K. Okuma et al. / Tetrahedron Letters 50 (2009) 2943–2945
2945
Sakamoto, T. Org. Lett. 2004, 6, 2953; Kamijo, S.; Sasaki, Y.; Yamamoto, Y.
Tetrahedron Lett. 2004, 45, 35; Koradin, C.; Dhohle, W.; Rodriguez, A. L.; Schmid,
B.; Knochel, P. Tetrahedron 2003, 59, 1571.
R
Zn/ BrCH2CH2Br
3. Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron Lett. 1975, 17, 4467–4470;
Sonogashira, K. J. Organomet. Chem. 2002, 653, 46.
R
EtOH
reflux
8 h
NO2
N
H
4. Kondo, Y.; Kojima, S.; Sakamoto, T. J. Org. Chem. 1997, 62, 6507; Ezquerra, J.;
Pedregal, C.; Lamas, C.; Barluenga, J.; Perez, M.; Garcia-Martin, M. A.; Gonzarez,
J. M. J. Org. Chem. 1996, 61, 5804; Kondo, Y.; Kojima, S.; Sakamoto, T.
Heterocycles 1996, 43, 2741; Rudisill, D. E.; Stille, J. K. J. Org. Chem. 1989, 54,
5856.
4a: R = Ph 84%
4g: R = butyl 76%
5a: R = Ph
5b: R = butyl
5. Hong, K. B.; Lee, C. W.; Yum, E. K. Tetrahedron Lett. 2004, 45, 693; Yin, Y.; Ma,
W.; Chai, Z. C.; Zhao, G. J. Org. Chem. 2007, 72, 5731.
Scheme 2.
6. Chen, G.; Zhu, X.; Cai, J.; Wan, Y. Synth. Commun. 2007, 37, 1355.
7. Black, T. H.. In Encyclopedia of Reagents for Organic Synthesis; Paquette, L. A., Ed.;
John Wiley & Sons: Chichister, UK, 1995; Vol. 6, p 4476.
8. Ding, Q.; Ye, Y.; Fan, R.; Wu, J. J. Org. Chem. 2007, 72, 5439.
9. Nakamura, M.; Ilies, L.; Otsubo, S.; Nakamura, E. Org. Lett. 2006, 8, 2803;
Nakamura, M.; Ilies, L.; Otsubo, S.; Nakamura, E. Angew. Chem., Int. Ed. 2006, 45,
944.
10. Ambrogio, I.; Arcadi, A.; Cacchi, S.; Fabrizi, G.; Marinelli, F. Synlett 2007, 1775;
Miyazaki, Y.; Kobayashi, S. J. Comb. Chem. 2008, 10, 355; Sakai, N.; Annaka, K.;
Fujita, A.; Sato, A.; Konakahara, T. J. Org. Chem. 2008, 73, 4160; Kondo, T.;
Okada, T.; Suzuki, T.; Mitsudo, T. J. Organomet. Chem. 2001, 622, 149.
11. The theoretical calculations for reaction of 2-(1-propynyl)aniline with ZnCl2
giving 2-methylindole are shown in the Supplementary data.
lene.6 When 5a was treated with zinc (8 equiv) and dibromoethane
in refluxing ethanol for 12 h, 2-phenylindole 4a was obtained in 86%
yield. Similarly, 2-heptynylnitrobenzene (5b) reacted with zinc/
dibromoethane to give 2-butylindole 4g in 76% yield (Scheme 2).
In conclusion, we have demonstrated that zinc halides serve as
effective catalysts for the intramolecular hydroamination of 2-alk-
ynylanilines. Thus a practical and cost effective method for the
preparation of unprotected indoles has been demonstrated by
using these catalysts.
12. Relative stabilization energies [kcal/mol] of intermediates A–D based on the
sum of all electron energy of 2-(1-propynyl)aniline and ZnCl2 were estimated
to be À24.9 for A, À18.9 for B, À29.3 for C, and À12.5 for D at the B3LYP/6-
31G(d) level. The molecular structures and theoretically optimized coordinates
of A–D are shown in Figure S8 and Tables S1–S4, respectively, in the
Supplementary data.
13. Naffziger, M. R.; Ashburn, B. O.; Perkins, J. R.; Carter, R. G. J. Org. Chem. 2007,
72, 9857; Maya, A. B. S.; Melero, C. P.; Mateo, C.; Alonso, D.; Fernandez, J. L.;
Gajate, C.; Mollinedo, F.; Pelaez, R.; Caballero, E.; Madarde, M. J. Med. Chem.
2005, 556; Aerssens, M. H. P. J.; Brandsma, L. J. Chem. Soc., Chem. Commun.
1984, 735.
14. Typical reaction is as follows: To a refluxing solution of 2-phenylethynylaniline
1a (1.0 mmol) in toluene was added zinc bromide (0.05 mmol) in one portion.
After refluxing for 6 h, the reaction mixture was washed with water and
extracted with dichloromethane. The combined extracts were dried over
sodium sulfate, filtered, and evaporated to give a pale brown solid, which was
chromatographed over silica gel by elution with hexane/ethyl acetate (5:1) to
afford 2-phenylindole 4a (0.90 mmol).
Supplementary data
Supplementary data associated with this article can be found, in
References and notes
1. Humphrey, G. R.; Kuethe, J. T. Chem. Rev. 2006, 106, 2875; Cacchi, S.; Fabrizi, G.
Chem. Rev. 2005, 105, 2873; Hibino, S.; Choshi, T. Nat. Prod. Rep. 2002, 19, 148;
Gupta, R.. In Heterocyclic Chemistry; Springer Publishing: New York, 1999; Vol. 2;
Rahman, A.; Basha, A. Indole Alkaloids; Harwood Academic: Amsterdam, The
Netherlands, 1998; Dewick, P. M. Medicinal Natural Products; Wiley & Sons:
Chichister, UK, 1997.
2. Sakai, N.; Annnaka, K.; Konakahara, T. Tetrahedron Lett. 2006, 47, 631; Hiroya,
K.; Itoh, S.; Skamaot, T. J. Org. Chem. 2004, 69, 1126; Hiroya, K.; Matsumoto, S.;