Baylis-Hillman reaction promoted by a recyclable protic-ionic-liquid solvent-catalyst system: DABCO-AcOH-H2O

Article abstract of DOI:10.1016/j.tet.2009.09.049

A recyclable protic-ionic-liquid solvent-catalyst system, DABCO-AcOH-H₂O, has been developed and used in the Baylis-Hillman reaction of aromatic aldehydes, aliphatic aldehydes, and cinnamaldehydes with acrylates and acrylonitrile, showing compa

Full text of DOI:10.1016/j.tet.2009.09.049

Tetrahedron 65 (2009) 9086–9090
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Baylis–Hillman reaction promoted by a recyclable protic-ionic-liquid
solvent–catalyst system: DABCO–AcOH–H2O
*
Ying Song, Haihua Ke, Nan Wang, Limin Wang, Gang Zou
Department of Fine Chemicals, East China University of Science and Technology, 130 Meilong Rd., Shanghai 200237, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 7 June 2009
Received in revised form 6 September 2009
Accepted 11 September 2009
Available online 15 September 2009
A recyclable protic-ionic-liquid solvent–catalyst system, DABCO–AcOH–H2O, has been developed and
used in the Baylis–Hillman reaction of aromatic aldehydes, aliphatic aldehydes, and cinnamaldehydes
with acrylates and acrylonitrile, showing comparable performance to free DABCO in traditional solvents.
The DABCO–AcOH–H2O solvent–catalyst system could be reused for at least five times without signifi-
cant loss of activity.
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
Baylis–Hillman reaction
Protic ionic liquid
Solvent catalyst
DABCO
1. Introduction
effects of both substrates and catalysts observed in Baylis–Hillman
reaction. Protic-ionic-liquids (PILs), liquid Brønsted acid–base salts
The Baylis–Hillman reaction, a tertiary amine catalyzed car-
bon–carbon bond forming reaction of an aldehyde with an a,b-
that could be readily formed by simple combination of a proper
Brønsted acid with a Brønsted base, have proven to be the most
practical ionic liquid solvent–catalysts and have been successfully
used in a wide range of Brønsted acid catalyzed organic reactions.13
However, to the best of our knowledge, there is no report on protic-
ionic-liquid promoted Baylis–Hillman reaction. Herein we describe
the development of a recyclable protic-ionic-liquid solvent–catalyst
system, DABCO–AcOH–H2O, for Baylis–Hillman reaction of aromatic
and aliphatic aldehydes and cinnamaldehydes with acrylates and
acrylonitrile.
unsaturated carbonyl compound, is an atom-economical reaction
going cleanly under very mild condition yet producing a highly
functionalized adduct.1 However, there is a major drawback, slow
reaction rate, associated with this important reaction. It is often
reported that days or even weeks have been required for the re-
action to complete. Therefore, a number of efforts have been made
to accelerate Baylis–Hillman reaction, including use of Lewisacids,2
ionic liquids,3 and H-bond donors,4 application of solvent-free,5
high pressure,6 ultrasound,7 and microwave8 techniques as well as
development of highly active catalysts.9 Most of these efforts were
just successful for a limited number of substrates. At present, the
most general and practical technique to accelerate Baylis–Hillman
reaction is the use of high loading, especially use of stoichiometric
or excess amount,10 of tertiary amine catalyst. For practical point
of view, it is necessary to recycle or, at least, recover the tertiary
amine catalysts when used in stoichiometric or excess amount.
Although soluble polymer-supported catalysts have recently been
explored in Baylis–Hillman reaction,11 utility of recyclable ionic
liquid dual solvent–catalysts12 that serve as both solvent and
catalyst looks like a more promising choice for making Baylis–
Hillman reaction more practical due to the strong concentration
2. Results and discussion
During our investigation of Baylis–Hillman reaction catalyzed by
1,4-diazabicyclic [2,2,2]octane (DABCO), we noticed that the re-
action with stock benzaldehyde contaminated with benzoic acid
proceeded as well as that with fresh-distilled acid-free benzalde-
hyde (Scheme 1).
OH
O
20mol%
DABCO
O
PhCHO
OnBu
+
Ph
OnBu
(PhCO2H)
CH3CN
rt. 5days
100%
88%
74%
( 0% )
82%
(91% based on PhCHO)
( 18% )
* Corresponding author. Tel.: þ86 21 64253881; fax: þ86 21 64252288.
E-mail address: zougang@ecust.edu.cn (G. Zou).
Scheme 1.
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.09.049

Y. Song et al. / Tetrahedron 65 (2009) 9086–9090
9087
The innocence of benzoic acid in the reaction was attributed to
the fact that Baylis–Hillman reaction is mainly promoted by the
nucleophilicity instead of basicity of a tertiary amine. Therefore, we
envision that it would be possible to develop a protic-ionic-liquid of
DABCO with a proper Brønsted acid as recyclable catalyst for Baylis–
Hillman reaction. It was explored at first that catalytic efficacy of
Brønsted acid salts of DABCO using the reaction of p-nitro-
benzaldehyde (1a) with butyl acrylate (2a) as model considering its
easy monitoring and fast reaction rate (Table 1).
Baylis–Hillman reaction of aromatic aldehydes with acrylates pro-
ceeded efficiently in dioxane even at lowconcentration of aldehydes
(0.1 M),10a however, the isolated yield of adduct 3aa was lower with
DABCO–AcOH salt using dioxane as co-solvent than those using
CH3CN and DMF (Table 1, entries 8–10). Similar to free DABCO,
a large concentration effect was observed in the reaction using
DABCO–AcOH salt. When the concentration of aldehyde 1a was
lower than 0.05 M the reaction became sluggish. Low temperature
slightly benefited the reaction but to a much less degree than that
reported in literature (Table 1, entry 13).15
There are reports that aqueous condition accelerated Baylis–
Hillman reaction.4a,10b,16 Therefore, some water (5 equiv) was de-
liberately added to the reaction mixture, but no remarkable
difference with respect to reaction rate and product yield was ob-
served. However, during our recovering the DABCO–AcOH salt, we
noticed that the recovered DABCO–AcOH was a liquid instead of
a crystalline material although no difference, expect for the peak
assigned to water, could be detected between the 1H NMR spectra
of recovered and separately prepared samples, implying a strong
freezing-point-depression by a small amount water for DABCO–
AcOH salt. In fact, it has been well known that some organic salts
melt at much lower temperature with a small amount of water or in
the form of hydrates. In our previous work, we have developed
ionic liquid media from high-melting-point organic ammonium
salts by adding a small amount of water.17 Therefore, we in-
vestigated the effects of small amount of water on melting point of
the DABCO–AcOH salt. A colorless viscous liquid formed at room
temperature when DABCO hydrate (1.7H2O), which was prepared
by crystallization from water, was mixed with 1 equiv AcOH.
However, the liquid DABCO$1.7H2O–AcOH was too viscous to be
used as reaction medium at room temperature. When the amount
of water in the DABCO–AcOH salt was increased to 3–5 equiv vis-
cosity of the corresponding liquid, 1/1/3–5 (mol) DABCO–AcOH–
H2O, significantly decreased at room temperature. The model
reaction of p-nitrobenzaldehyde with butyl acrylate was then in-
vestigated using this DABCO–AcOH–H2O solvent–catalyst system
(Table 2).
Table 1
Baylis–Hillman reaction of p-nitrobenzaldehyde with butyl acrylate promoted by
DABCO salts of weak organic acidsa
O
OH
O
OnBu
OnBu
H
DABCO
solvent, rt
+
O
O2N
O2N
1a
2a
3aa
Entry
Catalyst
Solvent
Time (h)
Yieldb (%)
1
2
3
4
5
6
7
8
0.2 equiv DABCO
0.2 equiv DABCO–PhCO2H
1.0 equiv DABCO
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
DMF
MeOH
Dioxane
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
d
18
18
9
84
90
94
95
21
88
95
96
15
81
91
93
90
10
12
52
19
90
1.0 equiv DABCO–PhCO2H
1.0 equiv DABCO–2PhCO2H
0.2 equiv DABCO–AcOH
1.0 equiv DABCO–AcOH
1.0 equiv DABCO–AcOH
1.0 equiv DABCO–AcOH
1.0 equiv DABCO–AcOH
1.0 equiv DABCO–EtCO2H
1.0 equiv DABCO–tBuCO2H
1.0 equiv DABCO–AcOH
1.0 equiv DABCO
9
18
18
9
9
9
18
18
9
9
6
24
24
12
12
12
10
11
12
13c
14d
15d
16e
17e
18
1.0 equiv DABCO–AcOH
1.0 equiv DABCO–AcOH
1.0 equiv DABCO
CH3CN
CH3CN
DABCO–AcOH–5H2O
a
Reaction run at 1.0 mmol scale with respect to 1a in 2 mL solvent.
Isolated yields and 1a recovered.
b
c
Run at 0–5 ꢀC.
d
e
20 mL CH3CN used.
Run at 80 ꢀC and 1a decomposed in stead of being recovered.
Table 2
Baylis–Hillman reaction of p-nitrobenzaldehyde with butyl acrylate promoted by
DABCO–AcOH–H2Oa
Catalystb
Co-solventc
Time (h)
Yield (%)
With the almost neutral DABCO benzoic acid salt (pHz7–8),
Entry
DABCO–PhCOOH, at both catalytic (20 mol %) and stoichiometric
amounts the model reaction even proceeded slightly faster than
that with free DABCO at the early stage of the reaction progress
(<50% conversion by TLC) although this acceleration diminished
along with the increase of the conversion of aldehyde 1a. When the
salt of DABCO–2PhCO2H was used the reaction became sluggish
under the otherwise identical conditions although it was reported
that Baylis–Hillman reaction could proceed under aqueous acidic
condition with tertiary amine catalysts14 (Table 1, entries 1–5). The
other DABCO salts of weak organic acids such as CH3CO2H, EtCO2H,
and tBuCO2H showed comparable efficacy to both DABCO–PhCOOH
and free DABCO (Table 1, entries 7, 11 and 12). However, the DABCO
salts of stronger acids such as H3PO4, TsOH, and CF3CO2H displayed
no activity. Unfortunately, no one of these DABCO salts tested is
liquid at room temperature (20–25 ꢀC), the most practical temper-
ature range for DABCO-promoted Baylis–Hillman reaction. When
the reaction was conducted at high temperature (80 ꢀC) at which
the DABCO–CH3CO2H salt could be used as both catalyst and me-
dium the isolated yield of adduct 3aa decreased significantly albeit
much better than that using free DABCO in CH3CN (Table 1, entries
16 and 17). Therefore an organic co-solvent has to be used for the
reaction at room temperature. The reaction occurred very slowly
using methanol as co-solvent while a fast reaction was observed
using DMF and CH3CN. It was reported that DABCO-catalyzed
1
2
3
4
5
6
7
DABCO–AcOH–5H2O
DABCO–AcOH–10H2O
DABCO$1.7H2O–AcOH
DABCO–AcOH–3H2O
DABCO–AcOH–10H2O
DABCO–AcOH–3H2O
DABCO–AcOH–3H2O
DABCO–AcOH–3H2O
First Recycle
Second Recycle
Third Recycle
Fourth Recycle
Fifth Recycle
d
12
12
6
6
12
6
6
4
4
4
86
55
96
94
73
95
83
97
96
95
93
96
95
d
0.8 mL CH3CN
0.8 mL CH3CN
3.5 mL CH3CN
0.5 mL DMF
1.8 mL dioxane
0.8 mL CH3CN
0.8 mL CH3CN
0.8 mL CH3CN
0.8 mL CH3CN
0.8 mL CH3CN
0.8 mL CH3CN
8d
9d
10
11
12
13
4
4
4
a
Reaction run at 1.0 mmol scale with respect to 1a.
1.0 equiv used based on DABCO.
The minimum amount added to form a homogeneous solution.
2.0 equiv used based on DABCO.
b
c
d
With DABCO–AcOH–3H2O as both catalyst and solvent the re-
action of p-nitrobenzaldehyde with butyl acrylate (3 equiv) gave
Baylis–Hillman adduct in 86% yield for 12 h, which is slightly slower
than the reaction with free DABCO in CH3CN (2 mL, c¼0.5 M) due to
the limited solubility of p-nitrobenzaldehyde in the DABCO–AcOH–
3H2O solvent–catalyst system. The reaction rate decreased further
in DABCO–AcOH–10H2O (Table 2, entries 1 and 2) and a biphasic
mixture was observed. Therefore, some CH3CN (0.8 mL) was added

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Y. Song et al. / Tetrahedron 65 (2009) 9086–9090
as co-solvent to form homogeneous solution and the reaction rate
restored giving the desired adduct in 94% yield in 6 h with DABCO–
AcOH–3H2O. Using DMF (0.5 mL) as co-solvent gave a comparable
result to that of CH3CN while a slower reaction was observed using
dioxane (Table 2, entries 4, 6 and 7). The reaction could complete
in 4 h with 2 equiv loading of DABCO–AcOH–3H2O.
reaction rate while a substituent on the carbon–carbon double
bond blocked the reaction. For example, reaction of p-nitro-
benzaldehyde with tert-butyl acrylate gave the corresponding ad-
duct in 72% yield for 48 h, much slower than the reaction of methyl
or n-butyl acrylates, which gave adducts in about 96–97% yields in
4 h (Table 3, entries 1 and 2). No reaction occurred for methyl
crotonate under the otherwise identical conditions. Acrylonitrile
reacted with p-nitrobenzaldehyde similarly to that of methyl and
butyl acrylates (Table 3, entries 1 and 3). Interestingly, reaction of
acrylonitrile with benzaldehyde proceeded significantly faster us-
ing DMF as co-solvent (Table 3, entry 7). Cinnamaldehyde and p- or
o-methoxycinnamaldehydes also reacted smoothly in the DABCO–
AcOH–H2O promoted Baylis–Hillman reaction (Table 3, entries
14–16). The reaction of p-nitrocinnamaldehyde with butyl acrylate
completed in 6 h, but the adduct was rather thermally unstable and
decomposed before full characterization. Aliphatic aldehydes, such
as 3-phenylpropionaldehyde and octyl aldehyde, reacted similarly
to the electron-neutral aromatic aldehydes, giving the corre-
sponding adducts in 67% and 41% yields, respectively, in 48 h (Table
3, entries 17–18). However, aldimines such as N-(p-methyl-
benzenesulfonyl) benzaldimine decomposed immediately to give
benzaldehyde upon contacting with DABCO–AcOH–H2O.
In summary, a recyclable protic-ionic-liquid solvent–catalyst
system, DABCO–AcOH–H2O, has been developed and used in the
Baylis–Hillman reaction of aromatic aldehydes, aliphatic aldehydes,
and cinnamaldehydes with acrylates and acrylonitrile. The protic-
ionic-liquid could be readily prepared by simply mixing the
components of DABCO, AcOH, and water at given ratios. The Baylis–
Hillman reaction promoted by the protic-ionic-liquid solvent–
catalyst system proceeded as well as that with free DABCO. The
DABCO–AcOH–H2O solvent–catalyst system could be recycled for at
least 5 times showing no significant loss of activity.
The recyclability of DABCO–AcOH–H2O solvent–catalyst system
was then investigated. After completion of the reaction, toluene
(10 mL) was added to dilute the reaction mixture and dissolve the
Baylis–Hillman adduct. The protic-ionic-liquid solvent–catalyst,
DABCO–AcOH–H2O, separated from the toluene phase. However,
there was still some DABCO–AcOH residue in the toluene phase.
Extraction of the toluene phase with water (5 mL) followed by re-
moval of water from the aqueous phase by rotavapour led to
complete recovering of the protic-ionic-liquid. Alternatively, water
(5 mL) and toluene (10 mL) were added to the reaction mixture
after completion of the reaction to dissolve the organics and the
DABCO–AcOH salt in toluene and water, respectively. No DABCO–
AcOH residue was detected in the organic phase using this work-up
procedure. Removal of extra water from the aqueous phase re-
covered the DABCO–AcOH–H2O solvent–catalyst system, which has
been reused for five times showing no significant loss of activity
(Table 2, entries 8–13).
Scope of the DABCO–AcOH–H2O solvent–catalyst system pro-
moted Baylis–Hillman reaction was explored (Table 3). Similar to
the Baylis–Hillman reaction with free DABCO, electron-neutral
aldehydes, such as benzaldehyde, p-methyl- and p-halogen-benz-
aldehydes, furaldehyde and electron-deficient aldehydes such as p-,
m-, and o-nitrobenzaldehydes (Table 3, entries 4–6 and 8–11),
reacted with methyl and butyl acrylates smoothly to give adducts in
good to excellent yields in reasonable time while electron-rich one,
p-methoxy benzaldehyde, reacted much slower (Table 3, entry 12).
3. Experimental
3.1. General
Table 3
Scope of the DABCO–AcOH–H2O solvent–catalyst promoted Baylis–Hillman
reactiona
OH
DABCO-AcOH-H2O
25 °C
EWG
All manipulations were carried out in the air. All commercially
available chemicals were used as-received. Products were identified
by NMR spectroscopy and HRMS.1H NMR (500 or 400 MHz),13C{1H}
NMR (125 or 100 MHz) spectra were recorded at ambient temper-
atures, using CDCl3 as solvent. 1H and 13C{1H} NMR chemical shifts
were reported in ppm relative to internal Me4Si or residue of CDCl3.
Mass spectra were obtained at an ionization potential of 70 eV.
R
EWG
2a-d
+
R
CHO
1a-o
3ab-ob
Entry
R
EWG
Time (h)
Yield (%)
1
2
3
4
5
6
7
8
p-NO2C6H4 (1a)
p-NO2C6H4 (1a)
p-NO2C6H4 (1a)
o-NO2C6H4 (1b)
m-NO2C6H4 (1c)
C6H5 (1d)
Me (2b)
Me3C (2c)
CN (2d)
Bu (2a)
Bu (2a)
Bu (2a)
CN (2d)
Me (2b)
Bu (2a)
Bu (2a)
Bu (2a)
Bu (2a)
Bu (2a)
Bu (2a)
Bu (2a)
4
48
4
96
72
92
97
6
12
48
24
48
48
48
48
48
24
48
56
76
48
48
98
3.2. Preparation of 1,4-diazabicyclic [2,2,2]octane hydrate
(DABCO$1.7H2O)
82(79)c
91b(71)c
70
C6H5 (1d)
p-ClC6H4 (1e)
p-CH3C6H4 (1f)
p-BrC6H4 (1g)
Commercially available DABCO (11.2 g) (Indeed, the commercial
DABCO from Alfa Aesar is partly hydrate) was dissolved in pure
water (50 mL) at 80 ꢀC. The solution was cooled to room temper-
ature to form a colorless crystalline material, which was filtrated
and dried in air. Elemental analyses showed that DABCO hydrate
contained 1.7H2O per molecule. Cacld for C6H12N2$1.7H2O: C, 50.47;
H, 10.87; N, 19.62; found: C, 50.24; H, 10.65; N, 19.75.
9
69c
87(85)c
89c
29
10
11
12
13
14
15
16
17
18
Furaldehyde (1h)
p-CH3OC6H4 (1i)
p-CHOC6H4 (1j)
trans-C6H5CH]CH (1k)
p-MeOC6H4CH]CH (1l)
69
63
22
38
67
41
o-MeOC6H4CH]CH (1m)
PhCH2CH2CHO (1n)
CH3(CH2)6CHO (1o)
Bu (2a)
Me (2b)
Me (2b)
3.3. General procedure for Baylis–Hillman reaction
a
Reaction run at 1.0 mmol scale with respect to 1a, using 2.0 equiv DABCO–
AcOH–3H2O based on DABCO and 0.8 mL CH3CN as co-solvent.
To a flask (10 mL) containing 0.5 g DABCO–AcOH–H2O (1/1/3 mol
ratio) (2 mmol based on DABCO) composite were added aldehyde
(1 mmol) and acrylate or acrylonitrile (3mmole) at room tempera-
ture (ca. 20 ꢀC). A few drops (about 0.5 mL) of CH3CN were added to
the mixture to form a homogeneous solution. (For liquid aldehydes
the co-solvent such as CH3CN was not necessary provided that
a homogeneous solution formed by the reaction mixture itself). The
reaction mixture was stirred at room temperature monitored by TLC
b
1.0 mL DMF as co-solvent.
No co-solvent used.
c
It is noteworthy to point out that for liquid aldehydes no co-
solvent, such as CH3CN or DMF is necessary. Terephthalaldehyde
reacted with butyl acrylate affording mono-adduct in 69% yield
while phthaldialdehyde gave a complicated mixture (Table 3, entry
13). The size of alkoxyl group of acrylates showed influences on

Y. Song et al. / Tetrahedron 65 (2009) 9086–9090
9089
until aldehyde was consumed. Then the reaction mixturewas diluted
with water (5 mL) and extracted with toluene (2ꢁ10 mL). The tolu-
ene extract was dried with Na2SO4, filtered and concentrated. The
resulting residue was purified by flash column chromatography to
offer the Baylis–Hillman adducts.
129.03, 126.68, 125.23, 72.79, 64.67, 30.52, 21.09, 19.10, 13.66. HREI-
MS m/z: calcd for C15H20O3: 248.1412, found: 248.1414.
3.3.9. 2-Hydroxyl-2-(4-bromophenyl)methyl acrylic acid butyl ester
1
(3ga). H NMR (500 MHz, CDCl3, 25 ꢀC),
d
(ppm): 7.46 (d, J¼8.4 Hz,
2H), 7.24 (d, J¼8.4 Hz, 2H), 6.33 (s, 1H), 5.81 (s, 1H), 5.48 (d,
J¼5.1 Hz, 1H, CHOH), 4.11 (t, J¼6.6 Hz, 2H), 3.25 (d, J¼5.6 Hz, 1H,
OH), 1.74–1.56 (m, 2H), 1.35–1.28 (m, 2H), 0.90 (t, J¼7.4 Hz, 3H). 13C
3.3.1. 2-Hydroxyl-2-(4-nitrophenyl)methyl acrylic acid butyl ester
(3aa)18 1H NMR (400 MHz, CDCl3, 25 ꢀC),
. d (ppm): 8.22 (d,
J¼8.4 Hz, 2H, Ar), 7.59 (d, J¼8.8 Hz, 2H, Ar), 6.41 (s, 1H), 5.87 (s, 1H),
5.63 (s, 1H, CHOH), 4.15 (t, J¼6.4 Hz, 2H), 3.43 (br s, 1H, OH), 1.66–
1.56 (m, 2H), 1.39–1.30 (m, 2H), 0.92 (t, J¼7.6 Hz, 3H). 13C NMR
NMR (125 MHz, CDCl3, 25 ꢀC),
d (ppm): 166.14, 141.98, 140.63,
131.41, 128.48, 125.79, 121.62, 72.31, 64.87, 30.46, 19.09, 13.67. HREI-
MS m/z: calcd for C14H17O3Br 312.0361, found: 312.0363.
(100 MHz, CDCl3, 25 ꢀC),
d (ppm): 166.01, 148.79, 147.40, 141.23,
127.35, 126.97, 123.58, 72.71, 65.16, 30.44, 19.08, 13.61.
3.3.10. 2-Hydroxyl-2-(4-methoxyphenyl)methyl acrylic acid butyl
1
ester (3ia). H NMR (500 MHz, CDCl3, 25 ꢀC),
d (ppm): 7.27 (d,
3.3.2. 2-Hydroxyl-2-(4-nitrophenyl)methyl acrylic acid methyl ester
J¼8.7 Hz, 2H), 6.86 (d, J¼8.6 Hz, 2H), 6.31 (s,1H), 5.84 (s,1H), 5.51 (s,
1H, CHOH), 4.14–4.07 (m, 2H), 3.78 (s, 3H), 3.09 (s, 1H, OH), 1.61–
1.55 (m, 2H), 1.34–1.26 (m, 2H), 0.89 (t, J¼7.4 Hz, 3H). 13C NMR
(3ab)18 1H NMR (400 MHz, CDCl3, 25 ꢀC),
. d (ppm): 8.19 (d,
J¼8.8 Hz, 2H, Ar), 7.57 (d, J¼8.8 Hz, 2H, Ar), 6.40 (s, 1H), 5.90 (s, 1H),
5.63 (s, 1H, CHOH), 3.74 (s, 3H), 3.49 (br s, 1H, OH). 13C NMR
(125 MHz, CDCl3, 25 ꢀC),
d (ppm): 166.44, 159.16, 142.50, 133.66,
(100 MHz, CDCl3, 25 ꢀC),
d
(ppm): 166.30, 148.93, 147.24, 141.14,
128.01, 125.20, 113.76, 72.61, 64.73, 55.21, 30.50, 19.09, 13.67. HREI-
127.47, 127.01, 123.52, 72.12, 52.14.
MS m/z: calcd for C15H20O4: 264.1362, found: 264.1363.
3.3.3. 2-Hydroxyl-2-(4-nitrophenyl)methyl acrylic acid tert-butyl
3.3.11. 2-Hydroxyl-2-(4-formylphenyl)methyl acrylic acid butyl ester
1
ester (3ac)19
.
1H NMR (400 MHz, CDCl3, 25 ꢀC),
d
(ppm): 8.20 (d,
(3ja). H NMR (400 MHz, CDCl3, 25 ꢀC),
d
(ppm): 9.94 (s, 1H, CHO),
J¼8.8 Hz, 2H, Ar), 7.57 (d, J¼8.8 Hz, 2H, Ar), 6.31 (s, 1H), 5.76 (s, 1H),
7.81 (d, J¼8.0 Hz, 2H), 7.52 (d, J¼7.6 Hz, 2H), 6.35 (s,1H), 5.86 (s,1H),
5.58 (s, 1H, CHOH), 4.08 (t, J¼6.4 Hz, 2H), 3.67–3.62 (m, 1H, OH),
1.59–1.52 (m, 2H), 1.32–1.23 (m, 2H), 0.86 (t, J¼7.6 Hz, 3H). 13C NMR
5.57 (d, J¼4.8 Hz, 1H, CHOH), 3.54 (br s, 1H, OH), 1.42 (s, 9H). 13C
NMR (100 MHz, CDCl3, 25 ꢀC),
d (ppm): 165.27, 149.08, 147.31,
142.29, 127.28, 126.54, 123.54, 82.35, 72.93, 27.95.
(100 MHz, CDCl3, 25 ꢀC),
d (ppm): 192.14, 165.95, 148.66, 141.83,
135.60, 129.78, 127.30, 126.14, 72.37, 64.84, 30.37, 19.00, 13.58.
HREI-MS m/z: calcd for C15H18O4: 262.1205, found: 262.1206.
3.3.4. 2-Hydroxyl-2-(4-nitrophenyl)methyl acrylonitrile (3ad)20
.
1H
NMR (400 MHz, CDCl3, 25 ꢀC),
d
(ppm): 8.23 (d, J¼8.8 Hz, 2H, Ar),
7.60 (d, J¼8.8 Hz, 2H, Ar), 6.19 (s, 1H), 6.10 (s, 1H), 5.45 (s, 1H,
3.3.12. (E)-Butyl 3-hydroxy-5-phenyl-2-methylenepent-4-enoate
13
1
CHOH), 3.57 (br s, 1H, OH). C NMR (100 MHz, CDCl3, 25 ꢀC),
(3ka). H NMR (500 MHz, CDCl3, 25 ꢀC),
d
(ppm): 7.38 (d, J¼7.4 Hz,
d
(ppm): 147.86, 146.35, 131.50, 127.41, 125.30, 124.02, 116.44, 73.1.
2H), 7.31 (t, J¼7.4 Hz, 2H), 7.24 (t, J¼7.4 Hz, 1H), 6.66 (d, J¼15.9 Hz,
1H), 6.30 (dd, J1¼16.8 Hz, J1¼6.3 Hz, 2H), 5.90 (s, 1H), 5.13 (dd,
J1¼J2¼6.1 Hz,1H, CHOH), 4.19 (t, J¼6.6 Hz, 2H), 3.07 (d, J¼6.1 Hz,1H,
OH), 1.72–1.63 (m, 2H), 1.44–1.37 (m, 2H), 0.93 (t, J¼7.4 Hz, 3H). 13C
3.3.5. 2-Hydroxyl-2-(2-nitrophenyl)methyl acrylic acid butyl ester
1
(3ba)21. H NMR (400 MHz, CDCl3, 25 ꢀC),
d (ppm): 7.97 (d,
J¼8.4 Hz, 1H, Ar), 7.75 (d, J¼8.0 Hz, 1H, Ar), 7.66 (t, J¼7.6 Hz, 1H, Ar),
7.48 (t, J¼8.0 Hz,1H, Ar), 6.40 (s, 1H), 6.19 (s, 1H), 5.77 (s, 1H, CHOH),
4.18–4.08 (m, 2H), 3.50 (br s, 1H, OH), 1.61–1.54 (m, 2H), 1.33–1.24
NMR (125 MHz, CDCl3, 25 ꢀC),
d (ppm): 166.40, 141.79, 136.58,
131.30, 129.52, 128.55, 127.77, 126.61, 125.38, 71.73, 64.85, 30.60,
19.22, 13.71. HREI-MS m/z: calcd for C16H20O3: 260.1412, found:
260.1415.
13
(m, 2H), 0.90 (t, J¼7.6 Hz, 3H). C NMR (100 MHz, CDCl3, 25 ꢀC),
d
(ppm): 166.31, 148.57, 141.76, 136.87, 133.76, 129.25, 128.93,
125.42, 124.83, 67.50, 65.33, 30.74, 19.35, 13.95.
3.3.13. (E)-Butyl 3-hydroxy-5-(4-methoxyphenyl)-2-methylene pent-
1
4-enoate (3la). H NMR (400 MHz, CDCl3, 25 ꢀC),
d (ppm): 7.34 (d,
3.3.6. 2-Hydroxyl-2-(3-nitrophenyl)methyl acrylic acid butyl ester
J¼8.4 Hz, 2H), 6.87 (d, J¼8.8 Hz, 2H), 6.62 (d, J¼16.0 Hz, 1H), 6.30 (s,
1H), 6.18 (dd, J1¼16.0 Hz, J1¼6.8 Hz, 1H), 5.91 (s, 1H), 5.12 (dd,
J1¼J1¼6.4 Hz, 1H, CHOH), 4.21 (t, J¼6.8 Hz, 2H), 3.82 (s, 3H), 2.97 (d,
(3ca)19 1H NMR (400 MHz, CDCl3, 25 ꢀC),
. d (ppm): 8.27 (s, 1H, Ar),
8.17–8.15 (dd, J1¼8.4 Hz, J2¼1.6 Hz,1H, Ar), 7.76 (d, J¼7.6 Hz,1H, Ar),
7.54 (t, J¼8.0 Hz, 1H, Ar), 6.42 (s, 1H), 5.91 (s, 1H), 5.64 (d, J¼6.4 Hz,
1H, CHOH), 4.15 (t, J¼6.8 Hz, 2H), 3.42–3.40 (m, 1H, OH), 1.66–1.59
(m, 2H),1.39–1.30 (m, 2H), 0.92 (t, J¼7.6 Hz, 3H). 13C NMR (100 MHz,
J¼6.4 Hz, 1H, OH), 1.70–1.65 (m, 2H), 1.47–1.38 (m, 2H), 0.95 (t,
13
J¼7.6 Hz, 3H). C NMR (100 MHz, CDCl3, 25 ꢀC),
d (ppm): 166.42,
159.33, 141.93, 130.92, 129.30, 127.77, 127.24, 125.14, 113.94, 71.90,
64.77, 55.20, 30.57, 19.18, 13.67. HREI-MS m/z: calcd for C17H22O4:
290.1518, found: 290.1520.
CDCl3, 25 ꢀC),
d (ppm): 165.93, 148.18, 143.91, 141.41, 132.83, 129.27,
126.66, 122.61, 121.64, 72.19, 65.05, 30.38, 19.03, 13.56.
3.3.7. 2-Hydroxyl-2-phenyl methyl acrylic acid butyl ester
3.3.14. (E)-Butyl 3-hydroxy-5-(2-methoxyphenyl)-2-methylene pent-
1
(3da)22
.
1H NMR (400 MHz, CDCl3, 25 ꢀC),
d
(ppm): 7.39–7.27 (m,
4-enoate (3ma). H NMR (400 MHz, CDCl3, 25 ꢀC),
d
(ppm): 7.44
5H, Ar), 6.35 (s, 1H), 5.84 (s, 1H), 5.56 (d, J¼6.4 Hz, 1H, CHOH), 4.12
(t, J¼6.4 Hz, 2H), 3.17 (t, J¼6.4 Hz, 1H, OH), 1.63–1.56 (m, 2H), 1.35–
1.29 (m, 2H), 0.91 (t, J¼7.6 Hz, 3H). 13C NMR (100 MHz, CDCl3,
(dd, J1¼7.6 Hz, J1¼1.2 Hz, 1H), 7.24 (td, J1¼8.0 Hz, J1¼1.2 Hz, 1H), 7.00
(d, J¼16.0 Hz, 1H), 6.92 (t, J¼7.6 Hz, 1H), 6.87 (d, J¼8.0 Hz, 1H), 6.34
(dd, J1¼16.0 Hz, J1¼7.6 Hz, 1H), 6.30 (s, 1H), 5.93 (s, 1H), 5.16 (dd,
J1¼J1¼5.6 Hz, 1H, CHOH), 4.21 (t, J¼6.4 Hz, 2H), 3.84 (s, 3H), 3.14 (br
25 ꢀC),
d (ppm): 166.42, 142.16, 141.36, 128.42, 127.80, 126.60,
125.92, 73.32, 64.81, 30.49, 19.10, 13.68.
s, 1H, OH), 1.71–1.64 (m, 2H), 1.47–1.38 (m, 2H), 0.95 (t, J¼7.6 Hz,
13
3H). C NMR (100 MHz, CDCl3, 25 ꢀC),
d (ppm): 166.41, 156.83,
3.3.8. 2-Hydroxyl-2-(4-methylphenyl)methyl acrylic acid butyl ester
142.11, 130.11, 128.79, 126.97, 126.23, 125.53, 125.09, 120.55, 110.82,
72.00, 64.71, 55.28, 30.56, 19.19, 13.68. HREI-MS m/z: calcd for
C17H22O4: 290.1518, found: 290.1519.
1
(3fa). H NMR (500 MHz, CDCl3, 25 ꢀC),
d
(ppm): 7.24 (d, J¼8.1 Hz,
2H), 7.14 (d, J¼7.9 Hz, 2H), 6.32 (s, 1H), 5.83 (s, 1H), 5.51 (s, 1H,
CHOH), 4.12–4.08 (m, 2H), 3.10 (s, 1H, OH), 2.33 (s, 3H), 1.60–1.54
(m, 2H), 1.34–1.25 (m, 2H), 0.89 (t, J¼7.40 Hz, 3H). 13C NMR
3.3.15. 2-Hydroxyl-2-phenyl methyl acrylonitrile (3dd)9a
.
1H NMR
(125 MHz, CDCl3, 25 ꢀC),
d
(ppm): 166.38, 142.55, 138.67, 137.32,
(400 MHz, CDCl3, 25 ꢀC),
d
(ppm): 7.42–7.35 (m, 5H, Ar), 6.06 (s,1H),

9090
Y. Song et al. / Tetrahedron 65 (2009) 9086–9090
5.98 (s, 1H), 5.22 (s, 1H, CHOH), 3.28 (br s, 1H, OH). 13C NMR
(100 MHz, CDCl3, 25 ꢀC),
(ppm): 138.16, 129.11, 127.83, 127.80,
125.52, 125.13, 116.01, 72.91.
2004, 45, 6425–6428; (e) Dupont, J. J. Braz. Chem. Soc. 2004, 15, 341–350; (f)
Kim, E. J.; Ko, S. Y.; Song, C. E. Helv. Chim. Acta 2003, 86, 894–899; (g) Aggarwal,
V. K.; Emme, I.; Mereu, A. Chem. Commun. 2002, 1612–1613; (h) Rosa, J. N.;
Afonso, C. A. M.; Santos, A. G. Tetrahedron 2001, 57, 4189–4193; (i) Porto, R. S.;
Amarante, G. W.; Cavallaro, M.; Poppi, R. J.; Coelho, F. Tetrahedron Lett. 2009,
50, 1184–1187.
4. (a) Aggarwal, V. K.; Dean, D. K.; Mereu, A.; Williams, R. J. Org. Chem. 2002, 67,
510–514; (b) Maher, Declan J.; Connon, Stephen, J. Tetrahedron Lett. 2004, 45,
1301–1305; (c) Ameer, F.; Drewes, S. E.; Freese, S.; Kaye, P. T. Synth. Commun.
1988, 18, 495–500; (d) Drewes, S. E.; Freese, S. D.; Emslie, N. D.; Roos, G. H. P.
Synth. Commun. 1988, 18, 1565–1572; (e) Yamada, Y. M. A.; Ikegami, S. Tetra-
hedron Lett. 2000, 41, 2165–2169.
d
3.3.16. 2-Hydroxyl-2-(4-chlorophenyl)methyl acrylic acid methyl ester
1
(3eb)21. H NMR (400 MHz, CDCl3, 25 ꢀC),
d (ppm): 7.31 (s, 4H, Ar),
6.34 (s,1H), 5.85 (s,1H), 5.51 (s,1H, CHOH), 3.72 (s, 3H), 3.33 (br s,1H,
13
OH). C NMR (100 MHz, CDCl3, 25 ꢀC),
d (ppm): 166.63, 141.62,
139.82, 133.56, 128.58, 128.02, 126.34, 72.55, 52.07.
5. Mack, J.; Shumba, M. Green Chem. 2007, 9, 328–330.
6. (a) Hill, J. S.; Issacs, N. S. Tetrahedron Lett. 1986, 27, 5007–5010; (b) Schuurman,
R. J. W.; v. d. Linden, A.; Grimbergen, R. P. F.; Nolte, R. J. M.; Scheeren, H. W.
Tetrahedron 1996, 52, 8307–8314.
7. Roos, G. H. P.; Rampersadh, P. Synth. Commun. 1993, 23, 1261–1266.
8. (a) Rodrigo de, S. O. M. A.; Andrea de, S. L. F.; Fernandez, T. L.; Silva, A. C.;
Pereira, V. L. P.; Esteves, P. M.; Vasconcellos, M. L. A. A.; Antunes, O. A. C. Lett.
Org. Chem. 2008, 5, 379–382; (b) Kundu, M. K.; Mukherjee, S. B.; Balu, N.;
Padmakumar, R.; Bhat, S. V. Synlett 1994, 444.
9. For successful examples see: (a) Aggarwal, V. K.; Emme, I.; Fulford, S. Y. J. Org.
Chem. 2003, 68, 692–700; (b) You, J.; Xu, J.; Verkade, J. G. Angew. Chem., Int. Ed.
2003, 42, 5054–5056; (c) Aggarwal, V. K.; Mereu, A. Chem. Commun. 1999,
2311–2312; (d) Shi, M.; Jiang, J.-K.; Cui, S.-C. Tetrahedron 2001, 57, 7343–7347;
(e) Shi, M.; Feng, Y.-S. J. Org. Chem. 2001, 66, 406–411; (f) Shi, M.; Jiang, J.-K.;
Feng, Y.-S. Org. Lett. 2000, 2, 2397–2400.
10. (a) Yu, C.; Liu, B.; Hu, L. J. Org. Chem. 2001, 66, 5413–5418; (b) Cai, J.; Zhou, Z.;
Zhao, G.; Tang, C. Org. Lett. 2002, 4, 4723–4725; (c) Drewes, S. E.; Roos, G. H. P.
Tetrahedron 1988, 44, 4653–4670; (d) Basavaiah, D.; Dharma, R. P.; Suguna, H. R.
Tetrahedron 1996, 52, 8001–8062.
11. (a) Kwong, C. K.-W.; Huang, R.; Zhang, M.; Shi, M.; Toy, P. H. Chem.dEur. J.
2007, 13, 2369–2376; (b) Zhao, L.-J.; He, H. S.; Shi, M.; Toy, P. H. J. Comb.
Chem. 2004, 6, 680–683; (c) Huang, J.-W.; Shi, M. Adv. Synth. Catal. 2003,
345, 953–958.
12. For examples see: (a) Cole, A. C.; Jensen, J. L.; Ntai, I.; Tran, K. L. T.; Weaver, K. J.;
Forbes, D. C.; Davis, J. H. J. Am. Chem. Soc. 2002, 124, 5962–5963; (b) Weng, J.;
Wang, C.; Li, H.; Wang, Y. Green Chem. 2006, 8, 96–99; (c) Kamal, A.; Chouhan,
G. Tetrahedron Lett. 2005, 46, 1489–1491; (d) Yadav, L. D. S.; Patel, R.; Rai, V. K.;
Srivastava, V. P. Tetrahedron Lett. 2007, 48, 7793–7795; (e) Kim, H. S.; Kim, Y. J.;
Lee, H.; Park, K. Y.; Lee, C.; Chin, C. S. Angew. Chem., Int. Ed. 2002, 41, 4300–4303;
(f) Dubreuil, J. F.; Bourahla, K.; Rahmouni, M.; Bazureau, J. P.; Hamelin, J. Catal.
Commun. 2002, 3, 185–190; (g) Ranu, B. C.; Banerjee, S. Org. Lett. 2005, 7,
3049–3052.
3.3.17. 2-Hydroxyl-2-(furan-2-yl) methyl acrylic acid butyl ester
(3ha)22 1H NMR (500 MHz, CDCl3, 25 ꢀC),
. d (ppm): 7.38 (s, 1H),
6.39 (s, 1H), 6.34–6.33 (dd, J1¼3.2 Hz, J2¼1.8 Hz, 1H), 6.26 (d,
J¼3.2 Hz, 1H), 5.93 (s, 1H), 5.59 (d, J¼6.6 Hz, 1H, CHOH), 4.19–4.14
(m, 2H), 3.19 (d, J¼6.7 Hz, 1H, OH), 1.65–1.59 (m, 2H), 1.39–1.32 (m,
13
2H), 0.92 (t, J¼7.4 Hz, 3H). C NMR (125 MHz, CDCl3, 25 ꢀC),
d
(ppm): 165.88, 154.52, 142.00, 140.14, 125.75, 110.16, 106.94, 65.97,
64.52, 30.33, 18.87, 13.43.
3.3.18. Methyl 3-hydroxy-2-methylene-5-phenylpentanoate (3nb)23,24
.
1H NMR (500 MHz, CDCl3, 25 ꢀC),
d (ppm): 7.30–7.17 (m, 5H), 6.24 (s,
1H), 5.81 (s, 1H), 4.42 (d, J¼6.0 Hz, 1H, CHOH), 3.77 (s, 3H), 2.83 (br s,
1H, OH), 2.73–2.67 (m, 2H), 2.02–1.95 (m, 2H). 13C NMR (125 MHz,
CDCl3, 25 ꢀC),
d (ppm): 166.57, 142.51, 141.39, 128.04, 127.97, 125.44,
124.54, 69.81, 51.40, 37.51, 31.67.
3.3.19. Methyl 3-hydroxy-2-methylenedecanoate (3ob)24 1H NMR
.
(500 MHz, CDCl3, 25 ꢀC),
d (ppm): 6.23 (s, 1H), 5.80 (s, 1H), 4.39 (d,
J¼6.26 Hz,1H, CHOH), 3.78 (s, 3H), 2.62 (d, J¼6.74 Hz,1H, OH),1.66–
1.61 (m, 2H), 1.33–1.26 (m, 10H), 0.88 (t, J¼6.6 Hz, 3H). 13C NMR
(125 MHz, CDCl3, 25 ꢀC),
d (ppm): 167.37, 143.60, 124.81, 71.17,
52.03, 36.82, 32.22, 29.91, 29.64, 26.14, 23.01, 14.38.
Acknowledgements
13. For an excellent review see: Greaves, T. L.; Drummond, C. J. Chem. Rev. 2008,
108, 206–237.
14. Caumul, P.; Hailes, H. C. Tetrahedron Lett. 2005, 46, 8125–8127.
15. Rafel, S.; Leahy, J. W. J. Org. Chem. 1997, 62, 1521–1522.
16. (a) Auge´, J.; Lubin, N.; Lubineau, A. Tetrahedron Lett. 1994, 35, 7947–7948; (b)
Luo, S.; Wang, G. P.; Cheng, J.-P. J. Org. Chem. 2004, 69, 555–558; (c) Roy, D.;
We thank ECUST and Shenzhen Tianding Fine Chemical Co. Ltd.
for financial support.
References and notes
Sunoj, R. B. Chem.dEur
. J. 2008, 14, 10530–10534.
17. Zou, G.; Wang, Z.; Zhu, J.; Tang, J.; He, M. Y. J. Mol. Catal. A: Chem. 2003, 206,
193–198.
18. Basavaiah, D.; Krishnamacharyulu, M.; Rao, A. J. Synth. Commun. 2000, 30,
2061–2069.
19. Patra, A.; Roy, A. K.; Joshi, B. S.; Roy, R.; Batra, S.; Bhaduri, A. P. Tetrahedron 2003,
59, 663–670.
20. Kataoka, T.; Iwama, T.; Tsujiyama, S.; Iwamura, T.; Watanabe, S. Tetrahedron
1998, 54, 11813–11824.
21. Zhao, S. H.; Chen, Z. B. Synth. Commun. 2005, 35, 121–127.
22. Fort, Y.; Berthe, M. C.; Caubere, P. Tetrahedron 1992, 48, 6371–6384.
23. Poly, W.; Schomburg, D.; Hoffmann, H. M. R. J. Org. Chem. 1988, 53,
3701–3710.
1. (a) Baylis, A.B.; Hillman, M.E.D. German Patent 2,155,113,1972; Chem. Abstr.1972,
77, 34174q; (b) For a recent review see: Basavaiah, D.; Rao, A. J.; Satyanarayana, T.
Chem. Rev. 2003, 103, 811–891; (c) Langer, P. Angew. Chem., Int. Ed. 2000, 39,
3049–3052.
2. (a) Aggarwal, V. K.; Tarver, G. J.; McCagure, R. Chem. Commun. 1996, 2713–2714;
(b) Aggarwal, V. K.; Mereu, A.; Tarver, G. J.; McCagure, R. J. Org. Chem. 1998, 63,
7183–7189; (c) Kataoka, T.; Iwama, T.; Tsujiyama, S. Chem. Commun. 1998, 197–
198; (d) Kataoka, T.; Kinoshita, H. Eur. J. Org. Chem. 2005, 45–58.
3. (a) Lin, Y.-S.; Lin, C.-Y.; Liu, C.-W.; Tsai, T. Y. R. Tetrahedron 2006, 62, 872–877;
(b) Zhao, S.-H.; Zhang, H.-R.; Feng, L.-H.; Chen, Z.-B. J. Mol. Catal. A: Chem. 2006,
258, 251–256; (c) Hsu, J.-C.; Yen, Y.-H.; Chu, Y.-H. Tetrahedron Lett. 2004, 45,
4673–4676; (d) Pe´got, B.; Vo-Thanh, G.; Gori, D.; Loupy, A. Tetrahedron Lett.
24. Shiina, I.; Yamai, Y.; Shimazaki, T. J. Org. Chem. 2005, 70, 8103–8106.