1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU): A powerful catalyst for the Michael addition reaction of β-ketoesters to acrylates and enones

Article abstract of DOI:10.1081/SCC-120014028

The Michael addition reaction of 1,3-dicarbonyl compounds and enones was carried out in the presence of a catalytic amount of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in ethanol under the mild reaction condition furnished Michael adducts in excellent yield.

Full text of DOI:10.1081/SCC-120014028

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1,8-DIAZABICYCLO[5.4.0]UNDEC-7-ENE (DBU): A
POWERFUL CATALYST FOR THE MICHAEL ADDITION
REACTION OF β-KETOESTERS TO ACRYLATES AND
ENONES
Sengodagounder Muthusamy a , Srinivasarao Arulananda Babu a & Chidambaram Gunanathan
a
a Silicates and Catalysis Discipline, Central Salt and Marine Chemicals Research Institute,
Bhavnagar, 364 002, India
Version of record first published: 16 Aug 2006.
To cite this article: Sengodagounder Muthusamy, Srinivasarao Arulananda Babu & Chidambaram Gunanathan (2002): 1,8-
DIAZABICYCLO[5.4.0]UNDEC-7-ENE (DBU): A POWERFUL CATALYST FOR THE MICHAEL ADDITION REACTION OF β-KETOESTERS TO
ACRYLATES AND ENONES, Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic
Chemistry, 32:21, 3247-3254
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SYNTHETIC COMMUNICATIONS
Vol. 32, No. 21, pp. 3247–3254, 2002
1,8-DIAZABICYCLO[5.4.0]UNDEC-7-ENE
(DBU): A POWERFUL CATALYST FOR
THE MICHAEL ADDITION REACTION
OF b-KETOESTERS TO ACRYLATES
AND ENONES
*
Sengodagounder Muthusamy, Srinivasarao Arulananda Babu,
and Chidambaram Gunanathan
Silicates and Catalysis Discipline,
Central Salt and Marine Chemicals Research Institute,
Bhavnagar 364 002, India
ABSTRACT
The Michael addition reaction of 1,3-dicarbonyl compounds
and enones was carried out in the presence of a catalytic
amount of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in etha-
nol under the mild reaction condition furnished Michael
adducts in excellent yield.
During the course of our recent[1,2] work on the synthesis of new oxa-
polycyclic systems, we require various tethered cycloalkanones as starting
materials. To prepare this type of compounds without forming any O-alkyl-
ation product, we initiated to explore the Michael addition reaction.
*Corresponding author. Fax: þ91 278 567562; E-mail: salt@csir.res.in
3247
DOI: 10.1081/SCC-120014028
Copyright & 2002 by Marcel Dekker, Inc.
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3248
MUTHUSAMY, BABU, AND GUNANATHAN
The Michael addition reaction is widely recognized as one of the most
important carbon–carbon bond forming reactions in organic synthesis and
can traditionally be carried out with bases[3–5] such as alkoxides or hydro-
xides. Although this base catalysis is commonly known as a very efficient
and high-yielding process, the strongly basic conditions are often a limiting
factor since they can lead to a number of side and subsequent reactions, like
auto condensations and retro-Michael type decompositions.
In order to circumvent strongly alkaline conditions several alterna-
tive methods have been developed in recent years[6–9] that make use of
weak Brønsted bases (e.g., Barium hydroxide, alkali metal fluorides) or
employ mild reaction conditions (e.g., basic zeolites, alumina, phase trans-
fer catalysts, solid base catalysts). Alternatively it has been reported that
transition metal (e.g., Iron(III) chloride hexahydrate),[10] lanthanide com-
pounds and some Lewis acids can catalyze the Michael addition reaction,
albeit not always with satisfactory efficiency. Recently it has been reported
that trifluoromethanesulfonic acid (TfOH)[11] catalyses the Michael addi-
tion reaction of b-keto esters under solvent-free conditions. The use of less
amount of TfOH retarded the reaction progress due to the competitive
polymerization of ethyl acrylate and no catalytic activity was observed. To
the best of our knowledge, only one report[12] deals with the Michael
addition reaction of b-keto thiolesters and vinyl ketones in the presence
of an excess amount of 1,4-diazabicyclo[2.2.2]octane (DABCO) in 1,2-
dimethoxyethane furnished the desired Michael adduct. DBU has been
applied in various reactions such as alkylation, acylation,[13,14] esterifica-
tion[15] and Hoffmann rearrangement.[16] We herein wish to report an
exceedingly mild and efficient method using DBU as a powerful catalyst
for the Michael addition reaction of various 1,3-dicarbonyl compounds
and enones.
A catalytic amount of DBU (0.25 equiv.) was added to a mixture of
one equivalent of 2-oxocyclopentanecarboxylic acid ethyl ester (1a) and 1.2
equivalent of ethyl acrylate (2a) in 4 mL of absolute ethanol under an argon
atmosphere at room temperature. The reaction was monitored by TLC until
the disapperance of the starting material. On the addition of DBU, the
characteristic color change of the reaction mixture was observed from color-
less to dark yellow. The reaction was completed in five minutes duration and
the reaction mixture concentrated followed by purification using silica gel
column chromatography afforded the corresponding Michael adduct 3a in
99% yield (Sch. 1). This result unequivocally reflects the astonishing activity
of DBU in ethanol to effect the Michael addition reaction and it is known
that ethyl acrylate (2a) is usually the least reactive[17,18] of several Michael
acceptors under normal Lewis acid-catalyzed conditions except for high-
pressure reaction.

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1,8-DIAZABICYCLO[5.4.0]UNDEC-7-ENE (DBU)
3249
Scheme 1.
Table 1. Michael Adducts Produced Using DBU via Sch. 1
Substrate
n
R1
R2
Time
Yielda (%)
a
b
c
d
e
f
1
1
1
2
3
3
OEt
OEt
OEt
OEt
OEt
OMe
OEt
OMe
Me
OEt
OEt
Me
5 min
10 min
3 min
5.0 h
30 min
5 min
99[11]
94
74[11]
99[11]
91[11]
69[10]
aYields (unoptimized) refer to chromatographically isolated compounds 3.
To generation this new methodology, we carried out reactions with
other 1,3-dicarbonyl compounds having different ring sizes and enones
(2a–c) like ethyl- or methyl acrylate, methyl vinyl ketone under similar reac-
tion condition (Sch. 1). Yields of the product 3 are very good and results
summarized in Table 1.
Further, we assembled various g-alkylated-b-keto esters (4–6) via retro-
Dieckmann condensation method[19] (Table 2). 1,3-dicarbonyl compounds
were subjected to Michael addition reaction under similar reaction condition
in the presence of DBU afforded the respective Michael adducts (9–11) in a
facile manner. In the case of ethyl cyanoacetate (8), the reaction seems to
be very facile and afforded the dialkylated Michael adduct 13 instead of
expected monoalkylated product under the same experimental condition.
The unreacted starting material was recovered when the reaction was carried
out with equimolar quantities of starting materials. The same reaction was
repeated with a half equivalent of ethyl cyanoacetate and one equivalent of
ethyl acrylate to afford the Michael adduct 13 in very good yield. It is
interesting to note that cyclic enones such as cyclopentenone and cyclohex-
enone also furnished Michael adducts 14 and 15 but only in moderate yield.
Yet whereas these Michael acceptors usually require long reaction times
under acidic catalysis,[11] it can be noted that under these new conditions
the reaction was complete within few minutes. A remarkable longer reaction

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3250
MUTHUSAMY, BABU, AND GUNANATHAN
Table 2. DBU–Ethanol Mediated Michael Addition Reaction of 1,3-Dicarbonyl
Compounds and Enones
Michael
Acceptor
Yielda
(%)
Michael Donor
Time
8 min
Product
2a
2a
2a
84b
82b
78b
5 min
5 min
2a
2a
5 h
80[11]
5 min
91
1a
1a
10 min
61[11]
8 min
58
b
aYields (unoptimized) refer to chromatographically isolated compounds; Obtained
as a mixture of diastereomers in the ratio of 1 : 2.5.
time was observed in the case of 2-oxocyclohexanecarboxylic acid ethyl ester
(1d) and ethyl acetoacetate (7) (Tables 1 and 2); the reason may be due to the
presence of a greater proportion of he enol-form in solution (based on their
NMR spectra) compared to other Michael donors studied in this work.
Representatively, the reaction was studied in dry benzene as a solvent
instead of absolute ethanol. The reaction of compound 1a and 1d with 2a
in dry benzene as a solvent at room temperature afforded the Michael

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1,8-DIAZABICYCLO[5.4.0]UNDEC-7-ENE (DBU)
3251
adduct 3a in 45 min duration with the comparable yield and 3d in 25%
yield after two days, respectively. The 25% yield of 3d might show a non-
catalytic activity of DBU in dry benzene seem to show the effect of EtOH
on the catalytic cycle. It is interesting to note that the Michael addition
reaction of compound 1a and Michael acceptor 2c in the presence of
triethylamine in dry benzene afforded the Michael adduct 3c only after
seven days.[20]
In summary, the mild reaction condition together with excellent yield
makes the DBU-ethanol mediated Michael addition reaction as an
important and superior alternative to the classic base catalysis and other
methods, since both side-reactions and subsequent reactions under strong
basic conditions are avoided. The notable advantages of this method are its
requirement of 25 mol% catalyst and do not require any work-up.
EXPERIMENTAL
IR spectra were recorded on a Perkin Elmer Spectrum GX FT-IR
1
spectrophotometer. H NMR and 13C NMR spectra were recorded on a
Bruker DPX 200 (200 MHz and 50.3 MHz respectively) spectrometer and
referenced to TMS. Carbon types were determined from DEPT 13C NMR
experiments. Mass analyses were performed on a Jeol M Station 700 (FDþ
method in absolute dichloromethane) mass spectrometer. Elemental ana-
lyses were performed on a Perkin Elmer Model 2400 analyzer. Thin layer
chromatography was performed on silica/alumina plates and components
were visualized by observation under iodine. Column chromatography was
performed on silica gel.
General Procedure for Michael Addition Reaction of 1,3-Dicarbonyl
Compounds and Enones in the Presence of DBU
DBU (0.25 equiv.) was added dropwise to a mixture of 1,3 dicarbonyl
compound (1 equiv.) and Michael acceptor (1.2 equiv.) in 4 mL of absolute
ethanol at room temperature, and the resultant yellow mixture was allowed
to stir under an argon atmosphere until the disappearance of starting
material in TLC. The reaction mixture was concentrated under reduced
pressure and followed by purification of the residue using silica gel
column chromatography afforded the desired Michael adducts.
Ethyl 1-(3-methoxy-3-oxopropyl)-2-oxocyclopentanecarboxylate (3b):
Colorless liquid. IR (CH2Cl2): ꢀmax 2986, 2946, 1734 (br), 1331, 1451,
1
1290, 1180 cmÀ1. H NMR (200 MHz, CDCl3): ꢁ 4.14 (2H, q, J ¼ 7.2 Hz,

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3252
MUTHUSAMY, BABU, AND GUNANATHAN
OCH2), 3.70 (3H, s, OCH3), 2.40–1.35 (10H, m), 1.22 (3H, t, J ¼ 7.2 Hz,
CH2CH3). 13C NMR (50.3 MHz, CDCl3): ꢁ 214.3 (C, C¼O), 172.8 (C,
COO), 170.9 (C, COO), 61.3 (C, OCH2), 59.2 (quat-C), 517 (OCH3), 37.6
(CH2), 33.3 (CH2), 29.6 (CH2), 28.2 (CH2), 19.4 (CH2), 14.0 (CH3). Mass
m/z: 242 (Mþ). Anal. calc. for C12H18O5: C 59.49, H 7.49. Found: C 59.39,
H 7.55%.
Ethyl
3-(2-ethoxy-2-oxoethyl)-1-(3-ethoxy-3-oxopropyl)-2-oxocyclo-
pentanecarboxylate (9): Colorless liquid. IR (CH2Cl2): ꢀmax 2982, 2940,
1
2877, 1732 (br), 1450, 1375, 1325, 1181, 1029 cmÀ1. H NMR (200 MHz,
CDCl3): ꢁ 4.20–4.10 (6H, m), 2.80–1.50 (11H, m), 1.20–1.30 (9H, m).
13C NMR (50.3 MHz, CDCl3): ꢁ 214.2 (C, C¼O), 177.0 (C, COO), 174.7
(C, COO), 173.4 (C, COO), 61.9 (C, OCH2), 60.9 (C, OCH2), 60.7 (C,
OCH2), 59.6 (quat-C), 46.0 (CH), 36.4 (CH2), 32.2 (CH2), 30.1 (CH2),
29.3(CH2), 27.4 (CH2), 14.5 (CH3), 14.4 (CH3). Mass m/z: 342 (Mþ).
Anal. calc. for C17H26O7: C 59.64, H 7.65. Found: C 59.60, H 7.59%.
Ethyl 3-allyl-1-(3-ethoxy-3-oxopropyl)-2-oxocyclopentanecarboxylate
(10): Colorless liquid. IR (CH2Cl2): ꢀmax 2980, 2936, 2870, 1735 (br),
1
1641, 1450, 1370 cmÀ1. H NMR (200 MHz, CDCl3): ꢁ 5.80–5.67 (1H, m),
5.06–4.91 (2H, m), 4.15 (2H, q, J ¼ 7.2 Hz, OCH2), 4.10 (2H, q, J ¼ 7.2 Hz,
OCH2), 2.50–1.60 (8H, m), 1.59–1.35 (3H, m), 1.25 (3H, t, J ¼ 7.2 Hz,
CH2CH3), 1.21 (3H, t, J ¼ 7.2 Hz, CH2CH3). 13C NMR (50.3 MHz,
CDCl3): ꢁ 214.0 (C, C¼O), 172.9 (C, COO), 171.9 (C, COO), 136.2 (C,
C¼CH2), 115.9 (C, C¼CH2), 61.3 (C, OCH2), 59.9 (C, OCH2), 59.6
(quat-C), 46.0 (CH), 37.1 (CH2), 33.9 (CH2), 29.9 (CH2), 29.6 (CH2), 22.0
(CH2), 14.1 (CH3), 13.9 (CH3). Mass m/z: 296 (Mþ). Anal. calc. for
C16H24O5: C 64.84, H 8.16. Found: C 64.76, H 8.09%.
Ethyl 3-allyl-1-(3-ethoxy-3-oxopropyl)-2-oxocyclohexanecarboxylate
(11): Colorless liquid. IR (CH2Cl2): ꢀmax 2981, 2938, 2871, 1736 , 1715,
1
1642, 1448, 1375, 1223, 1107, 1028 cmÀ1. H NMR (200 MHz, CDCl3): ꢁ
5.80–5.65 (1H, m), 5.06–4.96 (2H, m), 4.16 (2H, q, J ¼ 7.2 Hz, OCH2),
4.11 (2H, q, J ¼ 7.2 Hz, OCH2), 2.60–1.75 (10H, m), 1.43–1.17 (3H, m),
1.26 (3H, t, J ¼ 7.2 Hz, CH2CH3), 1.24 (3H, t, J ¼ 7.2 Hz, CH2CH3).
13C NMR (50.3 MHz, CDCl3): ꢁ 207.4 (C, C¼O), 172.8 (C, COO), 171.5
(C, COO), 136.1 (C, C¼CH), 115.9 (C, C¼CH2), 61.2 (C, OCH2), 60.2 (C,
OCH2), 49.3 (CH), 46.9 (quat-C), 37.0 (CH2), 34.3 (CH2), 33.6 (CH2), 29.7
(CH2), 29.4 (CH2), 22.6 (CH2), 14.0 (CH3), 13.9 (CH3). Mass m/z: 310 (Mþ).
Anal. calc. for C17H26O5: C 65.78, H 8.44. Found: C 65.73, H 8.39%.
Triethyl 3-cyanopentane-1,3,5-tricarboxylate (13): Colorless liquid. IR
(CH2Cl2): ꢀmax 2985, 2942, 2912, 2248, 1719, 1631, 1450, 1378, 1191, 1095,
1
1030 cmÀ1. H NMR (200 MHz, CDCl3): ꢁ 4.27 (2H, q, J ¼ 7.2 Hz, OCH2),
4.13 (2H, q, J ¼ 7.2 Hz, OCH2), 4.12 (2H, q, J ¼ 7.2 Hz, OCH2), 2.63–2.15
(8H, m), 1.37–1.23 (9H, m). 13C NMR (50.3 MHz, CDCl3): ꢁ 171.2

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1,8-DIAZABICYCLO[5.4.0]UNDEC-7-ENE (DBU)
3253
(C, COO), 171.1 (C, COO), 167.9 (C, COO), 117.8 (C, CꢀN), 63.0 (C,
OCH2), 60.7 (C, OCH2), 60.6 (C, OCH2), 47.9 (quat-C), 317 (CH2), 30.0
(CH2), 14.0 (CH3), 13.8 (CH3). Mass m/z: 297 (Mþ). Anal. calc. for
C15H23NO6: C 60.59, H 7.80, N 4.71. Found: C 60.50, H 7.86, N 4.73%.
Ethyl 2-oxo-1-(3-oxocyclohexyl)cyclopentanecarboxylate (15): Color-
less liquid. IR (CH2Cl2): ꢀmax 2960, 2874, 1736 (br), 1716, 1451, 1316,
1228, 1155, 1122, 1031, 913 cmÀ1 1H NMR (200 MHz, CDCl3): ꢁ 4.20
.
(2H, q, J ¼ 7.2 Hz, OCH2), 2.49–1.90 (12H, m), 1.80–1.40 (3H, m), 1.26
(3H, t, J ¼ 7.2 Hz, CH2CH3). 13C NMR (50.3 MHz, CDCl3): ꢁ 213.5 (C,
C¼O), 209.8 (C, C¼O), 169.5 (C, COO), 61.7 (C, OCH2), 50.8 (quat-C),
43.2 (CH2), 42.0 (CH), 41.2 (CH2), 38.8 (CH2), 29.8 (CH2), 26.9 (CH2), 26.5
(CH2), 19.8 (CH2), 14.2 (CH3). Mass m/z: 252 (Mþ). Anal. calc. for
C14H20O4: C 66.65, H 7.99. Found: C 66.60, H 7.96%.
ACKNOWLEDGMENTS
This research was supported by Young Scientist Scheme, CSIR, New
Delhi. We thank Dr. P. K. Ghosh, Director and Dr. R. V. Jasra, Head of
the division for their encouragement shown in this work. S.A.B. and C.G
acknowledge the CSIR for a fellowship.
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Received in the UK August 6, 2001