Saito et al.
SCHEME 1
indoles have been reported.10 The synthesis of 2,3-disubstituted
indoles through the intermolecular Pd-catalyzed Heck reactions
of o-iodoanilines with alkynes has also been reported.11,12 In
the described reactions, however, the procedures have been met
with the drawback of the scope and limitations on the substituent
of the substrate and/or poor regioselectivity.11b
the thermal19 or Cu-promoted conditions20,21 (path a′). Although
a few examples of the thermal rearrangements of N-propargy-
lanilines brought about the formation of indoles (path a), the
reactions required extremely high temperatures (240-260 °C)
and the products were obtained in low yields.19a Recently, we
reported on the mild synthesis of 2,3-substituted indole deriva-
tives through amino-Claisen rearrangement of N-propargyla-
niline derivatives (path a) catalyzed by [Rh(cod)2]OTf in
hexafluoroisopropyl alcohol (HFIP).22,23 In the reaction, how-
ever, there still remains a main drawback in terms of the
limitation on the substrate. In this full account, we describe that
further search for an efficient Rh(I) catalyst led to
RhH(CO)(Ph3P)3 and its use for the one-pot preparation of
indoles from a mixture of anilines and propargyl halides in the
presence of a base. Besides the synthetic work on indoles, we
elucidated that the real catalyst of the indole formation was
derived from RhH(CO)(Ph3P)3 with HFIP and the structure was
confirmed by single-crystal X-ray crystallographic analysis.
N-Propargylanilines are alternative candidates for the prepara-
tion of heterocycles, since regioselective intramolecular hy-
droarylation reactions of N-propargylanilines are considered to
be divergent methods for the preparation of quinoline or indole
frameworks (6-endo or 5-exo). Intramolecular hydroarylation
reactions have been achieved by various metal catalysts,13,14
and the reactions of N-propargylanilines have been known to
proceed via the 6-endo mode to give 1,2-dihydroquinolines (path
b, Scheme 1).15,16 On the other hand, amino-Claisen rearrange-
ments17,18 of N-propargylaniline derivatives, which could be
considered to be an alternative route to the quinoline ring system,
have been reported to proceed through o-allenylaniline under
Results and Discussion
(9) Alfonsi, M.; Arcadi, A.; Aschi, M.; Bianchi, G.; Marinelli, F. J. Org.
Chem. 2005, 70, 2265.
Formation of Indole Derivatives from N-Propargylanilines.
Initial studies focused on extending the limited scope of our
previous synthetic method22 of indoles from N-propargylanilines.
In the presence of 10 mol % of [Rh(cod)2]OTf and 15 mol %
of 1,3-diphenylphosphinopropane (dppp), the reaction of N-
propargylaniline 1a or 1b proceeded in HFIP to give the
corresponding indole 2a or 2b in high yield (Scheme 2). In the
(10) Recently, Rh(I)-catalyzed cyclization of o-alkynylaniline derivatives has
been reported through a vinylidenerhodium intermediate. Trost, B. M.; McClory,
A. Angew. Chem., Int. Ed. 2007, 46, 1.
(11) (a) Larock, R. C.; Yum, E. K. J. Am. Chem. Soc. 1991, 113, 6689. (b)
Larock, R. C.; Yum, E. K.; Refvik, M. D. J. Org. Chem. 1998, 63, 7652. (c)
Larock, R. C. Pure. Appl. Chem. 1999, 71, 1435. See: (d) Shen, M.; Li, G.; Lu,
B. Z.; Hossain, A.; Roschanger, F.; Farina, V.; Senanayake, C. H. Org. Lett.
2004, 6, 4129.
(12) (a) Chen, C.-Y.; Lieberman, D. R.; Larsen, R. D.; Reamer, R. A.;
Verhoeven, T. R.; Reider, P. J. Tetrahedron Lett. 1994, 35, 6981. (b) Yu, J.;
Wearing, X. Z.; Cook, M. J. Org. Chem. 2005, 70, 3963. (c) Parmentier, J.-G.;
Poissonnet, G.; Goldstein, S. Heterocycles. 2002, 56, 465. (d) Gathergood, N.;
Scammells, P. J. Org. Lett. 2003, 5, 921.
SCHEME 2
(13) For a review, see: Nevado, C.; Echavarren, A. M. Synthesis 2005, 167.
(14) For recent intramolecular hydroarylation type reaction, see: (a) Chatani,
N.; Inoue, H.; Ikeda, T.; Murai, S. J. Org. Chem. 2000, 65, 4913. (b) Mart´ın-
Matute, B.; Ca´rdenas, D. J.; Echavarren, A. M. Angew. Chem., Int. Ed. 2001,
40, 4754. (c) Furstner, A.; Mamane, V. J. Org. Chem. 2002, 67, 6264. (d) Thalj,
R. K.; Ahrendt, K. A.; Bergman, R. G.; Ellman, J. A. J. Am. Chem. Soc. 2001,
123, 9692. (e) Hashmi, A. S. K.; Blanco, M. C.; Kurpejovic, E.; Frey, W.; Bats,
J. W. AdV. Synth. Catal. 2006, 348, 709.
(15) (a) Pastine, S. J.; Youn, S. W.; Sames, D. Org. Lett. 2003, 5, 1055. (b)
Pastine, S. J.; Youn, S. W.; Sames, D. Tetrahedron 2003, 59, 8859. (c) Nishizawa,
M.; Takao, H.; Yadav, V. K.; Imagawa, H.; Sugihara, T. Org. Lett. 2003, 5,
4563. (d) Mart´ın-Matute, B.; Nevado, C.; Ca´rdenas, D. J.; Echavarren, A. M.
J. Am. Chem. Soc. 2003, 125, 5757. (e) Nieto-Oberhuber, C.; Mun˜oz, M. P.;
Bun˜uel, E.; Nevado, C.; Ca´rdenas, D. J.; Echavarren, A. M. Angew. Chem., Int.
Ed. 2004, 43, 2402.
(16) (a) Magnus, P.; Mitchell, I. S. Tetrahedron Lett. 1998, 39, 4595. (b)
Erzhanov, K. B.; Kolkhosova, S. S.; Sadykov, T. Zh. Org. Khim. 1989, 25, 1729.
(17) For a review, see: (a) Lutz, R. P. Chem. ReV. 1984, 84, 205. (b) Castro,
A. M. M. Chem. ReV. 2004, 104, 2939. (c) Kouznetsov, V. V. J. Heterocycl.
Chem. 2005, 42, 39.
(18) Related monograph: Krause, N. A. Hashmi, S. K. Modern Allene
Chemistry; Wiley-VCH: Weinheim, 2004; Vol. 1, pp 1-50.
(19) (a) Scheurer, H.; Zsindely, J.; Schmid, H. HelV. Chim. Acta 1973, 56,
478. (b) Majumdar, K. C.; Bhattacharyya, T. Tetrahedron Lett. 2001, 42, 4231.
(c) Brønsted acid-promoted rearrangement: Barmettler, P.; Hansen, H.-J. HelV.
Chim. Acta 1990, 73, 1515.
reaction of Ph derivative 1c or terminal alkyne 1d, however,
the product (2c or 2d) was obtained in a low yield or was not
detected. Thus, we examined miscellaneous rhodium(I) catalysts
(10 mol %) in the reaction of N-propargylaniline 1c, and the
(20) (a) Dillard, R. D.; Pavey, D. E.; Benslay, D. N. J. Med. Chem. 1973,
16, 253. (b) Barmettler, P.; Hansen, H.-J.; Dillard, R. D. J. Org. Chem. 1962,
27, 4713. (c) Holman, M. A.; Williamson, N. M.; Ward, A. D. Aust. J. Chem.
2005, 58, 368.
(21) The aromatic Claisen rearrangements of propargyl ether derivatives
usually afford 6-membered ring fused arenes; see: (a) Koch-Pomeranz, U.;
Hansen, H.-J.; Schmid, H. HelV. Chim. Acta 1973, 56, 2981. (b) Olsson, L. I.;
Claesson, A. Synthesis 1979, 743. (c) See also: Ishii, H.; Ishikawa, T.; Takeda,
S.; Ueki, S.; Suzuki, M.; Harayama, T. Chem. Pharm. Bull. 1992, 38, 1775.
(22) Saito, A.; Kanno, A.; Hanzawa, Y. Angew. Chem., Int. Ed. 2007, 46,
3931.
1518 J. Org. Chem. Vol. 74, No. 4, 2009