1778
I. Ambrogio et al.
CLUSTER
reutilization of the catalyst system. Only n-Bu4NAuCl4 tion–annulation–alkylation procedures can provide an
was recycled and reused for more than five runs23 without easy entry into 2,3-disubstituted and 1,2,3-trisubstituted
any significant loss of the catalyst activity (Table 4).
indoles, respectively.
Table 4 Recycling Studies for the Cyclization of 1a to 2a in
[bmim]BF4 in the Presence of n-Bu4NAuCl4
a
Acknowledgment
The authors are greatly indebted to the Ministero dell’Università e
della Ricerca Scientifica e Tecnologica, Rome, the University ‘La
Sapienza’ and the University of L’Aquila for financial support of
this research.
Run
1
Yield of 2a (%)b
98
98
97
98
85
2
3
References and Notes
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4
5
a Reactions were carried out on a 0.52-mmol scale in [bmim]BF4
(2.0 mL) at 50 °C for 24 h using the following molar ratio: 1/n-
Bu4NAuCl4·2H2O = 1:0.01.
b Determined by HPLC analysis.
To optimize this synthetic approach in terms of reaction
time, the cyclization of 1a to 2a was also attempted under
microwave irradiation conditions, which are known to ac-
celerate the gold-catalyzed homogeneous reactions.24 Us-
ing multimode irradiation with internal temperature
control, 2a was obtained in quantitative yield in 15 min-
utes at 100 °C. By comparison, one hour of conventional
heating was required at the same temperature to obtain 2a
in 90% yield.
Finally, the cyclization of 2-alkynylanilide 6a was briefly
investigated (Scheme 6). Below 120 °C the reaction failed
to give the desired product, most probably because of sol-
ubility problems. At 120 °C the indole derivative 7a was
formed in 90% yield after 24 hours. This result shows that
the amide 6a is less reactive than the amine 2a in this cy-
clization process, very likely because of the lower nucleo-
philicity of the nitrogen atom.
Cl
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(6) Imperato, G.; König, B.; Chiappe, C. Eur. J. Org. Chem.
2007, 1049.
NaAuCl4·2H2O
Cl
[bmim]BF4
120 °C, 24 h
N
NH
O
O
(7) (a) Ionic liquids IIIB: Fundamentals, Process, Challenges,
and Opportunities In ACS Symposium Series; Rogers, R. D.;
Seddon, K. R., Eds.; ACS: Washington DC, 2005. (b) Ionic
Liquids: Industrial Applications to Green Chemistry;
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Marinelli, F. J. Org. Chem. 2005, 70, 2265.
7a (90% yield)
6a
Scheme 6
In summary, we have shown that catalysis by gold in
[bmim]BF4 can represent an efficient tool for the cycliza-
tion of 2-alkynylanilines to 2-substituted indoles. The na-
ture of the gold salt plays a key role in the recyclability
and reuse of the catalyst system. 2-Alkynylanilides are
less reactive than 2-alkynylanilines. The reaction times
can be significantly reduced using microwave irradiation.
One-flask annulation–alkylation and aza-Michael addi-
Synlett 2007, No. 11, 1775–1779 © Thieme Stuttgart · New York