Suzuki coupling with ligandless palladium and potassium fluoride
George W. Kabalka,* Vasudevan Namboodiri and Lei Wang
Departments of Chemistry and Radiology, University of Tennessee, Knoxville, TN, USA. E-mail: kabalka@utk.edu;
Fax: +1(865)974-2997; Tel: +1(865)974-3260
Received (in Corvallis, OR, USA) 12th February 2001, Accepted 14th March 2001
First published as an Advance Article on the web 3rd April 2001
Table 2 Suzuki coupling of arylboronic acids with aryl iodidesa
A ligandless palladium catalyzed Suzuki coupling reaction is
described.
b
Boronic acid
Aryl iodide
Yield (%)
The palladium catalyzed carbon–carbon cross-couplings of
organometallics with organoelectrophiles is an important syn-
thetic reaction. Most organometallic compounds are sensitive
Naphthyl
Naphthyl
Naphthyl
Iodobenzene
1-Iodo-4-nitrobenzene
2-Iodoaniline
2-Iodothiophene
1-Iodo-4-nitrobenzene
Iodobenzene
2-Iodothiophene
1-Iodo-4-nitrobenzene
90
89
74
90
93
97
98
98
1
to air, moisture or are toxic and often will not tolerate functional
groups which may be important in complex syntheses. Boronic
acids constitute one of the few organometallic reagents that
tolerate a wide range of functional groups, are available and
generally environmentally benign. In addition, they are inert to
air, resistant to heat, and can be recrystallized from water or
alcohol.
2
-Methylphenyl
2-Methylphenyl
2-Methylphenyl
3-Formylphenyl
3
-Formylphenyl
a
Reactions carried out utilizing 1.0 mmol of aryl iodide and 1.1 mmol of
arylboronic acid in refluxing methanol (5 mL) for 4 h in the presence of
palladium powder. b Isolated yields.
2
The Suzuki reaction which uses boron-containing precursors
has gained considerable attention in recent years because a large
number of functionally substituted boron-containing reagents
are commercially available. The Suzuki reaction generally
employs expensive organic solvents such as tetrahydrofuran as
well as expensive complex palladium catalysts. These palla-
dium reagents tend to be difficult to manipulate and recover. We
recently reported an energy efficient modification of the Suzuki
reaction using an alumina surface and palladium powder which
solved some of these problems.3
utilized to couple benzyl bromides with arylboronic acids but
aryl bromides and aryl chlorides are ineffective substrates.
Aliphatic boronic acids are also not reactive.
From the data in Tables 1 and 2, it would appear that the
reaction is relatively insensitive to the electronic nature of
substituents on the aromatic ring.
The synthesis of 4-methylbiphenyl is representative: palla-
dium black (0.050 g), KF (0.380 g), p-methylphenylboronic
acid (0.150 g, 1.10 mmol) and iodobenzene (0.204 g, 1.0 mmol)
were added to a clean, dry, 50 mL round bottomed flask.
Methanol (5 mL) was added to the mixture and the solution was
refluxed for 4 h in the open air. After decanting the solution, the
,4
Earlier studies revealed that potassium fluoride was an
5
effective Suzuki base. Therefore we selected KF as the base for
the current study. We found that aromatic iodides readily couple
with arylboronic acids in the presence of palladium powder
when the reactions are carried out in methanol, Scheme 1. The
initial results are summarized in Table 1. The reaction can be
product was isolated via flash chromatography to yield
1
4
-methylbiphenyl (92.2%); m.p. 44.0–45.5 °C, H NMR
(
CDCl
3
; d ppm): 7.40 (m, 9 H), 2.37 (s, 3H).
It is important to note that the palladium metal can be
recovered and recycled by a simple decantation of the reaction
solution. In one series of experiments, we carried out eight
consecutive preparations of 4-methylbiphenyl with no sig-
nificant loss in product yields. In each case, the palladium
powder was recovered by decantation, washed with methanol,
and the experiment repeated. We made no effort to rigorously
exclude water from the reactions. In fact, successful syntheses
were achieved in 20% aqueous methanol.
Scheme 1
Table 1 Suzuki coupling of tolylboronic acid with aryl iodidesa
b
Boronic acid
Aryl iodide
Yield (%)
4
4
4
4
4
4
4
4
4
-Methylphenyl
-Methylphenyl
-Methylphenyl
-Methylphenyl
-Methylphenyl
-Methylphenyl
-Methylphenyl
-Methylphenyl
-Methylphenyl
1-Fluoro-2-iodobenzene
1-Iodo-4-nitrobenzene
2-Iodoaniline
4-Iodoacetophenone
4-Iodoanisole
2-Iodothiophene
2-Iodophenol
1-Fluoro-3-iodobenzene
4-Iodotoluene
91
94
77
93
83
93
76
98
89
We wish to thank the U.S. Department of Energy and the
Robert H. Cole Foundation for their support of this research.
Notes and references
1 N. Miyaura and A. Suzuki, Chem. Rev., 1995, 95, 2457.
2 A. R. Martin and Y. Yang, Acta Chem. Scand., 1999, 47, 221.
3 G. W. Kabalka, R. M. Pagni and C. M. Hair, Org. Lett., 1999, 1, 1423.
a
Reactions carried out utilizing 1.0 mmol of aryl iodide and 1.1 mmol of
tolylboronic acid in refluxing methanol (5 mL) for 4 h in the presence of
palladium powder. b Isolated yields.
4
S. V. Rajender and N. P. Kannan, Tetrahedron. Lett., 1999, 40, 439.
5 T. Ishiyama, H. Kizaki, T. Hayashi, A. Suzuki and N. Miyaura, J. Org.
Chem., 1998, 63, 4726.
DOI: 10.1039/b101470f
Chem. Commun., 2001, 775
775
This journal is © The Royal Society of Chemistry 2001