A direct phosphine-mediated synthesis of polyfunctionalized pyrroles from arylglyoxals and β-enaminones

Article abstract of DOI:10.1016/j.tetlet.2015.11.075

An efficient one-pot reaction for the synthesis of pyrroles from β-enaminones and arylglyoxals is reported. This reaction, which is mediated by triphenylphosphine, eliminates triphenylphosphine oxide resulting in aromatization and has been employed to access a broad range of pyrrole derivatives.

Full text of DOI:10.1016/j.tetlet.2015.11.075

Tetrahedron Letters 57 (2016) 103–104
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
A direct phosphine-mediated synthesis of polyfunctionalized
pyrroles from arylglyoxals and b-enaminones
Mozhgan Masoudi a,b, Mohammad Anary-Abbasinejad b,
⇑
a
Department of Chemistry, Rafsanjan Branch, Islamic Azad University, Rafsanjan, Iran
b
Department of Chemistry, Vali-e-Asr University, Rafsanjan 77176, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 30 May 2015
Revised 25 October 2015
Accepted 24 November 2015
Available online 25 November 2015
An efficient one-pot reaction for the synthesis of pyrroles from b-enaminones and arylglyoxals is
reported. This reaction, which is mediated by triphenylphosphine, eliminates triphenylphosphine oxide
resulting in aromatization and has been employed to access a broad range of pyrrole derivatives.
Ó 2015 Elsevier Ltd. All rights reserved.
Keywords:
Pyrrole
Arylglyoxals
b-Enaminone
Triphenylphosphine
Synthesis
Introduction
Results and discussion
Nitrogen-containing five-membered heterocycles, such as pyr-
roles, are among the most important building blocks in organic
chemistry. These heterocycles have found utility in various fields
such as materials science, medicinal chemistry, polymer synthesis,
and metal-coordinating ligands. Examples of these include diverse
Initially, to investigate the reaction between arylglyoxals and
enaminocarbonyls, p-chlorophenylglyoxal monohydrate was
reacted with 4-phenylamino-3-pentene-2-one in acetonitrile. After
10 min of stirring, triphenylphosphine was added and the reaction
progress was monitored by TLC. After 20 min of stirring at room
temperature, the starting materials were consumed and two spots
appeared on TLC, which were identified as pyrrole derivative 4a
and triphenylphosphine oxide. To investigate the generality of
the reaction, different arylglyoxals were treated with enaminones
and the related pyrrole derivatives were obtained in high yields
(Table1). The enaminones of both aromatic and aliphatic amines
reacted easily with arylglyoxals resulting in pyrrole derivatives,
but the enaminones of ethyl acetoacetate led to complex mixtures
and no pure product could be isolated (Scheme 1).
1
2–6
anti-inflammatory agents, antitumor agents,
and they are gen-
7
erally utilized in cytotoxicity and the treatment of hyperlipi-
8
demias. Various methodologies have been developed for the
synthesis of pyrroles.9–11 Moreover, the application of multi-com-
ponent reactions for the synthesis of pyrrole derivatives has been
9
recently reviewed. Multi-component reactions of arylglyoxals
and enaminocarbonyls in the presence of various nucleophiles
have recently been reported for the synthesis of poly-functional-
1
2–14
ized pyrroles.
However, to the best of our knowledge there
12,13
are no reports on the condensation of b-enaminones
with aryl-
Structures of compounds 4a–m were deduced from their spec-
1
glyoxals for the synthesis of pyrrole derivatives. In a continuation
tral and analytical data. For example the H NMR spectrum of 4a
of our studies on the application of arylglyoxals for the synthesis
exhibited two singlets at 2.43 and 2.51 ppm corresponding to the
two methyl groups. The CH of the pyrrole ring was observed as a
singlet at 6.74 ppm while the aromatic protons resonated between
of heterocyclic compounds,1
5–17
herein, we report the condensa-
tion reaction between arylglyoxal monohydrates and enaminones
in the presence of triphenylphosphine to afford substituted pyr-
roles in good yields.
1
3
6.97 and 7.50 ppm. The C NMR spectrum of 4a showed fifteen
distinct signals which were consistent with the proposed struc-
ture; note the carbonyl resonance at 195.3 ppm. The structure of
compound 4a was also confirmed by IR spectroscopy exhibiting
À1
À1
two absorption bands at 1549 cm and 1659 cm for the C@C
and C@O groups, respectively.
⇑
Corresponding author. Fax: +98 3913222963.
E-mail address: m.anary@vru.ac.ir (M. Anary-Abbasinejad).
http://dx.doi.org/10.1016/j.tetlet.2015.11.075
040-4039/Ó 2015 Elsevier Ltd. All rights reserved.
0

1
04
M. Masoudi, M. Anary-Abbasinejad / Tetrahedron Letters 57 (2016) 103–104
Table 1
Substrate scope
4
Ar
4-ClC
2-Naphthyl
2-Naphthyl
R
Yielda (%)
a
b
c
d
e
f
g
h
i
6
H
4
C
C
6
H
H
5
85
87
73
78
89
88
92
90
93
95
95
92
94
6
5
4-ClC
4-ClC
4-CH
4-CH
4-CH
C H
6 5
4-CH
4-CH
6
H
H
4
4-ClC
4-ClC
6
H
H
4
6
4
6
4
3
C
6
H
H
4
2-Naphthyl
2-Naphthyl
3
3
C
6
4
OC
6
H
4
CH
2
4-FC
2-Naphthyl
4-FC
4-CH
6
H
4
3
OC
6
H
4
j
k
l
6
H
4
3
C
6
H
4
3
C
6
H
H
4
2 6 5
CH C H
n-Butyl
n-Butyl
C
6
H
5
m
4-CH
3
C
6
4
a
Isolated yield. Conditions: MeCN, rt, 20 min.
O
CH
3
O
O
NHR
CH3
MeCN
H C
3
OH
+
+
PPh
3
+
PPh O
Ar
N
R
3
H C
rt, 30 min
3
OH
Ar
1
2
3
4
5
Scheme 1. Reaction between arylglyoxals, b-enaminones, and triphenylphosphine.
article can be found, in the online version, at http://dx.doi.org/10.
1016/j.tetlet.2015.11.075.
O
H
CH
O
3
O
O
NHR
CH
2
-H O
H C
NR
Ar
OH
O
3
Ar
+
H
3
C
3
References and notes
HO
OH
1
2
6
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CH3
O
CH3
PPh
3
3
H C
-
3
PPh O
H
3
C
NR
Ar
NR
Ar
4
3
Ph P
O
O
4, 363; For the general biological activity of pyrroles, see: (d) Bellina, F.; Rossi,
7
8
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3
4
5
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Scheme 2. Proposed mechanism for the formation of pyrrole derivatives 4a–m.
337.
A proposed mechanism for formation of pyrrole derivatives 4a–
m is shown in Scheme 2. On the basis of the well-established regio-
chemistry of the addition of enaminones to arylglyoxals it is rea-
sonable to assume that condensation of the arylglyoxal derivative
at the aldehyde carbon with the enaminone derivatives affords
intermediate 7. Subsequent conjugate addition of triphenylphos-
phine to intermediate 7 affords the phosphonium betaine interme-
diate 8 which after elimination of triphenylphosphine oxide gives
product 4.
Gupton, J. T.; Burnham, B. S.; Byrd, B. D.; Krumpe, K. E.; Stokes, C.; Shuford, J.;
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In summary, we report herein the reaction between b-enami-
nones and arylglyoxal monohydrates in the presence of triph-
enylphosphine to afford new pyrrole derivatives. The advantages
of the method are readily available starting materials, neutral reac-
tion conditions, and simple isolation and purification procedures
for the products.
13. Jiang, B.; Yi, M. S.; Shi, F.; Tu, S. J.; Pindi, S.; McDowell, P.; Li, G. Chem. Commun.
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1
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0.1007/s13738-015-0608-x. in press.
1
1
Supplementary data
Supplementary data (the experimental procedures and the IR,
H NMR, and C NMR spectra of products) associated with this
1
13