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R. Varala et al.
LETTER
electron-attracting groups. Interestingly, pyrrolidine gave In conclusion, bismuth triflate is found to be an excellent
an excellent yield with phenyl acrylate (entry 1). Pipera- chemoselective catalyst for Michael conjugate addition of
zine gave the bis-addition product (entry 2). Morpholine aliphatic amines to a,b-ethylenic compounds in acetoni-
also reacted well with different olefins in high yields trile under mild reaction conditions. Further, the catalyst
(entry 3). Cyclohexylamine gave the corresponding bis can be recovered and reused.
adduct in 30 minutes with ethyl acrylate (entry 4) and ami-
noethanol gave the corresponding bis-addition product in
one hour (entry 5). Many of the reactions are almost quan-
Acknowledgement
V. R and M. M. A. are thankful to the Head of the Division, Dr. B.
M. Choudary and the Director, Dr. K. V. Raghavan for their support
and encouragement.
titative in yield. Furthermore, when benzylamine was
treated with acrylonitrile, only 54% conversion was ob-
served even after prolonged reaction time (entry 6). Ex-
cess of the ethylenic component (3.5 equiv) was used to
complete the reactions for the entries 4–6. To further
explore the reaction, we have attempted several studies
but those were found unsuccessful. When L-proline was
treated with methyl acrylate, no reaction was observed
and when trans-ethyl cinnamate is treated with morpho-
line no reaction was observed even after longer times.
This may be attributed to the fact that bulky aromatic
group is causing steric and polar effects in the olefin.
These results confirm the efficiency of bismuth triflate as
a chemoselective LA catalyst for the conjugate addition of
aliphatic amines to a,b-ethylenic compounds.
References
(1) Ben Ayed, T.; Amiri, H.; El Gaied, M. M.; Villieras, J.
Tetrahedron 1995, 35, 9633; and references cited therein.
(2) Pfau, M. Bull. Soc. Chim. France 1967, 117.
(3) Perlmutter, P. Conjugate Addition Reaction in Organic
synthesis; Pergamon Press: Oxford, 1992.
(4) Furukawa, M.; Okawara, T.; Terawaki, Y. Chem. Pharm.
Bull. 1977, 25, 1319.
(5) D’Angelo, J.; Maddaluno, J. J. Am. Chem. Soc. 1986, 108,
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(8) Shaikh, S. N.; Deshpande, H. V.; Bedekar, A. V.
Tetrahedron 2001, 57, 9045.
(9) (a) Suzuki, H.; Ikegami, T.; Matano, Y. Synthesis 1997,
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(c) Vidal, S. Synlett 2001, 1194. (d) Desmurs, J. R.;
Labrouillere, M.; Le Roux, C.; Gaspard, H.; Laporterie, A.;
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(f) Repichet, S.; Le Roux, C.; Hernandez, P.; Dubac, J.;
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S.; Le Roux, C.; Dubac, J. Tetrahedron Lett. 1999, 40, 9233.
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(k) Yanagisawa, A.; Morodome, M.; Nakashima, H.;
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(11) General procedure for the Michael addition of Methyl-
(3-pyrrolidine)-propionate(1). A mixture of pyrrolidine
(0.2 mL, 2.3 mmol), methyl acrylate (0.414 mL, 4.6 mmol)
and bismuth triflate (2 mol%) in anhydrous acetonitrile (5
mL) was kept at ambient temperature under vigorous stirring
for 30 min. After completion of the reaction as indicated by
TLC, the reaction mixture was filtered and catalyst was
separated out, reaction mixture was extracted with ethyl
acetate and purified by using column chromatography on
silica gel to obtain pure product all most in quantitative
yield. Similar experimental procedures have been carried out
for other substrates and their chemical yields of isolated
products are summarized in Table 1. All isolated compounds
were fully characterized by comparing their physical data
(1H NMR, Mass Spectra, IR) of authentic compounds.
The feasibility of recovery and reuse of the catalyst in the
above solvents was also examined through a series of se-
quential Michael additions of morpholine with methyl
acrylate as model substrate. In a typical reaction, the cat-
alyst was simply filtered from the reaction mixture and re-
used for three cycles. In acetonitrile, the reaction
proceeded to completion giving excellent isolated yields,
although increases in reaction times were observed
(Table 2).
Table 2 Michael addition: Recycling Experiments of Morpholine
with Methyl Acrylate
Entry
Yield (%)
Time/h
0.5
1
2
3
95
93
95
6
18
A control experiment was conducted in the absence of cat-
alyst and it was observed that addition of morpholine to
methyl acrylate (entry 3, Table 2) resulted in the forma-
tion of the desired product only in low yields (25–30%)
even after 24 hours. Thus, it is highly likely that the data
shown for the recycling experiments occur under catalytic
conditions. The fact that, for the third recycling, the reac-
tion takes about 18 hours for good conversion of the de-
sired product clearly indicates some loss and deactivation
of the catalyst must have occurred during reaction and
work up.
Synlett 2003, No. 5, 720–722 ISSN 0936-5214 © Thieme Stuttgart · New York