Conjugate Addition of Indoles to Nitroalkenes
FULL PAPERS
Experimental Section
2002, 4, 88–93; e) J. H. Clark, Acc. Chem. Res. 2002,
3
5, 791–797.
[
2] a) P. Perlmutter, Conjugate Addition Reactions in Organ-
ic Synthesis Pergamon, Oxford, 1992; b) B. E. Rossiter,
N. M. Swingle, Chem. Rev. 1992, 92, 771–806.
General Remarks
GLC analyses were performed with an SE-54 fused silica capil-
lary column (25 m, 0.32 mm internal diameter), FID detector
and nitrogen as carrier gas. GS-MS analyses were carried out
by means of the EI technique (70 eV). All chemicals, included
[
3] a) M. Bandini, A. Melloni, S. Tommasi, A. Umani-Ron-
chi, Synlett 2005, 1199–1222; b) M. Bandini, M. Fagioli,
A. Umani-Ronchi, Adv. Synth. Catal. 2004, 346, 545–
548; Metal salts on solid supports have also found some
utilization: c) Z.-P. Zhan, K. Lang, Synlett 2005, 1551–
1554; d) G. Bartoli, M. Bosco, S. Giuli, A. Giuliani, L.
Lucarelli, E. Marcantoni, L. Sambri, E. Torregiani, J.
Org. Chem. 2005, 70, 1941–1944; e) G. Bartoli, M. Barto-
lacci, M. Bosco, G. Foglia, A. Giuliani, E. Marcantoni, L.
Sambri, E. Torregiani, J. Org. Chem. 2003, 68, 4594–
2-nitrostyrene and nitrocyclohexene were purchased and used
without further purifications. Nitroalkenes 2 were prepared by
dehydration from the corresponding nitro alcohols using
[17]
known procedures. Commercial basic alumina (Fluka) was
activated by heating at 1508C/1mmHg for 5 h before utiliza-
tion. 3-Substituted indoles 3 h, j are known compounds.
[3d, f]
4
597.
Typical Procedure for Addition of Indoles to
Nitroalkenes or Nitro Alcohols
[4] a) O. M. Berner, L. Tedeschi, D. Enders, Eur. J. Org.
Chem. 2002, 1877–1894; b) V. V. Perekalin, E. S. Lipina,
V. M. Berestovitskaya, D. A. Efremov, Nitroalkenes Con-
jugated Nitro Compounds, Wiley, Chichester, 1994.
5] a) R. J. Sundberg, The Chemistry of Indoles, Academic
Press, New York, 1996; b) H. Harada, Y. Hirokawa, K.
Suzuki, Y. Hiyama, M. Oue, H. Kawashima, H. Kato,
N. Yoshida, Y. Furutani, S. Kato, Chem. Pharm. Bull.
To a mixture of indole 1 (1.0 mmol) and nitroalkene 2
1.2 mmol) [or nitro alcohol 6 (1.4 mmol)] activated basic alu-
(
[
mina (1.2 g) was added at room temperature and the mixture
was warmed at 608C. After stirring for the appropriate time
(
see Table 1) the solid mixture was directly charged on a chro-
matography column and eluted (hexane-ethyl acetate, 9:1) to
afford pure product 3.
2
005, 53, 184–198; c) R. P. Herrera, V. Sgarzani, L. Ber-
nardi, A. Ricci, Angew. Chem. 2005, 117, 6734–6737; An-
gew. Chem. Int. Ed. 2005, 44, 6576–6579; d) E. D. Cox,
H. Diaz-Arauzo, Q. Huang, M. S. Reddy, C. Ma, B. Har-
ris, R. McKernan, P. Skolnick, J. M. Cook, J. Med. Chem.
Typical Procedure for the ꢀOne-Potꢁ Nitroaldol-
Elimination-Addition Sequence
1
998, 41, 2537–2552.
6] a) S. Mahboobi, W. Wiegrebe, A. Popp, J. Nat. Prod.
999, 62, 577–579. b) T. Koike, N. Takeuchi, M. Hagi-
wara, K. Yamazaki, S. Tobinaga, Heterocycles 1999, 51,
271–1280; c) T. Koike, M. Hagiwara, N. Takeuchi, S.
To a mixture of nitro compound 4 (1.4 mmol) and aldehyde 5
[
(
1.4 mmol), activated basic alumina (1.2 g) was added at 08C.
1
The resulting mixture was stirred for 1.5 h at room temperature
and after consumption of the reactants (reaction progress was
monitored by TLC or GLC) the appropriate indole 1
1
Tobinaga, Heterocycles 1997, 45, 1271–1280.
7] a) G. W. Kabalka, R. M. Pagni, Tetrahedron 1997, 53,
(
1.0 mmol), was added. The solid mixture was warmed at
[
608C and stirred for the appropriate time (see Table 1).
7
5
999–8065; b) G. H. Posner, Angew. Chem. 1978, 90,
27–536; Angew. Chem. Int. Ed. 1978, 17, 487–496.
Upon reaction completion, the solid mixture was directly
charged on a chromatography column and eluted (hexane-eth-
yl acetate, 9:1) to afford pure product 3.
[
8] a) R. Maggi, R. Ballini, G. Sartori, R. Sartorio, Tetrahe-
dron Lett. 2004, 45, 2297–2299; b) R. Ballini, G. Bosica,
Synthesis 1994, 723–726; c) R. Ballini, G. Bartoli, Syn-
thesis 1993, 965–967.
9] Neutral and basic alumina have been occasionally used
in alkylation of indoles using alkyl halides, 1-alkylation:
a) M. A. Tius, J. Busch-Petersen, Synlett 1997, 531–533;
b) W. J. Smith III, J. S. Sawyer, Tetrahedron Lett. 1996,
Acknowledgements
[
Financial support from University of Camerino and MIUR
(
National Project “Sintesi e Reattivit a` -attivit a` di Sistemi Insaturi
Funzionalizzati”) is gratefully acknowledged. R. R. C. thanks
the Spanish Ministerio de Cienciay Tecnologia for a predoctoral
fellowship.
3
7, 299–302; 3-alkylation: c) H. Ishibashi, K. Nishida,
M. Ikeda, Synth. Commun. 1993, 23, 2381–2387; d) H.
Ishibashi, N. Mita, N. Matsuba, T. Kubo, M. Nakanishi,
M. Ikeda, J. Chem. Soc. Perkin Trans. 1 1992, 2821–2825.
[
10] G. H. Posner, in: Preparative Chemistry Using Supported
Reagents, (Ed.: P. Laszlo), Academic Press, San Diego,
References and Notes
1
987.
[
[
11] J. H. Clark, Catalysis of Organic Reactions by Supported
Inorganic Reagents, VCH, New York, 1994.
12] a) D. E Bergbreiter, J. J. Lalonde, J. Org. Chem. 1987, 52,
[
1] a) K. Rueck-Braun, T. H. E. Freysoldt, F. Wierschem,
Chem. Soc. Rev. 2005, 34, 507–516; b) G. Sartori, R. Bal-
lini, F. Bigi, G. Bosica, R. Maggi, P. Righi, Chem. Rev.
1
601–1603; b) R. Giovannini, M. Petrini, Chem. Com-
2
004, 104, 199–250; c) C. Chung, Y. Wan, P. H. Toy, Tet-
mun. 1997, 1829–1830; c) J.-T. Li, W.-Z. Xu, L.-C.
Yang, T.-S. Li, Synth. Commun. 2004, 34, 4565–4571.
rahedron: Asymmetry 2004, 15, 387–399; d) M. H. Val-
kenberg, C. de Castro, W. F. Hoelderich, Green Chem.
Adv. Synth. Catal. 2006, 348, 191 – 196
ꢂ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
195