Imidazolylidene carbene ligated palladium catalysis of the Heck reaction in the presence of air.

Article abstract of DOI:10.1039/b306715g

Five 1,3-disubstituted imidazolium salts were synthesized. Their Heck reaction activities were evaluated. A convenient, efficient and high yielding procedure based on these compounds for the arylation of olefins was developed. Heck reactions mediated by these palladium-N-heterocyclic carbene complexes were conducted under air and even in the presence of several common oxidants.

Full text of DOI:10.1039/b306715g

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Imidazolylidene carbene ligated palladium catalysis of the Heck
reaction in the presence of air
Jingping Liu,a Yuanhong Zhao,a Yongyun Zhou,a Liang Li,a Tony Y. Zhangb and
Hongbin Zhang*a
a School of Pharmacy, Yunnan University, Kunming, Yunnan 650091, P. R. China.
E-mail: zhanghb@ynu.edu.cn
b Chemical Process Research and Development, Lilly Research Laboratories,
Lilly Corporate Center, Indianapolis, IN 46285-4813, USA
Received 16th June 2003, Accepted 5th August 2003
First published as an Advance Article on the web 19th August 2003
Five 1,3-disubstituted imidazolium salts were synthesized. Their Heck reaction activities were evaluated.
A convenient, efficient and high yielding procedure based on these compounds for the arylation of olefins was
developed. Heck reactions mediated by these palladium–N-heterocyclic carbene complexes were conducted
under air and even in the presence of several common oxidants.
Introduction
Over the past ten years, the Heck reaction has been intensiv-
ely studied for its important synthetic applications.1 The
palladium-catalyzed arylation and alkenylation of olefins have
turned out to be one of the most powerful means for the form-
ation of carbon–carbon bond in organic synthesis.2 Tradition-
ally, triarylphosphine palladium complexes and aryl iodide are
employed for Heck reactions, and the experiments are carried
out under inert atmosphere to minimize the deleterious effect
of oxygen in the air. Recently, great progress has been made in
the field of Heck catalysis.3,4 Modified phosphine ligands, such
as sterically demanding tri-t-butylphosphine and phosphine
containing palladacycles and their analogs, have shown espe-
cially high coupling activities for a variety of substrates.5 Apart
Scheme 1 Synthesis of 1,3-disubstituted imidazolium salts.
from phosphine related ligands, new types of non-phosphine
ligands, such as heterocyclic carbenes, imine and amine
palladacycles have emerged as an alternative for the palladium
catalyzed Heck reaction.6
1-substituted imidazoles were prepared according to a literature
procedure.10
With compound 1 as ligand, Heck reactions of aryl bromides
with tert-butyl acrylate were tested. It should be noted that
catalysts employed in this study were neither preformed nor
preactivated by any reducing agents. The catalysts were formed
simply by mixing Pd(OAc)2, K2CO3 and NHC ligands together
under reaction conditions. For both electron-poor and electron-
rich aryl bromides, Heck couplings proceeded equally well after
refluxing in 1,4-dioxane for 20 h under argon. To our delight,
further data indicated that these Heck reactions catalyzed by
the same NHC–palladium complex afforded the products
under air in excellent yield as well (see Table 1). Further study
indicated that anhydrous solvent was not necessary either, as
the reaction can proceed in commercial 1,4-dioxane with
detectable amount of water and peroxide. We also utilized the
zerovalent Pd2(dba)3 (dba = dibenzylidene acetone) as the
palladium source, but a low yield occurred in 1,4-dioxane (see
Table 1), while excellent yields were obtained in N-methyl-
pyrrolidone (NMP).
The activity evaluation of ligands 1 to 5 was carried out in
refluxing 1,4-dioxane under air. The results are shown in Fig. 1.
The reaction rates of complexes Pd2(dba)3/1 and Pd(OAc)2/1
were also studied by using 4-bromo-acetophenone with tert-
butyl acrylate in NMP in an oil bath at 120 ЊC. Quite con-
trary to Herrmann et al.’s case,11 no induction period was
observed with Pd(OAc)2/1 being used, whereas utilizing
Pd2(dba)3 as the palladium source in our catalytic process does
not enhance the arylation yield nor accelerate the reaction rate
(see Fig. 2).
With their ‘phosphine mimic’6a ligating properties, N-hetero-
cyclic carbenes (NHC) have attracted the attention of several
research groups.7 Various NHC ligands have been synthesized
within a short period of time, and some of them have been
successfully used for a variety of palladium catalyzed trans-
formations.8 Although NHC–palladium complexes used for
Heck reaction were claimed to be air and moisture stable, only a
few examples carried out under air were reported by Crabtree et
al.9 Most reactions catalyzed by NHC–palladium complexes
are conducted under an inert atmosphere. Therefore, easy to
handle while highly efficient catalytic processes that are stable
towards oxidants and moisture variations are still targets of
pursuit. We now report here a new group of multidentate
NHC–palladium() catalysts that exhibit outstanding activities
towards the Heck reactions. By using our catalytic system,
activation of aryl bromides is remarkably efficient. Good to
excellent conversions have been achieved for an array of aryl
bromides. Moreover, Heck reactions mediated by these com-
plexes can also be carried out under air and even in the presence
of several oxidants.
Results and discussion
Ligands used in this research are presented in Scheme 1. The
N,N-disubstituted imidazolium bromides 1 to 5 were pre-
pared simply by refluxing the corresponding benzyl bromide
derivatives with 1-substituted imidazoles in toluene. The
T h i s j o u r n a l i s © T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 3
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 3 2 2 7 – 3 2 3 1
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Table 1 Heck reaction of aryl bromides with tert-butyl acrylatea
Table 2 Heck reaction in the presence of oxidantsa
R
R1
Mol% Pd
Time
Oxidantb
Yieldc
b
ArBr
Atmosphere
Pd source
Solvent
Yield
t
MeO
MeO
MeO
MeO
MeCO
MeCO
MeCO
MeCO
MeO
CO2 Bu
Ph
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
20 h
10 h
20 h
14 h
20 h
20 h
20 h
14 h
70 h
45 h
NaBO3
NaBO3
NMO
NMO
NaIO4
NaBO3
NMO
NMO
Air
64%
85%
97%
98%
75%
78%
95%
91%
78%
92%d
A
B
A
B
A
B
A
B
A
B
B
A
B
Argon
Argon
Air
Air
Air
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd(OAc)2
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
1,4-dioxanec
1,4-dioxanec
1,4-dioxane
1,4-dioxane
1,4-dioxaned
1,4-dioxaned
1,4-dioxanec
1,4-dioxanec
1,4-dioxane
NMP
82%
99%
90%
98%
84%
93%
18(62)%
60(39)%
47(33)%
99%
t
CO2 Bu
Ph
Ph
Ph
t
CO2 Bu
Air
Ph
Argon
Argon
Air
Air
Air
Argon
Argon
t
CO2tBu
0.01
0.0004
MeCO
CO2 Bu
Air
a All reactions were conducted under air. Reactions in commercial 1,4-
dioxane were carried out in oil bath, 105 ЊC. b 1.5 mmol of oxidant was
added. c Yields represent isolated yield based on aryl bromide (average
of two runs). d Reaction was carried out in commercial NMP in oil
bath, 120 ЊC. NMO = N-methylmorpholine N-oxide.
NMP
97%
82%
98%
NMPc
NMPc
a For reaction conditions see Experimental. Reactions in anhydrous 1,4-
dioxane were carried out in oil bath, 105 ЊC, for 20 h. Reactions in
commercial NMP were carried out in oil bath, 120 ЊC, for 2 h. b Yield
represent isolated yield based on aryl bromide, yields in parentheses are
recovery of starting material. c Reaction system was thoroughly
degassed by vacuum and purged with argon at least three times.
d Commercial 1,4-dioxane was directly used without further purifi-
cation.
occurring in the presence of oxidant suggests that a catalytic
cycle such as Pd()–Pd()13 might be the possible pathway.
Results summarized in Table 2 are of valuable for better under-
standing of NHC-ligated palladium catalyzed Heck reaction.
To further demonstrate the efficiency of our ligands in pal-
ladium catalyzed arylation of olefins, various aryl bromides
were tested. The results are summarized in Table 3. It is note-
worthy that our catalytic system is efficient towards the highly
electron-rich aryl bromides (entries 1, 5, 11, 12). Unfortunately,
it is inactive towards the activation of electron-rich aryl chlor-
ides. For electron-poor 4-chloroacetophenone (entry 17), 57%
yield was obtained after stirring in NMP in an oil bath at 120 ЊC
for 24 h. Unlike phosphine ligated Pd catalysts, there was no
visible palladium black formation during the entire process,
either in the presence or absence of air.
In summary, the multidentate carbene ligated palladium-
catalyst system disclosed herein represents an easy to handle,
robust, and high yielding procedure for Heck couplings. The
catalytic system is especially stable towards air, moisture and
even oxidants. The ligands are also easily accessible. The result
of this research is not so much as providing an effective catalyst
for the Heck reaction, although it does, but as the first observ-
ation that Heck reaction mediated by NHC–palladium com-
plexes could take place in the presence of strong oxidizing
agents, which might be a valuable contribution to the under-
standing of the mechanism of the Heck reaction catalyzed by
imidazoylidene-ligated palladium.
Fig. 1 Activity evaluation of ligand 1 to 5: 4-bromoacetophenone (1
mmol), K2CO3 (1.5 mmol), Pd(OAc)2 (0.5% mmol), ligands 1, 2 and 3
(0.275% mmol), ligands 4 and 5 (0.55% mmol). The reaction was
conducted in 1,4-dioxane (10 ml) in an oil bath at 105 ЊC. ᭿ With
styrene (1.3 mmol) for 4 h. ᮀ With t-butyl acrylate (1.3 mmol) for 6 h.
Yields represent isolated yield based on aryl bromide.
Experimental
General experimental
Infrared (IR) spectra (νmax) were recorded on a Perkin-Elmer
1800 Fourier transform infrared spectrophotometer in KBr
plates. Proton nuclear magnetic resonance (1H-NMR) spectra
were recorded on a Bruker Avance 300 spectrometer at 300
MHz. Carbon-13 nuclear magnetic resonance (13C-NMR) was
recorded on a Bruker Avance 300 spectrometer at 75.5 MHz.
HRMS was recorded on an API QSTAR Pulsar I System. MS
(FABϩ) spectra were recorded on a VG AutoSpec 3000
spectrometer. Chemical shifts are reported as δ values in parts
per million (ppm) relative to tetramethylsilane (TMS) for all
recorded NMR spectra. Low resolution mass spectra were
recorded on a Finnigan Trace 2000 GC-MS spectrometer. Melt-
ing points were determined on an XT-4 microscopic melting-
point detector and are uncorrected. Starting materials and
reagents used in reactions were obtained commercially from
Fig. 2 Reaction rates of complexes Pd2(dba)3/1 vs. Pd(OAc)2/1. For
reaction operations see the Experimental. ᭿ Pd2(dba)3/1. ꢀ Pd(OAc)2/
1. The yields were determined by 1H-NMR. Samples were taken in
every 5 min in the first 30 min period, then at an interval of 20 min after
the initial 30 min period.
The mechanism for the Heck reaction with NHC–palladium
complexes has been proposed as proceeding through a cationic
Pd(0)/Pd() pathway.12 It is interesting to note that our catalytic
process is able to proceed in the presence of several oxidants
that appear to be incompatible with the commonly accepted
Pd(0)–Pd() catalytic cycle for the Heck reaction (see Table 2).
To the best of our knowledge, Heck reactions in the presence
of oxidants are not recorded in the literature. Although the
exact mechanism of this reaction is unclear, the Heck reaction
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 3 2 2 7 – 3 2 3 1
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Table 3 Heck reaction with tert-butyl acrylate/styrene by using 1 as
out under argon were degassed by high vacuum and purged
with argon at least three times. No precaution should be
excised when reactions are carried out under air.
liganda
Entry ArBr
1
Time Productc
16 h
Yieldb
92%
General method for preparation of ligands 1 to 5
1-Mesitylimidazole, [1-(2,6-diisopropylphenyl)imidazole or
1-tert-butylimidazole] (4.4 or 2.2 mmol) and 1,2,4,5-tetra-
bromomethylbenzene [1,3-dibromomethylbenzene or 1,2-
dibromomethylbenzene] (4 or 2 mmol) were stirred in toluene
(10 ml) at reflux for 16 h. The precipitate was filtered and
washed with dry ethyl ether (3 × 10 ml) to afford the product
(90–95%) as a white powder. Pure samples were obtained
after recrystallization from appropriate solvent (acetone or
methanol).
2
3
16 h
80 h
89%
70%
4
5
17 h
80 h
98%
58%
Compound 1. White crystals, mp 254–255 ЊC. IR νmax (KBr)/
cmϪ1: 3436 (s), 3119 (m), 3071 (m), 2966 (s), 2931 (m), 2871 (m),
1619 (w), 1546 (m), 1467 (m), 1460 (m), 1404 (w), 1388 (w),
1368 (m), 1313 (w), 1183 (m), 1145 (w), 1104 (w), 1069 (w), 1002
1
(w), 1018 (w), 958 (w), 936 (w). H-NMR (300 MHz, DMSO)
δ: 10.15 (4H, s, Himidazole-2), 8.29 (4H, t, J = 1.3 Hz, Himidazole-5),
8.23 (4H, t, J = 1.3 Hz, Himidazole-4), 7.99 (2H, s, Hbenzene), 7.63
(4H, t, J = 7.8 Hz, H2,6-diisopropylbenzene-4), 7.45 (8H, d, J = 7.8 Hz,
H2,6-diisopropylbenzene-3,5), 5.99 (8H, s, Hbenzyl), 2.29 (8H, septet,
J = 6.6 Hz, Me2CH), 1.14 (24H, d, J = 6.6 Hz, CH3), 1.12 (24H,
d, J = 6.6 Hz, CH3). 13C-NMR (75 MHz, DMSO) δ: 145.44,
138.42, 135.02, 134.30, 131.91, 130.81, 125.70, 124.80, 123.84,
49.35, 28.47, 24.21, 24.18. MS (FABϩ) m/z: 1280 (1.5%), 1202
(0.5), 1066 (0.3), 667 (1), 583 (1), 517 (1), 437 (3), 357 (6),
321 (12), 229 (100). HRMS (ESIϩ) m/z: found 1281.4978
[M ϩ 2H Ϫ Br]3ϩ, C70H92Br3N8 requires 1281.4995.
6
7
20 h
16 h
20 h
18 h
20 h
20 h
21 h
86%
98%
70%
67%
82%
98%
72%
8
Compound 2. White powder, mp 246–247 ЊC. IR νmax (KBr)/
cmϪ1: 3414 (s), 3123 (s), 2979 (m), 1659 (m), 1609 (m), 1548 (s),
1484 (m), 1447 (m), 1402 (m), 1330 (w), 1290 (w), 1199 (m),
1156 (m), 1108 (s), 1069 (w), 1036 (w), 987 (w), 935 (w).
1H-NMR (300 MHz, DMSO) δ: 9.77 (4H, s, Himidazole-2), 8.14
9
10
11
12
(4H, t, J = 1.6 Hz, Himidazole-5), 8.04 (4H, t, J = 1.6 Hz, Himidazole
-
4), 7.81 (2H, s, Hbenzene), 7.14 (8H, s, Hmesitylene-3,5), 5.88 (8H, s,
Hbenzyl), 2.33 (12H, s, CH3), 2.02 (24H, s, CH3). 13C-NMR
(75 MHz, DMSO) δ: 140.60, 138.26, 134.92, 134.69, 133.49,
131.46, 129.62, 124.41, 123.74, 49.27, 21.01, 17.76. MS (FABϩ)
m/z: 1116 (2%), 1034 (0.5), 848 (1), 661 (1), 583 (1.5), 499 (3),
314 (16), 279 (4), 187 (100), 146 (10). HRMS (ESIϩ) m/z: found
1115.3267 [M ϩ 4H Ϫ Br]5ϩ, C58H70Br3N8 requires 1115.3273.
13
14
16 h
15 h
94%
92%
Compound 3. Pale yellow powder, mp > 300 ЊC. IR νmax
(KBr)/cmϪ1: 3497 (m), 3425 (m), 3288 (m), 3129 (m), 3039 (s),
2980 (m), 1630 (w), 1563 (m), 1478 (w), 1446 (w), 1376 (w), 1349
(w), 1319 (w), 1292 (w), 1234 (w), 1209 (s), 1137 (m), 1017 (w).
1H-NMR (300 MHz, DMSO) δ: 9.68 (4H, s, Himidazole-2), 8.07
15
16
17
24 h
20 h
24 h
91%
80%
57%d
(4H, t, J = 1.8 Hz, Himidazole-5), 7.88 (4H, t, J = 1.8 Hz, Himidazole
-
4), 7.62 (2H, s, Hbenzene), 5.72 (8H, s, Hbenzyl), 1.62 (36H, s, CH3).
13C-NMR (75 MHz, DMSO) δ: 135.47, 134.53, 132.16, 123.10,
120.89, 60.27, 48.75, 29.39. MS (FABϩ) m/z: 867 (4%), 785 (1),
662 (4), 537 (2), 458 (3), 309 (3), 252 (11), 217 (14), 195 (7), 125
(100), 69 (35). HRMS (ESIϩ) m/z: found 867.2659 [M ϩ 4H Ϫ
Br]5ϩ, C38H62Br3N8 requires 867.2647.
Compound 4. White crystals, mp 291–292 ЊC. IR νmax (KBr)/
cmϪ1: 3429 (m), 3114 (m), 3055 (m), 2964 (s), 2930 (m), 2870
(m), 1662 (w), 1615 (w), 1558 (m), 1544 (m), 1461 (m), 1401 (m),
1368 (w), 1312 (w), 1253 (w), 1185 (m), 1105 (w), 1069 (w), 1060
a Reaction conditions and time are not optimized. b Yields represent
isolated yield based on aryl halides. c Mainly trans products were
obtained and confirmed by 1H-NMR, 13C-NMR and GC-MS.
d Reaction was carried out in NMP with 1% palladium/ligand 1 in oil
bath, 120 ЊC.
1
(w), 957 (w), 890 (w). H-NMR (300 MHz, CD3OD) δ: 9.72
(2H, s, Himidazole-2), 8.17 (2H, s, Himidazole-5), 8.06 (1H, s, Hbenzene
-
2), 7.96 (2H, s, Himidazole-4), 7.70–7.65 (5H, m), 7.48 (4H, d,
J = 7.7 Hz, H2,6-diisopropylbenzene-3,5), 5.79 (4H, s, Hbenzyl), 2.38 (4H,
septet, J = 6.6 Hz, Me2CH), 1.25 (12H, d, J = 6.6 Hz, CH3), 1.23
(12H, d, J = 6.6 Hz, CH3). 13C-NMR (75 MHz, CD3OD)
Acros, Aldrich and Fluka, and were used without purification,
unless otherwise indicated. Anhydrous 1,4-dioxane was freshly
distilled from sodium benzophenone ketyl. Reactions carried
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 3 2 2 7 – 3 2 3 1
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δ: 146.75, 139.23, 136.82, 133.04, 131.89, 131.79, 130.98,
130.55, 126.99, 125.79, 124.84, 54.09, 29.91, 24.55, 24.29. MS
(FABϩ) m/z: 641 (9%), 559 (9), 423 (6), 332 (35), 229 (52), 207
(46), 115 (100). HRMS (ESIϩ) m/z: found 641.3276 [M ϩ 2H Ϫ
Br]3ϩ, C38H50BrN4 requires 641.3218.
15.9 Hz), 7.07 (1H, dd, J = 1.8, 8.2 Hz), 7.03 (1H, d, J = 1.8 Hz),
6.84 (1H, d, J = 8.2 Hz), 6.23 (1H, d, J = 15.9 Hz), 3.90 (6H, s,
CH3O), 1.52 (9H, s, CH3). 13C-NMR (75 MHz, CDCl3)
δ: 166.94, 151.23, 149.54, 143.85, 128.04, 122.81, 118.31,
111.38, 109.87, 80.68, 56.32, 56.24, 28.62. MS (m/z): 208
(Mϩ Ϫ C4H8, 100%), 193 (40), 119 (35), 77 (50). HRMS
(ESIϩ) m/z: found 287.1263 [M ϩ Na]ϩ, C15H20O4Na requires
287.1259.
Compound 5. White powder, mp > 300 ЊC. IR νmax (KBr)/
cmϪ1: 3605 (m), 3253 (m), 3180 (m), 3136 (w), 3099 (m), 3045
(m), 2964 (s), 2941 (s), 2871 (w), 1669 (w), 1615 (w), 1563 (w),
1547 (m), 1464 (m), 1451 (m), 1369 (w), 1315 (w), 1283 (w),
1247 (w), 1192 (m), 1119 (w), 1001 (w), 906 (w). 1H-NMR (300
MHz, DMSO) δ: 9.95 (2H, s, Himidazole-2), 8.27 (2H, t, J =
1.6 Hz, Himidazole-5), 8.24 (2H, t, J = 1.6 Hz, Himidazole-4), 7.64
(2H, t, J = 7.8 Hz, H2,6-diisopropylbenzene-4), 7.55 (2H, dd, J = 3.3, 5.7
Hz, Hbenzene-3,6), 7.47 (4H, d, J = 7.8 Hz, H2,6-diisopropylbenzene-3,5),
7.31 (2H, dd, J = 3.3, 5.7 Hz, Hbenzene-4,5), 5.93 (4H, s, Hbenzyl),
2.28 (4H, septet, J = 6.7 Hz, Me2CH), 1.16 (12H, d, J = 6.7 Hz,
CH3), 1.14 (12H, d, J = 6.7 Hz, CH3). 13C-NMR (75 MHz,
DMSO) δ: 145.39, 138.68, 133.38, 131.90, 130.87, 130.12,
129.34, 125.94, 124.80, 124.23, 49.78, 28.54, 24.16, 24.02. MS
(FABϩ) m/z: 641 (30%), 561 (4), 413 (16), 331 (60), 229 (100),
144 (12), 104 (47). HRMS (ESIϩ) m/z: found 641.3240 [M ϩ 2H
Ϫ Br]3ϩ, C38H50BrN4 requires 641.3218.
(E )-3-(3-Formyl-4-methoxyphenyl) acrylic acid tert-butyl
ester. White needles, mp 120–121 ЊC. 1H-NMR (300 MHz,
CDCl3) δ: 10.45 (1H, s), 7.98 (1H, d, J = 2.3 Hz), 7.68 (1H, dd,
J = 2.3, 8.9 Hz), 7.53 (1H, d, J = 16.0 Hz), 7.01 (1H, d, J =
8.9 Hz), 6.32 (1H, d, J = 16.0 Hz), 3.96 (3H, s, CH3O), 1.52 (9H,
s, CH3). 13C-NMR (75 MHz, CDCl3) δ: 189.59, 166.57, 163.11,
142.19, 135.59, 128.39, 127.90, 125.25, 120.01, 112.52, 80.93,
56.33, 28.57. MS (m/z): 262 (Mϩ, 30%), 206 (100), 189 (98),
160 (41). HRMS (ESIϩ) m/z: found 285.1100 [M ϩ Na]ϩ,
C15H18O4Na requires 285.1102.
(E )-3-(4-Chlorophenyl) acrylic acid tert-butyl ester. Pale yel-
low crystals, mp 66–67 ЊC. 1H-NMR (300 MHz, CDCl3) δ: 7.54
(1H, d, J = 15.9 Hz), 7.45 (1H, d, J = 8.7 Hz), 7.35 (1H, d, J =
8.7 Hz), 6.35 (1H, d, J = 15.9 Hz), 1.54 (9H, s, CH3). 13C-NMR
(75 MHz, CDCl3) δ: 166.36, 142.43, 136.17, 133.53, 129.47,
129.46, 121.17, 81.01, 28.56. MS (m/z): 238 (Mϩ, 100%), 181
(30), 166 (55), 137 (75), 75 (65). HRMS (ESIϩ) m/z: found
239.0832 [M ϩ H]ϩ, C13H16O2Cl requires 239.0839.
General method for Heck couplings
Palladium acetate (2.8 mg, 0.0125 mmol), NHC ligand 5 (10.2
mg, 0.0075 mmol) and K2CO3 (517.5 mg, 3.75 mmol, 1.5 eq.) in
1,4-dioxane (5 ml) were stirred at room temperature under air
for 30 min. Aryl bromide (2.5 mmol) and tert-butyl acrylate or
styrene (3.25 mmol, 1.3 eq.) were added followed by another
portion of 1,4-dioxane (5 ml). The mixture was then heated to
reflux (105 ЊC, using an oil bath). An alternative way to carry
out the reaction is to put substrates with palladium, base and
ligand 5 together in 1,4-dioxane then heat to reflux (105 ЊC, oil
bath). The reaction was monitored by thin-layer chromato-
graphy. After removal of the solvent, the residue was diluted
with water (50 ml) and extracted with ethyl acetate (3 × 15ml).
The organic phases were combined and washed with brine
and dried over anhydrous Na2SO4. The solvent was removed
and the residue was chromatographed in silica gel to afford
the pure products. All compounds were subjected to 1H-NMR,
13C-NMR and GC-MS analysis. Physical data of selective
compounds were listed below.
(E )-3-[2-(Dimethoxymethyl)-4,5-methylenedioxyphenyl]
acrylic acid tert-butyl ester. Pale yellow needles, mp 73–74 ЊC.
1H-NMR (300 MHz, CDCl3) δ: 7.93 (1H, d, J = 15.7 Hz),
7.11 (1H, s), 7.04 (1H, s), 6.16 (1H, d, J = 15.7 Hz), 5.99 (2H, s),
5.51 (1H, s), 3.32 (6H, s, CH3O), 1.53 (9H, s, CH3). 13C-NMR
(75 MHz, CDCl3) δ: 166.69, 149.33, 148.34, 140.20, 132.68,
127.80, 120.49, 107.76, 106.28, 101.92, 101.11, 80.74, 53.68,
28.58. MS (m/z): 322 (Mϩ, 15%), 221 (72), 159 (100). HRMS
(ESIϩ) m/z: found 345.1317 [M ϩ Na]ϩ, C17H22O6Na requires
345.1314.
(E )-3-(4-Methoxy-2-methylphenyl) acrylic acid tert-butyl
ester. Colorless oil. 1H-NMR (300 MHz, CDCl3) δ: 7.83 (1H, d,
J = 15.8 Hz), 7.52 (1H, d, J = 8.3 Hz), 6.73 (1H, dd, J = 2.0,
8.3 Hz), 6.71 (1H, d, J = 2.0 Hz), 6.20 (1H, d, J = 15.8 Hz), 3.81
(3H, s, CH3O), 2.42 (3H, s, CH3), 1.52 (9H, s, CH3). 13C-NMR
(75 MHz, CDCl3) δ: 167.24, 161.18, 141.13, 139.93, 128.26,
126.54, 118.83, 116.18, 112.41, 80.58, 55.60, 28.63, 20.43. MS
(m/z): 248 (Mϩ, 60%), 192 (100), 175 (95), 146 (93), 131 (55).
HRMS (ESIϩ) m/z: found 271.1302 [M ϩ Na]ϩ, C15H20O3Na
requires 271.1310.
trans-3,4-Dimethoxystilbene. White needles, mp 103 ЊC.
1H-NMR (300 MHz, CDCl3) δ: 7.44 (2H, dd, J = 0.9, 7.8 Hz),
7.29 (2H, t, J = 7.8 Hz), 7.18 (1H, dd, J = 0.9, 7.8 Hz), 7.01 (1H,
brs), 7.00 (1H, d, J = 15.9 Hz), 6.99 (1H, d, J = 7.8 Hz), 6.90
(1H, d, J = 15.9 Hz), 6.79 (1H, d, J = 7.8 Hz), 3.88 (3H, s,
CH3O), 3.83 (3H, s, CH3O). 13C-NMR (75 MHz, CDCl3)
δ: 149.54, 149.36, 137.94, 130.87, 129.08, 128.88, 127.71,
127.22, 126.69, 120.32, 111.64, 109.18, 56.34, 56.27. MS (m/z):
240 (Mϩ, 92%), 225 (100), 197 (26), 181 (34), 178 (82), 165 (96),
152 (92). HRMS (ESIϩ) m/z: found 263.1046 [M ϩ Na]ϩ,
C16H16O2Na requires 263.1047.
(E )-3-(3-Fluorophenyl) acrylic acid tert-butyl ester. Pale yel-
1
low oil. H-NMR (300 MHz, CDCl3) δ: 7.47 (1H, d, J = 15.9
Hz), 7.26 (1H, m), 7.20 (1H, d, J = 5.7 Hz), 7.13 (1H, dd, J =
1.5, 7.9 Hz), 6.99 (1H, m), 6.28 (1H, d, J = 15.9 Hz), 1.46 (9H, s,
CH3). 13C-NMR (75 MHz, CDCl3) δ: 166.20, 163.35 (1JCF
=
246.4 Hz), 142.45 (4JCF = 2.7 Hz), 137.30 (3JCF = 7.7 Hz), 130.70
1
trans-2,4-Dimethoxystilbene. White needles, mp 62 ЊC. H-
(3JCF = 8.3 Hz), 124.28 (4JCF = 2.8 Hz), 121.96, 117.12 (2JCF
=
NMR (300 MHz, CDCl3) δ: 7.50 (2H, dd, J = 1.5, 7.5 Hz), 7.49
(1H, d, J = 8.4 Hz), 7.39 (1H, d, J = 16.4 Hz), 7.33 (2H, t, J =
7.5 Hz), 7.22 (1H, m), 7.00 (1H, d, J = 16.4 Hz), 6.52 (1H, dd,
J = 2.4, 8.4 Hz), 6.47 (1H, d, J = 2.4 Hz), 3.86 (3H, s, CH3O),
3.83 (3H, s, CH3O). 13C-NMR (75 MHz, CDCl3) δ: 160.96,
158.49, 138.74, 128.94, 127.64, 127.45, 127.34, 126.71, 123.74,
120.02, 105.44, 98.96, 55.93, 55.81. MS (m/z): 240 (Mϩ, 100%),
197 (22), 165 (36), 152 (16). HRMS (ESIϩ) m/z: found 263.1045
[M ϩ Na]ϩ, C16H16O2Na requires 263.1047.
21.4 Hz), 114.51 (2JCF = 21.9 Hz), 81.06, 25.80. MS (m/z): 222
(Mϩ, 19%), 207 (15), 165 (73), 149 (100), 121 (36), 101 (42).
HRMS (ESIϩ) m/z: found 245.0953 [M ϩ Na]ϩ, C13H15O2FNa
requires 245.0953.
Acknowledgements
This work was supported by a grant from the foundation of
the China Ministry of Education for the promotion of
Excellent Young Scholars and a grant for scientific research on
fundamental areas from Yunnan Provincial Natural Science
Foundation (2000B0022R).
(E )-3-(3,4-Dimethoxyphenyl) acrylic acid tert-butyl ester.
1
Pink syrup. H-NMR (300 MHz, CDCl3) δ: 7.52 (1H, d, J =
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 3 2 2 7 – 3 2 3 1
3230

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