LETTER
One-Pot, Three-Component Approach to a-Alkynyl Indoles
913
the conditions described above to generate the corre-
sponding indoles 4n, 4o, and 4p, respectively. To the best
of our knowledge, this three-component one-pot coupling
reaction represents the first example of such type,11 espe-
cially using the polyhalo compounds o-bromo-(2,2-dibro-
movinyl)benzenes.
Acknowledgment
This work was supported by NSFC. Y.L. is thankful for financial
support from the Postdoctorate Research Fund of China
(20090460144).
References and Notes
It should be noted that all three components are present at
the same time in the reaction system. The chemical selec-
tivity of the reaction is thus very high. Clearly, compared
with previously reported reactions involving one or two of
these components,6–10,12 the reaction mechanism of this
process is intriguing. We found that, without aniline, 1a
reacted with phenylacetene to form 5 in 17% isolated
yield (eq. 1). We also found that compound 5 could fur-
ther react with aniline smoothly to form 2-alknylindole 4a
in 68% isolated yield (eq. 2). Therefore, although the
reaction path I as proposed in Scheme 2 is more likely, the
reaction path II cannot be ruled out.
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Pd(OAc)2
Xantphos
+
1a 3a
(1)
(2)
Cs2CO3, NMP
120 °C, 4 h
(5, 17%)
Br
Pd(OAc)2
Xantphos
N
+
5
2a
Cs2CO3, NMP
120 °C, 4 h
(4a, 68%)
[Pd]
Br
[Pd]
R3
R3
Br
Br
R3
1
R3
[Pd]Br
path I
H2N R2
[Pd]
Br
A
H2N R2
Br
C
R3
path II
[Pd]
H
R3
N
[Pd]
R2
N
R2
D
B
R3
[Pd]
N
R2
[Pd]
4
Scheme 2 Proposed reaction pathways
In conclusion, we have described a novel and efficient
method for the synthesis of a-alkynyl indoles13 via a pal-
ladium-catalyzed, multi-component coupling of o-bromo-
(2,2-dibromovinyl)benzenes with arylamines and
alkynes.
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Synlett 2011, No. 7, 911–914 © Thieme Stuttgart · New York