9042
A. P. Esteves et al. / Tetrahedron Letters 48 (2007) 9040–9043
Vinyl sulfones 1 and 2 were reacted with several
aliphatic primary and secondary amines using
Amberlyst-15 as the catalyst according to experimental
conditions described in the literature8 (Scheme 2). The
reactivity of some aromatic amines was also investigated
under the same experimental conditions. The results
obtained are summarized in Table 1.
is observed. Aromatic amines are less reactive under
these experimental conditions probably due to their
lower nucleophilicity.
Acknowledgements
Thanks are due to Fundac¸ao para a Cieˆncia e a Tecno-
˜
logia and FEDER for financial support (POCI/QUI/
57400/2004).
Aliphatic primary amines (Table 1, entries 1–4 and
12–15) reacted under smoothly experimental condi-
tions14 (10 min–3 h; room temperature) either with
sulfones 1 or 2. The reaction gave moderate to high
yields (66–99%). Some of the final products were iso-
lated in a pure form with no further purification (Table
1). Acyclic (diethyl amine and N-methyl propargyl
amine) and cyclic (pyrrolidine and piperidine) secondary
aliphatic amines underwent the conjugate addition suc-
cessfully (Table 1, entries 5, 7–9, 16 and 18–20). Surpris-
ingly, when diisopropylamine was reacted with both
sulfones, only starting materials were recovered even
after a long period of reaction. The lack of reactivity
of diisopropylamine as nucleophile in this aza-Michael
reaction may be due to steric hindrance. In fact, after
the work-up procedure, the starting vinyl sulfone was
recovered unreacted in a pure form. Analysis of 1H
NMR spectrum of the residue showed no evidence for
an addition–elimination equilibrium.
References and notes
1. Perlmutter, P. Conjugate Addition Reactions in Organic
Synthesis; Pergamon Press: Oxford, 1992; p 114.
2. Yang, L.; Xu, L.-W.; Zhou, W.; Li, L.; Xia, C.-G.
Tetrahedron Lett. 2006, 47, 7723.
3. Ranu, B. C.; Banerjee, S. Tetrahedron Lett. 2007, 48,
141.
4. Verma, A. K.; Kumar, R.; Chaudhary, P.; Saxena, A.;
Shankar, R.; Mozumdar, S.; Chandra, R. Tetrahedron
Lett. 2005, 46, 5229.
5. Yeom, C.-E.; Kim, M. J.; Kim, B. M. Tetrahedron 2007,
63, 904.
6. Varala, R.; Sreelatha, N.; Adapa, S. R. Synlett 2006, 1549.
7. Cao, Y.-J.; Lai, W.-W.; Wang, X.; Li, Y.-J.; Xiao, W.-J.
Tetrahedron Lett. 2007, 48, 21.
8. Das, B.; Chowdhury, N. J. Mol. Catal. A: Chem. 2007,
263, 212.
Ethanolamine was reacted with both vinyl sulfones 1
and 2 in a completely chemoselective fashion affording
the expected amine in quantitative yields (Table 1,
entries 3 and 14).
9. Mikhailova, V. N.; Bulat, A. D.; Ezhova, L. A. J. Org.
Chem. USSR (Engl. Transl.) 1987, 23, 2073.
10. Derzhinskii, A. R.; Kalugin, V. E.; Prilezhaeva, E. N. Bull.
Acad. Sci. USSR Div. Chem. Sci. (Engl. Transl.) 1985, 34,
1484.
11. Lewis, D. M.; Smith, S. M. Dyes Pigments 1995, 29,
275.
12. Esteves, A. P.; Rodrigues, L. M.; Silva, M. E.; Gupta, S.;
Oliveira-Campos, A. M. F.; Machalicky, O.; Mendonc¸a,
A. J. Tetrahedron 2005, 61, 8625.
When sulfone 1 was treated with aniline (Table 1, entry
10) only traces of product were detected and a slight
improvement was obtained with p-methoxyaniline
(entry 11). These results seem to be consistent with the
lower reactivity of the aromatic amines in comparison
with cyclohexylamine (entry 4).
13. Galli, U.; Lazzarato, L.; Bertinaria, M.; Sorba, G.; Gasco,
A.; Parapini, S.; Taramelli, D. Eur. J. Med. Chem. 2005,
40, 1335.
All compounds were identified from spectroscopic
data.15
14. Typical experimental procedure: To a mixture of vinyl
sulfone (2.5 mmol) and Amberlyst-15 (30% w/w), the
amine (2 mmol) was added and stirred at room temper-
ature for the appropriate time (Table 1). The reaction was
followed by TLC. The final mixture was diluted with
dichloromethane (10 mL) and the catalyst removed by
filtration. The solvent was evaporated and the crude
residue afforded the pure compounds in some cases (Table
1). Some of the residues were purified by column
chromatography or preparative layer chromatography
using as eluent typically mixtures of chloroform–methanol
or ethyl acetate–light petroleum.
Piperidine and methyl vinyl sulfone 1 were reacted for
24 h in the presence and in the absence of the catalyst.
The yields obtained were 74% and 55%, respectively.
These results showed the efficiency of the Amberlyst-
15 as catalyst for this type of reaction.
The reusability of the catalyst was studied performing
the reaction of methyl vinyl sulfone 1 and N-propyl-
amine. The catalyst was used for three runs. Analysis
1
of the H NMR spectra of residues showed no sulfone
15. Spectroscopic data for selected compounds: 1-[2-(Methyl-
sulfonyl)ethyl]pyrrolidine (Table 1, entry 8): 1H NMR
(300 MHz, CDCl3) 1.84–1.89 (4H, m, 20-H2 and 30-H2),
2.73–2.78 (4H, m, 10-H2 and 40-H2), 3.01 (3H, s, CH3),
3.12 (2H, app t, J 6.9 Hz, 1-H2), 3.30 (2H, app t, J 6.6/
7.5 Hz, 2-H2) ppm; 13C NMR (75 MHz, CDCl3) 23.39
(C-20 and C-30), 41.76 (CH3), 48.81 (C-1), 52.67 (C-2),
53.78 (C-10and C-40) ppm. Anal. Calcd for C7H15NO2S:
C, 47.43; H, 8.53; N, 7.90; S, 18.09. Found: C, 47.15; H,
8.33; N, 8.05; S, 18.29.
1 after the first run. After second and third runs, 6%
and 37% of vinyl substrate were detected, respectively.
In conclusion, this clean, simple and cheap experimental
procedure proved to be an efficient methodology for
aza-Michael reaction using vinyl sulfones as Michael
acceptors and aliphatic (primary and secondary) amines
as nucleophiles. The catalyst displays an important role
in the improvement of the yields. Although the catalyst
may be reused a slight to moderate decrease in the yields
4-[20-(Pyrrolidin-10-yl)ethylsulfonyl]benzenamine (Table
1, entry 19): 1H NMR (300 MHz, CDCl3) 1.73–1.77