Ultrasound-assisted synthesis of Z and E stilbenes by Suzuki cross-coupling reactions of organotellurides with potassium organotrifluoroborate salts

Article abstract of DOI:10.1016/j.tet.2006.03.090

Palladium (0)-catalyzed cross-coupling reactions between potassium aryl- and vinyltrifluoroborate salts and aryl- and vinylic tellurides proceeds readily to afford the desired stilbenes in good to excellent yields. Stilbenes containing a variety of functional groups can be prepared.

Full text of DOI:10.1016/j.tet.2006.03.090

Tetrahedron 62 (2006) 5656–5662
Ultrasound-assisted synthesis of Z and E stilbenes by
Suzuki cross-coupling reactions of organotellurides
with potassium organotrifluoroborate salts
a
Rodrigo Cella and Helio A. Stefani
a,b,c,
*
´
a
´
˜
˜
Instituto de Quımica, Universidade de Sao Paulo, Sao Paulo, SP, Brazil
ˆ
b
ˆ
Faculdade de Ciencias Farmaceuticas, Universidade de Sa˜o Paulo, Sa˜o Paulo, SP, Brazil
´
Departamento de Biofısica, Universidade Federal de Sao Paulo, Sao Paulo, SP, Brazil
c
˜
˜
Received 16 January 2006; revised 21 March 2006; accepted 27 March 2006
Available online 27 April 2006
Abstract—Palladium (0)-catalyzed cross-coupling reactions between potassium aryl- and vinyltrifluoroborate salts and aryl- and vinylic
tellurides proceeds readily to afford the desired stilbenes in good to excellent yields. Stilbenes containing a variety of functional groups
can be prepared.
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
The interest for chemistry of organotellurium compounds
has increased and has been extensively explored in the last
20 years. As a consequence of these studies, many methods
employing tellurium compounds have been developed.5
Some metal-catalyzed cross-coupling reactions employing
organotellurium reagents as the electrophilic reagent6 have
been successfully demonstrated, among this cross-coupling
reactions we can mention the Sonogashira,7 Negishi,8
Heck,9 and Suzuki–Miyaura.10
The palladium-catalyzed cross-coupling reaction of an
organometallic (R1M) with an organic electrophile (R2X)
has emerged over the past 30 years as one of the most general
and selective methods for carbon–carbon bond formation.
Currently, it appears to be generally superior to related
methods involving the use of Ni, Cu, or Fe catalysts in its
scope and stereo-, regio-, and chemoselectivities.1 The R1
group of R1M can be aryl, alkenyl, alkynyl, allyl, benzyl,
propargyl, alkyl, cyano, or enoxy; while the R2 group of
R2X can be aryl, alkenyl, alkynyl, allyl, benzyl, propargyl,
alkyl, or acyl. The use of other related carbon groups as R1
and/or R2 is not only conceivable, but also known in the
literature. The direct cross-coupling of alkenes with aryl
and alkenyl halides is the most widely used and well known
cross-coupling procedure.2
Ultrasound has been utilized recently to accelerate a number
of synthetically useful reactions.11 The use of ultrasound in
chemistry is called sonochemistry and the ultrasound effects
observed on organic reactions are due to cavitation, a physi-
cal process that create, enlarge, and implode gaseous and
vaporous cavities in an irradiated liquid. Cavitation induces
very high local temperatures and pressure inside the bubbles
(cavities), leading to a turbulent flow in the liquid and
enhanced mass transfer.
Boronic acids and boronate esters are the most commonly
used derivatives in Suzuki cross-coupling reactions. Re-
cently, Molander et al.3 have explored the use of potassium
organotrifluoroborate salts as an alternative to these boron
reagents in Suzuki cross-coupling reactions. These salts
are readily prepared from organoboronic acids or esters by
the treatment with an aqueous solution of inexpensive and
widely available KHF2.4 The potassium organotrifluoro-
borates are monomeric solids and indefinitely stable in the
air.
Although stilbene itself (1,2-diphenylethene) is not a natural
product, a large number of its derivatives has been isolated
from various plant species. Among these naturally occurring
stilbenoid compounds, polyhydroxystilbenes, and their
glucosides are currently attracting considerable attention,
because of their wide range of biological activities and po-
tential therapeutic value.12 Stilbenes, the target of this paper,
exhibit some activities such as antineoplastic, antimicrobial,
multi-drug-resistant, antiangiogenesis, cytotoxic, and inhibit
cell proliferation.13
Keywords: Stilbenes; Suzuki; Tellurium compounds; Potassium organotri-
fluoroborate salt.
Since these early days, several catalytic approaches have
been proposed and investigated for the synthesis of
* Corresponding author. Tel.: +55 11 3091 3654; fax: +55 11 3815 4418;
e-mail: hstefani@usp.br
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.03.090

R. Cella, H. A. Stefani / Tetrahedron 62 (2006) 5656–5662
5657
stilbenoid compounds. Among them, methods based on the
Heck and Suzuki reactions stand out for their synthetic ver-
satility and efficiency.14
were lowered. The best result was achieved when 8 mol % of
catalyst was used. Thus, the careful analysis of the optimized
reactions revealed that the optimum conditions for the cou-
pling was found to be the use of Z-styryl n-butyltelluride (1a,
1 mmol), potassium organotrifluoroborate (2a, 1.2 equiv),
Pd(PPh3)4 (8 mol %), and silver oxide (2 equiv) diluted in
methanol (4 mL), under irradiation of ultrasound waves for
40 min at room temperature. Using this reaction condition
we were able to prepare the Z-stilbene (3a) in 82% yield.
The homocoupling reaction of phenyltrifluoroborate 2a un-
der these conditions was observed on a small scale. Because
of this, the phenyltrifluoroborate 2a is used in a little excess.
By taking advantage of the attractive features of sonochem-
istry and of potassium organotrifluoroborate salts and the
organotellurium compounds in cross-coupling reactions,
we report herein an efficient ultrasound-assisted method
for the synthesis of Z and E stilbene compounds by the
palladium-catalyzed cross-coupling reaction of aryl- and
vinyl tellurides and potassium aryl- and vinyltrifluoroborate
salts (Scheme 1).
This optimal condition was employed under conventional
reaction (magnetic stirring), but it was necessary a prolonged
time reaction (18 h) at reflux temperature. The product
Z-stilbene (3a) was obtained in medium yield, 63%. When
the reaction was carried out at room temperature after 24 h,
it remained many starting materials.
Pd[PPh3]4, Ag2O
Ar2BF3K
+
Ar1
Ar2
Ar1
Ph
TeBu-n
BF3K
MeOH, r.t., )))
2a-h
3a-i
1a-c
Ar
Pd[PPh3]4, Ag2O
ArTeBu-n
+
MeOH, K2CO3,
r.t., )))
Ph
5a-j
4
6a-j
With the optimized cross-coupling conditions at hand, we
examined the Z-stilbene derivates (3) formation with a range
of potassium aryltrifluoroborate salts and Z-styryl tellurides,
as shown in Table 2. The Pd (0)-catalyzed Suzuki reaction
proved to be active. It is clear that this is a general method
that tolerates the presence of functional groups. In addition,
even an ortho-substituted aryltrifluoroborate salt afforded
the corresponding stilbene compound in medium yield
(Table 2; entry 5). However, when the potassium heteroaryl-
trifluoroborate was used as a nucleophilic partner no reaction
was observed (Table 2, entries 9 and 10) and all of the start-
ing material was recovered.
Scheme 1. Cross-coupling reaction between potassium organotrifluoro-
borate salts and the organotellurium compounds.
2. Results and discussion
The ultrasound-assisted cross-coupling reaction between the
Z-styryl n-butyltellurides (1a) and potassium phenyltrifluo-
roborate (2a) in presence of silver oxide was chosen as the
model reaction and a variety of conditions were screened
(Table 1). Palladium (II) and (0) species were employed
in the cross-coupling reaction, and the best results were
reached with the catalysts of palladium (0) (Table 1, entries
3 and 6). Pd(PPh3)4 was chosen as the source of palladium.
When the reaction was performed without the silver oxide,
no reaction was observed (Table 1, entry 7). Other additives
were used in the reaction, like AgOAc and CuI (Table 1,
entries 9 and 10), however the results were worse. A base,
triethylamine was also used in combination of Pd(PPh3)4
(Table 1, entry 8), but the yield decreased.
In a next step of this report, we synthesized E-stilbenes from
the palladium (0)-catalyzed Suzuki–Miayura cross-coupling
reaction between the potassium E-styryltrifluoroborate (4)
and n-butyl(aryl)tellurides (5). Initially, we used the protocol
above, which describe the synthesis of Z-stilbenes. However,
the protocol described before to prepare Z-stilbenes did not
demonstrate to be efficient for this case, remaining many
starting material, under this condition. Using the E-styryl-
fluoroborate 4 and the aryl telluride 5a we observed that
just by addition of 1 equiv of potassium carbonate all start-
ing material was consumed and the stilbene 6a (Table 3,
entry 1) was obtained in 90% yield.
The catalyst loadings were analyzed (Table 1, entries 11–
13), and the reaction yield decreased as the catalyst loadings
Table 1. Study of catalyst effect on cross-coupling reaction using vinylic
telluride 1a and potassium phenyltrifluoroborate salt 2a
As shown in Table 3, a variety of aryl tellurides (5) were sub-
jected to the optimized palladium-catalyzed cross-coupling
reaction conditions with the E-styryltrifluoroborate (4).
When heteroaryl tellurides were employed, the products
were obtained in moderate yields (Table 3, entries 10 and
11), while in the other case (Table 2, entries 9 and 10), the
starting materials were unreactive.
Pd[PPh3]4, Ag2O
+
PhBF3K
2a
Ph
Ph
Ph
TeBu-n
MeOH, r.t., )))
3a
1a
Entry Catalyst
Additive Base Yield (%)
1
2
3
4
5
6
7
8
Pd(acac)2 10%
PdCl2 10%
Pd2(dba)3 10%
Ag2O (2 equiv)
Ag2O (2 equiv)
Ag2O (2 equiv)
Ag2O (2 equiv)
Ag2O (2 equiv)
Ag2O (2 equiv)
—
—
—
—
—
—
—
—
10
60
72
64
68
79
Nr
When aryl tellurides (5) containing halides attached to the
ring were used under the optimal conditions for Suzuki
cross-coupling, the reaction demonstrated high chemoselec-
tivity, with the substitution occurring only in the tellurium
group leaving the halide moiety intact. The E-1-chloro-4-
styryl-benzene (6g) (Table 3, entry 7), E-1-bromo-4-styryl-
benzene (6h) (Table 3, entry 8), and E-1-iodo-4-styryl-
benzene (6i) (Table 3, entry 9) were obtained in good yields.
We described similar results in a previous report,10a but
PdCl2(BnCN)2 10%
Pd(dppf)Cl2 10%
Pd(PPh3)4 10%
Pd(PPh3)4 10%
Pd(PPh3)4 10%
Pd(PPh3)4 10%
Pd(PPh3)4 10%
Pd(PPh3)4 8%
Ag2O (2 equiv) TEA 50
9
CuI (2 equiv)
AcOAg (2 equiv)
Ag2O (2 equiv)
Ag2O (2 equiv)
Ag2O (2 equiv)
—
—
—
—
—
Nr
15
82
73
60
10
11
12
13
Pd(PPh3)4 5%
Pd(PPh3)4 1%

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R. Cella, H. A. Stefani / Tetrahedron 62 (2006) 5656–5662
Table 2. Reaction of Z-vinylic tellurides with potassium aryltrifluoroborate salts
Pd[PPh3]4, Ag2O
MeOH, r.t., )))
Ar2BF3K
+
Ar1
TeBu-n
Ar1
Ar2
3a-i
1a-c
2a-h
Entry
1
Ar1
Ar2
Product
Yield (%)a
82
TeBu-n
3a
2a
1a
Cl
2
3
4
5
1a
1a
1a
1a
70
60
78
62
2b
3b
Cl
OMe
Me
MeO
2c
3c
Me
2d
3d
Me
2e
Me
3e
6
7
1a
70
3f
2f
TeBu-n
TeBu-n
76
78
2a
2a
3d
1b
Me
8
9
Br
3g
1c
Br
N
1a
1a
Nr
Nr
3h
N
2g
10
O
O
2h
3i
a
Isolated product yield.
here in this report we did not observe reaction when the
aryl telluride containing iodo (Table 3, entry 9) was used.
With these results at hand, we can rule that the general order
of reactivity for Suzuki cross-coupling is as follows:
BuTe>I>BrꢀOTf[Cl.
aryl tellurides are more reactive than aryl halides under these
conditions.
4. Experimental
4.1. General
3. Conclusion
IR spectra were recorded on Varian 3100 FTIR (n in cmꢁ1).
NMR spectra were performed on a Bruker DPX 300, chemi-
cal shifts d in parts per million, the following abbreviations
are used: singlet (s), doublet (d), multiplet (m). Low-resolu-
tion mass spectra were determined on a Shimadzu GCMS-
QP5050A. Chromatographic purifications were performed
by flash silica gel Merck. Palladium catalyst, potassium car-
bonate and silver (I) oxide were obtained from commercial
sources. The methanol was distilled from sodium methoxide
and kept over molecular sieves. THF was distilled from
sodiumbenzophenone. Vinylictellurides (1),15 aryl tellurides
In summary, we have developed general and good yielding
methods for accomplishing Suzuki cross-coupling reactions
between aryl- and vinylic tellurides and potassium aryl- and
vinyltrifluoroborate salts. The use of potassium organotri-
fluoroborate salts, as well as the use of ultrasound energy
makes this method useful, fast and attractive for the synthe-
sis of stilbenes and derivative compounds. One feature of
this method was the tolerance of functional groups in both
substrates. The Suzuki–Miyaura cross-coupling reaction
was highly chemoselective, and we have demonstrated that

R. Cella, H. A. Stefani / Tetrahedron 62 (2006) 5656–5662
5659
Table 3. Reaction of potassium E-vinylic trifluoroborates with aryl tellurides
BF3K
Ar
Pd[PPh3]4, Ag2O
ArTeBu-n
5a-k
+
Ph
Ph
MeOH, K2CO3,
r.t., )))
6a-k
4
Entry
1
Ar
Product
Yield (%)a
90
5a
6a
2
3
87
75
5b
6b
OMe
MeO
Me
5c
6c
Me
4
5
83
91
5d
6d
Me
Me
5e
6e
O
OMe
O
6
72
MeO
5f
6f
Cl
Br
I
Cl
7
8
77
91
71
5g
6g
Br
5h
6h
I
9
5i
6i
N
N
10
69
59
5j
6j
O
11
O
5k
6k
a
Isolated product yield.

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R. Cella, H. A. Stefani / Tetrahedron 62 (2006) 5656–5662
(5),10a,b aryltrifluoroborate (2), and vinyltrifluoroborate (4)3,4
were prepared according to literature procedures.
4H), 6.84 (d, J¼12.3 Hz, 1H). 13C NMR (75 MHz, CDCl3)
d ppm 132.0; 129.0; 128.6; 128.5; 128.4; 128.3; 128.0;
127.5; 127.0; 126.6; 126.5; 126.4; 126.0; 125.9; 125.6;
124.9. MS: m/z (%) 230 (90); 229 (100); 152 (27); 128
4.2. Representative procedure of Z-stilbenes (3a–g)
synthesis by Suzuki–Miyaura cross-coupling reaction
(7); 101 (25). IR (neat): 3062, 1383, 987, 790, 672 cmꢁ1
.
A suspension of Z-(2-butyltellanyl-vinyl)-benzene (1a)
(0.144 g, 0.5 mmol), potassium phenyltrifluoroborate (2a)
(0.110 g, 0.6 mmol), Pd(PPh3)4 (0.046 g, 0.04 mmol) and
silver (I) oxide (0.232 g, 1 mmol) in 4 mL of methanol
was irradiated in a water bath of an ultrasonic cleaner for
40 min. Then, the reaction was diluted with ethyl acetate
(30 mL). The organic layer was washed with saturated solu-
tion of NH4Cl (2ꢂ10 mL) and water (2ꢂ10 mL), dried over
MgSO4 and concentrated under vacuum. Purification by
silica gel chromatography (eluting with hexane/ethyl acetate
9.5:0.5) yielded Z-stilbene (3a).16 This product was obtained
in 82% yield with data identical to a commercial sample.
4.2.6. Z-1-Bromo-4-styryl-benzene (3g).19 This product
was obtained as a colorless oil in 78% yield from 1c and 2a
by the general method. 1H NMR (300 MHz, CDCl3) d ppm
7.40 (d, J¼9.8 Hz, 2H), 7.20–7.13 (m, 5H), 7.07 (d,
J¼6.4 Hz, 2H), 6.60 (d, J¼12.2 Hz, 1H), 6.46 (d,
J¼13.1 Hz, 1H). 13C NMR (75 MHz, CDCl3) d ppm 137.0;
136.3; 131.6; 131.3; 130.8; 129.2; 129.0; 128.6; 127.6;
121.2. MS: m/z (%) 259 (10); 258 (59); 179 (79);
178 (100); 76 (48). IR (neat): 2986, 1479, 1266, 1064,
751 cmꢁ1
.
4.3. Representative procedure of E-stilbenes (6a–k)
synthesis by Suzuki–Miyaura cross-coupling reaction
4.2.1. Z-1-Chloro-4-styryl-benzene (3b).17 This product
was obtained as a colorless oil in 70% yield from 1a and
2b by the general method. H NMR (300 MHz, CDCl3)
A suspension of potassium E-styryltrifluoroborate (4)
(0.126 g, 0.5 mmol), butyl(phenyl)tellane (5a) (0.131 g,
0.5 mmol), Pd(Ph3P)4 (0.046 g, 0.04 mmol), potassium
carbonate (0.138 g, 1 mmol), and silver (I) oxide (0.232 g,
1 mmol) in 4 mL of methanol was irradiated in a water
bath of an ultrasonic cleaner for 40 min. Then the reaction
was diluted with ethyl acetate (30 mL). The organic layer
was washed with saturated solution of NH4Cl (2ꢂ10 mL)
and water (2ꢂ10 mL), dried over MgSO4 and concentrated
under vacuum. Purification by silica gel chromatography
(eluting with hexane/ethyl acetate 9.5:0.5) yielded E-stil-
bene (6a).20 This product was obtained in 90% yield with
data identical to a commercial sample.
1
d ppm 7.18–7.10 (m, 9H), 6.58 (d, J¼12.2 Hz, 1H), 6.48
(d, J¼12.5 Hz, 1H). 13C NMR (75 MHz, CDCl3) d ppm
137.0; 135.8; 131.1; 130.3; 129.1; 128.9; 128.6; 128.5;
128.4; 127.47. MS: m/z (%) 216 (21); 214 (65); 179 (91);
178 (100); 76 (41). IR (neat): 3099, 1268, 937, 749 cmꢁ1
.
4.2.2. Z-1-Methoxy-4-styryl-benzene (3c).17 This product
was obtained as a colorless oil in 60% yield from 1a and
2c by the general method. H NMR (300 MHz, CDCl3)
1
d ppm 7.27–7.15 (m, 7H), 7.72 (d, J¼9.7 Hz, 2H), 6.50
(s, 2H), 3.74 (s, 3H). 13C NMR (75 MHz, CDCl3) d ppm
158.8; 137.8; 130.3; 129.9; 129.0; 128.9; 128.4; 127.9;
127.0; 113.7; 55.4. MS: m/z (%) 210 (100); 209 (18); 195
(18); 179 (15); 76 (8). IR (neat): 3016, 1512, 1267, 925,
4.3.1. E-1-Styryl-naphthalene (6b).21 This product was
obtained as a white solid in 87% yield from 4 and 5b by
747 cmꢁ1
.
the general method. Mp 68–72 ꢃC (lit., 70 ꢃC). H NMR
1
(300 MHz, CDCl3) d ppm 8.19 (d, J¼8.3 Hz, 1H), 7.88–
7.69 (m, 4H), 7.58–7.32 (m, 7H), 7.25 (q, J¼7.6 Hz, 1H),
7.07 (d, J¼10.4 Hz, 1H). 13C NMR (75 MHz, CDCl3)
d ppm 137.6; 135.0; 133.7; 131.7; 131.4; 129.2; 128.7;
128.6; 128.0; 127.7; 127.5; 126.7; 126.4; 126.0; 125.8;
125.7; 123.8; 123.6. MS: m/z (%) 230 (100); 229 (40); 152
4.2.3. Z-1-Methyl-4-styryl-benzene (3d).17 This product
was obtained as a colorless oil in 78% and 76% yield from
1a and 2d or from 1b and 2a, respectively, by the general
method. 1H NMR (300 MHz, CDCl3) d ppm 7.37–7.10
(m, 7H), 7.00–6.98 (m, 2H), 6.52 (s, 2H), 2.27 (s, 3H). 13C
NMR (75 MHz, CDCl3) d ppm 137.7; 137.1; 134.5; 130.4;
129.8; 129.2; 129.1; 129.0; 128.4; 127.2; 21.5. MS: m/z
(%) 194 (100); 193 (32); 179 (99); 76 (13). IR (neat):
(24); 101 (29). IR (neat): 3070, 1368, 967, 863, 651 cmꢁ1
.
4.3.2. E-1-Methoxy-4-styryl-benzene (6c).20 This product
was obtained as a white solid in 75% yield from 4 and 5c
2982, 1453, 820, 668 cmꢁ1
.
1
by the general method. Mp 133–136 ꢃC (lit., 135 ꢃC). H
4.2.4. Z-1-Methyl-2-styryl-benzene (3e).17 This product
was obtained as a colorless oil in 62% yield from 1a and
2e by the general method. H NMR (300 MHz, CDCl3)
NMR (300 MHz, CDCl3) d ppm 7.46–7.39 (m, 4H), 7.3
(t, J¼7.9 Hz, 2H), 7.21–7.16 (m, 1H), 7.06–6.95 (m, 2H),
6.90–6.84 (m, 2H), 3.75 (s, 3H). 13C NMR (75 MHz,
CDCl3) d ppm 159.6; 137.9; 130.4; 128.9; 128.5; 128.0;
127.5; 126.9; 126.5; 114.4; 55.5. MS: m/z (%) 210 (100);
209 (22); 195 (21); 179 (15); 89 (15). IR (neat): 3067,
1
d ppm 7.19–7.08 (m, 8H), 7.05–7.00 (m, 1H), 6.64 (d,
J¼12.4 Hz, 1H), 6.59 (d, J¼12.1 Hz, 1H), 2.26 (s, 3H).
13C NMR (75 MHz, CDCl3) d ppm 137.1; 137.0; 136.1;
130.5; 130.0; 129.5; 128.9; 128.8; 128.0; 127.2; 127.0;
125.5; 19.8. MS: m/z (%) 194 (83); 193 (14); 179 (100);
1416, 1046, 879, 649 cmꢁ1
.
178 (70). IR (neat): 3059, 2989, 1324, 816, 666 cmꢁ1
.
4.3.3. E-1-Methyl-4-styryl-benzene (6d).20 This product
was obtained as a white solid in 83% yield from 4 and 5d
1
4.2.5. Z-1-Styryl-naphthalene (3f).18 This product was
obtained as a colorless oil in 70% yield from 1a and 2f by
the general method. H NMR (300 MHz, CDCl3) d ppm
by the general method. Mp 119–122 ꢃC (lit., 120 ꢃC). H
NMR (300 MHz, CDCl3) d ppm 7.49 (d, J¼7.6 Hz, 2H),
7.41–7.31 (m, 4H), 7.26–7.21 (m, 1H), 7.16 (d, J¼8.3 Hz,
2H); 7.06 (s, 2H), 2.35 (s, 3H). 13C NMR (75 MHz,
CDCl3) d ppm 137.6; 134.6; 129.5; 129.3; 128.7; 127.8;
1
8.11–8.08 (m, 1H), 7.90–7.86 (m, 1H), 7.77 (d, J¼8.4 Hz,
1H), 7.53–7.47 (m, 2H), 7.40–7.28 (m, 4H), 7.10–7.04 (m,

R. Cella, H. A. Stefani / Tetrahedron 62 (2006) 5656–5662
5661
127.6; 127.5; 126.8; 126.5; 21.3. MS: m/z (%) 194 (100);
193 (32); 179 (99); 178 (96); 89 (20). IR (neat): 2991,
(%) 181 (14); 180 (100); 89 (23); 76 (22). IR (neat): 3068,
1400, 662 cmꢁ1
.
1421, 899, 753 cmꢁ1
.
4.3.10. E-2-Styryl-furan (6k).25 This product was obtained
as a white solid in 59% yield from 4 and 5k by the general
method. 1H NMR (300 MHz, CDCl3) d ppm 7.45–7.19 (m,
6H), 7.02 (d, J¼15.3 Hz, 1H), 6.86 (d, J¼15.0 Hz, 1H),
6.40–6.38 (m, 1H), 6.31 (d, J¼3.1 Hz, 1H). 13C NMR
(75 MHz, CDCl3) d ppm 153.5; 142.3; 137.2; 128.9;
127.8; 127.4; 126.5; 116.8; 111.8; 108.8. MS: m/z (%) 170
(100); 169 (64); 89 (10). IR (neat): 3072, 1369, 968,
4.3.4. E-1-Methyl-2-styryl-benzene (6e).20 This product
was obtained as a colorless oil in 91% yield from 4 and 5e
by the general method. 1H NMR (300 MHz, CDCl3)
d ppm 7.67 (d, J¼7.8 Hz, 1H), 7.59 (d, J¼8.5 Hz, 1H),
7.49–7.39 (m, 3H), 7.36–7.25 (m, 4H), 7.08 (d,
J¼16.1 Hz, 1H), 2.50 (s, 3H). 13C NMR (75 MHz, CDCl3)
d ppm 138.0; 136.7; 136.1; 130.8; 130.4; 129.0; 127.9;
126.9; 126.7; 126.6; 125.7; 20.2. MS: m/z (%) 194 (85);
193 (15); 179 (100); 178 (66); 89 (18). IR (neat): 3027,
651 cmꢁ1
.
Acknowledgements
1268, 923, 748 cmꢁ1
.
The authors are grateful to FAPESP for grant no. 03/01751-8
and for scholarships (03/13897-7).
4.3.5. E-4-Styryl-benzoic acid methyl ester (6f).22 This
product was obtained as a white solid in 72% yield from 4
and 5f by the general method. 1H NMR (300 MHz,
CDCl3) d ppm 8.20 (d, J¼9.2 Hz, 2H), 7.56–7.51 (m, 4H),
7.39–7.24 (m, 3H), 7.20 (d, J¼15.6 Hz, 1H), 7.10
(d, J¼15.4 Hz, 1H). 13C NMR (75 MHz, CDCl3) d ppm
167.0; 141.9; 136.9; 131.4; 130.2; 129.0; 128.9; 128.4;
127.7; 126.9; 126.4; 52.2. MS: m/z (%) 238 (92); 207 (44);
179 (89); 178 (100); 89 (72); 76 (34). IR (neat): 2977,
References and notes
1. For recent reviews of Pd-catalyzed cross-couplings, see: (a)
Handbook of Organopalladium Chemistry for Organic Synthe-
sis; Negishi, E., Ed.; Wiley-Interscience: New York, NY, 2002;
Vol. 1, Part III; (b) Metal-Catalyzed Cross-Coupling Reactions;
de Meijere, A., Diederich, F., Eds.; Wiley-VCH: Weinheim,
2004.
2. Beletskaya, I. P.; Cheprakov, A. V. Chem. Rev. 2000, 100, 3009.
3. (a) Molander, G. A.; Felix, L. A. J. Org. Chem. 2005, 70, 3950;
(b) Molander, G. A.; Ito, T. Org. Lett. 2001, 3, 393; (c)
Molander, G. A.; Rivero, M. R. Org. Lett. 2002, 4, 107; (d)
Molander, G. A.; Katona, B. W.; Machrouhi, F. J. Org.
Chem. 2002, 67, 8416; (e) Molander, G. A.; Biolatto, B. Org.
Lett. 2002, 4, 1867; (f) Molander, G. A.; Biolatto, B. J. Org.
Chem. 2003, 68, 4302; (g) Molander, G. A.; Yun, C.;
Ribagorda, M.; Biolatto, B. J. Org. Chem. 2003, 68, 5534;
(h) Molander, G. A.; Ribagorda, M. J. Am. Chem. Soc. 2003,
125, 11148; (i) Molander, G. A.; Bernardi, C. R. J. Org.
Chem. 2002, 67, 8424.
4. (a) Vedejs, E.; Chapman, R. W.; Fields, S. C.; Lin, S.; Schrimpf,
M. R. J. Org. Chem. 1995, 60, 3020; (b) Vedejs, E.; Fields,
S. C.; Hayashi, R.; Hitchcock, S. R.; Powell, D. R.; Schrimpf,
M. R. J. Am. Chem. Soc. 1999, 121, 2460.
5. For review: (a) Petragnani, N.; Stefani, H. A. Tetrahedron 2005,
61, 1613; (b) Petragnani, N.; Comasseto, J. V. Synthesis 1986,
1; (c) Petragnani, N.; Comasseto, J. V. Synthesis 1991, 793,
897; (d) Comasseto, J. V.; Ling, L. W.; Petragnani, N.; Stefani,
H. A. Synthesis 1997, 373.
1714, 1406, 1273, 1060, 713 cmꢁ1
.
4.3.6. E-1-Chloro-4-styryl-benzene (6g).20 This product
was obtained as a white solid in 77% yield from 4 and 5g
1
by the general method. Mp 127–130 ꢃC (lit., 128 ꢃC). H
NMR (300 MHz, CDCl3) d ppm 7.45–7.20 (m, 9H), 6.99
(s, 2H). 13C NMR (75 MHz, CDCl3) d ppm 137.2; 136.0;
133.4; 129.5; 129.0; 128.9; 128.1; 127.9; 127.5; 126.8.
MS: m/z (%) 216 (25); 214 (82); 179 (87); 178 (100); 89
(45); 76 (45). IR (neat): 3072, 1399, 1055 cmꢁ1
.
4.3.7. E-1-Bromo-4-styryl-benzene (6h).22 This product
was obtained as a white solid in 91% yield from 4 and 5h
by the general method. 1H NMR (300 MHz, CDCl3)
d ppm 7.52–7.38 (m, 4H), 7.33–7.17 (m, 5H), 7.04 (d,
J¼16.2 Hz, 1H); 6.96 (d, J¼16.1 Hz, 1H). 13C NMR
(75 MHz, CDCl3) d ppm 137.2; 136.5; 132.0; 129.6;
129.0; 128.2; 128.1; 127.6; 126.8; 121.5. MS: m/z (%) 260
(48); 258 (49); 179 (69); 178 (100); 89 (68); 76 (45). IR
(neat): 3010, 1267, 912, 746 cmꢁ1
.
4.3.8. E-1-Iodo-4-styryl-benzene (6i).23 This product was
obtained as a white solid in 71% yield from 4 and 5i by
the general method. H NMR (300 MHz, CDCl3) d ppm
1
6. Zeni, G.; Braga, A. L.; Stefani, H. A. Acc. Chem. Res. 2003, 36,
731.
7. (a) Zeni, G.; Perin, G.; Cella, R.; Jacob, R. G.; Braga, A. L.;
Silveira, C. C.; Stefani, H. A. Synlett 2002, 975; (b) Braga,
7.64 (d, J¼8.3 Hz, 2H), 7.47 (d, J¼8.4 Hz, 2H), 7.40–7.19
(m, 5H), 7.08 (d, J¼16.1 Hz, 1H), 6.97 (d, J¼16.1 Hz,
1H). 13C NMR (75 MHz, CDCl3) d ppm 137.9; 137.1;
137.0; 129.6; 128.9; 128.4; 128.1; 127.6; 126.8; 92.9. MS:
m/z (%) 306 (100); 179 (52); 178 (91); 89 (63); 76 (28). IR
A. L.; Ludtke, D. S.; Vargas, F.; Donato, R. K.; Silveira,
¨
C. C.; Stefani, H. A.; Zeni, G. Tetrahedron Lett. 2003, 44,
1779; (c) Braga, A. L.; Vargas, F.; Zeni, G.; Silveira, C. C.;
Andrade, L. H. Tetrahedron Lett. 2002, 43, 4399; (d) Zeni,
G.; Comasseto, J. V. Tetrahedron Lett. 1999, 40, 4619.
8. Zeni, G.; Alves, D.; Braga, A. L.; Stefani, H. A.; Nogueira,
C. W. Tetrahedron Lett. 2004, 45, 4823.
(neat): 3068, 1415, 879 cmꢁ1
.
4.3.9. E-3-Styryl-pyridine (6j).24 This product was ob-
tained as a white solid in 69% yield from 4 and 5j by the
general method. H NMR (300 MHz, CDCl3) d ppm 8.70
1
(s, 1H), 8.47 (d, J¼6.7 Hz, 1H), 7.79 (d, J¼6.7 Hz, 1H),
7.50 (d, J¼9.3 Hz, 2H), 7.39–7.23 (m, 4H), 7.14 (d,
J¼17.1 Hz, 1H), 7.07 (d, J¼15.0 Hz, 1H). 13C NMR
(75 MHz, CDCl3) d ppm 148.7; 136.8; 133.2; 132.8;
131.0; 129.0 (2C); 128.4; 126.9; 125.0; 123.7. MS: m/z
9. (a) Braga, A. L.; Rhoden, C. R. B.; Zeni, G.; Silveira, C. C.;
Andrade, L. H. J. Organomet. Chem. 2003, 682, 35; (b) Nishi-
bayashi, Y.; Cho, C.-S.; Ohe, K.; Uemura, S. J. Organomet.
Chem. 1996, 507, 197; (c) Nishibayashi, Y.; Cho, C.-S.; Ohe,
K.; Uemura, S. J. Organomet. Chem. 1996, 526, 335.

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Klitzke, C. F.; Stefani, H. A. J. Org. Chem. 2006, 71, 244; (b)
16. Mori, A.; Takahisa, E.; Yamamura, Y.; Kato, T.; Mudalige,
A. P.; Kajiro, H.; Hirabayashi, K.; Nishihara, Y.; Hiyama, T.
Organometallics 2004, 23, 1755.
Stefani, H. A.; Cella, R.; Dorr, F. A.; Pereira, C. M. P.; Zeni, G.,
¨
Jr.; Gomes, M. Tetrahedron Lett. 2005, 46, 563; (c) Kang,
S.-K.; Hong, Y.-T.; Kim, D. H.; Lee, S.-H. J. Chem. Res.
2001, 283.
17. Yamataka, H.; Nagareda, K.; Ando, K.; Hanafusa, T. J. Org.
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19. Leung, S. H.; Angel, S. A. J. Chem. Educ. 2004, 81, 1492.
20. Arvela, R. K.; Leadbeater, N. E. J. Org. Chem. 2005, 70, 1786.
21. Iyer, S.; Kulkarni, G. M.; Ramesh, C. Tetrahedron 2004, 60,
2163.
11. (a) Margulis, M. A. High Energ. Chem. 2004, 38, 135; (b)
Mason, T. J. Chem. Soc. Rev. 1997, 26, 443; (c) Suslick,
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12. Gorham, J. The Biochemistry of the Stilbenoids; Chapman &
Hall: London, 1995.
13. Pettit, G. R.; Rhodes, M. R.; Herald, D. L.; Hamel, E.; Schmidt,
J. M.; Pettit, R. K. J. Med. Chem. 2005, 48, 4087.
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´
14. For a review of stilbenes synthesis see: Ferre-Filmon, K.;
23. Ooe, M.; Murata, M.; Mizugaki, T.; Ebitani, K.; Kaneda, K.
J. Am. Chem. Soc. 2004, 126, 1604.
24. Yang, D.; Chen, Y.-C.; Zhu, N.-Y. Org. Lett. 2004, 6, 1577.
25. Zeni, G.; Alves, D.; Braga, A. L.; Stefani, H. A.; Nogueira,
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Delaude, L.; Demonceau, A.; Noels, A. F. Coord. Chem. Rev.
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15. Zeni, G.; Formiga, H. B.; Comasseto, J. V. Tetrahedron Lett.
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