A. Palmieri et al. / Tetrahedron Letters 48 (2007) 5653–5656
5655
n
-C5H11
Supplementary data
n-C5H11
NO2
Bu3SnH, AIBN
Supplementary data associated with this article can be
toluene, Δ, 4 h
N
N
H
H
60%
10
9c
References and notes
1. Bandini, M.; Melloni, A.; Tommasi, S.; Umani-Ronchi,
A. Synlett 2005, 1199–1222.
N
H
NO2
11 (50%)
2. (a) Berner, O. M.; Tedeschi, L.; Enders, D. Eur. J. Org.
Chem. 2002, 1877–1894; (b) Perekalin, V. V.; Lipina, E. S.;
Berestovitskaya, V. M.; Efremov, D. A. Nitroalkenes
Conjugated Nitro Compounds; Wiley: Chichester, 1994.
3. (a) Sundberg, R. J. The Chemistry of Indoles; Academic
Press: New York, 1996; (b) Harada, H.; Hirokawa, Y.;
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H.; Yoshida, N.; Furutani, Y.; Kato, S. Chem. Pharm.
Bull. 2005, 53, 184–198; (c) Herrera, R. P.; Sgarzani, V.;
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A.; Lucarelli, L.; Marcantoni, E.; Sambri, L.; Torregiani,
E. J. Org. Chem. 2005, 70, 1941–1944; (e) Bandini, M.;
Garelli, A.; Rovinetti, M.; Tommasi, S.; Umani-Ronchi,
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G.; Jørgensen, K. A. Org. Biomol. Chem. 2005, 3, 2566–
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Maichrzak, M. W.; Zobel, J. N.; Obradovich, D. J. Synth.
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5. (a) Iwao, M.; Motoi, O. Tetrahedron Lett. 1995, 36, 5929–
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P. H. H.; van Maarseveen, J. H.; Scheeren, H. W.; Kruse,
C. G. Rec. Trav. Chim. Pays–Bas 1993, 112, 131–136; (c)
Hermkens, P. H. H.; van Maarseveen, J. H.; Ottenheijm,
H. C. J.; Kruse, C. G.; Scheeren, H. W. J. Org. Chem.
1990, 55, 3998–4006; (d) Hermkens, P. H. H.; van
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5065–5071.
Bu3SnH, AIBN
+
toluene, Δ, 4 h
N
H
9h
N
H
12 (13%)
Scheme 4.
Although reduction of the nitro group in compounds 9
usually represents a viable entry to tryptamine deriva-
tives, other useful synthetic manipulations of the nitro
group can be envisaged.11 The nitro group can be
removed from derivatives 9 exploiting a radical substitu-
tion reaction with a hydrogen atom. This process is
also referred to as a denitration reaction that is
commonly carried out using Bu3SnH as hydrogen atom
donor.12 Removal of the nitro group from secondary
nitroalkanes requires higher temperatures compared to
tertiary or benzylic derivatives. However, an interesting
result is obtained for the reaction of nitro derivative 9c
with 2 equiv of Bu3SnH and a catalytic amount of a rad-
ical initiator (AIBN) in toluene at reflux that after 4 h is
converted into 2,3-dialkyl indole 10 in 60% yield
(Scheme 4).13
Similarly, denitration of nitro indole 9h gives 2,3-dialkyl
indole 11 in 50% yield, but in this reaction formation of
a certain amount (13%) of 2-methyl-3-isopropyl indole
12 is also observed. Formation of the latter product
can be easily rationalized accounting for a reverse pro-
cess that by elimination of nitroethane regenerates a
vinylogous imino derivative of type 3 which is promptly
reduced by Bu3SnH.
In conclusion, sulfonyl indoles 7 are able to react under
basic conditions with nitroalkanes leading to the
corresponding 3-(2-nitroalkyl) indoles 9 in good yields.
This procedure nicely complements the Friedel–Crafts
reaction of indoles to nitroalkenes allowing the prepara-
tion of some nitro indoles such as 9g,h that are not
directly accessible by the conjugate addition to
nitroolefins.
7. Ballini, R.; Palmieri, A.; Petrini, M.; Torregiani, E. Org.
Lett. 2006, 8, 4093–4096; A related procedure using
Yb(OTf)3 catalyzed reaction of a-amido sulfones with
electron-rich aromatics has recently appeared: Kuhakarn,
C.; Tangdenpaisal, K.; Kongsaeree, P.; Prabpai, S.;
Tuchinda, P.; Pohmakotr, M.; Reutrakul, V. Tetrahedron
Lett. 2007, 48, 2467–2470.
8. Palmieri, A.; Petrini, M. J. Org. Chem. 2007, 72, 1863–
1866.
9. General procedure for the preparation of 3-(2-nitroalkyl)
indoles 9. To a stirred suspension of NaH (4.0 mmol) in
dry THF (15 mL), nitroalkane 8 (1.2 mmol) and sulfonyl
indole 7 (1.0 mmol) were added at room temperature.
After stirring at reflux for 5 h, the reaction mixture was
cooled at room temperature and quenched with 2 N HCl
Acknowledgement
Financial support from University of Camerino (Na-
tional Project ‘Sintesi organiche ecosostenibili mediate
da nuovi sistemi catalitici’) is gratefully acknowledged.