J . Org. Chem. 2002, 67, 2721-2722
2721
Ta ble 1. P d /C-Ca ta lyzed Cou p lin g of 3-Iod op h en ol a n d
P h en ylbor on ic Acid
P d /C a s a Reu sa ble Ca ta lyst for th e
Cou p lin g Rea ction of Ha lop h en ols a n d
Ar ylbor on ic Acid s in Aqu eou s Med ia
Hidehiro Sakurai,† Tatsuya Tsukuda,‡ and
Toshikazu Hirao*,†
Department of Applied Chemistry, Faculty of Engineering,
Osaka University, Yamada-oka, Suita, Osaka 565-0871,
J apan, and Institute for Molecular Science, Myodaiji,
Okazaki 444-8585, J apan
entry
Pd/C (mol %)
base
time (h)
yield (%)
hirao@ap.chem.eng.osaka-u.ac.jp
Received December 3, 2001
1
2
3
4
5
6
7
8
9
0.3
0.3
0.3
0.3
0.3
0.2
0.1
0.3
0.3
0.3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K3PO4
KOH
3
6
9
12
24
12
12
12
12
12
30
64
88
97
97
89
88
81
65
48
Abstr a ct: Pd/C was found to catalyze the Suzuki-Miyaura
coupling reaction of halophenols in aqueous media. When
halophenols were treated with ArB(OH)2 and a catalytic
amount of 10% Pd/C (0.3 mol % Pd) in aqueous K2CO3
solution, the corresponding hydroxybiaryls were obtained in
a high yield or quantitatively. The palladium catalyst was
easily recovered and reused.
10
NaOH
Ta ble 2. P d /C-Ca ta lyzed Cou p lin g of Ha lop h en ol a n d
Ar ylbor on ic Acid in Aqu eou s Med ia a
Palladium-catalyzed coupling reaction of haloarenes
with arylboronic acids, the Suzuki-Miyaura reaction, is
one of the most versatile methods for the preparation of
biaryl compounds.1 Its usefulness mainly lies in the use
of less toxic substrates and aqueous organic solvent such
as toluene-H2O, as well as wide applicability. However,
it usually requires toxic phosphine ligands and high-
temperature conditions. From both scientific and envi-
ronmental points of view, development of a new catalytic
system without use of stabilizing phosphine ligands in
aqueous media under mild conditions has attracted much
attention. In this paper we report that Pd/C works as a
reusable catalyst for the Suzuki-Miyaura coupling reac-
tion of halophenols in aqueous media.
entry
halophenol
arylboronic acid
yield (%)
1
2
3
4
5
6
7
8
9
2-iodophenol
3-iodophenol
4-iodophenol
4-iodophenol
4-iodophenol
4-iodophenol
4-iodophenol
4-iodophenol
4-bromophenol
PhB(OH)2
PhB(OH)2
PhB(OH)2
4-FC6H4B(OH)2
4-MeOC6H4B(OH)2
4-MeC6H4B(OH)2
2-MeC6H4B(OH)2
2-MeOC6H4B(OH)2
PhB(OH)2
70
97
>99
>99
>99
>99
>99
98
35 (76b)
Pd/C is one of the most common heterogeneous pal-
ladium catalysts, and recent reports have demonstrated
the application of Pd/C for the Suzuki-Miyaura coupling
as a convenient and phosphine-free catalyst.2,3 Iodo-
phenols are readily soluble in basic aqueous media and
are important starting materials for the synthesis of
substituted biaryls. Therefore, they might be suitable
substrates for the Suzuki-Miyaura coupling in aqueous
media. However, since the early report from Beletskaya
et al.,4 no example for the Suzuki-Miyaura coupling of
iodophenols in aqueous media has been reported.
a
Reaction conditions: halophenol (1 mmol), ArB(OH)2 (1 mmol),
K2CO3 (3 mmol), Pd/C (3 mg, 0.3 mol %) in H2O (10 mL) at room
b
temperature for 12 h. The reaction was performed at 50 °C for
12 h.
As expected, Pd/C was found to catalyze the coupling
of 3-iodophenol and phenylboronic acid, giving 3-hydroxy-
biphenyl. The reaction conditions were optimized, and
the representative results are listed in Table 1. When
0.3 mol % of Pd/C (purchased from Wako Chemicals),
suspended in aqueous K2CO3 solution, was treated with
stoichiometric amounts of 3-iodophenol and PhB(OH)2,
the yields of 3-hydroxybiphenyl were 30%, 64%, 88%,
97%, and 97% with quenching after 3, 6, 9, 12, and 24 h,
respectively (entries 1-5). Next, the amount of Pd/C was
examined (entries 4, 6, and 7). Although 0.1 mol % of
Pd/C also worked sufficiently, the use of 0.3 mol % of Pd/C
realized almost quantitative yield with good reproduc-
ibility. Finally, the effect of base was screened as shown
in entries 8-10 to find that K2CO3 is suitable.
† Osaka University.
‡ Institute for Molecular Science.
(1) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2475.
(2) For Pd/C as a phosphine-free catalyst for the Suzuki-Miyaura
reaction, see: Marck, G.; Villiger, A.; Buchecker, R. Tetrahedron Lett.
1994, 35, 3277. Gala, D.; Stamford, A.; J enkins, J .; Kugelman, M. Org.
Process Res. Dev. 1997, 1, 163. Ennis, D. S.; McManus, J .; Wood-
Kaczmar, W.; Richardson, J .; Smith, G. E.; Carstairs, A. Org. Process
Res. Dev. 1999, 3, 248. LeBlond, R. R.; Andrews, A. T.; Sun, Y.; Sowa,
J . R., J r. Org. Lett. 2001, 3, 1555.
(3) For other studies for the phosphine-free catalyst system, see:
Wallow, T. I.; Novak B. M. J . Org. Chem. 1994, 59, 5034. Badone, D.;
Baroni, M.; Cardamone, R.; Ielmini, A.; Guzzi, U. J . Org. Chem. 1997,
62, 7170. Reetz, M. T.; Westermann, E. Angew. Chem., Int. Ed. 2000,
39, 165. Kabalka, G. W.; Namboodiri, V.; Wang, Lei. Chem. Commun.
2001, 775 and references therein.
The above procedure could be applied to the coupling
of a variety of iodophenols and arylboronic acids, giving
the corresponding hydroxybiphenyls as demonstrated in
Table 2. In many cases, the coupling product was
obtained quantitatively. When the coupling of 4-bromo-
phenol with PhB(OH)2 was performed under the same
(4) Bumagin, N. A.; Bykov, V. V.; Beletskaya, I. P. Bull. Acad. Sci.
USSR, Div. Chem. Sci. 1989, 38, 2206.
10.1021/jo016342k CCC: $22.00 © 2002 American Chemical Society
Published on Web 03/16/2002