Conjugate addition of indoles with electron-deficient olefins catalyzed by Fe-exchanged montmorillonite K10

Article abstract of DOI:10.1080/00397910500516357

Conjugate addition of indoles with a variety of electron-deficient olefins in the presence of Fe-exchanged montmorillonite K10 affords the corresponding Michael adduct in excellent yields with high selectivity. The catalyst was also found to be recyclable

Full text of DOI:10.1080/00397910500516357

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Conjugate Addition of Indoles with
Electron‐Deficient Olefins Catalyzed by
Fe‐Exchanged Montmorillonite K10
Pankajkumar R. Singh a , Shriniwas D. Samant a & Devendrapratap U. Singh a
a Organic Chemistry Research Laboratory, Institute of Chemical Technology,
University of Mumbai, Mumbai, India
Published online: 24 Feb 2007.
To cite this article: Pankajkumar R. Singh , Shriniwas D. Samant & Devendrapratap U. Singh (2006) Conjugate
Addition of Indoles with Electron‐Deficient Olefins Catalyzed by Fe‐Exchanged Montmorillonite K10, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry, 36:9,
1265-1271
To link to this article: http://dx.doi.org/10.1080/00397910500516357
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Synthetic Communicationsw, 36: 1265–1271, 2006
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910500516357
Conjugate Addition of Indoles
with Electron-Deficient Olefins Catalyzed
by Fe-Exchanged Montmorillonite K10
Devendrapratap U. Singh, Pankajkumar R. Singh,
and Shriniwas D. Samant
Organic Chemistry Research Laboratory, Institute of Chemical
Technology, University of Mumbai, Mumbai, India
Abstract: Conjugate addition of indoles with a variety of electron-deficient olefins in
the presence of Fe-exchanged montmorillonite K10 affords the corresponding Michael
adduct in excellent yields with high selectivity. The catalyst was also found to be
recyclable.
Keywords: Fe-exchanged montmorillonite K10, indole, Michael addition, a,b-
unsaturated compounds
INTRODUCTION
Addition reactions of indoles have received much interest for more than a
century because a number of their derivatives occur in nature and possess a
variety of biological activities.[1] Because the 3-position of indole is the
preferred site for electrophilic substitution reactions, 3-alkyl and acyl
indoles are versatile intermediates for the synthesis of wide range of indole
derivatives.[2]
The direct and simple method for the synthesis of 3-alkylated indoles
involve the conjugate addition of indoles to a,b-unsaturated compounds
Received September 26, 2005
Address correspondence to Shriniwas D. Samant, Organic Chemistry Research
Laboratory, Institute of Chemical Technology, University of Mumbai, N. M. Parekh
Marg, Matunga, Mumbai 400 019, India. Tel.: þ 91-022-24145616; Fax: þ91-022-
24145614; E-mail: samantsd@udct.org
1265

1266
D. U. Singh, P. R. Singh, and S. D. Samant
in the presence of either protic[3] or Lewis acids.[4] However, the acid-
catalyzed conjugated addition of indoles requires careful control of acidity
to prevent side reactions such as dimerization or polymerization. Further,
many of these procedures involve strongly acidic conditions, expensive
reagents, longer reaction times, low yields of products because of dimerization
of indoles or polymerization of vinyl ketones, and cumbersome experimental
or product-isolation procedures. There is a need for cheaper and more efficient
catalyst for Michael-type addition reactions.
In recent years, the use of solid acidic catalysts, such as clays and zeolites,
has received considerable attention in different areas of organic synthesis
because of their environmental compatibility, reusability, greater selectivity,
operational simplicity, nontoxicity, noncorrosiveness, low cost, and ease of
isolation. In particular, clay catalysts make the reaction convenient, more
economic, and environmentally benign. They act as both Brønsted and
Lewis acids in their natural and ion-exchanged forms.[5] We have recently
reported the high activity of Fe-modified clays for the Friedel–Crafts
sulfonylation of arenes with sulfonyl chloride,[6a] acylation of sulfonami-
des,[6b] the Friedel–Crafts benzylation of arenes with benzyl chlorides,[6c–e]
the Beckmann rearrangement,[6f] and nitrile formation.[6g]
In this report, we describe a remarkable catalytic activity of mont. K10 in
conjugate addition of indoles with a,b-unsaturated carbonyl compounds,
which provides an efficient route for the synthesis of b-indolylketones
(Scheme 1).
RESULTS AND DISCUSSION
The catalyst was prepared by treating mont. K10 clay with anhyd. FeCl3 in an
acetonitrile solution as described earlier.[6d] The catalyst was activated at
1208C for 5 h prior to use.
The reaction of indole with methyl vinyl ketones was selected as a model
to test the activity of different Fe-based catalysts viz. Fe–PILC,[7] K10–FeO,
K10–FeA,[6d] and K10–FePLS[6c] at room temperature (Table 1) in aceto-
nitrile solvent. It was found that the K10–FeO catalyst was superior to all
Scheme 1. Conjugate addition of indoles with electron-deficient olefins: R ¼ H, Me;
R0 ¼ methyl, aryl, anisyl, and piperonyl.

Conjugate Addition of Indoles
1267
Table 1. Conjugate addition of indole with methyl vinyl
ketone using different Fe-based catalysts at room temperature
Entry
Catalyst
Time (h)
Yield (%)a
1
2
3
4
5
K10–FeO
K10–FeA
K10–FePLS
Fe–PILC
K10
2.0
3.5
3.5
5.0
7.0
83
82
86
73
42
aIsolated yield.
other Fe-based catalysts and gave good yields of product in a short reaction
time (2 h), whereas the other catalysts took longer and the yields of the
products were less.
To extend the scope of the reaction and to generalize the procedure,
various a,b-unsaturated carbonyl compounds reacted well with indole (1,
R ¼ H) and 2-methyl indole (1, R ¼ Me) to give the 3-alkylated products
in high yields (Table 2, entries a–h) using K10–FeO as catalyst and aceto-
nitrile as a solvent at room temperature. Other electron-deficient olefins
such as 2-cyclohexen-1-one and 1,3 diphenyl propenone failed to react at
room temperature. Therefore, the reactions were carried out at higher tempera-
ture (Table 2, entries i–l). The reactions are clean, and products are obtained
in high yields, without the formation of any side products such as dimers and
trimers, which are normally observed under the influence of strong acids.[3a,b]
Some of the Michael acceptors such as methyl acrylate, nitrostyrene,
and acrylonitrile failed to react with indoles under the present reaction
conditions.
Recyclability of the catalyst, K10–FeO, was also studied. After each
cycle the used catalyst was filtered and activated at 1208C before use in the
next cycle. The activity of the catalyst was unaffected even after three to
five cycles.
CONCLUSIONS
In summary, we have demonstrated that K10–FeO is a superior catalyst for
the alkylation of indoles with electron-deficient olefins. The procedure has
the advantage of mild reaction conditions, good yields of products,
cleaner reactions with greater selectivity, short reaction times, operational
simplicity, compatibility with acid-sensitive substrates, recyclability of the
catalyst and simple experimental and product-isolation techniques, which
make it a useful and attractive process for the synthesis of alkylated
indole derivatives.

Table 2. Conjugate addition of indoles with electron-deficient olefins in the presence of K10–FeO
Reaction conditions
(time/temperature)
Entry
a
Nucleophile 1
Electrophile 2
Producta 3
Yield (%)b
2 h/rt
1.3/rt
83
b
c
d
e
f
90
87
90
89
91
1.45/rt
1.3 h/rt
2.0 h/rt
1.45 h/rt

g
h
2.5 h/rt
2.5 h/rt
78
82
i
j
6.0 h/408C
5.3 h/408C
78
76
k
l
6.0 h/808C
5.3 h/808C
73
77
1
aAll products were characterized by IR and H NMR spectroscopy.
bIsolated and unoptimized yield.

1270
D. U. Singh, P. R. Singh, and S. D. Samant
EXPERIMENTAL
General Procedure: Synthesis of 4-(1H-Indol-3-yl)-butan-2-one
A mixture of indole 1a (5 mmol), methyl vinyl ketone 2a (5 mmol), and
K10–FeO (0.5 g) in CH3CN (5 mL) was stirred at room temperature for an
appropriate time (Table 2). After the complete conversion as indicated by
TLC, the catalyst was filtered off. The combined organic layers were concen-
trated in vacuo and purified by column chromatography on silica gel (Merck,
60–120 mesh, EtOAc–pet. ether, 1 : 9) to afford the pure product 3a. Solid;
1
mp 70–718C. IR (KBr): 3400, 2925, 1715, 1355, 1160, 745 cm21. HNMR
(400 MHz, CDCl3): d ¼ 2.15 (s, 3H), 2.80 (t, J ¼ 6.4 Hz, 2H), 3.10
(t, J ¼ 6.4 Hz, 2H), 6.95 (d, J ¼ 2.4 Hz, 1H), 7.15 (t, J ¼ 7.2 Hz, 1H), 7.20
(t, J ¼ 7.2 Hz, 1H), 7.30 (d, J ¼ 7.1 Hz, 1H), 7.60 (d, J ¼ 7.1 Hz, 1H), 8.0
(br, s, 1H, NH). Anal. calcd. for C12H13NO: C, 76.98; H, 7.0; N, 7.48.
Found: C, 77.0; H, 7.03, N, 7.51.
ACKNOWLEDGMENTS
D. U. S. thanks CSIR, New Delhi, India, for the award of fellowships.
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