N-alkylimidazole as amphiphilic organocatalyst: 'Catalytic' Morita-Baylis-Hillman reaction on water without organic solvent

Article abstract of DOI:10.1055/s-0028-1087484

In the presence of water, a Morita-Baylis-Hillman reaction between methyl vinyl ketone and various aldehydes was performed with a catalytic amount of an imidazole carrying a hydrophobic group. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0028-1087484

LETTER
35
N-Alkylimidazole as Amphiphilic Organocatalyst: ‘Catalytic’ Morita–Baylis–
Hillman Reaction on Water without Organic Solvent
N
-Alkylimidazole
e
as
A
mphip
i
hilic
O
s
rganocatal
u
yst ke Asano, Seijiro Matsubara*
Department of Material Chemistry, Kyoto University, Kyoutodaigaku-katsura, Nishikyo, Kyoto 615-8510, Japan
Fax +81(75)3832459; E-mail: matsubar@orgrxn.mbox.media.kyoto-u.ac.jp
Received 16 September 2008
the imidazole derivative with/without adding water. An
Abstract: In the presence of water, a Morita–Baylis–Hillman reac-
tion between methyl vinyl ketone and various aldehydes was per-
formed with a catalytic amount of an imidazole carrying a
hydrophobic group.
introduction of a hydrophobic group on imidazole will
make a reaction in water possible (entries 1 and 2). To
improve the yield, an addition of catalytic amount of
Brønsted acid (20 mol%) was also examined. The addi-
tion of 1,1,1,3,3,3-hexafluoropropan-2-ol (5) improved
the yield (entry 3). The amount of acid was also optimized
to show that 20 mol% was enough for the reaction (entries
3–6). After these optimizations, the amount of imidazole
derivative was also decreased to the catalytic amount (en-
tries 6–10). The use of 20 mol% of 4b was shown to give
a reasonable yield of the product (entry 10). Without wa-
ter, the yield decreased to 37% from 65% (entries 10 and
11). Modification of the hydrophobic group on imidazole
was also examined. A length of carbon chain was ar-
ranged from C10 to C16 (entries 13–16). No reasonable
difference concerning the yield has been observed in any
of these cases. To increase the hydrophobicity, we intro-
duced a fluorine atom on the C14 chain.11 In these cases,
only a slight increase of the yield was observed (entries 18
and 19). The amount of water was also optimized. Sur-
prisingly, only a small amount of water was enough to im-
prove the yields (entries 10, 11, 20–23). While stoi-
chiometric amount of nucleophile had been used in the re-
ported MBH reactions in the polar solvent including wa-
ter,7,8f we can realize ‘catalytic MBH reaction’ in the
presence of water.
Key words: Morita–Baylis–Hillman reaction, organocatalyst, water,
imidazole
The use of water as a solvent for organic reactions has
been important since the pioneering work by Breslow.1
Some practical reasons, such as cost, safety, and environ-
mental concern, are mentioned specially; additionally wa-
ter as solvent often benefits the organic reaction itself
dynamically.2 The high polarity of water has a possibility
to stabilize an ionic intermediate.3 In addition, the hydro-
phobicity of organic compound may give rise to cohesion
of substrates, which often enhances reactions kinetically.4
The use of water as solvent has been expanded even to the
organometallic chemistry which includes air- and water-
sensitive reagents.5 As the chemistry of organocatalyzed
reactions has been developed in recent years, the argu-
ments about the contribution of water to these reactions
have been rekindled.6 In the use of organocatalysts, an
ionic intermediate is inevitable, so a use of water might be
effective.6a,b,7 We focused on Morita–Baylis–Hillman
(MBH) reactions which are initialized by an amine or
phosphine (Scheme 1).8 In the reaction, a betaine interme-
diate 1 is crucial. In order to stabilize such an ionic inter-
mediate, one can use water as solvent, however, addition
of water may cause a decrease of the nucleophilicity of
amine. Actually, in the reported methods, which show rate
enhancement of an MBH reaction in water, excess amount
of nucleophilic mediator was required.7,8f To solve this
contradiction, we designed an imidazole9 carrying a
hydrophobic group.10
Under the optimized conditions, we examined MBH reac-
tions of methyl vinyl ketone (3) with various aldehydes 2,
as shown in Table 2. Although the yields were not excel-
lent, we can show the possibility of the MBH reaction,
which is catalyzed by an imidazole derivative carrying
hydrophobic group; such reactions are also accelerated
with water.
In these reactions, vigorous stirring was not necessary. As
shown in Scheme 2, the reaction of benzaldehyde (2a) and
methyl vinyl ketone (3) in the presence of imidazole
As shown in Table 1, an MBH reaction of methyl vinyl
ketone and benzaldehyde was examined in the presence of
O–
R
OH
R
O–
R3N+
RCHO
+ R3N
O
R3N
R3N+
O
O
1
Scheme 1 Schematic Morita–Baylis–Hillman reaction catalyzed by amine
SYNLETT 2009, No. 1, pp 0035–0038
x
x.
x
x.
2
0
0
8
Advanced online publication: 12.12.2008
DOI: 10.1055/s-0028-1087484; Art ID: U09908ST
© Georg Thieme Verlag Stuttgart · New York

36
K. Asano, S. Matsubara
LETTER
Table 1 Morita–Baylis–Hillman Reaction between Benzaldehyde and Methyl Vinyl Ketone Catalyzed with Various Imidazole Derivativesa
O
OH
O
(CF3)2CHOH
N
N
O
R
(4)
H2O, 25 °C, 12 h
(5)
H
+
3
6a
2a
Entry
1
R in 4
4 (mol%)
100
100
100
100
100
100
50
5 (mol%)
0
H2O (mmol)
9.0
Yield of 6a (%)b
Me (4a)
<1
37
63
64
61
54
53
55
57
65
37
16
63
61
64
64
44
65
66
61
65
64
67
2
C14H29 (4b)
0
9.0
3
4b
100
60
40
20
20
20
20
20
20
20
20
20
20
20
20
20
20
20
20
20
20
9.0
4
4b
9.0
5
4b
9.0
6
4b
9.0
7
4b
9.0
8
4b
40
9.0
9
4b
30
9.0
10
11
12
13
14
15
16
17
18
19
20
21
22
23
4b
20
9.0
4b
20
0
Me (4a)
C10H21 (4c)
C12H25 (4d)
C15H31 (4e)
C16H33 (4f)
4fc
20
9.0
20
8.0
20
8.0
20
8.0
20
8.0
20
8.0
(R)-13-Fluorotetradecanyl (4g)
20
8.0
C4F9(CH2)11 (4h)
20
8.0
n-C14H29 (4b)
20
10.0
8.0
4b
4b
4b
20
20
5.0
20
2.5
a Benzaldehyde (2a, 0.5 mmol) and methyl vinyl ketone (3, 1.0 mmol) were used for the reaction, except entry 17.
b Isolated yields.
c Benzaldehyde (2a, 0.5 mmol) and methyl vinyl ketone (3, 0.5 mmol) were used for the reaction.
derivative 4b, alcohol 5, and water was examined with/ of the amphiphilic organocatalyst reaction using the sur-
without stirring. Both reactions gave the same yield. The face which is formed between water and organic com-
result showed that stirring was not necessary to carry out pounds.
the reaction. The fact means that the effect of water was
not due to forming emulsions.12 We suppose that the reac-
Preparation of 3-[Hydroxy(phenyl)methyl]but-3-en-2-one (6a)
tion proceeds in the range of the organic phase that is close
To a 5 mL vial, benzaldehyde (2a, 0.5 mmol), methyl vinyl ketone
(3, 1.0 mmol), N-tetradecylimidazole (4b, 0.1 mmol), 1,1,1,3,3,3-
hexafluoro-2-propanol (5, 0.1 mmol), and H2O (8.0 mmol) was add-
ed subsequently at 25 °C. The whole was stirred for 12 h at 25 °C.
The mixture was diluted with Et2O. The mixture was dried over an-
hyd Na2SO4. After a short silica gel column chromatography using
to the surface of the water, in other words on water.13
Although many impressive works using organocatalyst
have been reported recently, studies for acceleration of the
reaction rate have just begun.14 Our results show a possi-
bility of acceleration of the MBH reaction rate by means
Synlett 2009, No. 1, 35–38 © Thieme Stuttgart · New York

LETTER
N-Alkylimidazole as Amphiphilic Organocatalyst
37
Table 2 Morita–Baylis–Hillman Reaction between Various Aldehydes and Methyl Vinyl Ketone Catalyzed with N-Hexadecylimidazolea
N
N
C16H33
(CF3)2CHOH
(4f; 0.1 mmol)
(5; 0.1 mmol)
O
OH
O
O
+
R
R
H
H2O (8.0 mmol), 25 °C, 12–24 h
2 (0.5 mmol)
3 (1.0 mmol)
6
Entry
Substrate 2
Time (h)
12
Yield of 6 (%)b
6b 52
1
2
3
4
5
6
7
2-naphthaldehyde (2b)
4-fluorobenzaldehyde (2c)
4-nitrobenzaldehyde (2d)
3-pyridinecarbaldehyde (2e)
3-phenylpropanal (2f)
hexanal (2g)
12
6c 59
12
6d 29
12
6e 41
12
6f 37
24
6g 49
octanal (2h)
24
6h 50
a Aldehyde (2, 0.5 mmol), methyl vinyl ketone (3, 1.0 mmol), N-hexadecylimidazole (4f, 0.1 mmol), and H2O (8.0 mmol) were used for the
reaction.
b Isolated yields.
Scheme 2 The Morita–Baylis–Hillman reaction with/without stirring
hexane–EtOAc as an eluent, the title compound 6a was obtained in
65% yield.
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Acknowledgement
This work was supported financially by the Japanese Ministry of
Education, Culture, Sports, Science and Technology.
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