Facile synthesis of ethyl 2-arylpropenoates by cross-coupling reaction using electrogenerated highly reactive zinc

Article abstract of DOI:10.1016/S0040-4020(02)00830-X

Highly reactive zinc metal was prepared by electrolysis of a DMF solution containing naphthalene and a supporting electrolyte in a one-compartment cell fitted with a platinum cathode and a zinc anode. This reactive zinc was used for efficient transformation of ethyl 2-bromoacrylate into the corresponding organozinc compound, which was reacted with various aryl iodides or bromides in the presence of 5 mol% Pd(P(o-Tol)₃)₂Cl₂ to give the corresponding cross-coupling products in high yields. These cross-coupling reactions were successfully applied to a synthesis of the precursor of naproxen and cicloprofen, non-steroidal anti-inflammatory agent.

Full text of DOI:10.1016/S0040-4020(02)00830-X

Tetrahedron 58 (2002) 7477–7484
Facile synthesis of ethyl 2-arylpropenoates by cross-coupling
reaction using electrogenerated highly reactive zinc
*
Aishah A. Jalil, Nobuhito Kurono and Masao Tokuda
Division of Molecular Chemistry, Graduate School of Engineering, Hokkaido University, Sapporo 060-8628, Japan
Received 11 June 2002; accepted 8 July 2002
Abstract—Highly reactive zinc metal was prepared by electrolysis of a DMF solution containing naphthalene and a supporting electrolyte in
a one-compartment cell fitted with a platinum cathode and a zinc anode. This reactive zinc was used for efficient transformation of ethyl 2-
bromoacrylate into the corresponding organozinc compound, which was reacted with various aryl iodides or bromides in the presence of
5 mol% Pd(P(o-Tol)3)2Cl2 to give the corresponding cross-coupling products in high yields. These cross-coupling reactions were
successfully applied to a synthesis of the precursor of naproxen and cicloprofen, non-steroidal anti-inflammatory agent. q 2002 Elsevier
Science Ltd. All rights reserved.
1. Introduction
preparation of organozinc compounds from functionalized
alkyl iodides by using EGZn and their cross-couplings with
aryl halides.6 However, organozinc bromides were rarely
obtained or were only obtained in very low yields from the
corresponding organic bromides, even if the reactive EGZn
was used. Recently, we developed a new electrochemical
method for preparation of more highly reactive zinc (EGZn/
Naph) by using naphthalene as a mediator (Scheme 1).7 The
reaction of EGZn/Naph with ethyl 2-bromoacrylate gave
efficiently the corresponding organozinc bromide and
subsequent cross-coupling reaction with various aryl
iodides in the presence of palladium catalyst proceeded
efficiently to give ethyl 2-arylpropenoates in high yields.7
However, no cross-coupling reaction occurred under these
conditions when aryl bromide was used as one of the
coupling components. We examined various reaction
conditions and found that the cross-coupling using aryl
bromides could undergo when THF, instead of DMF, was
used as a solvent.
Organozinc compounds are very useful organometallic
compounds for the forming reaction of carbon–carbon
bonds.1 Organozinc halides can usually be prepared by
direct insertion of zinc metal into organic halides,1b but
commercially available zinc metal is generally poorly
reactive. Therefore, activation of the metal is necessary
for preparation of organozinc halides. Various methods of
zinc activation, such as the reduction of zinc halide with
alkaline metal or alkali metal naphthalenide, have been
reported.2 These methods, however, require high tempera-
ture and long reaction times, or vigorous stirring during the
reaction.
We have already reported a new method for the preparation
of reactive zinc by electrolysis and its use in facile
isoprenylation3 and allylation4,5 of aldehydes and ketones.
It was shown that this electrogenerated reactive zinc (EGZn)
was an aggregation of very fine crystalline zinc particles
with a large surface area.4 We have also reported a facile
In this paper, we report a facile synthesis of ethyl
Scheme 1.
Keywords: electrolysis; reactive zinc; coupling reactions; palladium catalyst; anti-inflammatory agent.
*
Corresponding author. Tel.: þ81-11-706-6599; fax: þ81-11-706-6598; e-mail: tokuda@org-mc.eng.hokudai.ac.jp
0040–4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(02)00830-X

7478
A. A. Jalil et al. / Tetrahedron 58 (2002) 7477–7484
Scheme 2.
Table 1. Cross-coupling reaction of organozinc bromide 2 with
iodobenzene (3a) using various zinc metals
2. Results and discussion
2.1. Electrochemical preparation of highly reactive zinc
(EGZn/Naph)
Entry
Type of zinc
Yield of 4a (%)a
1
2
3
4
Zn powderb
Zn–Cu couple
EGZn
0
11
19
98
Highly reactive zinc was readily prepared by electrolysis of
a DMF solution containing 0.1 M Et4NClO4 in the presence
of naphthalene in a one-compartment cell fitted with a
platinum plate cathode (2£2 cm2) and a zinc plate anode
(2£2 cm2). Electrolysis was carried out at a constant current
of 60 mA cm22 at 2108C under a nitrogen atmosphere. At
the cathode, a one-electron reduction of naphthalene
molecule readily occurred to give naphthalene radical
anion preferentially. The formation of the naphthalene
radical anions was shown by the dark green color appeared
on the surface of the cathode. On the other hand, at the
anode, dissolution of the zinc metal occurred to give zinc
ions, which were reduced by the naphthalene radical anions
to give zero-valence highly reactive zinc, EGZn/Naph
(Scheme 1). The EGZn/Naph was an aggregation of very
EGZn/Naph
Organozinc bromide 2, prepared from ethyl 2-bromoacrylate (1) (3 mmol)
and zinc (6 mmol), was reacted in DMF at 708C for 3 h with iodobenzene
(2 mmol) in the presence of 5 mol% of Pd(P(o-Tol)3)2Cl2.
a
Isolated yields.
Commercially available zinc from Kanto Chemical Co. Inc. was
activated according to Ref. 8.
b
2-arylpropenoates by cross-coupling reaction of organozinc
bromide derived from ethyl 2-bromoacrylate with various
aryl bromides and iodides. Application of these cross-
coupling reactions to a synthesis of the precursor of
non-steroidal anti-inflammatory agents such as naproxene
and cicloprofen was also reported.
Table 2. Synthesis of ethyl 2-arylpropenoates (4) by palladium catalyzed cross-coupling of aryl iodides (3) with organozinc bromide 2
Entry
1
ArI
Product
Yield (%)a
98
C6H5I (3a)
2
3
4
4-CH3OC6H4I (3b)
4-CH3C6H4I (3c)
3-CH3C6H4I (3d)
98
98
96
5
6
2-CH3C6H4I (3e)
4-NCC6H4I (3f)
84
97
7
4-CH3OOCC6H4I (3g)
98
8
9
2-CH3OOCC6H4I (3h)
4-BrC6H4I (3i)
51
96
Organozinc bromide 2, prepared from ethyl 2-bromoacrylate (1) (3 mmol) and EGZn/Naph (6 mmol), in DMF was reacted at 708C for 3 h with aryl iodides 3
(2 mmol) in the presence of 5 mol% of Pd(P(o-Tol)3)2Cl2.
a
Isolated yields. The yields are based on aryl iodides 3 employed.

A. A. Jalil et al. / Tetrahedron 58 (2002) 7477–7484
7479
fine zinc particles with much smaller sizes than those of
EGZn6 and was dispersed in the DMF solution. Although
the nature and structure of EGZn/Naph are not clear at the
present stage, it was found to be very reactive towards an
oxidative addition to organic bromides.
acrylate (1) and EGZn/Naph, with aryl iodides was
examined under various conditions. It was found that the
temperature in the forming step of 2 and the kind of metal
complex in the cross-coupling step are the most effective
factors in this reaction. The reaction of ethyl 2-bromo-
acrylate (1) with EGZn/Naph at 80, 0, or 2208C and the
following cross-coupling reaction with iodobenzene (3a)
using 5 mol% Pd(P(o-Tol)3)2Cl2 gave ethyl 2-phenyl-
acrylate (4a) in 72, 84, or 98% yield, respectively. A
palladium complex of Pd(PPh3)2Cl2 could also be used in
the same way as Pd(P(o-Tol)3)2Cl2, but the use of
Ni(PPh3)2Cl2 gave 4a in a low yield.
The high reactivity of EGZn/Naph was shown from the
transforming reaction of ethyl 2-bromoacrylate (1) into the
corresponding organozinc bromide 2 followed by its
cross-coupling with iodobenzene (3a; R¼H) to give ethyl
2-phenylpropenoate (4a; R¼H) (Scheme 2). When
activated zinc powder8 or zinc–copper couple was used in
this reaction, the cross-coupling product 4a was not
obtained or obtained in a very low yield. Even when
EGZn was used, the product 4a was obtained only in 19%
yield. However, when EGZn/Naph was used for preparation
of 2, the product 4a was obtained in 98% yield (Table 1).
Electrochemical preparation of EGZn/Naph in DMF and the
subsequent reaction with ethyl 2-bromoacrylate at 2208C
for 1 h gave efficiently the corresponding organozinc
bromide 2. Subsequent one-pot reactions of a DMF solution
containing 2 with various iodobenzenes (3a–3i) in the
presence of 5 mol% Pd(P(o-Tol)3)2Cl2 at 708C for 3 h gave
the corresponding cross-coupled products, ethyl 2-aryl-
propenoates (4a–4i), in high yields (Scheme 2). The results
are summarized in Table 2. The use of iodobenzene itself
2.2. Synthesis of ethyl 2-arylpropenoates (4) by cross-
coupling of organozinc compound 2 with aryl iodides
The cross-coupling of 2, derived from ethyl 2-bromo-
Scheme 3.
Table 3. Synthesis of ethyl 2-arylpropenoates (4) by palladium catalyzed cross-coupling of aryl bromides (5) with organozinc bromide 2
Entry
1
ArBr
Product
Yield (%)a
47
C6H5Br (5a)
2
3
4
5
6
7
4-CH3OC6H4Br (5b)
4-CH3C6H4Br (5c)
4-NCC6H4Br (5f)
4-CH3COC6H4Br (5j)
4-O2NC6H4Br (5k)
4-BrC6H4Br (5l)
98
98
96
93
67
40
8
92
A mixture of organozinc bromide 2, prepared from ethyl 2-bromoacrylate (1) (3 mmol) and EGZn/Naph (6 mmol), was reacted under reflux in THF for 3 h with
aryl bromides 5 (2 mmol) and 5 mol% of Pd(P(o-Tol)3)2Cl2.
Isolated yields. The yields are based on aryl bromides 5 employed.
a

7480
Table 4. Synthesis of the precursor of naproxen (7a) and cicloprofen (7b)
Entry ArX
A. A. Jalil et al. / Tetrahedron 58 (2002) 7477–7484
Product
Yield (%)a
1b
95
2c
97
a
Isolated yields.
b
Organozinc bromide 2 was prepared from ethyl 2-bromoacrylate (1) (3 mmol) and EGZn/Naph (6 mmol). Organozinc bromide 2 was reacted in DMF at
708C for 3 h with aryl iodides 6a (2 mmol) in the presence of 5 mol% of Pd(P(o-Tol)3)2Cl2.
Organozinc bromide 2 was reacted under reflux in THF for 3 h with aryl bromides 6b (2 mmol) and 5 mol% of Pd(P(o-Tol)3)2Cl2.
c
(3a) and substituted iodobenzenes carrying an electron-
donating (3b, 3c, or 3d) or an electron-withdrawing group
(3f or 3g) gave the corresponding products 4 in almost
quantitative yields. Iodobenzenes carrying ortho-sub-
stituents (3e and 3h) gave 4e and 4h in lower yields,
probably due to their steric hindrances. Cross-coupling of 2
with 4-bromo-iodobenzene 3i also took place efficiently to
give the product 4i in 96% yield.
bromide 2, readily prepared from ethyl 2-bromoacrylate and
EGZn/Naph, with aryl iodides or bromides gave ethyl
2-arylpropenoates 4 in excellent yields. Therefore we
attempted to apply this cross-coupling reaction to a
synthesis of the precursor of anti-inflammatory agents.
Reaction of organozinc bromide 2 with 2-iodo-6-methoxy-
naphthalene (6a) and 2-bromofluorene (6b) gave the
precursor of naproxen (7a) and cicloprofen (7b) in 95 and
97% yield, respectively (Table 4). Enantioselective hydro-
genation of 7a and 7b would give ethyl esters of (S )-
naproxen and (S)-cicloprofen in high yields and in high
enantioselectivities, since hydrogenation of a,b-unsaturated
acids with Ru-(S )-BINAP catalyst has been reported to give
(S )-alkanoic acids in a high enantioselective manner.9
2.3. Synthesis of ethyl 2-arylpropenoates (4) by cross-
coupling of organozinc compound 2 with aryl bromides
Cross-coupling reactions of organozinc bromide 2 with aryl
iodides took place efficiently to give the products 4 in high
yields. However, no products were obtained when aryl
bromides, instead of aryl iodides, were used under these
conditions. After examination of several reaction con-
ditions, we found that the expected cross-coupling reaction
took place to give 4 in high yields when THF, instead of
DMF, was used as a solvent in the reaction step of 2 with
aryl bromides (5) (Scheme 3).
2.5. Reaction pathways
Probable reaction pathways of the preparation of EGZn/
Naph are shown in Scheme 4. Electrolysis of a DMF
solution with a platinum cathode and a zinc anode results in
anodic dissolution of zinc metal to give zinc ions. On the
other hand, at the cathode, a one-electron reduction of
naphthalene molecule occurs to give radical anion of
naphthalene, which was shown by appearance of the dark
green color on the surface of the cathode. Reduction of zinc
ion with naphthalene radical anion would give zero-valent
reactive zinc (EGZn/Naph).
Results are summarized in Table 3. Cross-coupling reac-
tions with bromobenzenes carrying an electron-donating
(5b and 5c) or an electron-withdrawing groups (5f and 5j)
gave the corresponding cross-coupled products 4 in
excellent yields. Lower yields were observed from the
reaction of 4-nitro-bromobenzene (5k) (entry 6). In the case
of 1,4-dibromobenzene (5l) there are two reaction sites and,
therefore, the expected cross-coupling product (4i) was
obtained in a 40% yield together with 23% of 1,4-bis(1-
ethoxycarbonylvinyl)benzene. A reason of the low yield of
4a in the reaction of bromobenzene (5a) is not clear at the
present stage. Cross-coupling with 2-bromonaphthalene
proceeded efficiently to give the corresponding product
4m in 92% yield (entry 8).
Probable reaction pathways of the present cross-couplings
are shown in Scheme 5. Oxidative addition of Pd(0) to aryl
2.4. Application to a synthesis of the precursor of anti-
inflammatory agents
It appeared that the cross-coupling reaction of organozinc
Scheme 4.

A. A. Jalil et al. / Tetrahedron 58 (2002) 7477–7484
7481
4.2. Solvent and reagents
Commercially available anhydrous N,N-dimethylforma-
mide (DMF) and tetrahydrofuran (THF) packed under a
nitrogen atmosphere (Kanto Chemical) were used without
further purification. Tetraethylammonium perchlorate was
prepared according to the previous reported method.6 The
zinc metal plate (Nilaco) is commercially available in more
than 99.9% purities, and was washed with 2N HCl,
methanol, acetone and dried before electrolysis. Com-
mercially available naphthalene (Junsei Chemical, 99%)
was used after recrystallization from methanol. Most of aryl
iodides and aryl bromides are commercially available
and they were purified by distillation prior to use. Ethyl
2-bromoacrylate10 and 4-iodoanisole11 were prepared
according to the procedure reported in the literatures.
2-Iodo-6-methoxynaphthalene and 4-iodobenzonitrile was
prepared from the corresponding bromide according to the
reported method.12
4.2.1. Ethyl 2-bromoacrylate (1).10 82%; bp
Scheme 5.
808C/69 mm Hg; IR (neat) 1725, 1605, 1259, 1102 cm21
;
1H NMR (CDCl3) d 6.96 (1H, d, J¼1.7 Hz), 6.27 (1H, d,
J¼1.7 Hz), 4.29 (2H, q, J¼7.3 Hz), 1.34 (3H, t, J¼7.3 Hz);
13C NMR (CDCl3) d 161.72, 130.26, 121.47, 62.57, 13.93;
EIMS m/z (relative intensity) 180 (18), 178 (18), 150 (19),
133 (40), 105 (49), 99 (65), 45 (100); HRMS Calcd for
C5H7BrO2 m/z 177.9629. Found m/z 177.9622.
halides would give Ar–Pd–X (8), which undergoes metal
exchange reaction with organozinc bromide 2 to give an
intermediate 9. Reductive elimination of 9 would give the
cross-coupling product, ethyl 2-arylpropenoates 4.
4.2.2. 4-Iodoanisole (3b).11 55%; mp 51–528C (lit:11
3. Conclusion
1
528C); H NMR (CDCl3) d 7.56 (2H, dd, J¼2.3, 6.9 Hz),
6.68 (2H, dd, J¼2.3, 6.9 Hz), 3.78 (3H, s).
We developed a new electrochemical method for
preparation of highly reactive zinc (EGZn/Naph) by using
naphthalene as mediator in the electrolysis. The correspond-
ing organozinc bromide could readily be prepared under
mild conditions by the reaction of ethyl 2-bromoacrylate
with EGZn/Naph. Subsequent cross-coupling reaction of the
organozinc bromide with various aryl halides readily took
place in the presence of a palladium catalyst to give the
corresponding cross-coupled products, ethyl 2-arylpropeno-
ates, in high yields. It was also found that this cross-
coupling reaction could be applied to a synthesis of the
precursor of anti-inflammatory agents such as naproxen and
cicloprofen.
4.2.3. 4-Iodobenzonitrile (3f). 70%; IR (nujol) 2226, 1579,
1475, 1393 cm21; 1H NMR (CDCl3) d 7.85 (2H, dd, J¼1.7,
6.6 Hz), 7.37 (2H, dd, J¼1.7, 6.6 Hz).
4.2.4. Methyl 4-iodobenzoate (3g).13 A mixture of
4-iodobenzoic acid (2.48 g, 10 mmol), chlorotrimethyl-
silane (3.18 ml, 25 mmol), methanol (53 ml), and THF
(17.4 ml) was stirred for 36 h at room temperature.
Extraction of the reaction mixture was carried out
with dichloromethane (30 ml£3). After evaporation of
dichloromethane, the crude product was recrystallized
from ether and ethanol. 95%; IR (nujol) 1716, 1586,
1
1454, 1378 cm21; H NMR (CDCl3) d 7.82–7.79 (2H, dd,
J¼2.0, 8.6 Hz), 7.75–7.72 (2H, dd, J¼2.0, 8.6 Hz), 3.91
(3H, s).
4. Experimental
4.1. General methods
4.2.5. Methyl 2-iodobenzoate (3h). Esterification of
2-iodobenzoic acid according to the preparation of 3g
afforded the crude product. Distillation of the crude
product gave a colorless oil.13 49%; bp 1448C/20 mm Hg;
1H NMR (CDCl3) d 8.00 (1H, d, J¼7.6 Hz), 7.81 (1H, d,
J¼7.6 Hz), 7.41 (1H, t, J¼7.6 Hz), 7.16 (1H, t, J¼7.6 Hz),
3.94 (3H, s).
IR spectra were recorded on a JASCO IR-810 infrared
1
spectrometer (neat between NaCl plates). H NMR spectra
were recorded on a JEOL JNM-EX270 FT-NMR spec-
trometer operated at 270 MHz (solvent CDCl3). Proton-
decoupled 13C spectra were recorded at 67.8 MHz on a
JEOL JNM-EX270 spectrometer. 1H and 13C chemical
shifts are reported in ppm (d) using SiMe4 as an internal
standard. High and low resolution mass spectra were
determined with a JEOL JMS-AX500 or JEOL JMS-
SX102A spectrometer. Thin-layer chromatography and
column chromatography were carried out on a Merck
4.2.6. 2-Iodo-6-methoxynaphthalene (6a).12 38%; mp
1
145–1468C (lit.12 mp 146–1478C); H NMR (CDCl3) d
8.14 (s, 1H), 7.68–7.46 (m, 3H), 7.25–7.07 (m, 2H), 3.92
(s, 3H); 13C NMR (CDCl3) d 157.93, 136.19, 134.68,
133.30, 130.55, 128.34, 128.30, 119.52, 105.63, 88.05,
55.28.
Kieselgel 60 PF254
.

7482
A. A. Jalil et al. / Tetrahedron 58 (2002) 7477–7484
4.3. Preparation of electrogenerated highly reactive zinc
(EGZn/Naph)
129.45, 129.20, 124.92, 113.48, 61.03, 55.26, 14.20; IR
(neat) 1723, 1611, 1195, 1177, 1033, 836 cm21; EIMS m/z
(relative intensity) 206 (47), 162 (15), 133 (100), 118 (12),
90 (14), 77 (11), 63 (10); HRMS Calcd for C12H14O3 m/z
206.0943. Found m/z 206.0958; Anal. Calcd for C12H14O3:
C, 69.88; H, 6.84. Found: C, 69.72; H, 6.88.
A normal one-compartment cell equipped with a magnetic
stirrer and a serum cap was used. Electrogenerated highly
reactive EGZn/Naph (6 mmol) was prepared by the
electrolysis of a DMF solution (10 ml) containing 0.1 M
Et4NClO4 (230 mg) and naphthalene (12 mmol) in a one-
compartment cell fitted with a platinum plate cathode
(2£2 cm2) and a zinc plate anode (2£2 cm2). Electrolysis
was carried out at 2108C at a constant current of
60 mA/cm2 under nitrogen atmosphere. The quantity of
electricity passed was 0.012 F, which corresponded to 2 F
per mol of zinc metal. The amount of EGZn/Naph was
calculated from the weight of dissolved zinc anode metal. A
solution containing EGZn/Naph was directly used for the
preparation of organozinc compounds after the zinc anode
was removed from the electrolysis cell.
4.4.3. Ethyl 2-(4-tolyl)propenoate (4c). 1H NMR (CDCl3)
d 7.32 (2H, dd, J¼2.0, 6.6 Hz), 7.16 (2H, dd, J¼2.0,
6.6 Hz), 6.29 (1H, d, J¼1.0 Hz), 5.85 (1H, d, J¼1.0 Hz),
4.29 (2H, q, J¼7.3 Hz), 2.36 (3H, s), 1.33 (3H, t, J¼7.3 Hz);
13C NMR (CDCl3) d 166.88, 141.33, 137.86, 133.80,
128.70, 128.05, 125.59, 60.94, 21.08, 14.11; IR (neat) 1722,
1613, 1198, 1182, 1023, 825 cm21; EIMS m/z (relative
intensity) 190 (64), 146 (30), 117 (100), 115 (36), 91 (27);
HRMS Calcd for C12H14O2 m/z 190.0994. Found m/z
190.0981; Anal. Calcd for C12H14O2: C, 75.76; H, 7.42.
Found: C, 75.90; H, 7.28.
4.4. General procedure for cross-coupling reaction using
EGZn/Naph
4.4.4. Ethyl 2-(3-tolyl)propenoate (4d). 1H NMR (CDCl3)
d 7.24 (3H, m), 7.16 (1H, s), 6.32 (1H, d, J¼1.3 Hz), 5.87
(1H, d, J¼1.3 Hz), 4.29 (2H, q, J¼7.3 Hz), 2.37 (3H, s),
1.33 (3H, t, J¼7.3 Hz); 13C NMR (CDCl3) d 166.95, 141.69,
137.68, 136.73, 128.96, 128.89, 127.99, 126.22, 125.37,
61.08, 21.44, 14.23; IR (neat) 1721, 1606, 1226, 1174, 1026,
792, 715 cm21; EIMS m/z (relative intensity) 190 (69), 146
(31), 117 (100), 115 (42), 91 (24); HRMS Calcd for
C12H14O2 m/z 190.0994. Found m/z 190.0979; Anal. Calcd
for C12H14O2: C, 75.76; H, 7.42. Found: C, 75.63; H, 7.62.
Cross-coupling using aryl iodides. To the DMF solution
containing EGZn/Naph was added ethyl 2-bromoacrylate
(1) (3 mmol) and the mixture was stirred at 2208C under
nitrogen atmosphere for 1 h. DMF solution (5 ml) of aryl
iodide (2 mmol) and Pd(P(o-Tol)3)2Cl2 (0.11 mmol) was
added, and the reaction mixture was stirred at 708C for 3 h.
The resulting mixture was quenched with HCl solution and
filtered. The filtrate was extracted with diethyl ether
(50 ml£3) and the combined organic layers were washed
with water (100 ml£3), saturated Na2S2O3 solution
(100 ml£1) and saturated NaCl solution (100 ml£1) and
dried over MgSO4. After evaporation of diethyl ether, the
crude product was purified by column chromatography on
silica gel with ethyl acetate–hexane (1:5) to give ethyl
2-arylpropenoate 4.
4.4.5. Ethyl 2-(2-tolyl)propenoate (4e). 1H NMR (CDCl3)
d 7.18 (4H, m), 6.50 (1H, d, J¼1.7 Hz), 5.70 (1H, d,
J¼1.7 Hz), 4.24 (2H, q, J¼7.3 Hz), 2.21 (3H, s), 1.27 (3H, t,
J¼7.3 Hz); 13C NMR (CDCl3) d 166.66, 142.12, 137.34,
136.10, 129.83, 129.50, 128.28, 128.08, 125.62, 61.06,
19.84, 14.20; IR (neat) 1721, 1624, 1208, 1187, 1026,
746 cm21; EIMS m/z (relative intensity) 190 (34), 161 (29),
133 (40), 117 (83), 115 (100), 91 (29); HRMS Calcd for
C12H14O2 m/z 190.0994. Found m/z 190.0993; Anal. Calcd
for C12H14O2: C, 75.76; H, 7.42. Found: C, 75.93; H, 7.30.
Cross-coupling using aryl bromides: To the DMF solution
containing EGZn/Naph was added ethyl 2-bromoacrylate
(1) (3 mmol) and the mixture was stirred at 2208C under
nitrogen atmosphere for 1 h. The reaction mixture was
added to a THF solution (50 ml) of aryl bromide (2 mmol)
and Pd(P(o-Tol)3)2Cl2 (0.11 mmol). Similar work-up and
purification as those of the cross-coupling using aryl iodides
gave ethyl 2-arylpropenoate 4.
1
4.4.6. Ethyl 2-(4-cyanophenyl)propenoate (4f). H NMR
(CDCl3) d 7.65 (2H, dd, J¼2.0, 6.6 Hz), 7.54 (2H, dd,
J¼2.0, 6.6 Hz), 6.50 (1H, s), 5.98 (1H, s), 4.30 (2H, q,
J¼7.3 Hz), 1.34 (3H, t, J¼7.3 Hz); 13C NMR (CDCl3) d
165.62, 141.26, 140.05, 131.84, 129.08, 128.86, 118.63,
111.79, 61.46, 14.13; IR (neat) 2228, 1723, 1608, 1198,
1179, 848 cm21; EIMS m/z (relative intensity) 201 (27), 173
(20), 157 (23), 128 (100), 101 (24), 77 (15), 51 (13); HRMS
Calcd for C12H11O2N m/z 201.0790. Found m/z 201.0773;
Anal. Calcd for C12H11O2N: C, 72.88; H, 5.65; N, 6.54.
Found: C, 72.66; H, 5.72; N, 6.33.
4.4.1. Ethyl 2-phenylpropenoate (4a). 98%; IR (neat)
1
1724, 1602, 1497, 1199, 701 cm21; H NMR (CDCl3) d
7.44–7.33 (5H, m), 6.35 (1H, d, J¼1.3 Hz), 5.89 (1H, d,
J¼1.3 Hz), 4.29 (2H, q, J¼7.3 Hz), 1.33 (3H, t, J¼7.3 Hz);
13C NMR (CDCl3) d 166.07, 141.08, 136.28, 127.78,
127.60, 127.55, 125.80, 60.47, 13.66; EIMS m/z (relative
intensity) 176 (63), 131 (87), 103 (100), 77 (37); HRMS
Calcd for C11H12O2 m/z 176.0837. Found m/z 176.0848;
Anal. Calcd for C11H12O2: C, 74.98; H, 6.86. Found: C,
74.79; H, 6.96.
4.4.7. Ethyl 2-(4-methoxycarbonylphenyl)propenoate
1
(4g). H NMR (CDCl3) d 8.02 (2H, dd, J¼2.0, 6.9 Hz),
7.49 (2H, dd, J¼2.0, 6.9 Hz), 6.43 (1H, d, J¼1.0 Hz), 5.95
(1H, d, J¼1.0 Hz), 4.29 (2H, q, J¼7.3 Hz), 3.90 (3H, s),
1.32 (3H, t, J¼7.3 Hz); 13C NMR (CDCl3) d 166.49, 165.91,
141.02, 140.54, 129.45, 129.13, 128.16, 127.75, 61.06,
51.88, 13.95; IR (neat) 1720, 1610, 1194, 869 cm21; EIMS
m/z (relative intensity) 234 (68), 203 (67), 190 (44), 161
(100), 102 (46), 76 (17), 59 (16); HRMS Calcd for
C13H14O4 m/z 234.0892. Found m/z 234.0890; Anal.
4.4.2. Ethyl 2-(4-methoxyphenyl)propenoate (4b). 1H
NMR (CDCl3) d 7.37 (2H, dd, J¼2.0, 6.6 Hz), 6.89 (2H,
dd, J¼2.0, 6.6 Hz), 6.25 (1H, d, J¼1.3 Hz), 5.83 (1H, d,
J¼1.3 Hz), 4.29 (2H, q, J¼7.3 Hz), 3.82 (3H, s), 1.33 (3H, t,
J¼7.3 Hz); 13C NMR (CDCl3) d 167.08, 159.55, 140.88,

A. A. Jalil et al. / Tetrahedron 58 (2002) 7477–7484
7483
Calcd for C13H14O4: C, 66.66; H, 6.02. Found: C, 66.55; H,
6.19.
4.4.13. Ethyl 2-(6-methoxynaphthalen-2-yl)propenoate
1
(7a). H NMR (CDCl3) d 7.84 (1H, d, J¼1.7 Hz), 7.74
(2H, t, J¼8.3 Hz), 7.71 (1H, d, J¼8.3 Hz), 7.50 (1H, dd,
J¼1.7, 8.3 Hz), 7.15 (1H, dd, J¼2.0, 8.3 Hz), 7.13 (1H, s),
6.38 (1H, d, J¼1.0 Hz), 5.98 (1H, d, J¼1.0 Hz), 4.32 (2H, q,
J¼7.3 Hz), 3.91 (3H, s), 1.35 (3H, t, J¼7.3 Hz); 13C NMR
(CDCl3) d 166.72, 157.81, 141.22, 134.00, 131.70, 129.52,
128.27, 126.99, 126.34, 126.16, 125.61, 118.78, 105.27,
60.83, 54.92, 13.95; IR (neat) 1711, 1605, 1459, 1262, 1196,
1030, 859, 829, 813 cm21; EIMS m/z (relative intensity)
256 (100), 228 (14), 183 (71), 168 (15), 139 (19); HRMS
Calcd for C16H16O3 m/z 256.1099. Found m/z 256.1097;
Anal. Calcd for C16H16O3: C, 74.98; H, 6.29. Found: C,
75.24; H, 6.39.
4.4.8. Ethyl 2-(2-methoxycarbonylphenyl)propenoate
1
(4h). H NMR (CDCl3) d 7.99 (1H, dd, J¼1.3, 7.6 Hz),
7.56–7.39 (2H, dt, J¼1.3, 7.6 Hz), 7.30 (1H, dd, J¼1.3,
7.6 Hz), 6.42 (1H, d, J¼1.3 Hz), 5.73 (1H, d, J¼1.3 Hz),
4.20 (2H, q, J¼7.3 Hz), 3.82 (3H, s), 1.24 (3H, t, J¼7.3 Hz);
13C NMR (CDCl3) d 167.24, 166.15, 143.02, 138.89,
132.27, 130.96, 130.08, 129.45, 128.12, 125.43, 60.83,
51.88, 14.02; IR (neat) 1722, 1624, 1195, 773 cm21; EIMS
m/z (relative intensity) 234 (47), 175 (25), 161 (100), 129
(83), 101 (29), 76 (23), 51 (15); HRMS Calcd for C13H14O4
m/z 234.0892. Found m/z 234.0890; Anal. Calcd for
C13H14O4: C, 66.66; H, 6.02. Found: C, 66.40; H, 5.97.
1
4.4.14. Ethyl 2-(fluoren-2-yl)propenoate (7b). H NMR
4.4.9. Ethyl 2-(4-bromophenyl)propenoate (4i). 1H NMR
(CDCl3) d 7.41 (2H, dd, J¼2.0, 6.6 Hz), 7.30 (2H, dd,
J¼2.0, 6.6 Hz), 6.38 (1H, d, J¼1.0 Hz), 5.89 (1H, d,
J¼1.0 Hz), 4.29 (2H, q, J¼7.3 Hz), 1.33 (3H, t, J¼7.3 Hz);
13C NMR (CDCl3) d 166.20, 140.40, 135.58, 131.14,
129.92, 126.99, 122.28, 61.19, 14.13; IR (neat) 1721, 1617,
1200, 834 cm21; EIMS m/z (relative intensity) 256 (21), 254
(20), 183 (100), 155 (24), 102 (67), 76 (40), 50 (26); HRMS
Calcd for C11H11O2Br m/z 253.9942. Found m/z 253.9927;
Anal. Calcd for C11H11O2Br: C, 51.79; H, 4.35; Br, 31.32.
Found: C, 51.82; H, 4.39; Br, 31.07.
(CDCl3) d 7.80–7.62 (2H, m), 7.62 (1H, d, J¼0.7 Hz), 7.53
(1H, d, J¼0.7 Hz), 7.46–7.31 (3H, m), 6.35 (1H, d,
J¼1.3 Hz), 5.95 (1H, d, J¼1.3 Hz), 4.32 (2H, q,
J¼7.3 Hz), 3.92 (2H, s), 1.35 (3H, t, J¼7.3 Hz); 13C
NMR (CDCl3) d 167.08, 143.52, 143.31, 143.02, 141.74,
141.22, 135.20, 127.04, 126.85, 126.76, 125.89, 125.01,
124.91, 120.02, 119.43, 61.12, 36.88, 14.22; IR (neat) 1720,
1610, 1457, 1209, 738 cm21; EIMS m/z (relative intensity)
264 (85), 235 (22), 190 (100), 165 (16), 96 (7), 83 (6);
HRMS Calcd for C18H16O2 m/z 264.1150. Found m/z
264.1162; Anal. Calcd for C18H16O2: C, 81.79; H, 6.10.
Found: C, 81.84; H, 5.92.
4.4.10. Ethyl 2-(4-acetylphenyl)propenoate (4j). 1H NMR
(CDCl3) d 7.95 (2H, dd, J¼2.0, 6.6 Hz), 7.52 (2H, dd,
J¼2.0, 6.6 Hz), 6.45 (1H, d, J¼1.0 Hz), 5.97 (1H, d,
J¼1.0 Hz), 4.30 (2H, q, J¼7.3 Hz), 2.62 (3H, s), 1.34 (3H, t,
J¼7.3 Hz); 13C NMR (CDCl3) d 197.57, 166.04, 141.31,
140.61, 136.44, 128.48, 128.03, 127.98, 61.24, 26.56, 14.09;
IR (neat) 1719, 1689, 1607, 1201, 847 cm21; EIMS m/z
(relative intensity) 218 (29), 203 (100), 175 (24), 145 (12),
102 (10); HRMS Calcd for C13H14O3 m/z 218.0943. Found
m/z 218.0923; Anal. Calcd for C13H14O3: C, 71.54; H, 6.47.
Found: C, 71.38; H, 6.54.
Acknowledgments
This work was supported by a Grant-in-Aid for Scientific
Research (B) (No. 11450342) from the Ministry of
Education, Science, Sports and Culture.
References
4.4.11. Ethyl 2-(4-nitrophenyl)propenoate (4k). 1H NMR
(CDCl3) d 8.22 (2H, dd, J¼2.0, 6.9 Hz), 7.60 (2H, dd,
J¼2.0, 6.9 Hz), 6.54 (1H, s), 6.03 (1H, s), 4.32 (2H, q,
J¼7.3 Hz), 1.35 (3H, t, J¼7.3 Hz); 13C NMR (CDCl3) d
165.53, 147.49, 143.18, 139.78, 129.40, 129.33, 123.29,
61.55, 14.13; IR (neat) 1721, 1599, 1520, 1198, 858,
707 cm21; EIMS m/z (relative intensity) 221 (86), 193 (78),
177 (68), 148 (100), 102 (54), 76 (27); HRMS Calcd for
C11H11NO4 m/z 221.0688. Found m/z 221.0676; Anal.
Calcd for C11H11NO4: C, 59.73; H, 5.01; N, 6.33. Found: C,
59.87; H, 4.98; N, 6.11.
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1
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(CDCl3) d 167.31, 141.98, 134.65, 133.51, 133.41, 128.70,
128.21, 127.98, 127.89, 127.19, 126.72, 126.61, 126.58,
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m/z (relative intensity) 226 (85), 153 (100), 127 (12); HRMS
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