Copper(II) triflate immobilized in [bmim]BF4 ionic liquid: An efficient reaction medium for Michael addition of β-ketoesters to acceptor-activated alkenes

Article abstract of DOI:10.1246/cl.2005.102

1,3-Dicarbonyl compounds undergo smooth conjugate addition to α,β-unsaturated ketones in the presence of 10 mol % copper(II) triflate immobilized in air and moisture stable [bmim]BF₄ ionic liquid under extremely mild conditions to afford the co

Full text of DOI:10.1246/cl.2005.102

102
Chemistry Letters Vol.34, No.1 (2005)
Copper(II) Triflate Immobilized in [bmim]BF4 Ionic liquid: An Efficient Reaction Medium
for Michael Addition of ꢀ-Ketoesters to Acceptor-activated Alkenes
J. S. Yadav,Ã B. V. S. Reddy, Gakul Baishya, and A. Venkat Narsaiah
Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad-500 007, India
(Received September 14, 2004; CL-041073)
1,3-Dicarbonyl compounds undergo smooth conjugate addi-
Table 2. Cu(OTf)2-catalyzed conjugate addition of ꢁ-ketoester
to enones in [bmim]BF4 ionic liquid
tion to ꢀ,ꢁ-unsaturated ketones in the presence of 10 mol % cop-
per(II) triflate immobilized in air and moisture stable [bmim]BF4
ionic liquid under extremely mild conditions to afford the corre-
sponding Michael adducts in high to quantitative yield.
Entry
Enone
2
O
Producta
Time/h
3.5
Yield/%b
β
-Ketoester
1
3
O
O
a
CO2 Me
COMe
Co2 Et
CO2 Me
CO2 Et
92
85
83
88
CH3
O
O
b
c
d
The Michael reaction is widely recognized as one of the
most important carbon–carbon bond forming reactions in organ-
ic synthesis.1 Traditionally, the Michael reaction is conjugate ad-
dition of nucleophiles to unsaturated carbonyl compounds per-
formed under the influence of strong bases such as alkali metal
alkoxides or hydroxides.2 The strong basic conditions often
leads to a number of undesirable side reactions such as Aldol
cyclizations, ester solvolysis, base induced rearrangements, such
as retro-claisen or retro Michael reactions, and polymerization
reactions. Subsequently, Lewis acids are found to catalyze the
Michael reaction under mild conditions.3 However, most of
these catalysts cannot be recovered and reused because they de-
compose under quenching conditions. The presence of even a
small amount of water causes lower yields, probably due to
the rapid decomposition or deactivation of the catalyst and also
the solvolysis of ꢁ-keto esters. Furthermore, many of these
methods often involve the use of strong acids which always re-
quired aqueous work-up for the catalyst separation, recycling
and disposal. Therefore, in recent years, to circumvent these
problems, considerable attention has been focused on develop-
ing mild and neutral catalysts. The main improvement of these
reagents are the ability to limit to catalytic amounts4 instead of
using stoichiometric amounts. Since the Michael adducts have
become increasingly useful and important in the field of drugs
and pharmaceuticals, the development of simple, efficient, and
environmentally benign approaches are desirable.
”
4.5
COMe
O
O
O
O
O
”
H3C
CH3
5.0
H3C
OEt
CO2Et
O
CO2 Me
O
CO2 Me
4.5
O
O
O
O
e
f
CO2Et
”
5.0
85
H3C
OEt
O
O
O
O
O
CO2Et
CO2 Et
CO2 Et
”
5.0
4.5
5.0
6.0
82
91
85
89
O
O
CO2Et
g
h
i
O
O
O
O
CO2 Me
CO2 Me
”
”
O
O
O
CO2Et
Me
OEt
O
1
aAll the products were characterized by H NMR, IR, and MS.
bIsolated and unoptimized yields.
programme in developing new synthetic methodologies,8 we re-
port herein the use of ionic liquid as recyclable solvent for the
conjugate addition of 1,3-dicarbonyl compounds to ꢀ,ꢁ-unstatu-
rated ketones to produce the corresponding 1,4-adducts in high
to quantitative yields under mild reaction conditions (Table 1).
Accordingly, the treatment of ethyl 2-oxocyclopentane-1-
carboxylate with methyl vinyl ketone in the presence of
10 mol % copper(II) triflate immobilized in [bmim]BF4 resulted
the corresponding ethyl 2-oxo-1-(3-oxobutyl)cyclopentane-1-
carboxylate 3a in 90% yield. The reaction proceeded efficiently
at room temperature with in a short period (4 h). The product
thus obtained was isolated by simple extraction with diethyl
ether. The ionic liquid was further washed with ether and reused
several times without further purification. Encouraged by the re-
sults obtained with ethyl 2-oxocyclopentane-1-carboxylate and
methyl vinyl ketone, we turned our attention to various ꢁ-keto
esters and acceptor-activated alkenes to give the corresponding
1,4-adducts. The yields are generally high to quantitative and
the reaction time also few hours. In the absence of catalyst,
the reactions did not proceed even after a long reaction time
(10–15 h). Interestingly, no byproducts arising from 1,2-addition
or bis-addition were observed. Moreover, the reactions were
Room temperature ionic liquids (RTLs) have been recog-
nized as ‘‘green’’ recycle alternatives to the traditional volatile
organic solvents, because of their unique chemical and physical
properties such as being liquid at room temperature, air, and
moisture stability, high solubility and negligible vapor pressure.
Their high polarity, Lewis acidity and ability to solubilize both
organic and inorganic compounds can result in enhanced rates
of chemical process and can provide higher selectivities com-
pared to conventional solvents.
In view of the emerging importance of ionic liquids5–7 as
green solvents in organic synthesis, and as part of our on going
R1
O
O
O
O
Cu(OTf)2
CO2R
R2
R2
+
CO2R
[Bmim] BF4, rt
R1
1
2
3
Scheme 1.
Copyright Ó 2005 The Chemical Society of Japan

Chemistry Letters Vol.34, No.1 (2005)
103
Table 1. Reactivity of Cu(OTf)2 in various solvents for the
condensations of methyl 2-oxocyclopentane-1-carboxylate and
methyl vinyl ketonea
2
3
a) E. D. Bergmann, D. Ginsburg, and R. Pappo, Org. React.,
10, 179 (1959). b) H. O. House, ‘‘Modern Synthetic
Reactions,’’ 2nd ed., W. A. Benjamin, Inc. Menlo Park
(1972), p 595. c) S. Kobayashi, Synlett, 1994, 689.
Time Yield
Runs
Copper triflate
Reaction medium
a) N. Srivastava and B. K. Banik, J. Org. Chem., 68, 2109
(2003). b) M. Bandini, P. G. Cozzi, M. Giacomini, P.
Melchiorre, S. Selva, and A. Umani-Ronchi, J. Org. Chem.,
67, 3700 (2002). c) G. Bartoli, M. Bartolacci, M. Bosco,
G. Foglia, A. Giuliani, E. Marcantoni, L. Sambri, and E.
Torregiani, J. Org. Chem., 68, 4594 (2003). d) J. S. Yadav,
V. Geetha, and B. V. S. Reddy, Synth. Commun., 33, 3519
(2002). e) J. Christoffers, Eur. J. Org. Chem., 1998, 1259.
f) G. Bartoli, M. Bosco, M. C. Bellucci, E. Marcantoni, L.
Sambri, and E. Torregiani, Eur. J. Org. Chem., 1999, 617.
g) K. I. Shimizu, M. Miyagi, T. Kan-no, T. Kodama, and
Y. Kitayama, Tetrahedron Lett., 44, 7421 (2003).
a) M. P. Sibi and S. Manyem, Tetrahedron, 56, 8033 (2000).
b) J. S. Yadav, S. Abraham, B. V. S. Reddy, and G. Sabitha,
Synthesis, 2001, 2165. c) M. P. Sibi, J. Shay, M. Liu, and
C. P. Jasperse, J. Am. Chem. Soc., 120, 6615 (1998).
d) J. S. Yadav, S. Abraham, B. V. S. Reddy, and G. Sabitha,
Tetrahedron Lett., 42, 8063 (2001). e) J. Christoffers,
J. Chem. Soc., Perkin Trans. 1, 1997, 3141.
a) T. Welton, Chem. Rev., 99, 2071 (1999). b) P.
Wasserscheid and W. Keim, Angew. Chem., Int. Ed. Engl.,
39, 3772 (2000).
a) J. S. Yadav, B. V. S. Reddy, A. K. Basak, and A. V.
Narsaiah, Chem. Lett., 33, 248 (2004). b) R. Sheldon, J.
Chem. Soc., Chem. Commun., 2001, 2399.
a) J. S. Yadav, B. V. S. Reddy, A. K. Basak, and A. V.
Narsaiah, Chem. Lett., 32, 988 (2003). b) J. S. Yadav, B.
V. S. Reddy, A. K. Basak, and A. V. Narsaiah, Green Chem.,
1, 5 (2003). c) C. M. Gordon, Appl. Catal., A, 222, 101
(2001).
/h
/%
92
89
71
71
68
1
2
3
4
5
10 mol % Cu(OTf)2
10 mol % Cu(OTf)2
10 mol % Cu(OTf)2
10 mol % Cu(OTf)2
10 mol % Cu(OTf)2
[bmim]BF4
[bmim]PF6
CH3CN
3.5
4.0
8.0
7.0
8.0
MeOH
CH2Cl2
aReaction was carried out in 1 mmol scale.
clean and high yielding. Compared to conventional solvents en-
hanced reaction rates and improved yields are the notable fea-
tures observed by using Cu(OTf)2/[bmim]BF4 catalytic system.
The reactivity of copper triflate in various solvents has been
studied in the case of methyl 2-oxocyclopentane-1-carboxylate
and methyl vinyl ketone and the results are summarized in
Table 1.
In further experiments, the reactivity of various ꢁ-ketoesters
and enones were studied in both hydrophilic [bmim]BF4 and
hydrophobic [bmim]PF6 ionic liquids. Among them, [bmim]BF4
was found to be superior in terms of conversion and reaction
rates. The recovered ionic liquid containing copper(II) triflate
was reused four times without loss of activity, even after fourth
cycle the product 3e was obtained with the similar yield and
purity of those obtained in the first cycle. The commercially
available ionic liquids were used in this study. The purity of
[bmim]BF4 ionic liquid is ꢀ97:0% (NMR). The use of ionic liq-
uid as the reaction media for this transformation helps to recycle
the catalyst there by making the process quite simple, more
convenient and environmentally friendly.
4
5
6
7
In summary, we describe a mild, clean and efficient protocol
for the conjugate addition of ꢁ-ketoesters to ꢀ,ꢁ-unsaturated ke-
tones using copper(II) triflate/[bmim]BF4 as novel and recycla-
ble catalytic system. The enones show enhanced reactivity in
ionic liquids there by reducing the reaction times and improving
the yield significantly. The simple experimental procedure
combined with ease of recovery and reuse of this novel reaction
media is expected to contribute to the development of a green
strategy for the conjugate addition reactions.
8
9
a) J. S. Yadav, B. V. S. Reddy, and G. Baishya, J. Org.
Chem., 68, 7098 (2003). b) J. S. Yadav, B. V. S. Reddy,
P. S. R. Reddy, A. K. Basak, and A. V. Narsaiah, Adv. Synth.
Catal., 346, 77 (2004). c) J. S. Yadav, B. V. S. Reddy, A. K.
Basak, and A. V. Narsaiah, Tetrahedron, 60, 2131 (2004).
General Procedure for the conjugate addition of ꢁ-ketoesters
to ꢀ,ꢁ-unsaturated compounds: A mixture of ꢀ,ꢁ-unsaturat-
ed compounds (1 mmol), ꢁ-ketoester (1 mmol) and copper-
(II)triflate (10 mol %) in 1-butyl-3-methylimidazolium tetra-
fluoroborate (3 mL) was stirred at ambient temperature for
the appropriate time (Table 1). After completion of the reac-
tion, as indicated by TLC. The reaction mixture was extract-
ed with diethyl ether (3 Â 10 mL). The combined ether ex-
tracts were concentrated under reduced pressure and the re-
sulting product was directly charged on small silica gel col-
umn and eluted with a mixture of ethyl acetate and n-hexane
to afford the pure compound. The products thus obtained
were characterized by comparison of their 1H NMR, IR,
and MS. The spectral data of all the products were identical
with those of authentic samples.3–5 IICT Communication
No; 040907.
GB thanks CSIR New Delhi for the award of fellowship.
References and Notes
1
a) A. Michael, J. Prakt. Chem., 35, 349 (1887). b) P.
Perlmutter, ‘‘Conjugate Addition Reactions in Organic
Synthesis,’’ Tetrahedron Organic Chemistry Series,
pergamon, Oxford (1992), Vol. 9. c) M. E. Jung, ‘‘In
Comprehensive Organic Synthesis,’’ ed. by B. M. Trost
and I. Fleming, Pergamon, Oxford (1991), Vol. 4, p 1.
d) H. Kotsuki, K. Arimura, T. Ohishi, and R. Maruzasa,
J. Org. Chem., 64, 3770 (1999).
Published on the web (Advance View) December 18, 2004; DOI 10.1246/cl.2005.102