ORGANIC
LETTERS
2
007
Vol. 9, No. 4
27-630
Gold(III)-Catalyzed Double
Hydroamination of o-Alkynylaniline with
Terminal Alkynes Leading to
N-Vinylindoles
6
Yuhua Zhang, James P. Donahue,†,‡ and Chao-Jun Li*,†,§
†
Department of Chemistry, Tulane UniVersity, New Orleans, Louisiana 70118, and
Department of Chemistry, McGill UniVersity, 801 Sherbrooke Street West,
Montreal QC, Canada H3A 2K6
Received December 2, 2006
ABSTRACT
A highly efficient double-hydroamination reaction of o-alkynylanilines with terminal alkynes leading to N-alkenylindoles was developed by
using gold(III) as a catalyst under neat conditions.
Indoles are important chemicals that exhibit a wide range
of biological activities. Many naturally occurring compounds
Stille reported the palladium(II)-catalyzed intramolecular
cyclization of 2-alkynylanilines to produce 2-substituted
1
3
d
contain indole as a key structural motif. Because of the wide
application of indoles in pharmaceutical research, the de-
velopment of efficient methods for their synthesis has
continuously attracted the attentions of many chemists.
Among the various synthetic strategies, catalytic transfor-
mations by using transition-metal catalysts is one of the
modern approaches for forming indoles.1,2 In particular, the
use of functionalized o-alkynylaniline derivatives as the
indoles in high yield. Cacchi and co-workers reported a
regioselective synthesis of 3-allylindoles via the palladium-
catalyzed cyclization of o-alkynyltrifluoroacetanilides with
4
allyl esters. Knochel reported the synthesis of polyfunc-
tionalized indoles mediated by 1-4 equiv of cesium and
potassium bases (such as CsO-t-Bu, KO-t-Bu, and KH) in
5
N-methylpyrrolidinone. Hiroya and co-workers developed
an efficient Cu(II)-catalyzed indole formation and applied
3
6
starting materials are some of the most efficient approaches.
the method to natural product syntheses. Arcadi and co-
workers reported a synthesis via a reaction of o-alkynyl-
†
Tulane University.
To whom crystallography inquiries should be addressed.
McGill University.
aniline and R,â-enones to form C-3-alkylindoles catalyzed
‡
7
§
by gold catalyst. Yamamoto and co-workers reported that
(
1) For reviews on indole chemistry, see: (a) Sundberg, R. L. Indoles;
Academic: London, 1996. (b) Katritzky, A. R.; Pozharskii, A. F. Handbook
of Heterocyclic Chemistry; Pergamon: Oxford, 2000; Chapter 4. (c) Joule,
J. A. In Science of Synthesis (Houben-Weyl Methods of Molecular
Transformations); Thomas, E. J., Ed.; Georg Thieme: Stuttgart, 2000; Vol.
0, pp 361-652. (d) Li, J. J.; Gribble, G. W. In Palladium in Heterocyclic
Chemistry; Pergamon: Oxford, 2000; Chapter 3. For other references, see:
e) Gribble, G. W. J. Chem. Soc., Perkin Trans. 1 2000, 1045; (f) Gribble,
(3) (a) Kondo, Y.; Kojima, S.; Sakamoto, T. J. Org. Chem. 1997, 62,
6507. (b) Ezquerra, J.; Pedregal, C.; Lamas, C.; Barluenga, J.; P e´ rez, M.;
Garc ´ı a-Mart ´ı n, M. A.; Gonz a´ lez, J. M. J. Org. Chem. 1996, 61, 5804. (c)-
Kondo, Y.; Kojima, S.; Sakamoto, T. Heterocycles 1996, 43, 2741. (d)
Rudisill, D. E.; Stille, J. K. J. Org. Chem. 1989, 54, 5856. (e) Arcadi, A.;
Cacchi, S.; Marinelli, F. Tetrahedron Lett. 1989, 30, 2581.
(4) Cacchi, S.; Fabrizi, G.; Pace, P. J. Org. Chem. 1998, 63, 1001.
(5) Koradin, C.; Dohle, W.; Rodriguez, A. L.; Schmid, B.; Knochel, P.
Tetrahedron 2003, 59, 1571.
1
(
G. W. In ComprehensiVe Heterocyclic Chemistry II; Katritzky, A. R., Rees,
C. W., Scriven, E. F. V., Eds.; Pergamon Press: Oxford, UK, 1996; Vol.
2
, p 207.
2) (a) Hegedus, L. S. Angew. Chem., Int. Ed. Engl. 1988, 27, 1113. (b)
Sakamoto, T.; Kondo, Y.; Yamanaka, H. Heterocycles 1988, 27, 2225.
(6) (a) Hiroya, K.; Itoh, S.; Sakamoto, T. J. Org. Chem. 2004, 69, 1126.
(b) Hiroya, K.; Itoh, S.; Ozawa, M.; Kanamori, Y.; Sakamoto, T.
Tetrahedron Lett. 2002, 43, 1277.
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0.1021/ol062918m CCC: $37.00
© 2007 American Chemical Society
Published on Web 01/18/2007