Poly(ethyleneglycol) (PEG): A rapid and recyclable reaction medium for the DABCO-catalyzed Baylis-Hillman reaction

Article abstract of DOI:10.1016/j.tetlet.2004.05.153

PEG (400) has been used as a rapid and recyclable reaction medium for the Baylis-Hillman reaction with the conventional basic catalyst DABCO (20mol%) with very good yields of products. Recyclability is achieved with no further addition of DABCO to the rea

Full text of DOI:10.1016/j.tetlet.2004.05.153

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 5865–5867
Poly(ethyleneglycol) (PEG): a rapid and recyclable reaction
medium for the DABCO-catalyzed Baylis–Hillman reaction
S. Chandrasekhar,* Ch. Narsihmulu, B. Saritha and S. Shameem Sultana
Indian Institute of Chemical Technology, Hyderabad 500 007, India
Received 16 April 2004; revised 18 May 2004; accepted 28 May 2004
Abstract—PEG (400) has been used as a rapid and recyclable reaction medium for the Baylis–Hillman reaction with the conven-
tional basic catalyst DABCO (20 mol %) with very good yields of products. Recyclability is achieved with no further addition of
DABCO to the reaction medium over four runs without substantial loss in yields. Incidentally, DABCO is recycled for the first time
in this transformation.
ꢀ 2004 Elsevier Ltd. All rights reserved.
The Baylis–Hillman reaction1 is one of the very few
reactions wherein atom economy2 is perfectly preserved.
Also this reaction results in a new C–C bond between an
aldehyde and the a-carbon of an electron deficient olefin
generating multifunctional building blocks for further
synthetic manipulation.3 Unfortunately, however, the
applications and usefulness of this reaction in several
cases are hampered by low yields, high concentration of
catalyst and long reaction times (sometimes up to a
week for less than 50% conversion). Also the reaction is
generally inert to enones, a,b-substituted aldehydes and
hindered aldehydes. To overcome these problems, sev-
eral modifications have been attempted including new
catalysts,4 novel solvent media such as supercritical
CO2,5 ionic liquids,6 polar solvents,7 ultrasound,8 high
pressure,9 etc. Of all these methods, the ionic liquid
medium is the only protocol which allows recycling of
the solvent. However, recent findings have revealed that
ionic liquids under the influence of a mild base like
DABCO participate in a side reaction.10 Also, the most
ecofriendly solvent is not compatible with water, acry-
lates, which undergo hydrolysis in the presence of base.
Thus, further methodologies are necessary to overcome
these drawbacks. We recently found that poly(ethyl-
eneglycol) is an efficient, recyclable reaction medium for
the Heck reaction, catalytic hydrogenations and asym-
metric dihydroxylation reactions.11 Herein we report for
the first time, poly(ethyleneglycol) (400) as a recyclable
solvent medium for the rapid Baylis–Hillman reaction
between unreactive aldehydes and activated olefins.
Our initial experiment was carried out between benzal-
dehyde (Table 1, entry 1) (2 mmol), ethyl acrylate
(3 mmol) and DABCO (20 mol %) in poly(ethylenegly-
col) (400 MW) at room temperature. To our surprise the
reaction was found to be complete within 2 h and the
product was isolated by extraction with ether
(5 · 10 mL) (Scheme 1). Evaporation of the solvent and
purification of the crude product by column chroma-
tography yielded the required product in 92% yield; this
represents an improvement on earlier methods with re-
spect to reaction time, concentration of catalyst and
increased yields. The reactivity of benzaldehyde with
other activated olefins was also investigated. Treatment
with acrylonitrile (entry 2) or methyl vinyl ketone (entry
3) and 20 mol % DABCO in PEG gave similar results
with respect to time and yield (see Table 1).
4-Nitrobenzaldehyde (entries 4 and 5) reacted with ethyl
acrylate and acrylonitrile resulting in the corresponding
products in 96% and 93% yields after 2 h. 4-Fluoro-
benzaldehyde (entry 6) showed much faster reactivity in
PEG forming the required product in 89% yield in 4 h,
whereas the same reaction took over 60 h using tri-
methylamine.7 The other aromatic and heteroaromatic
aldehydes, 2-chloro-5-nitrobenzaldehyde (entry 7), 2-
furaldehyde (entries 9 and 10) and 2-thiophenecarbox-
aldehyde (entry 11) showed the same consistency in
Keywords: PEG; DABCO; Baylis–Hillman reaction; Recyclability.
* Corresponding author. Tel.: +91-40-7193434; fax: +91-40-27160512;
e-mail: srivaric@iict.res.in
0040-4039/$ - see front matter ꢀ 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.05.153

5866
S. Chandrasekhar et al. / Tetrahedron Letters 45 (2004) 5865–5867
Table 1. DABCO-catalyzed Baylis–Hillman reaction in PEG
Entry
Aldehyde
Activated olefin
Time (h)
2.0
Yield (%)a
O
O
H
OEt
1
2
92
94
O
O
CN
O
H
H
1.5
3
4
3.0
2.0
89
96
O
O
O
H
H
OEt
O2N
O2N
CN
5
2.0
93
O
O
H
O
6
7
4.0
1.5
89
94
OEt
F
O2N
CN
H
H
Cl
O
O
8
3.0
3.0
2.5
3.0
40
91
91
90
OEt
MeO
O
O
O
9
OEt
H
O
CN
10
11
O
S
H
O
O
OEt
H
O
CN
H
12
13
14
5.0
4.0
4.5
75
86
80
O
O
OEt
H
O
O
O
OMe
H
H
O
O
H
15
16
4.0
4.0
72
65
OEt
H
O
OMe
a Isolated yields. Products were characterized by 1H NMR and mass spectroscopy.
faster reactivity and very good product yields. However,
the yield was dramatically reduced for the reaction
between the electron-rich aldehyde, 4-methoxybenzal-
dehyde (entry 8) and ethyl acrylate (Table 1).

S. Chandrasekhar et al. / Tetrahedron Letters 45 (2004) 5865–5867
5867
Acknowledgements
OH
O
E
DABCO (20 mol%)
PEG, r.t
E
+
R
R
H
C.N., B.S. and S.S.S. thank CSIR, New Delhi for
financial support. IICT Communication No.: 030514.
R = H, alkyl
and aryl
E = COOEt, COOMe
CN and C(O)CH3
Scheme 1.
References and notes
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2. Trost, B. M. Science 1991, 254, 1471.
3. Basavaiah, D.; Rao, A. J.; Satyanarayana, T. Chem. Rev.
2003, 103, 811.
Table 2. Reusability of PEG and DABCO for the Baylis–Hillman
reaction between 4-nitrobenzaldehyde and ethyl acrylate
Run
1
2
3
4
Time (h)
Isolated
yield (%)
2
96
6
92
16
95
24
89
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The same trend of acceleration was also observed in
the reactivity of aliphatic aldehydes. 3-Phenylpropanal
(entry 12), isobutyraldehyde (entry 13) and hexanal
(entry 14) underwent the Baylis–Hillman reaction with
activated olefins in PEG resulting in 75%, 86% and 80%
yields, respectively. To check the efficiency of the
transformation, formaldehyde (entry 15) and trans-cin-
namaldehyde (entry 16) were also subjected to the
Baylis–Hillman reaction with acrylates in PEG to pro-
vide good yields of the desired products.
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35, 7947; (b) Yu, C.; Liu, B.; Hu, L. J. Org. Chem. 2001,
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The recyclability of the reaction was investigated and
revealed the important observation that no additional
catalyst was required for subsequent runs. After com-
pletion of the reaction between 4-nitrobenzaldehyde,
ethyl acrylate and DABCO (20 mol %), the reaction
mixture was extracted with ether (5 · 10 mL), concen-
trated in vacuo and purified by column chromatography
to give the product in 96% yield. For the next run,
the reactants were added and stirred without adding
DABCO. The reaction was complete in 6 h affording the
product in an excellent 92% yield. The third and fourth
runs were repeated without addition of catalyst, how-
ever, on these occasions extended reaction times were
necessary (see Table 2).
10. Aggarwal, V. K.; Emme, I.; Mereu, A. Chem. Commun.
2002, 1612.
11. (a) Chandrasekhar, S.; Narsihmulu, Ch.; Sultana, S. S.;
Reddy, N. R. K. Org. Lett. 2002, 4, 4399; (b) Chandrase-
khar, S.; Narsihmulu, Ch.; Sultana, S. S.; Reddy, N. R. K.
Chem. Commun. 2002, 1716; (c) Chandrasekhar, S.;
Narsihmulu, Ch.; Chandrasekhar, G.; Shyamsunder, T.
Tetrahedron Lett. 2004, 45, 2421; (d) Chandrasekhar, S.;
Shyamsunder, T.; Chandrasekhar, G.; Narsihmulu, Ch.
Synlett 2004, 522.
In conclusion, this communication describes for the first
time, the Baylis–Hillman reaction in (PEG), a recyclable
solvent medium. Also DABCO was found to be recycled
efficiently over four runs.