One-pot Wittig reactions in aqueous media: A rapid and environmentally benign synthesis of α,β-unsaturated carboxylic esters and nitriles

Article abstract of DOI:10.1080/00397910600773684

One-pot Wittig reactions of ethyl bromoacetate and bromoacetonitrile with aldehydes in the presence of PPh₃ and LiOH in water were investigated. Most of the olefination reactions completed within 5-120 min in refluxing water containing 1.2 M LiCl to afford the olefin products in 71-97% yields with 100:0-55:45 ratios of E:Z isomers. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910600773684

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One‐Pot Wittig Reactions in Aqueous Media: A
Rapid and Environmentally Benign Synthesis
of α,β‐Unsaturated Carboxylic Esters and
Nitriles
Jinlong Wu a & Congyong Yue a
a Laboratory of Asymmetric Catalysis and Synthesis, Department of
Chemistry , Zhejiang University , Hangzhou, China
Published online: 16 Feb 2007.
To cite this article: Jinlong Wu & Congyong Yue (2006) One‐Pot Wittig Reactions in Aqueous Media: A
Rapid and Environmentally Benign Synthesis of α,β‐Unsaturated Carboxylic Esters and Nitriles, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry, 36:20,
2939-2947, DOI: 10.1080/00397910600773684
To link to this article: http://dx.doi.org/10.1080/00397910600773684
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Synthetic Communicationsw, 36: 2939–2947, 2006
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910600773684
One-Pot Wittig Reactions in Aqueous
Media: A Rapid and Environmentally
Benign Synthesis of a,b-Unsaturated
Carboxylic Esters and Nitriles
Jinlong Wu and Congyong Yue
Laboratory of Asymmetric Catalysis and Synthesis, Department of
Chemistry, Zhejiang University, Hangzhou, China
Abstract: One-pot Wittig reactions of ethyl bromoacetate and bromoacetonitrile with
aldehydes in the presence of PPh3 and LiOH in water were investigated. Most of the
olefination reactions completed within 5–120 min in refluxing water containing 1.2
M LiCl to afford the olefin products in 71–97% yields with 100:0–55:45 ratios of
E:Z isomers.
Keywords: Aldehydes, aqueous reaction, one-pot reaction, Wittig reaction
In recent years, organic reactions carried out in water have become increas-
ingly popular for developing environmentally benign chemical processes.
Some reactions involving organometallic species have been successfully
transferred to aqueous media.[1] The Wittig reaction is one of the most
versatile synthetic methods for preparation of olefins from carbonyl
compounds. It classically requires use of a hydride or organometallic base
and is carried out in anhydrous aprotic solvents under an inert atmosphere.[2]
A number of variations on the reaction conditions have been reported for the
Wittig reaction. These include (a) use of silica gel;[3] (b) under high tempera-
tures[4] or pressures;[5] (c) use of additives;[6] (d) promoted by microwave,[7]
light,[8] or sonication;[9] (e) use of ionic liquids;[10] and (f) under solvent-free
Received in R.O.C. February 16, 2006
Address correspondence to Jinlong Wu, Laboratory of Asymmetric Catalysis and
Synthesis, Department of Chemistry, Zhejiang University, Hangzhou 310027, China.
E-mail: wyz@zju.edu.cn
2939

2940
J. Wu and C. Yue
conditions.[11] Recently, it was reported that water is a suitable solvent for the
Wittig reactions of stabilized and semistabilized phosphorus ylides with
aldehydes. The reaction in water is faster than in organic solvents with
higher yields and in similar E:Z selectivities of the olefin products.[12]
Green chemical approaches hold significant potential for establishment of
a sustainable society. They cover the areas such as reduction of waste and by-
products, use of safer and environmentally benign solvents, and reduction of
energy costs.[13] A one-pot protocol is an efficient and economic chemical
transformation coupling three or more components in a single operation. It
can avoid long operational times and use of large amount of solvents or
expensive purification techniques.[14]
The first one-pot Wittig reaction was reported as early as 1968,[15] but
since then only limited reports on this reaction were published.[16] The one-
pot reactions were carried out under either conventional conditions in
organic solvents,[16a–c] microwave irradiation conditions,[16d] mechanically
induced conditions,[16e] or in the presence of catalysts.[16f,g] Here we report
aqueous one-pot Wittig reactions of aldehydes with ethyl bromoacetate and
bromoacetonitrile, respectively, in the presence of PPh3 for synthesis of
a,b-unsaturated carboxylic esters and nitriles.
To examine the reactivity of PPh3 with the halides in water, we first investi-
gated the reactions of ethyl bromoacetate (2a) and bromoacetonitrile (2b) with
PPh3 in refluxing water. After the reaction of a slight excess of 2a or 2b with
PPh3 in refluxing water for 10 min in the presence of 1.2 M LiCl, no PPh3 was
detected in the organic extraction of the aqueous reaction mixture. The result
indicated that formation of the phosphonium salt completed within only 10 min
in refluxing water even for bromoacetonitrile (2b), which needed 336 h in
refluxing benzene.[17] There are two reasons to account for this result: (a) the salt
formation converts the hydrophobic substrates to the hydrophilic product and (b)
the hydrophobic effect,[18] which was enhanced by addition of LiCl, in water
favors aggregation of the reactants and facilitates the reaction. The unexpected
rapid formation of phosphonium salts in refluxing water encouraged us to investi-
gate the aqueous one-pot Wittig reaction starting from aldehydes, PPh3, and the
halides. We considered that deprotonation of the phosphonium salts should occur
readily in aqueous media by using an inorganic base. According to our reported
results of aqueous Wittig reactions of the stabilized ylide with aldehydes,[12a] the
success of the one-pot protocol depends on the competitive pathways of the
Wittig olefination and the decomposition of the phosphonium salt or ylide in water.
We investigated the effect of reagent ratios on the one-pot Wittig reactions
of ethyl bromoacetate (2a) with 4-methoxybenzaldehyde (1b), which is a less
reactive aldehyde, in refluxing water in the presece of 1.2 M LiCl (Table 1).
When the ratio of 1b–2a–PPh3–LiOH was 1.0:1.2:1.2:1.5, the aldehyde 1b
did not disappear after 6 h and the isolated yield of 3b is only 40% (Table 1,
entry 1). When the ratio was increased to 1.0:1.5:1.5:1.8, the aldehyde 1b dis-
appeared after 70 min and the isolated yield of the product reached 90%
(Table 1, entry 2). With higher ratios of 2a and PPh3 to the aldehyde 1b

One-Pot Wittig Reactions in Aqueous Media
2941
Table 1. Effect of ratios of ethyl bromoacetate 2a, PPh3, and LiOH to aldehyde 1b on
the Wittig reactiona
1b–2a–Ph3P–
LiOH
Entry
t (min)
Yield (%);b E:Zc
1
2
3
4
1.0:1.2:1.2:1.5
1.0:1.5:1.5:1.8
1.0:1.8:1.8:2.1
1.0:1.8:1.8:2.1
360
70
40; 93:7
90; 93:7
92; 91:9
nde
25
35d
aCarried out in refluxing H2O in the presence of 1.2 M LiCl.
bIsolated yield of both isomers.
cDetermined by 1H NMR.
dThe mixture was heated for 10 min in the absence of 1b and then for another 25 min
with 1b.
(Table 1, entry 3), the reaction completed within 25 min to afford the olefin
product in 92% isolated yield. However, no olefin product was detected
when the mixture of 2a, PPh3, and LiOH was heated for 10 min under
refluxing conditions in the absence of 1b followed by refluxing for another
25 min together with 1b. We only recovered 1b from this reaction mixture
(Table 1, entry 4). The result implied that competition existed between the
Wittig reaction of the in situ–generated phosphorus ylide with aldehyde and
the decomposition of the ylide or its phosphonium precursor. It is clear that
slightly excessive amounts of the reagents to the aldehyde was beneficial for
high yields of the aqueous one-pot Wittig reactions. In addition, the
isomeric ratios of the olefin product are almost uninfluenced by changing
the reagent ratios (Table 1, entries 1–3).
With the optimized reaction conditions in hand, we investigated the
aqueous one-pot Wittig reactions for synthesis of a,b-unsaturated carboxylic
esters from ethyl bromoacetate (2a) with a collection of representative
aldehydes 1a–h. It should be emphasized that all substrates including ethyl
bromoacetate and the aldehydes are not water soluble except for 2-hydroxy-
benzaldehyde (1d) and 4-hydroxybenzaldehyde (1e). All reactions were
performed in refluxing H2O in the presence of 1.2 M LiCl, and the results
are summarized in Table 2. In general, the reactions of ethyl bromoacetate
(2a) with aromatic aldehydes 1a–g gave both good to excellent yields and
high E:Z isomer ratios (Table 2, entries 1–7). However, the E:Z selectivity
decreased to 74:26 for the reaction of crotonaldehyde (1h) (Table 2,
entry 8). These results are comparable with those obtained in the reactions
of the stabilized phosphorus ylide, carbethoxymethylenetriphenylphospho-
rane, with the corresponding aromatic aldehydes 1a–c, 1e, and 1g.[12a]

2942
J. Wu and C. Yue
Table 2. Aqueous one-pot Wittig reactions for synthesis of a,b-unsaturated
carboxylic estersa
Entry
1: R
t (min)
Yield (%)b
E:Zc
1
2
3
4
5
6
7
8
1a: 4-NO2C6H4
1b: 4-MeOC6H4
1c: Ph
30
25
3a: 84
3b: 92
3c: 87
3d: 89
3e: 72
3f: 92
3g: 97
3h: 80
86:14
93:7
98:2
97:3
94:6
93:7
99:1
74:26
15
10
1d: 2-HOC6H4
1e: 4-HOC6H4
1f: 4-ClC6H4
1g: 2-furanyl
1h: 2-butenyl
120
20
15
40
aCarried out in refluxing H2O with a 1.0:1.8:1.8:2.1 ratio of 1, 2a, PPh3, and LiOH in
the presence of 1.2 M LiCl.
bIsolated yield of both isomers.
cDetermined by 1H NMR.
The reaction time was found to be not parallel to the intrinsic reactivity of
the aldehydes in the order of 2-hydroxybenzaldehyde (1d) (10 min) ,
benzaldehyde (1c) ꢀ 2-furaldehyde (1g) (15 min) , 4-chlorobenzaldehyde
(1f) (20 min) , 4-anisaldehyde (1b) (25 min) , 4-nitrobenzaldehyde 1a
(30 min) , crotonaldehyde (1h) (40 min). For 4-hydroxybenzaldehyde (1e),
because of its low reactivity, a much longer reaction time (120 min) was
needed, and the product 3e was obtained with a lower yield (72%) (Table 2,
entry 5). It is interesting to find that the phenolic hydroxy group in 1d and
1e does not require protection (Table 2, entries 4 and 5). The results shown
in Table 2 indicate that the reactions of 2a with aldehydes gave high stereo-
selectivity (.93:7 of E:Z ratios) except for 4-nitrobenzaldehyde (1a) and
crotonaldehyde (1h).
We extended the aqueous one-pot Wittig reactions to the synthesis of a,b-
unsaturated nitriles. For the reactions of bromoacetonitrile (2b) with
aldehydes, the reaction time was parallel to the reactivity of aldehydes
except for 4-nitrobenzaldehyde (1a). This is somewhat different from the
reactions of ethyl bromoacetate. For the aldehydes bearing an electron-
donating group, because of the lower reactivity, a much longer reaction
time (65–120 min) was needed (Table 3, entries 2, 4, and 5). For 4-hydroxy-
benzaldehyde, only 14% conversion was observed when it reacted with
bromoacetonitrile (2b) (Table 3, entry 5).
Because of the less sterically demanding nitrile group, the ratios of the
product isomers decreased significantly (Table 3, entries 1, 3, and 5–7). For
example, 2b reacted with 1a and 1g to afford the olefins 4a and 4g as the

One-Pot Wittig Reactions in Aqueous Media
2943
Table 3. Aqueous one-pot Wittig reactions for synthesis of a,b-unsaturated nitrilesa
Entry
1:R
t (min)
Yield (%)b
E:Zc
1
2
3
4
5
6
7
1a: 4-NO2C6H4
1b: 4-MeOC6H4
1c: Ph
15
65
15d
20
120
5
4a:97
4b:71
4c:95
4d:92
4e:14e
4f:90
4g:96
55:45
99:1
62:38
100:0
71:29
78:22
56:44
1d: 2-HOC6H4
1e: 4-HOC6H4
1f: 4-ClC6H4
1g: 2-furanyl
5
aCarried out in refluxing H2O with a 1.0:1.8:1.8:2.1 ratio of 1, 2b, PPh3, and LiOH in
the presence of 1.2 M LiCl.
bIsolated yield of both isomers.
cDetermined by 1H NMR.
dCarried out in H2O at room temperature.
1
eConversion of the aldehyde to the olefin as determined by H NMR of the crude
reaction mixture.
55:45 and 56:44 mixtures of E:Z isomers, respectively (Table 3, entries 1
and 7). However, for the reaction of 2b with 1b and 1d, higher E:Z selectivity
(99:1 and 100:0 of E:Z ratios; Table 3, entries 2 and 4) was observed. It is
interesting to emphasize that the heterogeneous one-pot Wittig reaction of
2b with 1c took place in H2O even at room temperature (Table 3, entry 3)
to give a high yield of the olefin 4c.
In summary, we have established a general protocol for aqueous one-pot
Wittig reactions for synthesis of a,b-unsaturated carboxylic esters and nitriles
by mixing organic bromides, aldehydes, PPh3, LiOH, and LiCl in refluxing
water for 5–120 min. The reactions afford olefin products in 71–97% isolated
yields with E:Z ratios ranging from 55:45 to 100:0. Our study suggests that
H2O may be used to directly substitute organic solvents in other types of
organic reactions without structural modification on the substrates.
EXPERIMENTAL
Representative Procedure
A suspension of the organic bromide 2 (1.8 mmol), the aldehyde 1 (1.0 mmol),
and PPh3 (472.1 mg, 1.8 mmol) in H2O (5 mL) containing LiOH (50.4 mg,
.
2.1 mmol) and LiCl H2O (362.5 mg, 6.0 mmol) was refluxed in air for the
indicated time. After cooling to room temperature, the reaction mixture was

2944
J. Wu and C. Yue
extracted with EtOAc (10 mL Â 3), and the combined organic layer was
washed with brine, dried over Na2SO4, filtered, and condensed under
reduced pressure. The residue was then purified by column chromatography
over silica gel (10–30% EtOAc in hexane) to give the olefin products 3 and
4, respectively. The results are listed in Tables 2 and 3.
Data
Ethyl (E)-3-(4-nitrophenyl)prop-2-enoate 3a:[7a] (as an 86:14 mixture of E:Z
isomers) (400 MHz, CDCl3) d 8.25 (d, J ¼ 8.8 Hz, 2H), 7.71 (d, J ¼ 16.0 Hz,
1H), 7.68 (d, J ¼ 8.8 Hz, 2H), 6.56 (d, J ¼ 16.0 Hz, 1H), 4.30 (q, J ¼ 7.1 Hz,
2H), 1.36 (t, J ¼ 7.1 Hz, 3H). Ethyl (Z)-3-(4-nitrophenyl)prop-2-enoate
3a:[7a] (as an 86:14 mixture of E:Z isomers) (400 MHz, CDCl3) d 8.21
(d, J ¼ 8.8 Hz, 2H), 7.68 (d, J ¼ 8.8 Hz, 2H), 7.01 (d, J ¼ 12.4 Hz, 1H),
6.13 (d, J ¼ 12.4 Hz, 1H), 4.18 (q, J ¼ 7.2 Hz, 2H), 1.25 (t, J ¼ 7.2 Hz, 3H).
Ethyl (E)-3-(4-methoxyphenyl)prop-2-enoate 3b:[5a] (as a 93:7 mixture of E:Z
isomers) (500 MHz, CDCl3) d 7.65 (d, J ¼ 16.0 Hz, 1H), 7.48 (d, J ¼ 8.7 Hz,
2H), 6.91 (d, J ¼ 8.7 Hz, 2H), 6.31 (d, J ¼ 16.0 Hz, 1H), 4.26 (q, J ¼ 7.1 Hz,
2H), 3.84 (s, 3H), 1.34 (t, J ¼ 7.1 Hz, 3H).
Ethyl (E)-3-phenylprop-2-enoate 3c:[5a,7a] (as a 98:2 mixture of E:Z isomers)
(500 MHz, CDCl3) d 7.68 (d, J ¼ 16.0 Hz, 1H), 7.54–7.52 (m, 2H),
7.39–7.38 (m, 3H), 6.44 (d, J ¼ 16.0 Hz, 1H), 4.26 (q, J ¼ 7.1 Hz, 2H),
1.34 (t, J ¼ 7.1 Hz, 3H).
Ethyl (E)-3-(2-hydroxyphenyl)prop-2-enoate 3d:[19] (as a 97:3 mixture of E:Z
isomers) (400 MHz, CDCl3) d 8.08 (d, J ¼ 16.0 Hz, 1H), 7.46 (d, J ¼ 7.6 Hz,
1H), 7.32 (s, 1H), 7.25–7.21 (m, 1H), 6.92–6.88 (m, 2H), 6.67
(d, J ¼ 16.0 Hz, 1H), 4.30 (q, J ¼ 7.2 Hz, 2H), 1.36 (t, J ¼ 7.2 Hz, 3H).
Ethyl (E)-3-(4-hydroxyphenyl)prop-2-enoate 3e:[5a] (as a 94:6 mixture of E:Z
isomers) (400 MHz, CDCl3) d 7.64 (d, J ¼ 16.0 Hz, 1H), 7.41 (d, J ¼ 8.5 Hz,
2H), 7.14 (bs, 1H), 6.87 (d, J ¼ 8.5 Hz, 2H), 6.29 (d, J ¼ 16.0 Hz, 1H), 4.26
(q, J ¼ 7.1 Hz, 2H), 1.34 (t, J ¼ 7.1 Hz, 3H).
Ethyl (E)-3-(4-chlorophenyl)prop-2-enoate 3f:[7a] (as a 93:7 mixture of E:Z
isomers) (400 MHz, CDCl3) d 7.64 (d, J ¼ 16.0 Hz, 1H), 7.47 (d, J ¼ 8.8 Hz,
2H), 7.37 (d, J ¼ 8.8 Hz, 2H), 6.42 (d, J ¼ 16.0 Hz, 1H), 4.29 (q, J ¼ 7.2 Hz,
2H), 1.34 (t, J ¼ 7.2 Hz, 3H). Ethyl (Z)-3-(4-chlorophenyl)prop-2-enoate
3f:[7a] (as a 93:7 mixture of E:Z isomers) (400 MHz, CDCl3) d 7.56
(d, J ¼ 8.8 Hz, 2H), 7.34 (d, J ¼ 8.8 Hz, 2H), 6.90 (d, J ¼ 12.8 Hz, 1H), 5.98
(d, J ¼ 12.8 Hz, 1H), 4.20 (q, J ¼ 7.2 Hz, 2H), 1.27 (t, J ¼ 7.2 Hz, 3H).
Ethyl (E)-3-(2-furanyl)prop-2-enoate 3g:[16f,20] (as a 99:1 mixture of E:Z
isomers) (400 MHz, CDCl3)
d
7.47 (d, J ¼ 1.6 Hz, 1H), 7.42
(d, J ¼ 15.6 Hz, 1H), 6.60 (d, J ¼ 3.2 Hz, 1H), 6.46 (dd, J ¼ 3.2 Hz,

One-Pot Wittig Reactions in Aqueous Media
2945
1.6 Hz, 1H), 6.31 (d, J ¼ 15.6 Hz, 1H), 4.24 (q, J ¼ 7.2 Hz, 2H), 1.32
(t, J ¼ 7.2 Hz, 3H).
Ethyl (2E, 4E)-hexa-2,4-dienoate 3h:[21,22] (as a 74:26 mixture of 2E, 4E–2Z,
4E isomers) (400 MHz, CDCl3) d 7.25 (dd, J ¼ 15.4 Hz, 9.8 Hz, 1H), 6.22–
6.09 (m, 2H), 5.76 (d, J ¼ 15.6 Hz, 1H), 4.18 (q, J ¼ 7.2 Hz, 2H), 1.84
(d, J ¼ 5.6 Hz, 3H), 1.28 (t, J ¼ 7.2 Hz, 3H). Ethyl (2Z, 4E)-hexa-2,4-
dienoate 3h:[21] (as a 74:26 mixture of 2E, 4E–2Z, 4E isomers) (400 MHz,
CDCl3) d 7.37 (dd, J ¼ 15.0 Hz, 10.4 Hz, 1H), 6.53 (t, J ¼ 11.2 Hz, 1H),
6.10–6.03 (m, 1H), 5.54 (d, J ¼ 11.6 Hz, 1H), 4.17 (q, J ¼ 7.6 Hz, 2H),
1.88 (d, J ¼ 7.2 Hz, 3H), 1.29 (t, J ¼ 7.2 Hz, 3H).
(E)-3-(4-Nitrophenyl)prop-2-enenitrile 4a:[16b,23] (as a 55:45 mixture of E:Z
isomers) (400 MHz, CDCl3)
d
8.28 (d, J ¼ 8.4 Hz, 2H), 7.63
(d, J ¼ 8.4 Hz, 2H), 7.47 (d, J ¼ 16.8 Hz, 1H), 6.05 (d, J ¼ 16.8 Hz, 1H);
(Z)-3-(4-Nitrophenyl)prop-2-enenitrile 4a:[16b,23] (as a 55:45 mixture of E:Z
isomers) (400 MHz, CDCl3)
d
8.31 (d, J ¼ 8.4 Hz, 2H), 7.96
(d, J ¼ 8.4 Hz, 2H), 7.24 (d, J ¼ 12.4 Hz, 1H), 5.71 (d, J ¼ 12.4 Hz, 1H).
(E)-3-(4-Methoxyphenyl)prop-2-enenitrile 4b:[23,24] (as a 99:1 mixture of E:Z
isomers) (400 MHz, CDCl3) d 7.39 (d, J ¼ 8.4 Hz, 2H), 7.33 (d, J ¼ 16.4 Hz,
1H), 6.91 (d, J ¼ 8.4 Hz, 2H), 5.71 (d, J ¼ 16.4 Hz, 1H), 3.84 (s, 3H).
(E)-3-Phenylprop-2-enenitrile 4c:[16b,23–25] (as a 62:38 mixture of E:Z
isomers) (400 MHz, CDCl3) d 7.44–7.37 (m, 6H), 5.87 (d, J ¼ 16.8 Hz,
1H). (Z)-3-Phenyl-2-propenentrile 4c:[16b,23–25] (as a 62:38 mixture of E:Z
isomers) (400 MHz, CDCl3) d 7.81–7.79 (m, 2H), 7.44–7.42 (m, 3H), 7.12
(d, J ¼ 12.0 Hz, 1H), 5.44 (d, J ¼ 12.0 Hz, 1H).
(E)-3-(2-Hydroxyphenyl)prop-2-enenitrile 4d:[26] (as a pure (E) isomer)
(400 MHz, CDCl3) d 7.60 (d, J ¼ 16.8 Hz, 1H), 7.37 (dd, J ¼ 7.2 Hz,
1.6 Hz, 1H), 7.29–7.25 (m, 1H), 6.97–6.83 (m, 1H), 6.82 (d, J ¼ 8.0 Hz,
1H), 6.14 (d, J ¼ 16.8 Hz, 1H), 5.81 (bs, 1H).
(E)-3-(4-Chlorophenyl)prop-2-enenitrile 4f:[16b,24,25] (as a 78:22 mixture of
E:Z isomers) (400 MHz, CDCl3)
d
7.39–7.33 (m, 5H), 5.86
(d, J ¼ 16.4 Hz, 1H). (Z)-3-(4-Chlorophenyl)prop-2-enenitrile 4f:[16b,24,25]
(as a 78:22 mixture of E:Z isomers) (400 MHz, CDCl3) d 7.75
(d, J ¼ 8.0 Hz, 2H), 7.41 (d, J ¼ 8.0 Hz, 2H), 7.09 (d, J ¼ 12.6 Hz, 1H),
5.48 (d, J ¼ 12.6 Hz, 1H).
(E)-3-(2-Furanyl)prop-2-enenitrile 4g:[16b,20,24,25] (as a 56:44 mixture of E:Z
isomers) (400 MHz, CDCl3) d 7.49 (s, 1H), 7.11 (d, J ¼ 16.4 Hz, 1H), 6.62
(d, J ¼ 3.2 Hz, 1H), 6.50 (dd, J ¼ 3.2, 1.6 Hz, 1H), 5.76 (d, J ¼ 16.4 Hz,
1H). (Z)-3-(2-Furanyl)prop-2-enenitrile 4g:[16b,20,24,25] (as a 56:44 mixture
of E:Z isomers) (400 MHz, CDCl3) d 7.57 (s, 1H), 7.04 (d, J ¼ 3.2 Hz,
1H), 6.95 (d, J ¼ 12.4 Hz, 1H), 6.54 (dd, J ¼ 3.2, 1.6 Hz, 1H), 5.23
(d, J ¼ 12.4 Hz, 1H).

2946
J. Wu and C. Yue
ACKNOWLEDGMENT
This work was supported in part by a research grand to J. Wu from Zhejiang
Province Natural Science Fund (Y404302), China. The authors also thank
Wei-Min Dai for his encouragement and discussion during the course of
this study.
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(b) Li, C.-J. Chem. Rev. 1993, 93, 2023–2035; (c) Lubineau, A.; Auge, J.;
Queneau, Y. Synthesis 1994, 741–760; (d) Lubineau, A. Chem. Ind. (London),
1996, 123–126; (e) Li, C.-J. Tetrahedron 1996, 52, 5643–5668; (f) Li, C.-J.;
Chan, T.-H. Organic Reactions in Aqueous Media; John Wiley & Sons:
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