Hexamethylenetetramine as a cheap and convenient alternative catalyst in the Baylis-Hillman reaction: Synthesis of aromatic compounds with anti-malarial activity

Article abstract of DOI:10.1055/s-2004-822409

Hexamethylenetetramine (7, HMT) is a cheap alternative catalyst in the Baylis-Hillman reaction between aromatic aldehydes and methyl acrylate or acrylonitrile. The use of 0.1 equiv or 1.0 equiv of HMT proved to be an efficient catalyst for the preparation

Full text of DOI:10.1055/s-2004-822409

PAPER
1595
Hexamethylenetetramine as a Cheap and Convenient Alternative Catalyst in
the Baylis–Hillman Reaction: Synthesis of Aromatic Compounds with
Anti-Malarial Activity
H
examethylenete
.
tramine as
a
O
C
atalyst inthe
B
a
.
ylis–Hillman
M
R
eaction . A. de Souza,a Bruno A. Meireles,a Lúcia C. S. Aguiar,b M. L. A. A. Vasconcellos*a
a
Lab. H0-027, Núcleo de Pesquisas de Produtos Naturais, Universidade Federal do Rio de Janeiro, Bloco H, CCS, Ilha do Fundão, Rio de
Janeiro, RJ, Brazil
Fax +55(21)22702683; E-mail: mlaav@nppn.ufrj.br
b
Lab. H1-029, Núcleo de Pesquisas de Produtos Naturais, Universidade Federal do Rio de Janeiro, Bloco H, CCS, Ilha do Fundão, Rio de
Janeiro, RJ, Brazil
Received 5 February 2004; revised 29 March 2004
1,4-Diazabicyclo[2.2.2]octane (2, DABCO) is the usually
Abstract: Hexamethylenetetramine (7, HMT) is a cheap alternative
catalyst in the Baylis–Hillman reaction between aromatic aldehydes
and methyl acrylate or acrylonitrile. The use of 0.1 equiv or 1.0
equiv of HMT proved to be an efficient catalyst for the preparation
of 1, 8a–c,h, 9a–c and 10 in good to high yieds. The Baylis–Hillman
adducts 9c and 10 show high potency against P. falciparum in vitro
(anti-malarial activity), and new compounds 9f,h,i are also effi-
ciently prepared using our methodology.
employed catalyst (Scheme 1).4
Due to the synthetic utility of these adducts,several proto-
cols have been proposed to improve this reaction, such as
the use of microwaves,5ultrasound,6 salt and metal addi-
tion,7high pressure 8and ionic liquids.9
An inconvenience to this reaction is, in most cases, the
high cost of the tertiary amines employed. It is often nec-
essary to use almost stoichiometric amounts of these
amines (0.65–1 equivalents),4 rendering the procedure un-
economic on an industrial scale. A large number of organ-
ic bases (Figure 1), such as DMAP (3), imidazole (4),
DBU (5), tetramethylguanidine (6) and others,4 have been
used instead of the (expensive) DABCO (2, USD 343.60/
2 kg). Hexamethylenetetramine (7, HMT), a very cheap
tertiary amine (Figure 1) is a non hygroscopic and stable
reagent of low toxicity. HMT (7) can be prepared by al-
lowing a mixture of aqueous formalin and concentrated
ammonia solution to evaporate.10 This versatile synthetic
reagent has been used in the preparation of primary
amines and N-heterocycles10 and, recently, evaluated as
an efficient catalyst precursor for the microwave-assisted
Knoevenagel reaction.11 In a recent paper, Tang described
one experiment using urotropine (HMT) as promoter (1
equivalents) with dioxane–water (1:1) as solvent, to pre-
pare 1 in moderated yield (52%).12
KeyWords: nucleophilic additions, aldehydes, amines, catalysis,
drugs
Today, approximately 40% of the world's population,
mostly those living in the world's poorest countries, are at
risk of malaria. The disease was once more widespread
but it was successfully eliminated from many countries
with temperate climates during the mid 20th century. Ma-
laria is found throughout the tropical and sub-tropical re-
gions of the world and causes more than 300 million acute
illnesses and at least one million deaths annually.1 In con-
nection with our experimental efforts towards an efficient
methodology to prepare bioactive products,2 we describe
in this article reactions between methyl acrylate or acryl-
onitrile with several aromatic aldehydes, aiming to pre-
pare some Baylis–Hillman adducts with anti-malarial
activity.1
The Baylis–Hillman reaction affords adducts, such as 1
(Table 1), from simple starting materials. This reaction
was first reported in 1972,3 and involves the coupling of
alkenes containing electron withdrawing groups (EWG)
with aldehydes, ketones and imines (among others), and
using tertiary amines as nucleophilic catalysts (0.1 equiv-
alents or less) or promoters (more than 0.1 equivalents).
N
N
NH
N
N
N
N
N
N
N
N
N
N
N
N
H
Dabco
2
3
4
5
6
7 HMT
XH
X
EWG
EWG
R1
Figure 1 Tertiary amines as catalysts in Baylis–Hillman reaction
+
R
R1
R
¨
(Catalyst)
R3N
adduct
In Table 1, we noticed that 0.1 equiv of the amine 7 as cat-
alyst was sufficient to prepare the adduct 1 in excellent
Scheme 1 The Baylis–Hillman reaction: R = alkyl, aryl, heteroaryl;
R1 = H, CO2R, alkyl, X = O, NTs, NSO2Ph; EWG = electron with- isolated yield with aprotic solvent or when the reaction is
drawing group: COR, CHO, CN, CO2R, others.
performed neat (entries 3, 7 and 8, Table 1). We also ob-
served that the use of water as co-solvent decreases the
yields (entries 1 vs. 2, 3 vs. 4, and 5 vs. 6, Table 1). This
data could be explained as a fast acid–basic equilibrium
SYNTHESIS 2004, No. 10, pp 1595–1600
Advanced online publication: 16.06.2004
DOI: 10.1055/s-2004-822409; Art ID: M01004SS
© Georg Thieme Verlag Stuttgart · New York
x
x.
x
x
.
2
0
0
4

1596
R. O. M. A. de Souza et al.
PAPER
between HMT and water. The rates of the reactions were vanillin 8h (entry 16; Table 2) represents a potential inter-
dramatically accelerated at higher temperature (entries 7 mediate in the synthesis of natural products.4
vs. 9, and 8 vs. 10). It was also observed that the use of
stoichiometric amounts of HMT (7) as a promoter reduces
the reaction time (entries 7 vs. 11, and 10 vs. 14; Table 1),
which is in agreement with the kinetic studies of Isaacs et
It is important to point out that the adducts derived from
the aldehydes vanillin, 2,5-dimethoxybenzaldehyde and
4-hydroxybenzaldehyde, respectively 9h,i and f are new
compounds and represent potential leads as anti-malarial
al., where they concluded that the reaction rate is third-or-
compounds.1,2
der or pseudo second-order.13 The use of acetonitrile and
In order to evaluate the use of HMT as a catalyst, we in-
dioxane–water (1:1) as solvents, recently reported as ac-
vestigated the reaction of acrylonitrile and 4-nitrobenzal-
dehyde using different conditions (Table 4). The adduct
10 was prepared in high yields (entries 2 and 4; Table 4)
in neat conditions and in quantitative yields in DMSO at
60 °C, using 0.1 equiv of HMT (entry 6; Table 4).
celerating agents for the Baylis–Hillman reaction,14 did
not improve the yields (entry 15 and 16; Table 1).
The reaction was carried out with other aromatic and het-
eroaromatic aldehydes (Table 2, Figure 2), methyl acry-
late and HMT (0.1 equiv). The yields obtained with the
activated aromatic aldehydes (entries 1–6; Table 2,
Figure 2) ranged from good to excellent. Considering the
results presented in Table 2, we could observe that there
is no obvious relationship between the electrophilicity of
the carbonyl group of aldehydes and the yield; i.e. vanil-
lin, which is less electrophilic than benzaldehyde, led to
the adduct 8h in excellent yield (entries 8 vs. 16; Table 2).
It is important to point out that the adduct prepared from
Aiming to increase the scope of our methodology and to
prepare other potential adducts with anti-malarial activi-
ty,2 the Baylis–Hillman reaction between acrylonitrile and
aryl aldehydes were investigated. Considering the fact
that large amounts of HMT accelerate the reaction
(Table 1), we investigated these reactions using HMT (1
equiv) in DMSO at 60 °C (Table 3). Adducts 9a–c,i were
prepared in good to excellent yield after 24 hours of reac-
tion (entries 1, 2, 3, and 9; Table 3, Figure 3).
Table 1 The Baylis–Hillman Reaction between p-Nitrobenzaldehyde and Methyl Acrylate
OH
O
O
O
HMT
O
O
+
O2N
O2N
1
Entry
HMT
(equiv)
Solvent
Temp.
(°C)
Reaction time
(days)
Yield
(%)
1
2
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
1.0
1.0
1.0
1.0
1.0
1.0
MeOH
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
60
60
r.t
27
27
13
27
27
27
12
6
50
10
90
40
70
30
>99
80
70
80
80
72
83
70
57
43
MeOH–H2O (1:1)
THF
3
4
THF–H2O (1:1)
DMF
5
6
DMF–H2O (1:1)
DMSO
7
8
No solvent
DMSO
9
5
10
11
12
13
14
15
16
No solvent
DMSO
2
5
DMSO
60
r.t
2
No solvent
No solvent
Dioxane–H2O (1:1)
MeCN
6
60
r.t
1
5
r.t
5
Synthesis 2004, No. 10, 1595–1600 © Thieme Stuttgart · New York

PAPER
Hexamethylenetetramine as a Catalyst in the Baylis–Hillman Reaction
1597
Table 2 The Baylis–Hillman Reaction between Several Aromatic
and Heteroaromatic Aldehydes and Methyl Acrylate
Table 3 The Baylis-Hillman Reaction between Selected Aromatic
and Heteroaromatic Aldehydes and Acrylonitrile
O
OH
1 equiv HMT
60 °C
OH
O
O
O
HMT
0.1 equiv
CN
CN
9a-i
+
O
+
Ar
Ar
O
Ar
Ar
DMSO
8a-h
Temp Reaction Adduct Yield
Entry Aldehydes
Reaction
time (days)
Adduct Yield
(%)
Entry Aldehydes
(°C) time
(days)
(%)
1
2
3
4
5
6
7
8
2-Nitrobenzaldehyde
2-Pyridinecarboxaldehyde
1
1
9a
9b
9c
9d
9e
9f
80
89
81
69
20
90
43
65
1
2
2-Nitrobenzaldehyde
2-Nitrobenzaldehyde
r.t.
60
r.t.
60
r.t.
60
r.t.
60
r.t.
60
r.t
7
8a
8a
8b
8b
8c
8c
8d
8d
8e
8e
8f
79
60
70
71
84
79
12
18
63
27
22
45
39
47
57
3-Pyridinecarboxaldehyde
Benzaldehyde
1
10
11
10
9
16
4
3
2-Pyridinecarboxaldehyde
2-Pyridinecarboxaldehyde
3-Pyridinecarboxaldehyde
3-Pyridinecarboxaldehyde
Benzaldehyde
2-Naphthaldehyde
4
4-Hydroxybenzaldehyde
4-Methoxybenzaldehyde
3
5
16
7
9g
9h
6
10
8
4-Hydroxy-3-methoxybenzalde-
hyde (Vanillin)
7
8
Benzaldehyde
8
9
2,5-Dimethoxybenzaldehyde
1
9i
85
9
2-Naphthaldehyde
11
10
20
13
17
16
20
10
11
12
13
14
15
2-Naphthaldehyde
In conclusion, we described applications of hexamethyl-
enetetramine (7) (HMT) as a cheap alternative catalyst for
the Baylis–Hillman reaction between aromatic aldehydes
and methyl acrylate or acrylonitrile. Our methodology is
very efficient for preparing adducts such as 1, 9a–c,i and
10, which were prepared in high to quantitative yields af-
ter 24 h reaction. The low price of this tertiary amine
(USD10.0/kg) allows its use in stoichiometric amounts
when necessary, however the use of 0.1 equiv of HMT
was good enough to obtain excellent yields of several ad-
ducts. The Baylis–Hillman adducts, 9c and 10 which have
the highest potency against P. falciparum in vitro (anti-
malarial activity), andthe new adducts 9f,h,i, were also ef-
ficiently prepared using this metodology. The potential
4-Hydroxybenzaldehyde
4-Hydroxybenzaldehyde
4-Methoxybenzaldehyde
4-Methoxybenzaldehyde
60
r.t
8f
8g
8g
8h
60
4-Hydroxy-3-methoxybenzal- r.t
dehyde (Vanillin)
16
4-Hydroxy-3-methoxybenzal- 60
dehyde (Vanillin)
16
8h
83
Table 4 The Baylis–Hillman Reaction Between 4-Nitrobenzaldehyde and Acrylonitrile
OH
O
HMT
CN
CN
+
O2N
O2N
10
Entry
HMT
(equiv)
Solvent
Temp (°C)
Reaction
time (days)
Yield
(%)
1
2
3
4
5
6
1.0
0.1
1.0
0.1
1.0
0.1
No solvent
No solvent
No solvent
No solvent
DMSO
r.t.
r.t.
60
60
r.t.
60
3
7
2
6
2
1
82
75
85
90
62
DMSO
>99
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1598
R. O. M. A. de Souza et al.
PAPER
OH
OH
OH
NO2 OH
OH
N
CO2CH3
CO2CH3
CO2CH3
CO2CH3
CO2CH3
N
O2N
8c
8b
8d
8a
1
OH
OH
OH
OH
CO2CH3
H3CO
HO
CO2CH3
CO2CH3
CO2CH3
HO
H3CO
8g
8h
8f
Figure 2 Adducts prepared from methyl acrylate
8e
Figure 3 Adducts prepared from acrylonitrile
anti-malarial activities of these compounds are now under
investigation.
Methyl 3-Hydroxy-2-methylene-3-(4-nitrophenyl)propanoate
(1)6b
1H NMR (CDCl3,200 MHz): d = 8.71 (d, 2 H, J = 8.75 Hz), 7.54 (d,
2 H, J = 8.82 Hz), 6.38 (s, 1 H), 5.89 (s, 1 H), 5.62 (d, 1 H, J = 5.86
Hz, CHOH), 3.73 (s, 3 H).
Commercially available reagents were purchased from Aldrich and
used without further purification. 1H and 13C NMR spectra were ob-
tained on Varian Spectra (200 Mz) in CDCl3 with CHCl3 as internal
reference (d = 7.26) and 13C NMR Varian Spectra (50 Mz) in CDCl3
solution with CHCl3 (d = 77.0) as internal reference. TLC were per-
formed with 0.2–0.5 mm precoated silica gel plates (GF-254). Ele-
mental analyses were performed on Vario EL instrument.
Methyl 3-Hydroxy-2-methylene-3-(2-nitrophenyl)propanoate
(8a)15
1H NMR (CDCl3,200 MHz): d = 8.82 (d, 1 H, J = 8.47 Hz), 8.56 (t,
1 H, J = 7.55, 7.35 Hz), 8.42 (t, 1 H, J = 8.47, 7.35 Hz), 8.33 (d, 1
H J = 8.47 Hz), 6.36 (s, 1 H), 6.31 (s, 1 H), 5.59 (d, 1 H, J = 5.3 Hz,
CHOH), 3.74 (s, 3 H).
Typical Procedure
Reactions were carried out using solvent (1 mL), aldehyde (0.6
mmol) and activated alkene (0.6 mmol) (methyl acrylate or acryl-
onitrile), until all starting aldehyde was consumed (TLC analysis;
2:8 HOAc–hexane). The mixture was evaporated and filtered
through silica gel. Purification of the products was by silica-gel col-
umn chromatography (30 cm × 1.5 cm column; 15 g of silica gel;
230–400 mesh; 1:9, HOAc–hexane). Solvent free reactions were
conducted using 1 mL of activated alkene.
Methyl 3-Hydroxy-2-methylene-3-(2-pyridyl)propanoate (8b)6b
1H NMR (CDCl3,200 MHz): d = 8.43 (d, 2 H, J = 4.55 Hz), 7.40 (d,
2 H, J = 4.58 Hz,), 6.39 (s, 1 H), 6.00 (s, 1 H), 5.70 (1 H, s), 3.66 (s,
3 H).
Methyl 3-Hydroxy-2-methylene-3-(3-pyridyl)propanoate (8c)6b
1H NMR (CDCl3, 200 MHz): d = 8.49 (d, 1 H, J = 1.5 Hz), 8.30
(dd,1 H, J = 4.70, 1.47 Hz), 7.72 (dt, 1 H, J = 8.00, 1.80 Hz), 7,1
(dd, 1 H, J = 7.1, 5.3 Hz), 6.30 (s, 1 H), 5.99 (s, 1 H), 5.35 (s,1 H),
4.66 (s, 3 H).
Purification of the Adducts
When the reaction was carried out in DMSO and DMF, the work up
involved adding H2O (8 mL) to the reaction mixture followed by ex-
traction with HOAc (3 × 6 mL). The combined organic phases were
dried (Na2SO4), evaporated and purificated by silica-gel column
chromatography. The structures of substances previously reported
were confirmed by comparison with NMR data.
Methyl 3-Hydroxy-2-methylene-3-phenylpropanoate (8d)6b
1H NMR (CDCl3, 200 MHz): d = 7.4–7.2 (m, 5 H), 6.30 (s, 1 H),
5.90 (s, 1 H), 5.45 (1 H, s), 3.70 (s, 3 H).
Synthesis 2004, No. 10, 1595–1600 © Thieme Stuttgart · New York

PAPER
Hexamethylenetetramine as a Catalyst in the Baylis–Hillman Reaction
1599
Methyl 3-Hydroxy-2-methylene-3-(2-naphthyl)propanoate
(8e)16
Anal. Calcd for C11H11NO3: C, 64.38; H, 5.40; N, 6.83; O, 23.39.
Found: C, 64.40; H, 5.39; N, 6.84; O, 23.36.
1H NMR (CDCl3, 200 MHz): d = 7.9–7.3 (m, 7 H), 6.31 (s, 1 H),
6.36 (s, 1 H), 5.19 (m, 1 H), 3.74 (s, 3 H).
3-Hydroxy-2-methylene-3-(2,5-dimethoxyphenyl)propane-
nitrile (9i)
Methyl 3-Hydroxy-2-methylene-3-(4-hydroxyphenyl)pro-
panoate (8f)6b
1H NMR (CDCl3,200 MHz): d = 7.13 (d, 1 H, J = 3.01 Hz), 6.9 (dd,
1 H, J = 9.14, 2.99 Hz), 6.4 (m, 1 H), 6.05 (d, 1 H, J = 0.7 Hz), 5.82
(d, 1 H, J = 0.9 Hz), 5.38 (m, 1 H), 3.77 (s, 3 H), 3.65 (s, 3 H), 2.50
(s, 1 H, CHOH).
1H NMR (CDCl3, 200 MHz): d = 7.00 (d, 2 H, J = 8.2 Hz), 6.5 (d,
2 H, J = 8.2 Hz), 6.61 (s, 1 H), 5.80 (t, 1 H, J = 1.0 Hz), 5.48 (s, 1
H), 3.70 (s, 3 H).
13C NMR (CDCl3, 200 MHz): d = 154.79, 151.55, 130.81, 127.59,
126.66, 118.89, 117.06, 114.41, 114.18, 71.44, 56.61, 55.57.
Methyl 3-Hydroxy-2-methylene-3-(4-methoxyphenyl)pro-
panoate (8g)6b
Anal. Calcd for C12H13NO3: C, 65.74; H, 5.98; N, 6.39; O, 21.89.
Found: C, 65.77; H, 5.95; N, 6.41; O, 21.86.
1H NMR (CDCl3,200 MHz): d = 7.28–7.23 (m, 2 H), 6.72–6.69 (m,
2 H), 6.36 (s, 1 H), 6.31(s, 1 H), 5.10 (s, 1 H), 3.75 (s, 3 H), 3.74 (s,
3 H).
3-Hydroxy-2-methylene-3-(4-nitrophenyl)propanenitrile (10)20
1H NMR (CDCl3, 200 MHz): d = 8.51 (d, 2 H, J = 7.6 Hz), 8.3 (d,
2 H, J = 7.55 Hz), 6.15 (s, 1 H), 5.82 (s, 1 H), 4.70 (d, 1 H, J = 5.81
Hz), 2.0 (s, 1 H, CHOH).
Methyl 3-Hydroxy-2-methylene-3-(4-hydroxy-3-methoxyphe-
nyl)propanoate (8h)6b
1H NMR (CDCl3,200 MHz): d = 7.00 (s, 1 H), 6.9 (dd, 1 H, J = 8.2,
1.39 Hz), 6.30 (s, 1 H), 6.39 (s, 1 H), 5.75 (t, 2 H, J = 1.12 Hz), 3.80
(s, 3 H), 3.70 (s, 3 H).
Acknowledgment
We thanks Capes and CNPq for financial support.
3-Hydroxy-2-methylene-3-(2-nitrophenyl)propanenitrile (9a)14
1H NMR (CDCl3, 200 MHz): d = 8.86 (m, 1 H), 8.64 (m, 1 H), 8.49
(m, 2 H), 6.05 (s, 1 H), 5.82 (s, 1 H), 5.23 (s, 1 H).
References
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M. E.; Fernandes, P. D.; Vasconcellos, M. L. A. A. Bioorg.
Med. Chem. Lett. 2004, 14, 1573.
3-Hydroxy-2-methylene-3-(2-pyridyl)propanenitrile (9b)6b
1H NMR (CDCl3, 200 MHz): d = 8.55 (m, 1 H), 7.75 (m, 1 H), 7.35
(m, 1 H), 7,25 (m, 1 H), 6.22 (s, 1 H), 6.05 (s, 1 H), 5.30 (s, 1 H).
3-Hydroxy-2-methylene-3-(3-pyridyl)propanenitrile (9c)17
1H NMR (CDCl3, 200 MHz): d = 8.70 (m, 1 H), 8.54 (m, 1 H), 7.79
(m, 1 H), 7,13 (m, 1 H), 6.05 (s, 1 H), 5.82 (s, 1 H), 4.76 (s, 1 H).
(3) Baylis, A. B.; Hillman, M. E. D. German Patent 2155113,
1972; Chem. Abstr. 1972, 77, 34174q.
3-Hydroxy-2-methylene-3-phenylpropanenitrile (9d)18
1H NMR (CDCl3, 200 MHz): d = 7.4–7.2 (m, 5 H) 6.15 (s, 1 H),
5.95 (s, 1 H), 4.73 (s, 1 H).
(4) (a) Basavaiah, D.; Rao, P. D.; Hyma, R. S. Tetrahedron
1996, 52, 8001. (b) Drewes, S. E.; Roos, G. H. P.
Tetrahedron 1988, 44, 4653. (c) Ciganek, E. Org. React.
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1999, 1, 1383.
3-Hydroxy-2-methylene-3-(2-naphthyl)propanenitrile (9e)19
1H NMR (CDCl3, 200 MHz): d = 8.9–7.3 (m, 7 H) 6.07 (s, 1 H),
5.84 (1 H, s), 4.81 (s, 1 H), 2.35 (s, 1 H, CHOH).
3-Hydroxy-2-methylene-3-(4-hydroxyphenyl)propanenitrile
(9f)
1H NMR (CDCl3, 200 MHz): d = 7.4 (d, 2 H, J = 8.46 Hz), 6.8 (d, 2
H, J = 8.40 Hz), 6.05 (s, 1 H), 5.82 (s, 1 H), 4.73 (s, 1 H), 3,61 (s, 1
H, CHOH).
13C NMR (CDCl3, 200 MHz): d = 161.0, 132.34, 130.81, 129.47,
127.52, 118.59, 115.51, 76.38.
Anal. Calcd for C10H9NO2: C, 68.56; H, 5.18; N, 8.00; O, 18.27.
Found: C, 68.53; H, 5.16; N, 8.02; O, 18.28.
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Synthesis 1979, 161.
3-Hydroxy-2-methylene-3-(4-methoxyphenyl)propanenitrile
(9g)19
1H NMR (CDCl3, 200 MHz): d = 7.4 (m, 2 H), 6.75 (m, 2 H), 6.33
(s, 1 H), 6.05 (s, 1 H), 4.73 (s, 1 H), 3.75 (s, 3 H).
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3-Hydroxy-2-methylene-3-(4-hydroxy-3-methoxyphenyl)pro-
panenitrile (9h)
1H NMR (CDCl3, 200 MHz): d = 7.15 (dd, 1 H, J = 8.46, 1.71 Hz),
7.06 (m, 1 H), 6.95 (dd, 1 H, J = 8.46, 1.45 Hz), 6.05 (t, 1 H, J = 1.1
Hz) 5.82 (t, 1 H, J = 1.2 Hz), 4.89 (m, 1 H), 3.86 (s, 3 H).
13C NMR (CDCl3, 200 MHz): d = 149.77, 148.49, 133.91, 130.81,
127.52, 118.89, 120.88, 116.42, 112.86, 77.87, 56.12.
Synthesis 2004, No. 10, 1595–1600 © Thieme Stuttgart · New York

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Synthesis 2004, No. 10, 1595–1600 © Thieme Stuttgart · New York