LETTER
Enamination of b-Dicarbonyl Compounds Catalyzed by CeCl ·7H O
1983
3
2
In this procedure, aliphatic amines react efficiently to pro-
duce the corresponding enaminones. In the case of 1,2-
ethandiamine reactions, two equivalents of b-dicarbonyls
were used and the products got two enaminone groups
(2) (a) Foster, J. E.; Nicholson, J. M.; Butcher, R.; Stables, J. P.;
Edafiogho, I. O.; Goodwin, A. M.; Henson, M. C.; Smith, C.
A.; Scott, K. R. Bioorg. Med. Chem. 1999, 7, 2415.
(b) Edafiogho, I. O.; Moore, J. A.; Alexander, M. S.; Scott,
K. R. J. Pharm. Sci. 1994, 83, 1155. (c) Sweeney, T. R.;
Strube, R. E. In Burger’s Medicinal Chemistry, 4th ed., Part
II; Wolff, M. E., Ed.; Wiley: New York, 1979, 333.
(
Table 2, entries 2, 15 and 20). It has also been observed
that both weakly activated and deactivated anilines are
transformed to enaminones in good to high yields. This
method was successfully applied to enamination of linear
b-ketoesters (Table 2, entries 1–7), cyclic b-ketoesters
(3) (a) Cimarelli, C.; Palmieri, G.; Volpini, E. Synth. Commun.
2001, 31, 2943. (b) Palmieri, G.; Cimarelli, C. J. Org. Chem.
1
996, 61, 5557. (c) Bartoli, G.; Cimarelli, C.; Marcantoni,
E.; Palmieri, G.; Petrini, M. J. Org. Chem. 1994, 59, 5328.
d) Lubell, W. D.; Kitamura, M.; Noyori, R. Tetrahedron:
(
1
Table 2, entries 8–13) and b-diketones (Table 2, entries
4–22).
(
Asymmetry 1991, 2, 543. (e) Potin, D.; Dumas, F.;
d’Angelo, J. J. Am. Chem. Soc. 1990, 112, 3483.
It is pertinent to note that the b-enaminone formations in
(
(
4) Beholz, L. G.; Benovsky, R.; Ward, D. L.; Barta, N. S.;
Stille, J. R. J. Org. Chem. 1997, 62, 1033.
5) (a) David, O.; Blot, J.; Bellec, C.; Fargeau-Bellassoued, M.-
C.; Haviari, G.; Célérier, J. P.; Lhommet, G.; Gramain, J.-C.;
Gardette, D. J. Org. Chem. 1999, 64, 3122. (b) Michael, J.
P.; Parsons, A. S. Tetrahedron 1999, 55, 10915.
the presence of CeCl ·7H O immobilized on TBAB gave
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2
consistently excellent yields in very short reaction times.
However, the yields obtained by CeCl ·7H O under sol-
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2
vent-free conditions were good to high and the reaction
times were longer. Also, in both conditions, regiochemis-
try observed from these b-dicarbonyls, limited to prefer-
ential amines attack at the acetyl position and no by-
product was observed (Table 2, entries 3 and 8).
(6) (a) Popov, S. A.; Gatilov, Y. V.; Rybalova, T. V.; Tkachev,
A. V. Tetrahedron: Asymmetry 2003, 14, 233. (b) Popov, S.
A.; Tkachev, A. V. Synth. Commun. 2001, 31, 233.
(c) Popov, S. A.; Tkachev, A. V. Tetrahedron: Asymmetry
Another advantage of the method for this transformation
is recyclability of the catalyst. Since CeCl ·7H O/TBAB
1995, 6, 1013.
(7) (a) Rechsteiner, B.; Texier-Boullet, F.; Hamelin, J.
Tetrahedron Lett. 1993, 34, 5071. (b) Martin, D. F.;
Janusonis, G. A.; Martin, B. B. J. Am. Chem. Soc. 1961, 83,
3
2
or CeCl ·7H O under solvent-free conditions were weakly
3
2
soluble in CH Cl , thus they can be separated by washing
2
2
73.
with CH Cl and dried at 80 °C under reduced pressure
2
2
(8) Valduga, C. J.; Squizani, A.; Braibante, H. S.; Braibante, M.
and reused in three runs without any loss of activity.
E. F. Synthesis 1998, 1019.
In summary, the present procedure demonstrates a novel
method for the enamination of aromatic and aliphatic
amines with b-dicarbonyl compounds by catalytic
amounts of CeCl ·7H O in TBAB as an ionic liquid or un-
der solvent-free conditions. The notable features of this
procedure are mild reaction conditions, clear reaction pro-
files, improved yields, enhanced rates and simplicity in
operation, which make it a useful and attractive process
for the synthesis of enaminones. Moreover, reusability,
stability and non-toxicity of the catalyst and ionic liquid
are the other noteworthy advantages of this method.
(9) Arcadi, A.; Bianchi, G.; Di Giuseppe, S.; Marinelli, F. Green
Chem. 2003, 64.
10) Bartoli, G.; Bosco, M.; Locatelli, M.; Marcantoni, E.;
Melchiorre, P.; Sambri, L. Synlett 2004, 239.
11) Khosropour, A. R.; Khodaei, M. M.; Kookhazadeh, M.
Tetrahedron Lett. 2004, 45, 1725.
12) (a) Bartoli, G.; Marcantoni, E.; Sambri, L. Synlett 2003,
2101. (b) Yadav, J. S.; Reddy, B. V. S.; Rao, C. V.; Chand,
P. K.; Prasad, A. R. Synlett 2002, 137. (c) Yadav, J. S.;
Reddy, B. V. S.; Reddy, M. S.; Sabitha, G. Synlett 2001,
(
(
(
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2
1134. (d) Bellucci, M. C.; Bosco, M.; Sambri, L. J. Org.
Chem. 2000, 65, 2830.
(
(
13) (a) Ranu, B. C.; Dey, S. S. Tetrahedron Lett. 2003, 44,
2865. (b) Ranu, B. C.; Dey, S. S.; Hajra, A. Tetrahedron
2003, 44, 2417.
Acknowledgment
14) Typical Experimental Procedure (Method A): To a
mixture of ethyl acetoacetate (1.0 mmol) and aniline (1.0
mmol) under solvent-free conditions, CeCl ·7H O (0.1
We are thankful to the Razi University Research Council for partial
support of this work.
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2
mmol) was added and the reaction mixture stirred at r.t. for
the appropriate time according to Table 2. After completion
of the reaction as indicated by TLC, the mixture was washed
with EtOAc. The crude products were separated by
preparative chromatography on silica gel using n-heptane–
EtOAc (10:1) as eluent. The pure b-enaminones were
prepared in 50–87% yields.
References
(
1) (a) The Chemistry of Enamines, Part 1; Rappoport, Z., Ed.;
John Wiley and Sons: Chichester, New York, Brisbane,
Toronto, Singapore, 1994. (b) Alan, C.; Spivey, A. C.;
Srikaran, R.; Diaper, C. M.; David, J.; Turner, D. J. Org.
Biomol. Chem. 2003, 1, 1638. (c) Hassneen, H. M.;
(
15) Typical Experimental Procedure (Method B): To the
molten of TBAB (0.5 mmol), CeCl ·7H O (0.1 mmol) was
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2
Abdallah, T. A. Molecules 2003, 8, 333. (d) Michael, J. P.;
Koning, C. B.; Gravestock, D.; Hosken, G. D.; Howard, A.
S.; Jungmann, C. M.; Krause, R. W. M.; Parsons, A. S.;
Pelly, S. C.; Stanbury, T. V. Pure Appl. Chem. 1999, 71,
added and the mixture cooled to r.t., then ethyl acetoacetate
1.0 mmol) and aniline (1.0 mmol) were added to it. The
(
reaction mixture stirred magnetically at r.t. for the
appropriate time as shown in Table 2. The reaction was
followed by TLC. When the reaction was completed, the
mixture washed with EtOAc. The crude products were
separated by preparative chromatography on silica gel using
n-heptane/EtOAc (10:1) as eluent. The pure b-enaminones
were prepared in 74–99% yields. Selected characterization
979.
Synlett 2004, No. 11, 1980–1984 © Thieme Stuttgart · New York