The first Et3N-mediated transesterification of β-keto esters using Baylis-Hillman alcohols

Article abstract of DOI:10.1016/j.tet.2011.06.012

A simple and efficient Et₃N-mediated transesterification between β-keto esters and Baylis-Hillman alcohols in toluene solution at reflux using a Dean-Stark apparatus, is described. Allylic esters are exclusively obtained in moderate to good yie

Full text of DOI:10.1016/j.tet.2011.06.012

Tetrahedron 67 (2011) 6322e6326
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The first Et3N-mediated transesterification of b-keto esters using
BayliseHillman alcohols
*
Olfa Mhasni, Farhat Rezgui
ꢀ
ꢀ
Universite de Tunis EL Manar, Laboratoire de Chimie Organique Structurale, Faculte des Sciences Campus Universitaire, 2092 Tunis, Tunisia
a r t i c l e i n f o
a b s t r a c t
Article history:
A simple and efficient Et3N-mediated transesterification between b-keto esters and BayliseHillman al-
Received 14 February 2011
Received in revised form 21 May 2011
Accepted 6 June 2011
cohols in toluene solution at reflux using a DeaneStark apparatus, is described. Allylic esters are ex-
clusively obtained in moderate to good yields, with no trace amounts of
expected from the Carroll decarboxylative rearrangement.
g,d-unsaturated ketones usually
Available online 14 June 2011
Ó 2011 Elsevier Ltd. All rights reserved.
Dedicated to Professors A. Baklouti and
M. M. El Gaied on the occasion of their 70th
birthdays
1. Introduction
O
O
O
O
O
DMAP, 110 °C
R1
OH
b
-Keto esters have been found to be useful intermediates in
+
R2
R1
°
R2
organic chemistry1 and for the synthesis of natural and bioactive
compounds.2 Therefore, several synthetic methods have been
reported on the preparation of these compounds. In this regard, the
transesterification, known as an ester-to-ester transformation, is
toluene, 4A MS
O
1a
2
R1 = Me, Et, Ph
R2 = Me, Et, Ph, OMe, OEt, OBz
Scheme 1. DMAP-mediated allylation of b-dicarbonyl compounds with alcohol 1a.
one of the most common procedures for the preparation of b-keto
esters, which has attracted much interest during the last decades.
In the 1980s, two common methods were mainly employed for the
transesterification of enolisable b-keto esters, i.e., the reaction of
With the exception of the DMAP-catalysed ester exchange re-
actions,4 it is notable that none of the above methods reported that
diketene with primary or secondary alcohols3 and DMAP-catalyzed
ester exchange reactions in the presence of molecular sieves in
toluene solution at reflux.4 As diketene is corrosive and DMAP is
both toxic and expensive, the two previous methods became less
attractive since a large number of acid or basic catalysts have been
reported for this purpose, including mainly the recently described
catalysis by Zinc(II) oxide,5 boric acid,6 niobium(V) oxide,7 borate
tertiary bases, such as Et3N could catalyse transesterification of
keto esters. In continuation of our previous study on the chemistry
of BH adducts towards
-dicarbonyl compounds,14e16 we report
herein a simple and efficient procedure for the transesterification of
-keto esters with various alcohols 1aec and 4aec,13,17 using
b-
b
b
commercially available and inexpensive triethylamine, for the first
time, as a Brønsted base catalyst.
9
zirconia,8 I2 and Zn/I2.10 Alternatively, a lot of effort has been put
into better developing Green Chemistry for the transesterification
of b-keto esters, using non-corrosive and environmentally benign
2. Results and discussion
catalysts. In this context, recent reports have demonstrated that
boric acid,6 montmorillonite K-1011 and natural clays12 can be used
as efficient and reusable catalysts.
In order to disclose the role of triethylamine in the present
protocol, our preliminary attempt between ethyl acetoacetate
(2 equiv) and allylic alcohol 1a (1 equiv) was carried out without
any additive, using a DeaneStark apparatus. We have observed that
the starting materials were recovered, even after stirring the re-
action mixture during 72 h in toluene at reflux.
Therefore, we investigated, in toluene at reflux, the trans-
esterification reaction of ethyl acetoacetate with allylic alcohol 1a,
in the presence of triethylamine18 with azeotropic removal of EtOH.
Under these conditions, a mixture of transesterification and C-
Although DMAP is well known as the common catalyst for the
transesterification of
under the above reaction conditions, there has been surprisingly
a direct allylic substitution of alcohol 1a13 with
-keto esters and
diketones, affording compounds 2 (Scheme 1).14
b
-keto esters,4 we have recently reported that,
b
b-
* Corresponding author. E-mail address: rez_far@yahoo.fr (F. Rezgui).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.06.012

O. Mhasni, F. Rezgui / Tetrahedron 67 (2011) 6322e6326
6323
allylation products, respectively, 3a and 2a (3a/2a¼95/5), was
obtained in 98% overall yield (Scheme 2, Table 1, entry 1).
Next, in order to improve the selectivity of this procedure in fa-
vour of the transesterification product 3a, we selected DMAP, as
nucleophilicone, owing tothe steric effects of the two methylgroups
on the pyridine nucleus. The results of this study are summarised in
Table 1.
In contrast to Et3N (Table 1, entry 1) that mainly mediated the
transesterification of ethyl acetoacetate with alcohol 1a (3a/2a¼95/
5), DMAP (Table 1, entry 2) afforded exclusively the C-allylation
product 2a in 58% yield.14 More interestingly, the 2,6-lutidine (Table 1,
entry3), isfound to be the suitable amine for the transesterification of
ethyl acetoacetate with alcohol 1a, affording exclusively the desired
allylic ester 3a, in a good yield (90%), with no trace amounts of the
Carroll decarboxylative rearrangement ketone.19
a
highly nucleophilic amine, and 2,6-lutidine, as
a
weakly
O
O
O
O
O
O
O
O
Et3N
OH
O
+
+
OEt
toluene, reflux
O
OEt
1a
3a (95%)
2a (5%)
It is notable that when we have used less than 2 equiv of amines
(Et3N or 2,6-lutidine), the title reaction did not go to completion
even after a prolonged reaction time of 72 h. For this reason, in all
our experiments, 2 equiv of amine were required.
Scheme 2. Et3N-mediated transesterification of ethyl acetoacetate with alcohol 1a.
Table 1
Amine-mediated reaction of alcohol 1a with ethyl acetoacetate
In order to demonstrate the scope of this synthetic methodol-
ogy, we investigated a variety of commercially available
esters and diethyl malonate with alcohol 1a (Scheme 3, Table 2,
entries 1e5) as well as differentially -substituted BH alcohols 1b,c
(Scheme 3, Table 2, entries 6e9), using amines as Brønsted bases
b-keto
Entry
Amine
2a (yield %)
3a (yield %)
Ratio of 2a:3a
1
2
3
Et3N
DMAP
2,6-Lutidine
6
58
0
92
0
90
5/95
100/0
0/100
a
O
OH
R1
O
O
O
O
O
R
R
R
O
O
Et3N
R1
O
O
OH
+
R1
OEt
toluene, reflux
1a-c
R = H, alkyl
3a-i
54-96%
R1 = alkyl, Ph, OEt
Scheme 3. Et3N-mediated transesterification of b-keto esters with alcohols 1aec.
Table 2
Amine-mediated transesterification of b-keto esters with alcohols 1aec
Entry
1
R (alcohol)
b
-Keto ester
Amine
t/h
25
Product 3
Yield %
90
Ratio of keto:enol
92/8
O
O
O
O
O
H (1a)
2,6-Lutidine
O
3a :
3b :
3c :
3d :
OEt
O
O
O
O
O
2
3
4
H (1a)
H (1a)
H (1a)
Et3N
Et3N
Et3N
24
24
24
85
54
90
81/19
100/0
34/66
O
Ph
OEt
Ph
O
O
O
O
O
O
O
O
O
O
OEt
OEt
O
O
O
O
O
O
O
5
6
H (1a)
Et3N
Et3N
48
48
72
76
100/0
92/8
O
OEt
OEt
3e :
3f :
3g :
3h :
EtO
O
O
O
O
O
Me (1b)
O
OEt
O
O
O
O
O
7
8
Me (1b)
Et3N
Et3N
24
29
96
89
80/20
91/9
Ph
O
OEt
Ph
n-Pr
O
O
O
O
O
n-Pr (1c)
O
OEt
n-Pr
O
O
O
O
O
9
n-Pr (1c)
Et3N
24
90
78/22
Ph
O
OEt
Ph
3i :

6324
O. Mhasni, F. Rezgui / Tetrahedron 67 (2011) 6322e6326
with azeotropic removal of EtOH. As is shown in Table 2, entries
2e9, the corresponding allylic esters 3bei were exclusively
obtained in 54e90% yields.
latter reaction, based on the strong nucleophilic character of DMAP,
was previously proposed.14
In contrast, Et3N is usually used as a nitrogen Brønsted base,
stronger than both DMAP and 2,6-lutidine.24 The latter is weakly
nucleophilic and is usually used in organic synthesis as a hindered
mild base, weaker than Et3N.25 The high selectivity of the reaction
of 1a with ethyl acetoacetate in favour of 3a, suggested that both
Et3N and 2,6-lutidine remarkably acted in this protocol as Brønsted
bases. Moreover, a difference in the nucleophilicity of Et3N and 2,6-
lutidine has been previously reported.26 Accordingly, we believe
that the formation of small amounts of the C-allylation product 2a
(2a/3a¼5/95) when Et3N was used, reveals that this amine is
slightly more nucleophilic than 2,6-lutidine, which has a large
steric effect.
b-keto esters 3 exist as a mixture of two tautomeric forms in
CDCl3 solution, whose relative ratios were determined by means of
1H NMR spectroscopy (Table 2). For example, the singlet at dH 3.50
of 3a was assigned to the methylene proton (eCOeCH2eCOe) of
the corresponding keto tautomer whereas the two singlets at dH
5.02 and dH 12.03 were, respectively, assigned to the vinyl proton
(eC(eOH)]CHe) and the hydroxyl one (OH) of the corresponding
enol tautomer.
Encouraged by these successful results on the transesterification
of b-dicarbonyl compounds with alcohols 1aec in the presence of
Et3N or 2,6-lutidine, we attempted to extend this methodology to
five-membered allylic alcohols 4aec (Scheme 4, Table 3). Our results
show that the present transesterification procedure, using Et3N
(Table 3, entries 1, 3 and 4) or 2,6-lutidine (Table 3, entries 2 and 5),
still works well, yielding the corresponding transesterification
products 5aee in moderate to good yields (Table 3, entries 1e5).
Therefore, ethyl acetoacetate, for instance, can undergo, in the
presence of Et3N or 2,6-lutidine, a
-keto ketene intermediate I, highly reactive, on which further ad-
dition of allylic alcohols ROH, generates esters 3 and 5 (Scheme 5). It
b-elimination of EtOH to form an
a
is notable that such reaction mechanism, involving a-keto ketene,
b-Keto esters 5 have also two tautomeric forms in CDCl3 solution
was previously proposed by other authors27 and supported by
Witzeman studies.28
(Table 3). For instance, the singlet at dH 4.06 of 5b was assigned to
O
O
O
OH
R
O
R
O
O
R
O
O
Et N
3
1
1
1
R
R
O
O
2
OH
+
R
OR
toluene, reflux
50-89%
5a-e
4a-c
Scheme 4. Et3N-mediated transesterification of
b-keto esters with alcohols 4aec.
Table 3
Amine-mediated transesterification of
b
-keto esters with alcohols 4aec
Entry
R (alcohol)
b
-Keto ester
Amine
t/h
24
Product 5
Yield %
Ratio of keto:enol
100/0
O
O
O
O
O
O
1
H (4a)
Et3N
53
50
56
O
OEt
Ph
OEt
OEt
EtO
Ph
5a :
O
O
O
O
2
3
H (4a)
H (4a)
2,6-Lutidine
Et3N
5
9
83/17
44/56
O
5b :
5c :
O
O
O
O
O
O
OEt
O
O
n-Pr
O
O
O
O
O
O
O
O
4
5
n-Pr (4b)
Ph (4c)
Et3N
5
6
89
63
82/18
82/18
O
O
Ph
Ph
OEt
OEt
Ph
Ph
5d :
Ph
2,6-Lutidine
5e :
the methylene protons (eCOeCH2eCOe) of the corresponding keto
tautomer. The two singlets at dH 5.72 and dH 12.44 were, re-
spectively, assigned to the vinyl proton (eC(eOH)]CHe) and the
hydroxyl one (OH) of the corresponding enol tautomer.
O
O
O
O
O
O
ROH
Et3N, 110 °C
- EtOH
C
O
OR
I
3, 5
Scheme 5. Proposed mechanism of the Et3N-mediated transesterification of ethyl
2.1. On the contrast between the behaviours of DMAP, Et3N
and 2,6-lutidine
acetoacetate.
3. Conclusion
It is well known that DMAP is a powerful nucleophilic catalyst,
usually used in the esterification of alcohols20,21 as well as related
reactions.22,23 In addition, we have previously shown that DMAP
efficiently catalysed BH reactions on cyclic enones13 as well as
In conclusion, Et3N-mediated transesterification of b-keto esters
and diethyl malonate proceeds with five- and six-membered ring
alcohols 1aec and 4aec in toluene at reflux. Work is in progress in
our laboratory to investigate the generality of this simple
allylation of b-dicarbonyl compounds. A reaction mechanism of the

O. Mhasni, F. Rezgui / Tetrahedron 67 (2011) 6322e6326
6325
transesterification method of
b-keto esters with a wide range of
0.57; n
(CHCl3) 1717, 1671, 1647 cmꢁ1; keto (34%)-enol (66%); dH
allylic, propargylic as well as aliphatic alcohols.
(keto, CDCl3) 7.09 (t, J¼4.0 Hz, 1H), 4.84e4.81 (m, 4H), 3.41 (t,
J¼8.4 Hz, 1H), 2.49e2.43 (m, 4H), 2.15e2.10 (m, 2H), 2.05e2.00 (m,
4H), 1.69e1.59 (m, 4H); dH (enol, CDCl3) 12.09 (s, 1H), 6.98 (t,
J¼4.0 Hz, 1H), 4.84e4.81 (m, 2H), 2.49e2.43 (m, 4H), 2.28e2.24 (m,
4H), 2.05e2.00 (m, 2H), 1.69e1.59 (m, 4H); dC (keto, CDCl3) 206.2,
197.9, 169.6, 148.5, 134.0, 61.8, 57.1, 38.1, 30.0, 27.1, 25.7, 23.3 (2C),
22.6; dC (enol, CDCl3) 197.9, 172.4, 172.1, 147.5, 134.4, 97.5, 60.8, 41.6,
38.1, 29.1, 25.7, 22.6, 22.4, 22.3; HRMS (EI): Mþ, found 250.1201.
C14H18O4 requires 250.1205.
4. Experimental
4.1. General
IR spectra were recorded on a Bruker (IFS 66v/S) spectrometer.
1H NMR and 13C NMR spectra were recorded either on a Bruker AC-
300 spectrometer (300 MHz for 1H and 75 MHz for 13C) in CDCl3,
using TMS as an internal standard (chemical shifts in
d values, J in
Hz). High resolution mass spectra (HRMS) were recorded as EI-
HRMS on an Autospec Ultima/micromass mass spectrometer.
Analytical thin layer chromatography (TLC) was performed us-
ing Fluka Kieselgel 60 F254 precoated silica gel plates. Visualization
was achieved by UV light (254 nm). Flash chromatography was
performed using Merck silica gel 60 and a gradient solvent system
(pet-ether/ether as eluant).
4.2.5. Ethyl 6-oxocyclohex-1-enylmethyl malonate 3e. Yellow oil
(0.864 g, 72% yield); Rf (80% Et2O/petroleum ether) 0.51;
n (CHCl3)
1750, 1732, 1674 cmꢁ1; keto (100%)-enol (0%); dH (300 MHz, CDCl3)
7.06 (t, J¼4.0 Hz,1H), 4.81 (s, 2H), 4.20 (q, J¼6.9 Hz, 2H), 3.40 (s, 2H),
2.48e2.42 (m, 4H), 2.07e2.01 (m, 2H), 1.28 (t, J¼6.9 Hz, 3H); dC
(75 MHz, CDCl3) 197.7, 166.4, 166.2, 148.6, 133.8, 62.2, 61.2, 41.4,
38.1, 25.7, 22.6, 14.0; HRMS (EI): Mþ, found 240.0995. C12H16O5
requires 240.0998.
4.2. Typical procedure for transesterification reactions of
cyclic BeH adducts with
b
-keto esters
4.2.6. 1-(6-Oxocyclohex-1-enyl)ethyl 3-oxobutanoate 3f. Yellow
liquid (0.851 g, 76% yield); Rf (80% Et2O/petroleum ether) 0.49;
n
A mixture of allyl alcohol 1a (0.63 g, 5 mmol), ethyl acetoacetate
(1.30 g, 10 mmol) and 2,6-lutidine (1.07 g, 10 mmol) in toluene
(50 mL) was heated to 110 ꢀC in a two-necked round bottomed flask
provided with a distillation condenser to remove ethanol. After
completion (TLC), the reaction mixture was cooled, washed with
brine and dried. The toluene was removed and the residue was
purified by column chromatography on silica gel (40% ether/pe-
troleum ether) to give the pure allylic ester 3a (0.945 g, 90%).
(CHCl3): 3534, 1741,1716,1673 cmꢁ1; keto (92%)-enol (8%); dH (keto,
CDCl3) 7.01 (t, J¼4.0 Hz, 1H), 5.76 (q, J¼6.2 Hz, 1H), 3.48 (s, 2H),
2.45e2.41 (m, 4H), 2.27 (s, 3H), 2.02e1.95 (m, 2H), 1.35 (d, J¼6.2 Hz,
3H); dH (enol, CDCl3) 12.03 (s, 1H), 7.01 (t, J¼4.0 Hz, 1H), 5.76 (q,
J¼6.2 Hz,1H), 5.03 (s,1H), 2.45e2.41 (m, 4H), 2.27 (s, 3H), 2.02e1.95
(m, 2H), 1.35 (d, J¼6.2 Hz, 3H); dC (keto, CDCl3) 200.8, 197.4, 166.0,
145.4, 139.1, 68.1, 50.1, 38.3, 30.1, 25.6, 22.5, 20.0; dC (enol, CDCl3)
197.5, 175.7, 171.4, 144.8, 139.7, 89.8, 66.5, 38.3, 25.6, 22.5, 21.1, 20.4;
HRMS (EI): Mþ, found 224.1047. C12H16O4 requires 224.1049.
4.2.1. 6-Oxocyclohex-1-enylmethyl 3-oxobutanoate 3a. Yellow oil
(0.945 g, 90% yield); Rf (90% Et2O/petroleum ether) 0.55;
n
(CHCl3)
4.2.7. 1-(6-Oxocyclohex-1-enyl)ethyl 3-oxo-3-phenylpropanoate
3530, 1743, 1716, 1672 cmꢁ1; keto (92%)-enol (8%); dH (keto, CDCl3)
7.08 (t, J¼4.0 Hz, 1H), 4.79 (s, 2H), 3.50 (s, 2H), 2.48e2.43 (m, 4H),
2.26 (s, 3H), 2.07e2.01 (m, 2H); dH (enol, CDCl3) 12.03 (s, 1H), 7.08
(t, J¼4.0 Hz,1H), 5.02 (s,1H), 4.79 (s, 2H), 2.48e2.43 (m, 4H), 2.26 (s,
3H), 2.07e2.01 (m, 2H); dC (keto, CDCl3) 200.7, 197.8, 166.8, 149.2,
133.7, 62.0, 49.8, 38.0, 30.1, 25.7, 22.6; dC (enol, CDCl3) 197.8, 175.8,
172.1, 148.6, 134.1, 89.5, 60.6, 38.0, 25.7, 22.6, 21.1; HRMS (EI): Mþ,
found 210.0895. C11H14O4 requires 210.0892.
3g. Yellow liquid (1.372 g, 96% yield); Rf (60% Et2O/petroleum
ether) 0.51;
n
(CHCl3) 3550, 1739, 1678, 1603, 1451 cmꢁ1; keto
(80%)-enol (20%); dH (keto, CDCl3) 7.95e7.91 (m, 2H), 7.60e7.45 (m,
3H), 6.86 (t, J¼4.4 Hz, 1H), 5.79 (q, J¼6.6 Hz, 1H), 4.00 (s, 2H),
2.41e2.31 (m, 4H), 2.00e1.91 (m, 2H), 1.31 (d, J¼6.6 Hz, 3H); dH
(enol, CDCl3) 12.54 (s, 1H); 7.78e7.75 (m, 2H), 7.60e7.45 (m, 3H),
7.00 (t, J¼4.4 Hz, 1H), 5.89 (q, J¼6.2 Hz, 1H), 5.70 (s, 1H), 2.41e2.31
(m, 4H), 2.00e1.91 (m, 2H), 1.40 (d, J¼6.2 Hz, 3H); dC (keto, CDCl3)
197.3, 192.5, 166.2, 145.1, 139.1, 136.0e126.0 (aromatics), 68.3, 46.2,
38.3, 25.6, 22.5, 15.2; dC (enol, CDCl3) 197.4, 172.0, 171.6, 144.8, 139.7,
133.3e128.5 (aromatics), 87.4, 67.0, 38.3, 25.6, 22.5, 15.3; HRMS
(EI): Mþ, found 286.1208. C17H18O4 requires 286.1205.
4.2.2. 6-Oxocyclohex-1-enylmethyl 3-oxo-3-phenylpropanoate
3b. Viscous yellow liquid (1.156 g, 85% yield); Rf (60% Et2O/petro-
leum ether) 0.40; n
(CHCl3) 3550, 1742, 1675, 1629, 1451 cmꢁ1; keto
(81%)-enol (19%); dH (keto, CDCl3) 7.94e7.90 (m, 2H), 7.61e7.33 (m,
3H), 6.99 (t, J¼4.0 Hz, 1H), 4.82 (s, 2H), 4.03 (s, 2H), 2.43e2.33 (m,
4H), 2.15e1.92 (m, 2H); dH (enol, CDCl3) 12.50 (s, 1H), 7.77e7.74 (m,
2H), 7.61e7.33 (m, 3H), 7.07 (t, J¼4.0 Hz, 1H), 5.70 (s, 1H), 4.88 (s,
2H), 2.43e2.33 (m, 4H), 2.15e1.92 (m, 2H); dC (keto, CDCl3)197.8,
192.4, 167.1, 148.8, 135.8, 133.7e126.0 (aromatics), 62.0, 45.8, 38.0,
25.7, 22.6; dC (enol, CDCl3) 197.9, 172.7, 171.6, 148.7, 135.8,
133.1e128.5 (aromatics), 87.1, 61.0, 38.0, 25.7, 22.6; HRMS (EI): Mþ,
found 272.1046. C16H16O4 requires 272.1049.
4.2.8. 1-(6-Oxocyclohex-1-enyl)butyl 3-oxobutanoate 3h. Yellow
liquid (1.413 g, 89% yield); Rf (60% Et2O/petroleum ether) 0.46;
n
(CHCl3) 3535, 1742, 1717, 1672 cmꢁ1; keto (91%)-enol (9%); dH (keto,
CDCl3) 6.94 (t, J¼4.0 Hz, 1H), 5.68 (t, J¼6.6 Hz, 1H), 3.49 (s, 2H),
2.45e2.40 (m, 4H), 2.26 (s, 3H), 2.00e1.95 (m, 2H), 1.65e1.60 (m,
2H), 1.34e1.26 (m, 2H), 0.90 (t, J¼7.3 Hz, 3H); dH (enol, CDCl3) 12.03
(s, 1H), 6.94 (t, J¼4.0 Hz, 1H), 5.68 (t, J¼6.6 Hz, 1H), 5.03 (s, 1H),
2.45e2.40 (m, 4H), 2.26 (s, 3H), 2.00e1.95 (m, 2H), 1.65e1.60 (m,
2H), 1.34e1.26 (m, 2H), 0.90 (t, J¼7.3 Hz, 3H); dC (keto, CDCl3) 200.7,
197.4, 166.1, 145.6, 138.4, 71.6, 50.1, 38.3, 36.4, 30.2, 25.6, 22.5, 18.6,
13.7; dC (enol, CDCl3) 198.1, 175.7, 171.6, 145.0, 139.0, 89.7, 69.8, 38.3,
36.7, 25.6, 22.5, 21.1, 18.7, 13.8; HRMS (EI): Mþ, found 252.1362.
C14H20O4 requires 252.1362.
4.2.3. 6-Oxocyclohex-1-enylmethyl 2-oxocyclopentanecarboxylate
3c. Yellow oil (0.637 g, 54% yield); Rf (80% Et2O/petroleum ether)
0.43;
n
(CHCl3) 1750, 1726, 1670 cmꢁ1; keto (100%)-enol (0%); dH
(300 MHz, CDCl3) 7.06 (t, J¼4.0 Hz, 1H), 4.88e4.76 (m, 2H), 3.19 (t,
J¼8.8 Hz, 1H), 2.48e2.41 (m, 4H), 2.34e2.22 (m, 4H), 2.21e1.81 (m,
4H); dC (75 MHz, CDCl3) 212.3, 197.9, 169.0, 148.2, 133.9, 62.0, 54.7,
38.0 (2C), 27.3, 25.7, 22.6, 20.9; HRMS (EI): Mþ, found 236.1053.
C13H16O4 requires 236.1049.
4.2.9. 1-(6-Oxocyclohex-1-enyl)butyl 3-oxo-3-phenylpropanoate
3i. Viscous yellow liquid (1.121 g, 90% yield); Rf (60% Et2O/petro-
leum ether) 0.60;
n
(CHCl3) 3540, 1740, 1674, 1632, 1452 cmꢁ1; keto
(78%)-enol (22%); dH (keto, CDCl3) 7.95e7.92 (m, 2H); 7.60e7.48 (m,
3H); 6.78 (t, J¼4.0 Hz,1H); 5.71e5.69 (m,1H); 4.04 (s, 2H); 2.41e2.29
(m, 4H); 2.00e1.93 (m, 2H); 1.65e1.57 (m, 2H); 1.34e1.20 (m, 2H);
4.2.4. 6-Oxocyclohex-1-enylmethyl 2-oxocyclohexanecarboxylate
3d. Yellow oil (1.125 g, 90% yield); Rf (60% Et2O/petroleum ether)

6326
O. Mhasni, F. Rezgui / Tetrahedron 67 (2011) 6322e6326
0.84(t, J¼6.9 Hz, 3H); dH (enol, CDCl3) 12.52(s,1H);7.79e7.76 (m, 2H);
7.60e7.48 (m, 3H); 6.93 (t, J¼4.0 Hz, 1H); 5.80 (t, J¼6.2 Hz, 1H);
5.71e5.69 (m, 1H); 2.41e2.29 (m, 4H); 2.00e1.93 (m, 2H); 1.65e1.57
(m, 2H); 1.34e1.20 (m, 2H); 0.92 (t, J¼6.9 Hz, 3H); dC (keto, CDCl3)
197.4, 192.4, 166.4, 145.4, 138.4, 136.0e126.0 (aromatics), 71.9, 46.2,
38.3, 36.4, 25.6, 22.5, 18.6, 13.7; dC (enol, CDCl3) 197.5, 172.2, 171.7,
145.1, 139.1, 133.3e128.5 (aromatics), 87.3, 70.4, 38.3, 36.7, 25.6, 22.5,
18.7,13.8;HRMS (EI):Mþ, found314.1520. C19H22O4 requires314.1518.
(m, 4H); 6.68 (s, 1H); 5.76 (s, 1H); 2.59e2.56 (m, 2H); 2.41e2.38 (m,
2H); dC (keto, CDCl3) 206.3, 192.3, 166.1, 159.4, 144.7, 137.3e126.1
(aromatics), 71.8, 46.0, 34.9, 26.7; dC (enol, CDCl3) 206.4,172.1, 171.8,
159.3, 145.3, 137.9e128.4 (aromatics), 87.0, 70.2, 34.9, 26.7; HRMS
(EI): Mþ, found 334.1201. C21H18O4 requires 334.1205.
Acknowledgements
We are grateful to the DGRST, Ministry of Higher Education,
Tunisia, for financial support of this work. We would like to thank
Dr. Philippe Kahn, University of Paris 7, for running mass spectra,
fruitful discussions and helpful suggestions.
4.2.10. Ethyl 5-oxocyclopent-1-enylmethyl malonate 5a. Yellow oil
(0.598 g, 53% yield); Rf (90% Et2O/petroleum ether) 0.57;
n (CHCl3)
1740, 1702, 1643 cmꢁ1; keto (100%)-enol (0%); dH (300 MHz, CDCl3)
7.66 (t, J¼4.0 Hz,1H), 4.84 (s, 2H), 4.21 (q, J¼6.9 Hz, 2H), 3.43 (s, 2H),
2.70e2.67 (m, 2H), 2.46e2.43 (m, 2H), 1.28 (t, J¼6.9 Hz, 3H); dC
(75 MHz, CDCl3) 207.5, 166.4, 166.2, 161.2, 140.6, 61.6, 58.9, 41.3,
34.6, 26.9, 14.0; HRMS (EI): Mþ, found 226.0839. C11H14O5 requires
226.0841.
References and notes
1. (a) Majima, K.; Takita, R.; Okada, A.; Ohshima, T.; Shibasaki, M. J. Am. Chem. Soc.
2003, 125, 15837; (b) Fraga, C. A. M.; Teixeira, L. H. P.; Menezes, C. M. S.; San-
t’Anna, C. M. R.; Ramos, M. C. K. V.; Aquino Neto, F. R.; Barreiro, E. J. Tetrahedron
2004, 60, 2745.
4.2.11. 5-Oxocyclopent-1-enylmethyl 3-oxo-3-phenylpropanoate
5b. Viscous yellow liquid (0.645 g, 50% yield); Rf (80% Et2O/petro-
2. Benetti, S.; Romagnoli, R.; De Risi, C.; Spalluto, G.; Zanirato, V. Chem. Rev. 1995,
95, 1065.
leum ether) 0.44; n
(CHCl3) 1745, 1701, 1635 cmꢁ1; keto (83%)-enol
3. Wilson, S. R.; Price, M. F. J. Org. Chem. 1984, 49, 722.
4. Gilbert, J. C.; Kelly, T. A. J. Org. Chem. 1988, 53, 449.
(17%); dH (keto, CDCl3) 7.94e7.90 (m, 2H), 7.65e7.39 (m, 4H), 4.84 (s,
2H), 4.06 (s, 2H), 2.60e2.56 (m, 2H), 2.45e2.36 (m, 2H); dH (enol,
CDCl3) 12.44 (s, 1H), 7.80e7.70 (m, 2H), 7.65e7.39 (m, 4H), 5.72 (s,
1H), 4.88 (s, 2H), 2.60e2.56 (m, 2H), 2.45e2.36 (m, 2H); dC (keto,
CDCl3) 207.5, 192.4, 167.1, 161.1, 140.5, 135.8e126.0 (aromatics),
58.9, 45.6, 34.6, 26.6; dC (enol, CDCl3) 207.6,172.6,171.8,161.3,140.9,
133.0e128.6 (aromatics), 86.8, 57.7, 34.6, 26.6; HRMS (EI): Mþ,
found 258.0896. C15H14O4 requires 258.0892.
ꢁ
5. Pericas, A; Shafir, A.; Vallribera, A. Tetrahedron 2008, 64, 9258.
6. Kondaiah, G. C. M.; Amarnath Reddy, L.; Srihari Babu, K.; Gurav, V. M.; Huge, K.
G.; Bandichhor, R.; Pratap Reddy, P.; Bhattacharya, A.; Vijaya Anand, R. Tetra-
hedron Lett. 2008, 49, 106.
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7. De Sairre, M. I.; Bronze-Uhle, E. S.; Donate, P. M. Tetrahedron Lett. 2005, 46, 2705.
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Dongare, M. K. Catal. Commun. 2004, 5, 353.
9. Chavan, S. P.; Kale, R. R.; Shivasankar, K.; Chandake, S. I.; Benjamin, S. B. Syn-
thesis 2003, 2695.
10. Chavan, S. P.; Shivasankar, K.; Sivappa, R.; Kale, R. Tetrahedron Lett. 2002, 43, 8583.
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43, 1165.
4.2.12. 5-Oxocyclopent-1-enylmethyl 2-oxocyclohexanecarboxylate
5c. Yellow oil (0.66 g, 56% yield); Rf (60% Et2O/petroleum ether)
0.50; n
(CHCl3) 1747,1703,1656,1613 cmꢁ1; keto (44%)-enol (56%); dH
13. Rezgui, F.; El Gaï, M. M. Tetrahedron Lett. 1998, 39, 5965.
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18. Et3N only catalyses the esterification of highly reactive substrates, e.g., dike-
tenes and oxazolinones, see:Esterification; Otera, J., Nishikido, J., Eds.; Wiley-
VCH: Weinheim, Germany, 2010; p 79.
(keto, CDCl3) 7.71 (t, J¼4.0 Hz, 1H), 4.94e4.76 (m, 2H), 3.48e3.42 (m,
1H), 2.69e2.64 (m, 2H), 2.52e2.38 (m, 4H), 2.18e2.10 (m, 2H),
1.77e1.59 (m, 4H); dH (enol, CDCl3) 12.05 (s,1H), 7.60 (t, J¼4.0 Hz,1H),
4.94e4.76 (m, 2H), 2.69e2.64 (m, 2H), 2.52e2.38 (m, 2H), 2.29e2.23
(m, 4H), 1.77e1.59 (m, 4H); dC (keto, CDCl3) 207.6, 206.2, 169.6, 161.0,
140.8, 58.7, 57.1, 34.7, 30.0, 27.1, 26.9, 23.4 (2C); dC (enol, CDCl3) 207.7,
172.7, 172.1, 160.6, 141.3, 97.4, 57.8, 41.6, 34.7, 29.1, 26.9, 22.3, 21.8;
HRMS (EI): Mþ, found 236.1049. C13H16O4 requires 236.1049.
19. (a) Martin Castro, A. M. Chem. Rev. 2004, 104, 2939; (b) Li, J. J. Name Reactions,
4th ed.; Springer: Berlin, 2009.
20. (a) Litivinenko, L. M.; Kirichenko, A. I. Dokl. Akad. Nauk SSSR 1967, 176, 97; (b)
€
€
Steglich, W.; Hofle, G. Angew. Chem., Int. Ed. Engl. 1969, 8, 981; (c) Hofle, G.;
Steglich, W. Synthesis 1972, 619.
€
21. For selected reviews on applications of DMAP, see: (a) Hofle, G.; Steglich, W.;
€
Vorbruggen, H. Angew. Chem., Int. Ed. Engl. 1978, 17, 569; (b) Scriven, E. F. V.
4.2.13. 1-(5-Oxocyclopent-1-enyl)butyl 3-oxo-3-phenylpropanoate
Chem. Soc. Rev. 1983, 12, 129; (c) Ragnarsson, U.; Grehn, L. Acc. Chem. Res. 1998,
31, 494; (d) Grondal, C. Synlett 2003, 1568; (e) Spivey, A. C.; Arseniyadis, S.
Angew. Chem., Int. Ed. 2004, 43, 5436; (f) Hassner, A. In Encyclopedia of Reagents
for Organic Synthesis; Paquette, L. A., Ed.; Wiley: Chichester, UK, 1995; p 2022.
22. (a) Inanaga, J.; Hirata, K.; Saeki, H.; Katsuki, T.; Yamaguchi, M. Bull. Chem. Soc.
Jpn. 1979, 52, 1989; (b) Boden, E. P.; Keck, G. E. J. Org. Chem. 1985, 50, 2394.
23. Chaudhary, S. K.; Hernandez, O. Tetrahedron Lett. 1979, 20, 99.
5d. Viscous yellow liquid (1.335 g, 89% yield); Rf (60% Et2O/petro-
leum ether) 0.48;
n
(CHCl3) 1741, 1697, 1637 cmꢁ1; keto (82%)-enol
(18%); dH (keto, CDCl3) 7.95e7.92 (m, 2H); 7.60e7.41 (m, 4H);
5.61e5.57 (m 1H); 4.09e4.03 (m, 2H); 2.56e2.54 (m, 2H); 2.41e2.38
(m, 2H); 1.72e1.67 (m, 2H); 1.29e1.25 (m, 2H); 0.90e0.85 (m, 3H);
dH (enol, CDCl3) 12.46 (s, 1H); 7.77e7.76 (m, 2H); 7.60e7.41 (m, 4H);
5.72e5.70 (m, 2H); 2.56e2.54 (m, 2H); 2.41e2.38 (m, 2H); 1.72e1.67
(m, 2H); 1.29e1.25 (m, 2H); 0.90e0.85 (m, 3H); dC (keto, CDCl3)
207.2, 192.6, 166.7, 159.0, 144.8, 136.0e126.1 (aromatics), 70.8, 46.1,
35.2 (2C), 26.6, 18.3, 13.7; dC (enol, CDCl3) 207.3, 172.4, 171.9, 158.8,
145.5,133.4e128.6 (aromatics), 87.2, 69.3, 35.5, 35.2, 26.6,18.6,13.8;
HRMS (EI): Mþ, found 300.1369. C18H20O4 requires 300.1362.
24. The pKa values (25 ꢀC) are taken from (a) (DMAP and 2,6-lutidine) Chrystuik, E.;
Williams, A. J. Am. Chem. Soc. 1987, 109, 3040; (b) (Triethylamine) Kuna, S.;
Pawlak, Z.; Tusk, M. J. Chem. Soc., Faraday Trans. 1982, 78, 2685; (c) For related
ꢀ
reactions using DBU, see: Price, K. E.; Larrivee-Aboussafy, C.; Lillie, B. M.;
McLaughlin, R. W.; Mustakis, J.; Hettenbach, K. W.; Hawkins, J. M.; Vaidyana-
than, R. Org. Lett. 2009, 11, 2003.
25. (a) Taira, S.; Danjo, H.; Imamoto, T. Tetrahedron Lett. 2002, 43, 2885; (b) Boger,
D. L.; Ichikawa, S.; Zhong, W. J. Am. Chem. Soc. 2001, 123, 4161; (c) Oliveira, D. F.;
Miranda, P. C. M. L.; Correia, C. R. D. J. Org. Chem. 1999, 64, 6646.
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66, 5016.
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54, 13237; (d) Sasidharan, M.; Kumar, R. J. Mol. Catal. A: Chem. 2004, 210, 93; (e)
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Tetrahedron Lett. 2007, 48, 2231.
4.2.14. (5-Oxocyclopent-1-enyl)phenylmethyl 3-oxo-3-phenylpropan-
oate 5e. Viscous yellow liquid (1.052 g, 63% yield); Rf (80% Et2O/
petroleum ether) 0.53; n
(CHCl3) 1744, 1700, 1635 cmꢁ1; keto (82%)-
enol (18%); dH (keto, CDCl3) 7.93e7.90 (m, 2H); 7.58e7.27 (m, 4H);
6.57 (s, 1H); 4.04 (AB, J¼15.4 Hz, 2H); 2.59e2.56 (m, 2H); 2.41e2.38
(m, 2H); dH (enol, CDCl3) 12.34 (s, 1H); 7.78e7.74 (m, 2H); 7.58e7.27
28. (a) Witzeman, J. S. Tetrahedron Lett. 1990, 31, 1401; (b) Witzeman, J. S.; Not-
tingham, W. D. J. Org. Chem. 1991, 56, 1713.