions of Nitromethane to (E)-2-Styryl-
chromones 1a–d Using DBU as Basea
Entry
R
1a–d
Yield
Time
(h)
Solvent
(recovered, %) (%)b
1
2
H
–
84
47
71
6
6.5
6.5
24
–
OMe
OMe
NO2
NO2
NO2
NO2
NO2
Cl
36
14
75
52
75
39
–
–
3c
4
–
These results led us to consider bases with similar or high-
er basicity, namely DBN and TBD, but their use led to a
decrease in the yield (Table 1, entries 2–4).
6.5
6.5
72
–
5d
6e
7e
8f
11
4
–
THF
Table 1 Base Screening for the Addition of Nitromethane to (E)-
Styrylchromone 1aa
7
72
MeCN
Entry Base
Time (h) 1a (recovered, %) Yield (%) of 2ab
50
28
26
72
2
DMSO
1
2
3
4
DBU
6.5
24
–
–
7
3
84
59
70
64
9
30
38
–
6.5
48
–
–
–
10c
11d
Cl
DBN
TBD
48
30
Cl
6.5
PSTBD
a Reactions were carried out using 1a–d (30 mg), 20 mol% of base,
and nitromethane (0.33 mL) at r.t. under a nitrogen atmosphere.
b Yield of isolated products after chromatography.
a Reactions were carried out using 1a (30 mg, 0.121 mmol), 20 mol%
of base, and nitromethane (0.33 mL) at r.t. under a nitrogen atmo-
sphere.
c Conditions: 0.4 equiv of DBU were used.
d This reaction was carried out at 65 °C.
b Yield of isolated product 2a after chromatography.
e Reactions were carried out under reflux using 0.5 mL of solvent.
f This reaction was carried out at 100 °C and using 3 mL of solvent.
The next step was the extension of the 1,6-conjugate addi-
tion of nitromethane to other (E)-2-styrylchromones using
the DBU as the chosen organocatalyst.15 The correspond-
ing 2-(2-aryl-3-nitropropyl)chromone derivatives 2b–d
were obtained in moderate to good yields (Scheme 1,
Table 2).
ing the reaction that the solubility of 1c was a problem.
The use of refluxing THF or MeCN led to no improve-
ment on the product yield (Table 2, entries 6 and 7). How-
ever, when DMSO was used in sufficient amount to
dissolve the starting material completely (Table 2, entry
8) the yield was improved. After two hours, the desired
product 2c was obtained in 50% yield, and no starting ma-
terial was recovered.
The formation of 2a–d is dependent on the B-ring substit-
uent of the starting materials 1a–d. The unsubstituted
compound 1a is the most reactive leading to the formation
of the 2-(3-nitro-2-phenylpropyl)chromone (2a) in good
yield (Table 2, entry 1). The introduction of a substituent
at the para position of the ring B clearly diminishes the re-
activity towards the 1,6-conjugate addition of ni-
tromethane. To achieve similar yields (Table 2, entry 3)
for the reaction of compound 1b, bearing an electron-do-
nating substituent (R = OMe), it was required to use 0.4
mol equivalents of base and increase the reaction time.
With compound 1d (R = Cl), the 1,6-conjugate addition
only took place at 65 °C when compound 2d was obtained
in 72% (Table 2, entry 11). The difficulty came when
compound 1c, bearing an electron-withdrawing substitu-
ent (R = NO2), was used as starting material. The reaction,
carried out using 1c and nitromethane in the presence of
DBU at room temperature under a nitrogen atmosphere,
yielded the desired product 2c in only 6% yield with re-
covery of 75% of the starting material 1c (Table 2, entry
4). Heating the reaction mixture did not increase the yield
significantly (11%, Table 2, entry 5). It was then decided
to exploit the use of a polar solvent since it was clear dur-
We subsequently considered a further transformation of
the new derivatives 2a–d to prepare the corresponding
amino derivatives 4a–d. We initiated reduction studies us-
ing compound 2a and ammonium formate (5 equiv) in the
presence of Pd/C (10%) using methanol as solvent (Meth-
od A, Scheme 2), which had been successfully used for
the preparation of 3-aminoflavones.17 In this study, the au-
thors found that, if the reaction did not occur in the first
five minutes, it was necessary to add more catalyst for re-
action evolution. For compound 2a, even after the addi-
tion of more catalyst, the reaction did not take place.
When using acetone, described as an appropriate solvent
for the reduction of 3-aminoflavones,17 a new compound
was formed in small quantities (15% yield) after leaving
the reaction overnight with recovery of 42% of compound
2a. This new compound was found to be the pyrrole de-
rivative 3a18 (Scheme 2), formed through a 1,4-Michael-
type addition of the primary amino group to the a,b-unsat-
urated system in the intermediate 4a with concurrent
opening of the chromone nucleus.
Synlett 2011, No. 18, 2740–2744 © Thieme Stuttgart · New York

2742
E. M. P. Silva et al.
LETTER
R
tion of compound 3a in a trace amount. The reduction of
the 2-(3-nitro-2-phenylpropyl)chromone (2a) was also
performed using method B [Sn (powder) and HCl (aq),
Scheme 2],20,21 which afforded, once more, compound 3a
but in a slightly higher yield (30%). The reduction reac-
tion using method B was also extended to the other 2-(2-
aryl-3-nitropropyl)chromones 2b–d (Table 3), leading to
compounds 3b–d being obtained in better yields. Interest-
ingly, with this method it was possible to isolate com-
pound 3c (R = NH2) in a good yield (56%). In this case,
not only the 1,4-Michael addition of the primary amino
group had occurred with concurrent opening of the
chromone nucleus but also the reduction of the aromatic
nitro group had taken place leading to 3c.
NO2
2
2''
3''
3'
1
2'
1) HCO2NH4,
Pd/C
O
O
4'
2'''
R
O
HN
1'
OH
2) Sn (powder),
HCl (aq)
5'
3a R = H
3b R = OMe
3c R = NH2
3d R = Cl
2a R = H
2b R = OMe
2c R = NO2
2d R = Cl
R
NH2
O
O
The formation of compound 3c was confirmed by analysis
of the 1H NMR data. The low frequency values observed
in the 1H NMR spectrum for the two doublets correspond-
ing to the proton resonances of H-2¢¢,6¢¢ and H-3¢¢,5¢¢ at
d = 7.04 and 6.67 ppm, respectively (see Scheme 2 for
numbering), confirm the presence of the aromatic amino
group. This set of signals in the presence of an aromatic
nitro group normally show resonances at higher frequen-
cies values, typically at around d = 8.00 and 7.50 ppm for
4a R = H
4b R = OMe
4c R = NH2
4d R = Cl
Scheme 2 Transformation of 2-(2-aryl-3-nitropropyl)chromones
2a–d into (Z)-2-hydroxyphenyl (4-phenylpyrrolidin-2-ylidene)me-
thyl ketones 3a–d
Attempting to obtain the 2-(3-amino-2-phenylpro-
pyl)chromone (4a), it was decided to repeat the reaction the protons at the ortho and meta positions, respectively,
but using double the quantities of catalyst [Pd/C (10%)] to the nitro group. The 1H NMR spectrum of compound 3c
and ammonium formate (10 equiv). After four hours, no also exhibits, among other characteristic signals for this
starting material was observed by TLC, and the reaction group of compounds, two sharp singlets at d = 13.83 and
was quenched by filtrating through Celite.19 This reaction 9.93 ppm, assigned to the proton resonances of the hy-
led once more, after purification through column chroma- droxy and pyrrolic amino groups, respectively.
tography, to the isolation of pure compound 3a in 20%
Table 3 Reduction Reaction of 2-(2-Aryl-3-nitropropyl)chromones
2a–d
yield. Method A was subsequently extended to the re-
maining nitropropyl derivatives 2b–d. Formation of de-
rivative 3c (R = NO2) could be observed during TLC
Entry
R
Yield of method A Yield of method B
(%)a,b
(%)a,b
analysis of the reaction, but it was not isolated in signifi-
cant quantities. Compound 3d (R = Cl) was obtained in a
similar yield to the unsubstituted 3a (23%) while, for
compound 2b, the desired product 3b (R = OMe) was ob-
tained in low yield (13%, Table 3).
1
2
3
4
H
20
30
OMe
NO2
Cl
13
32
–
56
Unequivocal proton assignments for all the pyrrole deriv-
atives were achieved with COSY, HSQC, HMBC, and
23
21
1
NOESY experiments. The H NMR spectrum of com-
a Yield of isolated products after chromatography.
b No starting material was recovered.
pound 3a exhibited two sharp singlets at d = 13.80 and
9.95 ppm, assigned to the hydroxy and pyrrolic amino
proton resonances, respectively. These two sharp signals
indicate the presence of two highly deshielded protons
due to two intramolecular hydrogen bonds with the carbo-
nyl group. The NOESY spectrum of 3a presented NOE
cross peaks between the signals of H-2 with those of H-3¢
of the pyrrole ring and also H-6¢¢¢ of the phenyl ring A,
supporting the close proximity between them and thus
pointing out for a Z-configuration of the double bond (see
Scheme 2 for numbering).
In conclusion, we have described herein the successful
1,6-conjugate addition of nitromethane to (E)-2-styryl-
chromones in the presence of DBU as an organocatalyst.
The reduction of the 2-(2-aryl-3-nitropropyl)chromone
derivatives so obtained by two different methods that lead
to novel 2-substituted 4-arylpyrrole derivatives is also de-
scribed. The formation of these compounds involves ni-
tro-group reduction, followed by a 1,4-Michael-type
addition of the primary amine intermediate at carbon C-2
of the chromone moiety with concurrent opening of the
chromone nucleus to form (Z)-(4-arylpyrrolidin-2-
ylidene)methyl 2-hydroxyphenyl ketones.
In order to improve the yield of compounds 3a–d a differ-
ent approach was attempted. Treatment of the 2-(3-nitro-
2-phenylpropyl)chromone (2a) with an excess of hydrat-
ed stannous chloride,20 in a 1:3 mixture of hydrochloric
acid and acetic acid at 65 °C, similarly led to the forma-
Synlett 2011, No. 18, 2740–2744 © Thieme Stuttgart · New York

LETTER
Synthesis of Novel 2-Substituted 4-Arylpyrrole Derivatives
2743
(13) Review: (a) Krause, N.; Thorand, S. Inorg. Chim. Acta 1999,
296, 1. (b) Csákÿ, A. G.; de la Herrán, G.; Murcia, M. C.
Chem. Soc. Rev. 2010, 39, 4080.
(14) (a) Oliva, C. G.; Silva, A. M. S.; Paz, F. A. A.; Cavaleiro, J.
A. S. Synlett 2010, 1123. (b) Oliva, C. G.; Silva, A. M. S.;
Resende, D. I. S. P.; Paz, F. A. A.; Cavaleiro, J. A. S. Eur. J.
Org. Chem. 2010, 3449.
Acknowledgment
Thanks are due to the University of Aveiro, to the Portuguese Foun-
dation for Science and Technology (FCT), and FEDER for funding
the Organic Chemistry Research Unit and the Portuguese National
NMR Network. E.M.P. Silva is grateful to FCT for a Post-Doctoral
grant (SFRH/BPD/66961/2009).
(15) Typical Procedure for the Preparation of 2-(2-Aryl-3-
nitromethyl)chromones 2a–d
References and Notes
A flask containing the appropriate (E)-2-styrylchromone
1a–d (0.104 mmol), nitromethane (0.33 mL), and DBU
(3 mL, 0.021 mmol) was flushed with nitrogen and stirred
vigorously at r.t. After the appropriate time (Table 2), the
solvent was evaporated under reduced pressure. The residue
was taken in EtOAc and purified by preparative TLC on
silica. Elution with hexane–EtOAc (7:3 or 1:1) gave the
desired products 2a–d (for yields see Table 2).
(16) Physical Data of 2-(3-Nitro-2-phenylpropyl)-4H-
chromen-4-one (2a)
(1) (a) Gerwick, W. H.; Lopez, A.; Van Duyne, G. D.; Clardy,
J.; Ortiz, W.; Baez, A. Tetrahedron Lett. 1986, 27, 1979.
(b) Gerwick, A. W. H. J. Nat. Prod. 1989, 52, 252.
(c) Yoon, J. S.; Lee, M. K.; Sung, S. H.; Kim, Y. C. J. Nat.
Prod. 2006, 69, 290.
(2) (a) Gomes, A.; Freitas, M.; Fernandes, E.; Lima, J. L. F. C.
Mini-Rev. Med. Chem. 2010, 10, 1. (b) Silva, A. M. S.;
Pinto, D. C. G.; Cavaleiro, J. A. S.; Levai, A.; Patonay, T.
ARKIVOC 2004, (vii), 106.
Colourless oil. 1H NMR (300 MHz, CDCl3): d = 8.12 (1 H,
dd, J = 1.6, 8.1 Hz, H-5), 7.65 (1 H, ddd, J = 1.6, 7.0, 8.5 Hz,
H-7), 7.41–7.18 (7 H, m, H-Ph, H-6, and H-8), 6.03 (1 H, s,
H-3), 4.72 (2 H, d, J = 7.6 Hz, b-CH2NO2), 4.11–4.01 (1 H,
m, H-b), 3.09 (1 H, dd, J = 6.5, 14.5 Hz, H-a), 3.00 (1 H, dd,
J = 8.8, 14.5 Hz, H-a). 13C NMR (75 MHz, CDCl3): d =
177.7 (C-4), 164.8 (C-2), 156.2 (C-9), 137.2 (C-1¢), 133.7
(C-7), 129.2 (C-3¢,5¢), 128.3 (C-4¢), 127.2 (C-2¢,6¢), 125.7
(C-5), 125.2 (C-6), 123.5 (C-10), 117.7 (C-8), 111.8 (C-3),
79.4 (b-CH2NO2), 41.9 (C-b), 38.1 (C-a). HRMS (ESI+):
m/z calcd for C18H16NO4 [M + H]+: 310.1074; found:
310.1074.
(3) Pinto, D. C. G. A.; Silva, A. M. S.; Almeida, L. M. P. M.;
Cavaleiro, J. A. S.; Levai, A.; Patonay, T. J. Heterocycl.
Chem. 1998, 35, 217.
(4) Doria, G.; Romeo, C.; Forgione, A.; Sberze, P.; Tibolla, N.;
Corno, M. L.; Cruzzola, G.; Cadelli, G. Eur. J. Med. Chem.
1979, 347.
(5) (a) Momoi, K.; Sugita, Y.; Ishihara, M.; Satoh, K.; Kikuchi,
H.; Hashimoto, K.; Yokoe, I.; Nishikawa, H.; Fujisawa, S.;
Sakagami, H. In Vivo 2005, 19, 157. (b) Marinho, J.; Pedro,
M.; Pinto, D. C. G. A.; Silva, A. M. S.; Cavaleiro, J. A. S.;
Sunkel, C. E.; Nascimento, M. S. J. Biochem. Pharmacol.
2008, 75, 826. (c) Shaw, A. Y.; Chang, C. Y.; Liau, H. H.;
Lu, P. J.; Chen, H. L.; Yang, C. N.; Li, H. Y. Eur. J. Med.
Chem. 2009, 2552. (d) Pinto, D. C. G. A.; Silva, A. M. S.;
Cavaleiro, J. A. S. New J. Chem. 2000, 24, 85.
(6) (a) Desideri, N.; Conti, C.; Mastromarino, P.; Mastropaolo,
F. Antivir. Chem. Chemother. 2000, 11, 373. (b) Desideri,
N.; Mastromarino, P.; Conti, C. Antivir. Chem. Chemother.
2003, 14, 195. (c) Conti, C.; Mastromarino, P.; Goldoni, P.;
Portalone, G.; Desideri, N. Antivir. Chem. Chemother. 2005,
16, 267.
(7) (a) Fernandes, E.; Carvalho, F.; Silva, A. M. S.; Santos, C.
M. M.; Pinto, D. C. G. A.; Cavaleiro, J. A. S.; Bastos, M. L.
J. Enzyme Inhib. Med. Chem. 2002, 17, 45. (b) Fernandes,
E.; Carvalho, M.; Carvalho, F.; Silva, A. M. S.; Santos, C.
M. M.; Pinto, D. C. G. A.; Cavaleiro, J. A. S.; Bastos, M. L.
Arch. Toxicol. 2003, 77, 500. (c) Filipe, P.; Silva, A. M. S.;
Morliere, P.; Brito, C. M.; Patterson, L. K.; Hug, G. L.;
Silva, J. N.; Cavaleiro, J. A. S.; Maziere, J.-C.; Freitas, J. P.;
Santus, R. Biochem. Pharmacol. 2004, 67, 2207.
(d) Gomes, A.; Fernandes, E.; Silva, A. M. S.; Santos, C. M.
M.; Pinto, D. C. G. A.; Cavaleiro, J. A. S.; Lima, J. L. F. C.
Bioorg. Med. Chem. 2007, 15, 6027.
(17) Patoilo, D. T.; Silva, A. M. S.; Cavaleiro, J. A. S. Synlett
2010, 1381.
(18) (Z)-(2-Hydroxyphenyl) (4-Phenylpyrrolidin-2-
ylidene)methyl Ketone (3a)
Yellow solid; mp 113–115 °C. 1H NMR (500 MHz, CDCl3):
d = 13.80 (1 H, s, OH), 9.95 (1 H, s, NH), 7.65 (1 H, dd, J =
1.4, 8.0 Hz, H-6¢¢¢), 7.37–7.24 (6 H, m, H-Ph and H-4¢¢¢),
6.93 (1 H, dd, J = 1.0, 8.3 Hz, H-3¢¢¢), 6.82–6.79 (1 H, m, H-
5¢¢¢), 5.87 (1 H, s, H-2), 4.08 (1 H, ddd, J = 1.0, 7.7, 10.6 Hz,
H-5¢), 3.71 (1 H, dd, J = 7.7, 10.6 Hz, H-5¢), 3.64 (1 H, quin,
J = 7.7 Hz, H-4¢), 3.19 (1 H, dd, J = 7.7, 16.9 Hz, H-3¢), 2.93
(1 H, dd, J = 7.6, 16.9 Hz, H-3¢). 13C NMR (75 MHz,
CDCl3): d = 191.3 (C-1), 168.6 (C-2¢), 162.3 (C-2¢¢¢), 141.8
(C-1¢¢), 133.5 (C-4¢¢¢), 128.9 (C-3¢¢,5¢¢), 127.7 (C-6¢¢¢), 127.2
(C-4¢¢), 126.8 (C-2¢¢,6¢¢), 120.3 (C-1¢¢¢), 118.2 (C-3¢¢¢), 118.1
(C-5¢¢¢), 85.4 (C-2), 55.2 (C-5¢), 41.2 (C-3¢), 40.7 (C-4¢).
HRMS (ESI+): m/z calcd for C18H18NO2 [M + H]+: 280.1332;
found: 280.1332.
(19) Typical Procedure for the Preparation of the 2-
Substituted 4-Arylpyrrole Derivatives 3a–d Using
Method A
Ammonium formate (0.864 mmol) and Pd/C (10%; 7.0 mg)
were added to a solution of the appropriate 2-(2-aryl-3-
nitropropyl)-4H-chromen-4-one 2a–d (0.082 mmol) in
acetone (1 mL), and the reaction mixture was refluxed for 1
h. After cooling to r.t., the reaction mixture was filtered
through Celite, and the organic layer was evaporated to
dryness. The residue was purified by preparative TLC on
silica and eluted with a mixture of hexane–EtOAc (7:3) to
give 3a–d (for yields see Table 3).
(8) Gomes, A.; Fernandes, E.; Silva, A. M. S.; Pinto, D. C. G.
A.; Santos, C. M. M.; Cavaleiro, J. A. S.; Lima, J. L. F. C.
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(21) Typical Procedure for the Preparation of the 2-
Substituted 4-Arylpyrrole Derivatives 3a–d Using
Method B
To a solution of the appropriate 2-(2-aryl-3-nitropropyl)-4H-
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E. M. P. Silva et al.
LETTER
H2O and CHCl3. The filtrate was extracted with CHCl3
(3 × 15 mL), the organic layer dried over Na2SO4, and
concentrated in vacuo. The residue was purified by
preparative TLC on silica eluting with a mixture of hexane–
EtOAc (7:3) to afford 3a–d (for yields see Table 3).
chromen-4-one 2a–d (0.082 mmol) in CHCl3 (10 mL), tin
(powder, 0.81 g) and concd HCl (2.7 mL) were added, and
the reaction mixture was stirred for 2 h at r.t. After this
period, the reaction mixture was neutralized with NaHCO3,
filtered through Celite, and the solid residue washed with
Synlett 2011, No. 18, 2740–2744 © Thieme Stuttgart · New York

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