A Simple and Highly Efficient Catalytic System for Suzuki Cross-Coupling Using Ligandless Palladium Chloride

Article abstract of DOI:10.1055/s-2003-44992

Ligandless palladium chloride catalyzed Suzuki cross-coupling reaction of a series of aryl bromides and arylboronic acids in pyridine, with K ₂CO₃ as the base, afforded the corresponding biaryls in surprisingly high yields. The quantities of PdCl₂ employed were especially low (0.2-0.3 mol%) and the solvent pyridine could be recovered in high amounts (>90%).

Full text of DOI:10.1055/s-2003-44992

LETTER
359
A Simple and Highly Efficient Catalytic System for Suzuki Cross-Coupling
Using Ligandless Palladium Chloride
a
a
b
E
X
fficient
C
atalytic
i
System
a
f
or Suzuk
o
i
Cross-Coup
c
ling hun Tao, Yinyan Zhao, Dong Shen*
a
Laboratory of Organometallic Chemistry, East China University of Science and Technology, Shanghai 200237, P. R. China
b
Laboratory of Chemical Physics, East China University of Science and Technology, Shanghai 200237, P. R. China
E-mail: shen@ecust.edu.cn
Received 1 November 2003
Table 1 PdCl -Catalyzed Suzuki Cross-Coupling of 4-Bromo-
toluene with Phenylboronic Acid
2
Abstract: Ligandless palladium chloride catalyzed Suzuki cross-
coupling reaction of a series of aryl bromides and arylboronic acids
in pyridine, with K CO as the base, afforded the corresponding bi-
a
2
3
aryls in surprisingly high yields. The quantities of PdCl employed
2
were especially low (0.2–0.3 mol%) and the solvent pyridine could
be recovered in high amounts (>90%).
Entry
PdCl (mol%) Time (h)
Yield (%)b
2
Key words: ligandless, palladium chloride, Suzuki cross-coupling,
aryl bromide, arylboronic acid
1
2
3
4
5
6
7
1
3
100
100
88
71
39
30
0
0.5
0.3
0.2
0.1
0.01
0
3
The transition metal-catalyzed Suzuki cross-coupling re-
action is one of the most efficient methods for the forma-
4.5
5
2
2
1
tion of C(sp )–C(sp ) bonds. These procedures generally
employ complex phosphine- or NHC-based catalyst sys-
7
2
tems to obtain satisfactory results. But when cross-cou-
pling was catalyzed by phosphine ligand catalysts1
b,3,4
,
18
there were side reactions due to aryl-aryl exchange be-
7
7
tween phosphines and arylpalladium halides and self-
8
1
0c
4
coupling of aryl groups of the arylboronic acids which
occurred when the cross-coupling was very slow. Such
a
Reaction conditions: 4-Bromotoluene (2.0 mmol), phenylboronic
side reactions and self-coupling could be avoided if phos- acid (3.0 mmol), K CO ( 4.0 mmol), pyridine (3 mL), reflux.
2
3
b
c
phine-free palladium were used and the catalytic activity
can be improved by approximately one order of magni-
Isolated yields (average of two runs).
Without the addition of K CO .
2
3
1
b
tude. Deng et al. reported ligand-free Pd(OAc) or
2
PdCl -catalyzed Suzuki coupling under mild conditions
2
and besides, there still have been a number of reports on
ligand-free Suzuki coupling reactions. Comparatively
the advantages of our system lie in the low quantity of
tend such simple and economical reaction conditions to a
series of aryl bromides and arylboronic acids. The results
of the extensive application were surprisingly excellent as
listed in Table 2.
5
PdCl and the surprisingly high cross-coupling yields.
2
The PdCl -catalyzed reaction of 4-bromotoluene and
2
Both phenyl bromides and substituted aryl bromides
containing electron-withdrawing and electron-donating
groups were coupled to provide the corresponding biaryl
phenylboronic acid was chosen as a model reaction for
investigating the optimal quantities of PdCl . The two
2
6
substrates were refluxed in pyridine with K CO as the
7
2
3
products in yields between 90–100%. When 0.2 mol%
base (Table 1). PdCl (1 mol%) was initially used and its
2
PdCl was used for the cross-coupling of phenyl bromide
2
high efficiency led to 4-methylbiphenyl in 100% yields.
with 4-methylphenylboronic acid, a high yield of 90%
was still obtained (entry 13) and it may be inferred that
reactions of other aryl bromides with substituted phenyl-
boronic acids may achieve similar high cross-coupling
With a reduction in the quantity of PdCl used, the reac-
2
tion yields declined correspondingly. No product was
found in the absence of PdCl (entry 7).
2
Although pyridine itself is a base, interestingly, the reac- yields under 0.2 mol% catalyst quantity. To compare
tion could not be carried out in the absence of K CO
2
3.
entry 3 and 6 with other entries, substituted arylboronic
When 0.3 mol% PdCl was employed, a satisfactory yield acids seem to be easier to couple with aryl bromides than
2
of 88% was achieved and this result encouraged us to ex- phenylboronic acid does. The solvent pyridine can be
recovered in high amounts (>90%) under vacuum. The
mechanism of this catalytic process would be our further
focus.
SYNLETT 2004, No. 2, pp 0359–0361
Advanced online publication: 16.12.2003
0
2.
0
2.
2
0
0
4
DOI: 10.1055/s-2003-44992; Art ID: U23003ST
©
Georg Thieme Verlag Stuttgart · New York

3
60
X. Tao et al.
LETTER
Table 2 PdCl -Catalyzed Suzuki Cross-Coupling of Aryl Bromides with Arylboronic Acidsa
2
Entry
1
R
H
R¢
Biaryl
Yield (%)b
100
Time (h)
CH3
3
2
3
4
5
6
7
8
9
H
OCH3
H
99
88
4
CH3
CH3
CH3
OCH3
OCH3
CN
4.5
4
CH3
OCH3
H
100
100
90
4
10
CH3
CH3
OCH3
CH3
CH3
98
5
3
3
9
3
3
3
97
CN
98
1
1
1
1
0
1
2
3
Ph
99
Br
95c
Br
H
OCH3
CH3
95c
90d
a
b
c
d
Reaction conditions: aryl bromide (2.0 mmol), arylboronic acid (3.0 mmol), K CO (4.0 mmol), PdCl (0.3 mol%), pyridine (3 mL), reflux.
Isolated yields.
Using 1,4-dibromobenzene (1.0 mmol).
2
3
2
0
.2 mol% PdCl used.
2
In conclusion, we have found a highly efficient catalyst References
system for the Suzuki cross-coupling of aryl bromides
(
1) (a) Suzuki, A. J. Organomet. Chem. 1999, 576, 147; and
references therein. (b) Miyaura, N.; Suzuki, A. Chem. Rev.
with arylboronic acids based on ligandless PdCl , which is
2
stable, comparatively cheap and widely available.
1995, 95, 2457. (c) Suzuki, A. In Metal-catalyzed cross-
coupling reactions; Diederich, F.; Stang, P. J., Eds.; Wiley-
VCH: Veinheim, 1997. (d) Geissler, H. In Transition Metals
for Organic Synthesis, Vol. 1; Beller, M.; Bolm, C., Eds.;
Wiley-VCH: Veinheim, 1998.
Acknowledgment
This work was supported by Ministry of Education, P. R. China.
(
2) See for example: (a) Wolfe, J. P.; Singer, R. A.; Yang, B. H.;
Buchwald, S. L. J. Am. Chem. Soc. 1999, 121, 9550.
(
b) Liu, S.-Y.; Choi, M. J.; Fu, G. C. Chem. Commun. 2001,
408. (c) Grasa, G. A.; Viciu, M. S.; Huang, J. K.; Zhang, C.
M.; Trudell, M. L.; Nolan, S. P. Organometallics 2002, 21,
866.
2
2
Synlett 2004, No. 2, 359–361 © Thieme Stuttgart · New York

LETTER
Efficient Catalytic System for Suzuki Cross-Coupling
361
(
(
(
3) Goodson, F. E.; Wallow, T. I.; Novak, B. M. J. Am. Chem.
Soc. 1997, 119, 12441.
4) Moreno-Manax, M.; Perez, M.; Pleixats, R. J. Org. Chem.
(7) General Procedure: A Schlenk tube was charged with aryl
bromide (2.0 mmol), arylboronic acid (3.0 mmol), K CO
2
3
(4.0 mmol), PdCl (0.3 mol%) and pyridine (3 mL). The
2
1996, 61, 2346.
Schlenk tube was then put under an atmosphere of Ar and
placed in an oil bath and heated to the reflux. Upon complete
consumption of the aryl bromides as determined by TLC
analysis, the reaction mixture was allowed to cool down to
r.t. and the solvent was recovered under vacuum (volume
recovered was greater than 2.7 mL). The remains were
isolated by column chromatography. All biaryl products
5) (a) Deng, Y. J.; Gong, L. Z.; Mi, A. Q.; Liu, H.; Jiang, Y. Z.
Synthesis 2003, 3, 337. (b) Klingensmith, L. M.;
Leadbeater, N. E. Tetrahedron. Lett. 2003, 44, 765.
(
c) LeBlond, C. R.; Andrews, A. T.; Sun, Y.; Sowa, J. R.
Org. Lett. 2001, 3, 1555. (d) Kabalka, G. W.; Pagni, R. M.;
Hair, C. M. Org. Lett. 1999, 1, 1423. (e) Bumagin, N. A.;
Bykov, V. V. Tetrahedron. 1997, 53, 14437.
1
were characterized by melting points and H NMR spectra.
(
6) Pyridine was used as an effective solvent for some cross-
coupling reactions, see: (a) Gao, C.; Tao, X.; Qian, Y.;
Huang, J. Chem. Commun. 2003, 1444. (b) Gao, C.; Tao,
X.; Qian, Y.; Huang, J. Synlett 2003, 1716.
Synlett 2004, No. 2, 359–361 © Thieme Stuttgart · New York