A catalyst- and solvent-free three-component reaction for the regioselective one-pot access to polyfunctionalized pyrroles

Article abstract of DOI:10.1016/j.tetlet.2013.07.153

A facile method for the regioselective synthesis of tetrasubstituted pyrroles, from readily accessible 1,3-dicarbonyls, benzoin derivatives and ammonium acetate, has been developed. The one-pot three-component reactions were performed to afford tetrasubst

Full text of DOI:10.1016/j.tetlet.2013.07.153

Tetrahedron Letters xxx (2013) xxx–xxx
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
A catalyst- and solvent-free three-component reaction
for the regioselective one-pot access to polyfunctionalized
pyrroles
⇑
Subrahmanya Ishwar Bhat, Darshak R. Trivedi
Supramolecular Chemistry Laboratory, Department of Chemistry, National Institute of Technology Karnataka (NITK), Srinivasnagar, Surathkal, Mangalore 575025, Karnataka, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A facile method for the regioselective synthesis of tetrasubstituted pyrroles, from readily accessible 1,3-
dicarbonyls, benzoin derivatives and ammonium acetate, has been developed. The one-pot three-compo-
nent reactions were performed to afford tetrasubstituted pyrroles under solvent- and catalyst-free
conditions.
Received 17 June 2013
Revised 25 July 2013
Accepted 28 July 2013
Available online xxxx
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Pyrrole
1,3-Dicarbonyls
Solvent-free
One-pot
Three-component
Green chemistry
Pyrroles represent an important class of nitrogen containing
heterocycles, which can be found as a structural fragment in a
broad range of natural products,1 pharmaceuticals,2 material sci-
ence3 and widely employed as versatile building blocks in syn-
thetic organic chemistry.4 Further, substituted pyrroles found
importance in molecular sensors.5 Within diversified derivatives
of pyrroles, tetrasubstituted pyrroles are of great importance due
to their tremendous application in bioactive molecules.6 Owing
to their widespread applications, in addition to the classical
approaches,7 continuous efforts have been directed towards the
development of new and efficient synthetic protocols for the syn-
thesis of pyrrole nucleus under traditional and green conditions.8,9
However, only a few reports are available in the literature for the
synthesis of functionalized pyrroles under solvent- and catalyst-
free conditions.10 Hence, the development of efficient synthetic
approach for the construction of polysubstituted pyrroles under
solvent- and catalyst-free condition is still an attractive goal for
synthetic chemists.
heterocycles. On the other hand, benzoins/a-hydroxy ketones have
found potential value as building blocks in the construction of
various heterocycles.12 Procopiou et al.13 developed a three-com-
ponent synthesis of tetrasubstituted pyrroles using benzoin deriv-
atives, ethyl isobutyrylacetate and ammonium acetate. However,
this method requires the reaction under acetic acid reflux condi-
tion followed by solvent evaporation and tedious work-up proce-
dure. Recently, solvent-free catalytic synthesis of tetrasubstituted
pyrroles using 1,3-dicarbonyls, benzoin derivatives and ammo-
nium acetate has been reported.14 Despite the satisfactory yield,
these methods require much effort in the preparation and reuse
of solid acid catalyst and in the extraction of product. The repeated
reuse of catalyst resulted in the decreased product yield. Further,
cyclic diketones and less reactive benzoins such as anisoin failed
to yield the corresponding product using these conditions.
Considering the above factors and in the context of our effort on
developing solvent- and catalyst-free reactions in organic transfor-
mations,15 herein we report a much improved and green protocol
for the synthesis of tetrasubstituted pyrroles using 1,3-dicarbonyl
compounds, benzoin derivatives and ammonium acetate under
solvent-free reaction condition in the absence of any additional
catalyst (Scheme 1). High product yields were obtained in short
reaction time and after simple recrystallization with a mixture of
water and ethanol.
1,3-Dicarbonyl compounds have drawn much attention in the
synthesis of many important heterocycles, particularly in one-pot
multicomponent approach.11 Their advantages such as easy avail-
ability, unique reactivity and simple handling procedure make
them privileged starting materials for structurally diversified
Initially, the one pot, three-component reaction was carried out
using equimolar amounts of ethyl acetoacetate (EAA) (1a), benzoin
(2a) and ammonium acetate and heated to 80 °C under
⇑
Corresponding author. Tel.: +91 824 2474000x3205; fax: +91 824 2474033.
E-mail address: darshak_rtrivedi@yahoo.co.in (D.R. Trivedi).
0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2013.07.153
Please cite this article in press as: Bhat, S. I.; Trivedi, D. R. Tetrahedron Lett. (2013), http://dx.doi.org/10.1016/j.tetlet.2013.07.153

2
S. I. Bhat, D. R. Trivedi / Tetrahedron Letters xxx (2013) xxx–xxx
O
O
R3
90oC
R3
R3
O
O
R2
NH4OAc
R1
R2
HO
Solvent free
Catalyst free
R1
N
H
R3
1
2
3
4
Scheme 1. One-pot three-component synthesis of tetrasubstituted pyrroles.
Table 1
Optimization of the reaction
3
O
O
O
O
NH4OAc
O
O
OH
N
H
4a
1a
2a
Entry
Molar ratio of 1a:2a:3
Reaction temperature/time
Yield of 4a (%)
1
2
3
4
5
6
7
1:1:1
80 °C/180 min
80 °C/180 min
90 °C/120 min
90 °C/120 min
90 °C/120 min
90 °C/120 min
100 °C/120 min
42
48
74
83
93
80
84
1:1:1.2
1:1:1.2
1:1:1.5
1.1:1:1.5
1.1:1:1.2
1.1:1:1.5
In order to highlight the yield of the product at optimized condition, the number "93" is highlighted with bold font.
solvent-free condition. The reaction mass got slowly converted to a
suspension and partial conversion was observed after 60 min (the
reaction was monitored by TLC). Continuation of the reaction
yielded 42% of the product after 180 min. The reaction was then
optimized by varying the molar ratio of starting materials and tem-
perature of the reaction (Table 1). The molar ratio 1.1:1:1.5 of EAA
(1a), benzoin (2a) and ammonium acetate at 90 °C was found to be
the optimal condition for better conversion. The reaction mass got
converted to a homogeneous liquid under these conditions and the
desired product was obtained in high yield. Further, increasing the
temperature to 100 °C resulted in decreased yield due to the for-
mation of unknown impurities. The pure solid product was ob-
tained after recrystallization with ethanol–water (80:20) mixture.
In order to explore the synthetic utility of the current protocol, a
series of reactions were carried out using various 1,3-dicarbonyls
(1), benzoin derivatives (2) and ammonium acetate under opti-
mized conditions.16 The reaction proceeded smoothly with various
1,3-dicarbonyls. However, the reaction with dibenzoylmethane
failed to yield the products through condensation with benzoin
even at elevated temperature. This may be attributed to the poor
reactivity of carbonyl groups due to the presence of adjacent bulky
phenyl groups. Also, increasing the reaction temperature (>130 °C)
resulted in the decomposition of starting materials. Unlike the
reaction with symmetrical 1,3-dicarbonyls, in the case of unsym-
metrical 1,3-dicarbonyl compounds, mixtures of regioisomeric
products are possible. However, with all unsymmetrical 1,3-dicar-
bonyls (1a, 1b, 1d) used, only one regioisomer has been obtained in
high yield under present reaction conditions. This may be attrib-
uted to the difference in reactivity of carbonyl groups influenced
by the nature of substitution on it. The resonance effect in the ester
group (Table 2, entries 1–6) and steric effect in the benzoyl group
(Table 2 entries 10–12) reduced the reactivity of the carbonyl
group and hence remained as side chain in the corresponding pyr-
roles. The structural evidence was ascertained by 13C NMR analysis
of the pyrroles. The carbonyl signal of pyrroles 4a–4f appeared
ꢀ165 ppm corresponding to the ester carbonyl group and carbonyl
signal of pyrroles 4j–4l appeared ꢀ194 ppm corresponding to the
benzoyl carbonyl group while carbonyl signal of pyrroles 4g–4i ap-
peared ꢀ197 ppm corresponding to the acetyl carbonyl group. In
addition, from the SXRD (Single Crystal X-ray diffraction) analysis
of 4c, it was clearly found that the ester group was untouched
and remained as side chain in pyrrole 4c. Thus, the difference in
reactivity of carbonyl groups of 1,3-dicarbonyls leads to the forma-
tion of single regioisomer and hence the present protocol can be
considered as regioselective.
In order to evaluate the scope of the present protocol, the reac-
tion was extended to less reactive anisoin and heteroaromatic 2,20-
furoin. Interestingly, anisoin underwent smooth reaction under the
present conditions to afford the corresponding pyrrole derivatives
in good yield (Table 2, entries 2, 8 and 11). As a main reason for this
conversion, we assume that, the increased temperature (90 °C) and
a small excess of 1,3-dicarbonyls (1.1 equivalence), resulted in a
homogeneous reaction mixture facilitating the reaction. This was
supported by the early experiments, when equimolar ratios of
EAA and benzoin were reacted at 80 °C; the reaction mixture re-
mained as a suspension and resulted in poor product yield (42%).
The three-component reaction proceeded smoothly and good
product yields were obtained with heteroaromatic 2,20-furoin (Ta-
ble 2, entries 3, 6, 9 and 12).
The structure of the products was confirmed by spectral data
and elemental analysis. The 1H NMR and 13C NMR of known com-
pounds are in agreement with the earlier reports.14 Further, to con-
firm the structure of tetrasubstituted pyrroles unambiguously, 4c
was selected as a representative compound and characterized by
single crystal X-ray diffraction analysis19 (see Supplementary data
Fig. 1).
On the basis of electronic effects and regioselectivity of the
reaction, two plausible pathways for the present three-component
protocol are illustrated in Scheme 2. The reaction of the carbonyl
group of benzoin with ammonium acetate can form
a-hydroxy
Please cite this article in press as: Bhat, S. I.; Trivedi, D. R. Tetrahedron Lett. (2013), http://dx.doi.org/10.1016/j.tetlet.2013.07.153

S. I. Bhat, D. R. Trivedi / Tetrahedron Letters xxx (2013) xxx–xxx
3
Table 2
Three-component synthesis of tetrasubstituted pyrroles under solvent- and catalyst-free conditions
Entry
1,3-Dicarbonyls
Benzoin derivatives
Producta
Yieldb (%)
O
O
OH
O
O
O
1
4a
93c
O
O
N
H
O
O
OH
O
O
O
O
O
2
4b
89c
O
O
N
H
OH
O
O
O
O
O
O
O
O
O
O
3
4
4c
84c
O
O
O
O
O
NH
OH
O
c
4d
85
N
H
O
O
OH
O
O
O
O
O
O
O
5
4e
Trace
O
O
O
N
H
OH
O
O
O
O
O
O
O
6
7
4f
92c
O
O
O
NH
OH
O
O
4g
90c
N
H
O
O
O
OH
O
O
O
O
O
8
4h
86c
O
N
H
OH
O
O
O
O
O
O
9
4i
4j
83c
O
O
NH
O
OH
O
O
c
10
86
N
H
(continued on next page)
Please cite this article in press as: Bhat, S. I.; Trivedi, D. R. Tetrahedron Lett. (2013), http://dx.doi.org/10.1016/j.tetlet.2013.07.153

4
S. I. Bhat, D. R. Trivedi / Tetrahedron Letters xxx (2013) xxx–xxx
Table 2 (continued)
Entry
1,3-Dicarbonyls
Benzoin derivatives
Producta
Yieldb (%)
O
OH
O
O
O
O
O
11
4k
82c
O
O
N
H
OH
O
O
O
O
O
O
c
12
13
4l
85
O
O
N
H
O
OH
O
O
4m
82d
O
N
H
O
OH
O
O
14
4n
76d
O
N
H
a
Reaction conditions: 1,3-dicarbonyls (1.1 mmol), benzoin derivatives (1 mmol), ammonium acetate (1.5 mmol) at 90 °C, 120 min.
Yield of pure product.
Purified by recrystallization using 80:20 ethanol water mixture.
Purified by column chromatography.
b
c
d
R1
O
H
Condensive
Cyclization
H
N
O
NH4OAc
Ar
Ar
R1
O
N
Ar
Ar
II
NH2
O
Ar
Ar
NH
OH
R1
R2
R2
Path A
Ar
Ar
[1,5] H shift
R2
O
H2O
H2O
O
O
R2
R1
I
III
IV
Ar
Ar
Ar
O
N
OH
Ar
H
Condensive
Cyclization
R2
O
R2
4
Ar
R2
R1
Ar
O
Path B
NH4OAc
H2O
[1,5] H shift
Ar
O
R1
R2
Ar
R1
Ar
H2O
O
O
Ar
R1
HO
H2O
HN
OH NH2
H
OHO
V
VI
VII
Scheme 2. Possible mechanistic pathways for the formation of tetrasubstituted pyrroles.
imine I, which can undergo isomerization17 to form intermediate
II. The reaction of the amine group in intermediate II with more
reactive carbonyl group of 1,3-dicarbonyls can form enaminone
intermediate III.10a The cyclization of intermediate III followed
by [1,5] proton shift, leads to the formation of pyrrole 4 (Path A,
Scheme 2). Alternatively, condensation of 1,3-dicarbonyls with
the carbonyl group of benzoin can form intermediate V. Further,
condensation of ammonium acetate with more reactive carbonyl
of intermediate V can form intermediate VI, which on rearrange-
ment and simultaneous cyclization yielded product 4 (Path B,
Scheme 2).
benzoin in the presence of ammonium acetate (Scheme 3), poly-
functionalized indoles were obtained in high yield after 120 min
of heating at 90 °C (Table 2, entries 13 and 14).
In order to expand the one pot protocol for the synthesis of tet-
rasubstituted pyrroles, 1,3-dicarbonyls were reacted with phenyl-
glyoxal to yield the corresponding products (Table 3).16 The pure
pyrrole products were obtained in high yield after recrystallization
with 70:30 ethanol water mixture. It was found that, the require-
ment of ammonium acetate to yield the pyrrole product reduced
significantly compared to the earlier water mediated protocol.18
This may be attributed to the improved molecular interaction be-
tween ammonium acetate and other water insoluble starting
materials under solvent-free conditions compared to aqueous
The current protocol was further extended to cyclic 1,3-dike-
tones. When, dihydroresorcinol and dimedone were reacted with
Please cite this article in press as: Bhat, S. I.; Trivedi, D. R. Tetrahedron Lett. (2013), http://dx.doi.org/10.1016/j.tetlet.2013.07.153

S. I. Bhat, D. R. Trivedi / Tetrahedron Letters xxx (2013) xxx–xxx
5
O
Solvent free
O
O
Catalyst free
NH4OAc
R
R
N
H
HO
90°C
R
O
R
R = H, CH3
Scheme 3. One-pot three-component synthesis of polysubstituted indoles.
Table 3
Three-component synthesis of tetrasubstituted pyrroles under solvent- and catalyst-free conditions
O
OH
R1
NH4OAc
O
O
O
R1
N
Solvent free
Catalyst free
H
OH
HO
Entry
1
1,3-Dicarbonyls
Producta
Yieldb,c (%)
O
O
O
O
O
O
O
O
O
O
OH
O
O
4o
92
O
O
N
H
OH
2
3
4
4p
4q
4r
83
N
H
O
OH
91
N
H
O
OH
Trace
N
H
a
b
c
Reaction conditions: 1,3-dicarbonyls (1.1 mmol), phenyl glyoxal (1 mmol), ammonium acetate (1.5 mmol) at 50 °C, 120 min.
Yield of pure product.
Purified by recrystallization using 70:30 ethanol water mixture.
media. Further, only one regioisomer was obtained with unsym-
metrical 1,3-dicarbonyls.
Supplementary data
In summary, herein we report an improved and greener one-
pot protocol for the synthesis of tetrasubstituted pyrroles
through a three-component reaction of 1,3-dicarbonyls, benzoin
derivatives and ammonium acetate. Notably, this solvent- and
catalyst-free approach leads to the formation of regioselective
products from readily accessible starting materials and circum-
vents several limitations associated with earlier reported cata-
lytic protocols. Further, the present protocol finds application in
the synthesis of polyfunctionalized indoles and substituted 4-hy-
droxy pyrroles with improved reaction efficiency and reduced
waste. Hence it is conceivable that this method could find wide
application in the synthesis of various other complex pyrrole-
containing compounds.
Supplementary data associated with this article can be found,
in the online version, at http://dx.doi.org/10.1016/j.tetlet.2013.
07.153.
References and notes
1. (a) Fujita, M.; Nakao, Y.; Matsunaga, S.; Seiki, M.; Itoh, Y.; van Yamashita, J.;
Soest, R. W. M.; Fusetani, N. J. Am. Chem. Soc. 2003, 125, 15700; (b) Furstner, A.
Angew. Chem., Int. Ed. 2003, 42, 3582; (c) Lindel, T.; Breckle, G.; Hochgurtel, M.;
Volk, C.; Grube, A.; Kock, M. Tetrahedron Lett. 2004, 45, 8149; (d) Grube, A.;
Kock, M. Org. Lett. 2006, 8, 4675.
2. (a) Walsh, C. T.; Garneau-Tsodikova, S.; Howard-Jones, A. Nat. Prod. Rep. 2006,
23, 517; (b) Rochais, C.; Lisowski, V.; Dallemagne, P.; Rault, S. Bioorg. Med.
Chem. 2006, 14, 8162; (c) Santo, R. D.; Costi, R.; Artico, M.; Miele, G.; Lavecchia,
A.; Novellino, E.; Bergamini, A.; Cancio, R.; Maga, G. ChemMedChem 2006, 1,
1367; (d) Zeng, L.; Miller, E. W.; Pralle, A.; Isacoff, E. Y.; Chang, C. J. J. Am. Chem.
Soc. 2006, 128, 10; (e) Clark, B. R.; Capon, R. J.; Lacey, E.; Tennant, S.; Gill, J. H.
Org. Lett. 2006, 8, 701; (f) La Regina, G.; Silvestri, R.; Artico, M.; Lavecchia, A.;
Novellino, E.; Befani, O.; Turini, P.; Agostinelli, E. J. Med. Chem. 2007, 50, 922.
3. (a) Groenendaal, L.; Meijer, E.-W.; Vekemans, J. A. J. M. Electronic Materials: The
Oligomer Approach; Wiley-VCH: Weinheim, 1997; (b) Lee, C. F.; Yang, L. M.;
Hwu, T. Y.; Feng, A. S.; Tseng, J. C.; Luh, T. Y. J. Am. Chem. Soc. 2000, 122, 4992;
(c) Domingo, V. M.; Aleman, C.; Brillas, E.; Julia, L. J. Org. Chem. 2001, 66, 4058.
4. (a) Bellina, F.; Rossi, R. Tetrahedron 2006, 62, 7213; (b) Trofimov, B. A.;
Sobenina, L. N.; Demenev, A. P.; Mikhaleva, A. I. Chem. Rev. 2004, 104, 2481;
Acknowledgments
D.R.T. and S.I.B. acknowledge the Director and the HOD (Depart-
ment of Chemistry), NITK, Surathkal for providing the research
infrastructure. S.I.B. is thankful to NITK for research fellowship.
D.R.T. and S.I.B. are also thankful to CSMCRI Bhavnagar and IISc
Bangalore, for providing analytical support.
Please cite this article in press as: Bhat, S. I.; Trivedi, D. R. Tetrahedron Lett. (2013), http://dx.doi.org/10.1016/j.tetlet.2013.07.153

6
S. I. Bhat, D. R. Trivedi / Tetrahedron Letters xxx (2013) xxx–xxx
(c)Pyrroles, the Synthesis Reactivity and Physical Properties of Substituted Pyrroles,
Part II; Jones, R. A., Ed.; Wiley: New York, 1992.
5. See for example: Sessler, J. L.; Pantos, G. D.; Gale, P. A.; Light, M. E. Org. Lett.
2006, 8, 1593.
12. Some selected example: (a) Sithambaram, S.; Ding, Y.; Li, W.; Shen, X.;
Gaenzler, F.; Suib, S. L. Green Chem. 2008, 10, 1029; (b) Bhosale, S. V.;
Kalyankar, M. B.; Nalage, S. V.; Bhosale, D. S.; Pandhare, S. L.; Kotbagi, T. V.;
Umbarkar, S. B.; Dongare, M. K. Synth. Commun. 2011, 41, 762; (c) Bhattacharya,
T.; Sarma, T. K.; Samanta, S. Catal. Sci. Technol. 2012, 2, 2216; (d) Nagargoje, D.;
Mandhane, P.; Shingote, S.; Badadhe, P.; Gill, C. Ultrason. Sonochem. 2012, 19,
94; (e) Xue, W.-J.; Li, Q.; Zhu, Y.-P.; Wang, J.-G.; Wu, A.-X. Chem. Commun. 2012,
3485.
13. Procopiou, P. A.; Draper, C. D.; Hutson, J. L.; Inglis, G. G. A.; Ross, B. C.; Watson,
N. S. J. Med. Chem. 1993, 36, 3658.
14. (a) Tamaddon, F.; Farahi, M. Synlett 2012, 1379; (b) Tamaddon, F.; Farahi, M.;
Karami, B. J. Mol. Catal. A: Chem. 2012, 356, 85.
6. (a) Almerico, A. M.; Diana, P.; Barraja, P.; Dattolo, G.; Mingoia, F.; Putzolu, M.;
Perra, G.; Milia, C.; Musiu, C.; Marongiu, M. E. Farmaco 1997, 52, 667; (b)
Lehuede, J.; Fauconneau, B.; Barrier, L.; Ourakow, M.; Piriou, A.; Vierfond, J. M.
Eur. J. Med. Chem. 1999, 34, 991; (c) Pinna, G. A.; Loriga, G.; Murineddu, G.;
Grella, G.; Mura, M.; Vargiu, L.; Murgioni, C.; La Colla, P. Chem. Pharm. Bull.
2001, 49, 1406; (d) Iwao, M.; Takeuchi, T.; Fujikawa, N.; Fukuda, T.; Ishibashi, F.
Tetrahedron Lett. 2003, 44, 4443.
7. Some selected example: (a) Manley, J. M.; Kalman, M. J.; Conway, B. G.; Ball, C.
C.; Havens, J. L.; Vaidyanathan, R. J. Org. Chem. 2003, 68, 6447; (b) Shiner, C. M.;
Lash, T. D. Tetrahedron 2005, 61, 11628; (c) Chen, J.; Wu, H.; Zheng, Z.; Jin, C.;
Zhang, X.; Su, W. Tetrahedron Lett. 2006, 47, 5383; (d) Minetto, G.; Raveglia, L.
F.; Sega, A.; Taddei, M. Eur. J. Org. Chem. 2005, 24, 5277.
15. (a) Bhat, S. I.; Choudhury, A. R.; Trivedi, D. R. RSC Adv. 2012, 2, 10556; (b) Bhat,
S. I.; Trivedi, D. R. Environ. Chem. Lett. 2013, 11, 91.
16. General procedure for the synthesis of tetrasubstituted pyrrole derivatives: 1,3-
dicarbonyl 1 (1.1 mmol), benzoin derivative/phenyl glyoxal 2 (1.0 mmol) and
ammonium acetate 3 (1.5 mmol) were charged into a 10 ml round-bottom
flask fitted to condenser and the mixture was heated to 90 °C/50 °C using
conventional oil bath. The reaction mixture was stirred to 120 min until the
8. (a) Balme, G. Angew. Chem., Int. Ed. 2004, 43, 6238; (b) Estevez, V.; Villacampa,
M.; Menendez, J. C. Chem. Soc. Rev. 2010, 39, 4402.
9. Some selected example: (a) Liu, W.; Jiang, H.; Huang, L. Org. Lett. 2010, 12, 312;
(b) Estevez, V.; Villacampa, M.; Menendez, J. C. Chem. Commun. 2013, 591; (c)
Reddy, G. R.; Reddy, T. R.; Joseph, S. C.; Reddy, K. S.; Pal, M. RSC Adv. 2012, 2,
3387; (d) Suresh, R.; Muthusubramanian, S.; Nagaraj, M.; Manickam, G.
Tetrahedron Lett. 2013, 54, 1779.
10. (a) Attanasi, O. A.; Favi, G.; Mantellini, F.; Moscatelli, G.; Santeusanio, S. J. Org.
Chem. 2011, 76, 2860; (b) Palmieri, A.; Gabrielli, S.; Cimarelli, C.; Ballini, R.
Green Chem. 2011, 13, 3333.
11. Some selected examples: (a) Simon, C.; Constantieux, T.; Rodriguez, J. Eur. J.
Org. Chem. 2004, 4957; (b) Wan, J.-P.; Liu, Y. RSC Adv. 2012, 2, 9763; (c)
Bonne, D.; Coquerel, Y.; Constantieux, T.; Rodriguez, J. Tetrahedron:
Asymmetry 2010, 21, 1085; (d) Singh, M. S.; Chowdhury, S. RSC Adv. 2012,
2, 4547.
starting material
2 was consumed to the maximum extent. The reaction
mixture was then cooled and recrystallized with ethanol water mixture to
obtain pure product 4. (The reaction mixture was dissolved in ethyl acetate
(2 ml) and washed with water (2 ꢁ 2 ml) and the organic layer was separated
and adsorbed to silica gel (60–120 mesh size) and column chromatographed
using ethyl acetate and petroleum ether (80:20) as eluents to obtain pure
polyfunctionalized indoles 4m and 4n). All the products were confirmed by
spectral and elemental analyses (see Supplementary data).
17. Paquette, L. A.; Hofferberth, J. E. Org. React. 2004, 477.
18. Khalili, B.; Jajarmi, P.; Eftekhari-Sis, B.; Hashemi, M. M. J. Org. Chem. 2008, 73,
2090.
19. CCDC No. 929558 for compound 4c.
Please cite this article in press as: Bhat, S. I.; Trivedi, D. R. Tetrahedron Lett. (2013), http://dx.doi.org/10.1016/j.tetlet.2013.07.153