An efficient two-step synthesis of 3-allylindoles

Article abstract of DOI:10.1016/j.tetlet.2005.11.134

A two-step synthetic sequence for an efficient synthesis of 3-allylindoles is described.

Full text of DOI:10.1016/j.tetlet.2005.11.134

Tetrahedron
Letters
Tetrahedron Letters 47 (2006) 1003–1005
An efficient two-step synthesis of 3-allylindoles
*
Mukund G. Kulkarni, Saryu I. Davawala, Attrimuni P. Dhondge,
Dnyaneshwar D. Gaikwad, Ajit S. Borhade and Sanjay W. Chavhan
Department of Chemistry, University of Pune, Ganeshkhind, Pune 411 007, India
Received 25 October 2005; revised 17 November 2005; accepted 24 November 2005
Available online 15 December 2005
Abstract—A two-step synthetic sequence for an efficient synthesis of 3-allylindoles is described.
Ó 2005 Elsevier Ltd. All rights reserved.
1
. Introduction and discussion
This clearly indicated that the two reactions, namely,
Claisen rearrangement of the allyl vinyl ether to the cor-
responding 4-pentenal and reduction of the nitro group
with FeSO –NH to the corresponding amine were
effected simultaneously. The resulting amino aldehyde
underwent in situ cyclisation to furnish 3-allylindole.
Thus, the synthesis of 3-allylindole was achieved in only
two steps. Reaction of substituted o-nitrobenzaldehydes
also furnished, under the above reaction conditions,
substituted 3-allylindoles in good yields.
Several methods have been developed for the synthesis
of indoles and substituted indoles as they are a key fea-
ture of many natural products and pharmaceutical com-
4
3
1
–20
pounds.
However, there is still a need to develop
newer methods for their synthesis. Alkylation of indoles
or salts of indoles under drastic conditions yields a com-
plex mixture of 1-substituted, 1,3-disubstituted, 3-substi-
2
1–24
25
tuted indoles
and/or indolenines. The conversion
of indoles to 3-allylindoles was effected via zinc-medi-
2
6
ated Barbier reactions or palladium catalysed allyl-
Furthermore, reaction of the substituted o-nitrobenz-
aldehydes with potassium tertiary butoxide and another
Wittig salt, namely, crotyloxymethylenetriphenylphos-
phonium chloride, gave the corresponding allyl vinyl
ethers 4 in good yields (Scheme 2). These allyl vinyl
ethers, under the above reaction conditions, furnished
novel 3-(3-butenyl)indoles 5. The present protocol offers
a general method for the synthesis of 3-allylindoles
in two simple steps. The utility of these 3-allylindoles
in the synthesis of complex natural products is being
actively investigated.
2
7
ation. In yet another method, acid-catalysed Claisen
rearrangement of 1-allylindole furnished 3-allylindole.
All the above methods utilise indoles as starting mate-
2
8
2
8–32
rial.
We herein describe an application of the Wittig olefin-
3
3
ation–Claisen rearrangement methodology towards a
short and efficient synthesis of 3-allylindoles in just
two steps using simple starting materials viz. o-nitrobenz-
aldehydes. Wittig olefination of o-nitrobenzaldehyde
3
3
1
a, under standard conditions, with allyloxymethyl-
enetriphenylphosphorane furnished the corresponding
allyl vinyl ether 2a. The allyl vinyl ether 2a was then
subjected to a Claisen rearrangement by heating in
refluxing diglyme–water solvent system (1:1) in the pres-
ence of excess FeSO and NH (Scheme 1). To our
2
. Experimental procedure for Claisen rearrangement/
ring closure (3a)
4
3
To a stirred suspension of ferrous sulfate (16 g,
2 mmol) in diglyme–water (1:1, 5:5 ml), the allyl vinyl
ether 2a (mixture of E and Z isomers) (1 g, 1 mmol)
pleasant surprise, 3-allylindole 3a was obtained from
the reaction mixture.
1
was added. After refluxing the mixture for 15–20 min
(TLC check), excess ammonia was added. The resulting
*
0
Corresponding author. Tel.: +91 020 2560 1225; fax: +91 020 2569
728; e-mail: saryu@chem.unipune.ernet.in
solution was refluxed for 24 h (TLC check). The reac-
tion mixture as such was purified by silica gel column
1
040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.11.134

1004
M. G. Kulkarni et al. / Tetrahedron Letters 47 (2006) 1003–1005
R4
R4
R4
R3
R3
R2
R3
R2
CHO
NO2
O
i
ii
R2
NO
N
2
R1
R1
H
R1
1a - h
2a - h
3a - h
1
2
3
4
a
R
R
R
R
% Yield
2
75
72
73
70
70
71
70
72
3
77
80
79
76
75
74
76
76
a
b
c
d
e
f
H
H
H
H
H
Cl
H
H
H
H
H
OMe
H
H
H
H
H
H
H
Cl
H
OMe
OMe
H
OMe
OMe
OH
Br
H
g
h
H
2
-OCH O-
a
Isolated yields
+
À
À
+
Scheme 1. Reagents and conditions: (i) CH
2
@CHCH
2
OCH
2
P Ph
3
4 3
Cl , t-BuO K , THF, 0 °C, 30 min; (ii) FeSO , NH , diglyme–water (1:1), reflux.
R4
R4
Me
R4
R3
i
R3
O
CHO
R3
ii
NO2 R2
R2
NO
2
N
R2
R1
R
1
Me
H
R1
1
a-h
4a-h
5a-h
1
2
3
4
a
R
R
R
R
% Yield
4
5
75
74
74
78
76
79
78
75
a
b
c
H
H
H
H
H
Cl
H
H
H
H
H
70
OMe
H
H
H
70
H
H
71
d
e
H
H
Cl
73
H
OMe
OMe
H
OMe
OMe
OH
72
f
Br
H
73
g
75
h
a
H
-OCH O-
73
2
Isolated yields
+
À
À
+
Scheme 2. Reagents and conditions: (i) MeCH@CHCH
2
OCH
2
P Ph
3
4 3
Cl , t-BuO K , THF, 0 °C, 30 min; (ii) FeSO , NH , diglyme–water (1:1),
reflux.
chromatography using the hexane–ethyl acetate (98:2)
solvent system.
D.G., A.B. and S.C. would like to thank CSIR, New
Delhi, for Fellowships.
References and notes
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