Chemoselective cross-coupling Suzuki-Miyaura reaction of (Z)-(2-chlorovinyl)tellurides and potassium aryltrifluoroborate salts

Article abstract of DOI:10.1016/j.tetlet.2008.05.129

An ultrasound-assisted synthesis of functionalized vinylic chlorides is described by palladium-catalyzed cross-coupling reaction of potassium aryltrifluoroborate salts and (Z)-2-chloro vinylic tellurides. This procedure offers easy access to vinylic chlor

Full text of DOI:10.1016/j.tetlet.2008.05.129

Tetrahedron Letters 49 (2008) 4713–4716
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Chemoselective cross-coupling Suzuki–Miyaura reaction of
(Z)-(2-chlorovinyl)tellurides and potassium aryltrifluoroborate salts
Rafael C. Guadagnin a, Carlos A. Suganuma a, Fateh V. Singh a, Adriano S. Vieira a,
Rodrigo Cella b, Hélio A. Stefani a,b,c,
*
a Departamento de Farmácia, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, São Paulo, SP, Brazil
b Instituto de Química, Universidade de São Paulo, São Paulo, SP, Brazil
c Departamento de Biofísica, Universidade Federal de São Paulo, São Paulo, SP, Brazil
a r t i c l e i n f o
a b s t r a c t
Article history:
An ultrasound-assisted synthesis of functionalized vinylic chlorides is described by palladium-catalyzed
cross-coupling reaction of potassium aryltrifluoroborate salts and (Z)-2-chloro vinylic tellurides. This
procedure offers easy access to vinylic chlorides architecture that contains sterically demanding groups
in good yields.
Received 15 April 2008
Revised 23 May 2008
Accepted 28 May 2008
Available online 2 June 2008
Ó 2008 Elsevier Ltd. All rights reserved.
The main target of transition metal-catalyzed organic synthesis
is carbon–carbon bond formation, being the Suzuki–Miyaura reac-
tion one of the most efficient methods for construction of C–C
bonds.1 Organotellurium compounds have attained remarkable
development as synthons and intermediates in synthetic organic
chemistry.2 In current decade, the organotellurium compounds
have been identified as alternative to halogens as electrophilic
partners in some palladium-catalyzed cross-coupling reactions,
among these reactions we can mention the Heck,3 Negishi,4 Sono-
gashira5 and Suzuki–Miyaura.6 Recently, we have demonstrated
the use of some organotellurium compounds in Suzuki–Miyaura
reaction using potassium organotrifluoroborate salts as a nucleo-
philic partners.6
Herein, we report the palladium-catalyzed cross-coupling reac-
tions of (Z)-butyl(2-chlorovinyl)tellurides with potassium aryltri-
fluoroborate salts and the chemoselectivity of these reactions.
The novelty of this cross-coupling reaction is that of the (Z)-2-
chloro vinylic tellurides containing two electrophilic centers, C-2
connected with a chloro atom and C-1 having aryl/butyltellurium
groups, only tellurium moiety takes part in the cross-coupling
reaction and chloro atom remain intact during the process.
In order to explore the organotellurium chemistry, the starting
materials were prepared through the addition reaction of organo-
tellurium trihalides, generated from the corresponding diaryl/
dibutyl ditelluride, to alkynes to produce 2-halovinyl tellurium
dihalides containing chloro, bromo, and iodo atoms using sufuryl
chloride, molecular bromine, and iodine as halide sources, followed
by reduction with sodium borohydride leading to (Z)-aryl/butyl-
(2-halovinyl)tellurides (Scheme 1).11,12
Next, with the starting materials in hand we started the cross-
coupling reactions that worked nicely only with those tellurium
compounds which had chlorine atom while the vinylic telluride
containing bromine and iodine led to the formation of several
undesired byproducts. The difference in the electronegativity of
the halides may be an explanation for this behavior with different
halogens in the reaction (Scheme 2).
Chemoselectivity was observed during the palladium-catalyzed
cross-coupling reactions of aryl tellurium compounds containing
halide moiety with potassium organotrifluoroborate salts.6a The
reaction was observed exclusively at the tellurium moiety, and
none at the halide.
Molander7 and his research group introduced potassium
organotrifluoroborate salts as a nucleophilic partner in the Suzu-
ki–Miyaura reaction instead of unstable organoborons. These
reagents are readily prepared by addition of KHF2 salt to
organoboron intermediates,8 and are crystalline solids indefinitely
stable in the air.
Our recent efforts9 indicated that the metal-assisted cross-cou-
pling reaction of potassium organotrifluoroborate salts and
organotellurium compounds can be successfully achieved in few
minutes by using ultrasonic waves as a source of energy. The ultra-
R
X
R
X
NaBH4
6 X, 0 ºC,
R
2 R1TeX3
R1Te TeR1
TeR1
50-89%
TeR1
X
X
Benzene,
Benzene
THF/EtOH
30 min
sound effects are attributed to
a
physical process called
cavitation.10
R= Ph, C5H11, C3H7, CH3OCH2, (CH3)3C, CH3(CH2=)C, 1-cyclohexenyl
R1=Ph, C4H9, (
-CH3O)Ph,
X=Cl, Br, I (of SO2Cl2, Br2 and I2)
p
* Corresponding author. Tel.: +55 11 818 3654; fax: +55 11 3 815 4418.
E-mail address: hstefani@usp.br (H. A. Stefani).
Scheme 1.
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.05.129

4714
R. C. Guadagnin et al. / Tetrahedron Letters 49 (2008) 4713–4716
Table 3
R
R
R
R2
R2BF3K, Pd(Ph3P)4
Ag2O, Et3N, MeOH
R
R1
Te
Study of additive and base effect using potassium 4-methoxyphenyltrifluoroborate
salt 2 and (Z)-butyl(2-chloro-2-phenylvinyl)telluride 1d
+
+
R2
R2
R2
20-30%
X
X
30-35%
30-40%
)
)
)
Entry
Base (equiv)
Additive (equiv)
Pd(PPh3)4 (mol %)
Yielda (%)
R= Phenyl, propyl
R1= Aryl, butyl
R2= 4-MeOC6H4
X= Br, I
1
2
3
4
5
6
7
8
9
K2CO3
Ag2O (1)
Ag2O (1)
Ag2O (1)
Ag2O (1)
AgOAc (1)
Ag2CO3 (1)
AgOAc (2)
AgOAc (4)
Ag2O (2)
Ag2O (4)
Ag2O (2)
Pd(PPh3)4 (10)
Pd(PPh3)4 (10)
Pd(PPh3)4 (10)
Pd(PPh3)4 (10)
Pd(PPh3)4 (10)
Pd(PPh3)4 (10)
Pd(PPh3)4 (10)
Pd(PPh3)4 (10)
Pd(PPh3)4 (10)
Pd(PPh3)4 (10)
Pd(PPh3)4 (10)
60
66
73
nr
55
22
60
40
80
64
58b
Cs2CO3
Et3N (1)
—
Et3N (1)
Et3N (1)
Et3N (2)
Et3N (3)
Et3N (2)
Et3N (3)
Et3N (2)
Scheme 2.
After we have selected chlorine containing aryl/butyl vinylic
tellurides for the study as electrophilic partners in the Suzuki–
Miyaura cross-coupling reaction, we investigate the best transfer
group connected to tellurium atom preparing (Z)-butyl(2-chloro-
2-cyclohexenylvinyl)telluride, (Z)-phenyl(2-chloro-2-cyclohexenyl-
vinyl)telluride, and (Z)-4-methoxyphenyl(2-chloro-2-cyclohexenyl-
vinyl)telluride.
10
11
a
Isolated yields.
Conventional condition.
b
The cross-coupling reaction was performed using potassium 4-
methoxyphenyltrifluoroborate salt as nucleophilic partner leading
to the coupling product 3 in 85%, 72%, and 65% yield, respectively
(Table 1). The 1H NMR of isolated compound 3 showed one singlet
at 3.75 and 6.13 ppm due to 4-methoxyl group hydrogens and one
vinylic hydrogen, respectively. Two doublets appeared at 6.78 and
7.32 ppm due to aromatic ring hydrogens, one triplet at 7.50 ppm
and two multiplets at 1.54–1.65 and 2.07–2.33 ppm due to cyclo-
hexene ring hydrogens. Further the m/z peak at 248 (M+) and
250 (M++2) in GC–MS confirmed the structure of compound 3a
as (Z)-1-(2-chloro-2-cyclohexenylvinyl)-4-methoxybenzene and
presence of chlorine atom in the product.
With the collected information about the halogen and that
butyltellurium group is more reactive in cross-coupling reaction
with potassium organotrifluoroborate salts, the next step was the
screening of several common catalyst/additive combinations,
bases, and solvents (Tables 2 and 3) to try find the best cross-
coupling reaction conditions.
screened (Tables 2 and 3). All reactions were monitored by TLC
or GC.
First of all, the palladium catalyst was determinated and Pd(II)
or (0) species were used in the coupling reactions and the best
result was reached with Pd(PPh3)4 (Table 2, entry 6). AgOAc was
used as additive, K2CO3 as base, and methanol as solvent, and
the reaction was irradiated for 30 min in ultrasound bath. The
product was obtained in 60% isolated yield.
After finding the appropriate Pd catalyst, we turned our atten-
tion to search an appropriate solvent. In order to select the best
solvent we checked the reaction with several polar and non-polar
solvents such as methanol, ethanol, DMF, DME, isopropyl alcohol,
and THF, but the desired compound was isolated in best yield
(60%) with methanol.
The next step was the determination of the best base and the
necessity of an additive in the reaction (Table 3). Initially we used
inorganic bases, like potassium and cesium carbonates (Table 3,
entries 1 and 2), in presence of Ag2O and cesium carbonate affor-
ded the best result, 66% isolated yield. When the organic base, tri-
ethylamine, (1 equiv) was used, the desired compound was
isolated in 73% yield (Table 3, entry 3). No reaction was observed
in the absence of base (Table 3, entry 4).
Toward this end, potassium 4-methoxyphenyltrifluoroborate
salt (2) and (Z)-butyl(2-chloro-2-phenylvinyl)telluride 1d were
chosen as model substrates and a variety of conditions were
Table 1
Further to check the effect of additive, we performed the same
reaction with different additives, such as Ag2O, AgOAc, and Ag2CO3,
and isolated desired product in 73%, 55% and 22% yields, respec-
tively (Table 3, entries 3, 5, and 6). No reaction was observed in
the absence of additive.
The reaction stoichiometry was checked using different equiva-
lents of triethylamine with different amounts of Ag2O and AgOAc
(Table 3, entry 8–11) and the best result (80%) was obtained with
2 equiv of triethylamine and Ag2O (Table 3, entry 9). Further to
obtain more appropriate conditions we attempted the same reac-
tion under conventional condition (stirring at room temperature
for 2 h), but the desired compound was isolated in 58% yield (Table
3, entry 11).
Study of the best transfer tellurium group
MeO
MeO
Cl
RTe
Pd(PPh3)4, Ag2O
Et3N, MeOH
Cl
+
BF3K
1
2
3
Entry
R (1)
Yield (%) (3)
1
2
3
n-Bu
C6H5
4-MeOC6H4
85
72
65
During the optimization studies for (Z)-vinylic chlorides 3, it
was observed that the reaction mixture of 1.1 equiv of potassium
aryltrifluoroborate salt 2, 1 equiv of (Z)-butyl-(2-chloro-2-phenyl-
vinyl) telluride 1d, 2 equiv Ag2O, 2 equiv of triethylamine, and
10 mol % of Pd(PPh3)4 in methanol irradiated under ultrasonic
waves for 20 min, was the best reaction condition for the synthesis
of (Z)-1-(2-chloro-2-phenylvinyl)-4-methoxybenzene 3d. After
achieving the best condition for the synthesis of 3, we synthesized
a series of these (Z)-vinylic chlorides 3a–h using the optimized
condition in 58–85% yields (see Table 4).13 After completion the
reaction mixture was poured into water and neutralized with
ammonium chloride solution followed by extraction with ethyl
acetate. The crude product was purified by flash column chroma-
Table 2
Study of catalyst effect using potassium 4-methoxyphenyltrifluoroborate salt 2 and
(Z)-butyl(2-chloro-2-phenylvinyl)telluride 1d
Entry
Catalysta
Yieldb (%)
1
2
3
4
5
6
PdCl2
Pd(acac)2
Pd2(dba)3
Pd(AcO)2
5
18
40
44
41
60
PdCl2(dppf)ÁCH2Cl2
Pd(PPh3)4
a
10 mol % of catalyst was used.
Isolated yields.
b

R. C. Guadagnin et al. / Tetrahedron Letters 49 (2008) 4713–4716
4715
Table 4
Suzuki–Miyaura reaction of (Z)-n-butyl(2-chloro-2-organovinyl)telluride and potassium 4-aryltrifluoroborate salt
Cl
Cl
R2
TEA, Pd(PPh3)4
R2
+
KF3B
R
R
n-BuTe
Ag2O, MeOH,
)
)
)
3a-h
1
2
Entry
Vinyl tellurides (1)
Products
Reaction time (min)
Yields (%)
85
Cl
Cl
30
1
MeO
n-BuTe
1a
3a
Cl
Cl
MeO
2
30
82
n-BuTe
1b
3b
Cl
Cl
MeO
MeO
3
4
60
20
58
80
n
-BuTe
-BuTe
1c
3c
Cl
Cl
n
1d
3d
Cl
O
O
Cl
5
MeO
40
73
n-BuTe
1e
3e
Cl
Cl
Cl
MeO
MeO
6
7
40
60
82
74
n
-BuTe
-BuTe
1f
3f
Cl
n
1g
3g
Cl
Cl
Cl
8
n-BuTe
60
69
1h
3h
tography using hexane as eluent. The reaction was monitored by
TLC and GC. All the synthesized compounds were characterized
by spectroscopic analysis.
In summary, we have shown that tellurium moiety can be a
good electrophile alternative to the traditional halides in cross-
coupling Suzuki–Miyaura reaction. Further studies associated with
the bromine and iodide containing tellurides as electrophilic part-
ners in the Suzuki–Miyaura reaction are currently in progress.
Supplementary data
Supplementary data associated with this article can be found,
in the online version, at doi:10.1016/j.tetlet.2008.05.129.
References and notes
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Weinheim, 1998; Chapter 2; (c) Suzuki, A. J. Organomet. Chem. 1999, 576, 147;
(d) Kotha, S.; Lahiri, K.; Kashinath, D. Tetrahedron 2002, 58, 9633.
Acknowledgement
The authors are grateful to FAPESP (Grant 05/59141-6) and
CNPq (154976/2006-7) for their generous support of our program.

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