Ligandless palladium chloride-catalyzed homo-coupling of arylboronic acids in aqueous media

Article abstract of DOI:10.1016/S0040-4039(02)00437-9

In the presence of p-toluenesulfonyl chloride, ligandless palladium chloride catalyzes the homo-coupling of arylboronic acids to afford symmetrical biaryls in excellent yields.

Full text of DOI:10.1016/S0040-4039(02)00437-9

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 3067–3068
Ligandless palladium chloride-catalyzed homo-coupling of
arylboronic acids in aqueous media
George W. Kabalka* and Lei Wang
Departments of Chemistry and Radiology, The University of Tennessee, Knoxville, TN 37996-1600, USA
Received 23 January 2002; accepted 19 February 2002
Abstract—In the presence of p-toluenesulfonyl chloride, ligandless palladium chloride catalyzes the homo-coupling of arylboronic
acids to afford symmetrical biaryls in excellent yields. © 2002 Published by Elsevier Science Ltd.
The palladium-catalyzed coupling of arylboronic acids
and esters with organic halides (Suzuki reaction) is an
excellent method for preparing unsymmetrical biaryls,
which are important building blocks in natural products
water/ethanol mixture (v/v, 1/1), at room temperature in
the presence of p-toluenesulfonyl chloride in the absence
of oxygen. Excellent yields of the desired biaryl products
are obtained (Scheme 1).
1
and in the material sciences. The synthesis of symmet-
rical biaryls via homo-coupling of arylboronic acids is
also of interest to synthetic organic chemists. Suzuki
reported a self-coupling reaction of arylboronic acids,
carried out under anhydrous conditions using Pd(OAc)2
A variety of sulfonyl chlorides were investigated and our
results are summarized in Table 1. In the absence of an
additive, homo-coupling occurs but the yield is poor.
Addition of an arylsulfonyl chloride improves the yield
dramatically (95%, entry 4, Table 1). Among the sulfonyl
chlorides we tested, p-toluenesulfonyl chloride and
phenylsulfonyl chloride were the most effective. p-Tolu-
enesulfonyl chloride was chosen for the study since it is
readily available. The optimum quantity of p-toluenesul-
fonyl chloride was found to be 0.5 equiv. p-Toluenesul-
fonamide, p-toluenesulfonic acid and thionyl chloride
were not effective.
2
along with PPh3 and a Cu(OAc)2 catalyst. Wong
reported self-coupling of organoboroxines catalyzed by
3
Pd(PPh ) in a methanol/toluene solvent system. Tamao
3
4
then found that palladium(II) complexes catalyzed the
oxidative homo-coupling of areneboronic acids in the
4
presence of acrylate dibromides to afford biaryls, but the
phenyl groups in PPh can also couple with arylboronic
3
5
acids to give an unsymmetrical biaryl. Jackson reported
the homo-coupling of arylboronic acids catalyzed by
Pd(OAc) in the presence of oxygen, but the reaction
proceeds rather slowly and affords only moderate yields.
2
6
The results of the arylboronic acid homo-coupling study
are summarized in Table 2. For arylboronic acids,
Most recently, Wong found that phosphine and phos-
phite are efficient ligands for palladium-catalyzed homo-
containing groups such as Cl, F or CH , the reaction
3
7
affords excellent yields of biaryl products. The addition
of ethanol increases the solubility of the arylboronic acid
and has little, if any, effect on reaction yields. (Compare
entries 2 and 6 in Table 2.)
coupling of arylboronic acids in DMF.
We report a ligandless palladium chloride catalyzed
homo-coupling of arylboronic acids in water, or a
PdCl ( 3 mole %)
2
Na CO (2 eq.)
2
3
B(OH)2
p-Toluenesulfonyl chloride
R
R
R
H O
2
Scheme 1.
*
0
Corresponding author. Tel.: 865-974-3260; fax: 865-974-2997; e-mail: kabalka@utk.edu
040-4039/02/$ - see front matter © 2002 Published by Elsevier Science Ltd.
PII: S0040-4039(02)00437-9

3
068
G. W. Kabalka, L. Wang / Tetrahedron Letters 43 (2002) 3067–3068
a
Table 1. Homocoupling of p-tolueneboronic acid
Scheme 2). However, heteroaromatic boronic acids and
aliphatic boronic acids are not reactive.
Entry
Additive
Yield (%)b
The mechanism of the reaction has not been investi-
gated but a sulfonyl chloride is required. We have
carried out the reaction in the presence of sodium
p-toluenesulfonate and sodium chloride and the results
were not satisfactory. Furthermore, the addition of
either p-toluenesulfonic acid or hydrochloric acid does
not induce homo-coupling.
1
2
3
4
5
6
7
8
9
None
35
17
46
95
95
84
92
83
66
77
70
11
p-Toluenesulfonamide
p-Toluenesulfonic acid
p-Toluenesulfonyl chloride
Phenylsulfonyl chloride
p-Bromophenylsulfonyl chloride
m-Nitrophenylsulfonyl chloride
2-Mesitylenesulfonyl chloride
2,4-Dinitrophenylsulfonyl chloride
p-Toluenesulfonyl chloride
n-Butylsulfonyl chloride
Thionyl chloride
General procedure: The synthesis of 4,4%-dimethyl-
biphenyl is representative. To a stirred solution of
p-tolueneboronic acid (1.0 mmol), palladium(II) chlo-
ride (3 mol%), sodium carbonate (2 mmol in 20 mL of
10
11
12
a
H O), was added p-toluenesulfonyl chloride in one
2
Reaction conditions: p-tolueneboronic acid (1.0 mmol), PdCl (0.03
2
portion (0.5 mmol). The solution was stirred at room
temperature overnight. Hexane (2×20 mL) was added
to extract the product. The combined organic phase
was dried over anhydrous sodium sulfate and the sol-
vent evaporated under reduced pressure to yield 4,4%-
dimethylbiphenyl (87 mg, 95%).
mmol), Na CO3 (2.0 mmol), additive (0.5 mmol), H O (20 mL)
room temperature under nitrogen atmosphere for 12 h with stirring.
Isolated yield.
2
2
b
Table 2. Ligandless palladium-catalyzed homo-coupling of
a
arylboronic acids
Entry
Boronic acid
C H B(OH)
Reaction media Yield (%)b
In conclusion, a simple, environmentally friendly, pro-
cedure for the synthesis of symmetrical biaryls from
corresponding arylboronic acids has been developed.
The procedure does not require anhydrous conditions
and utilizes ligandless palladium chloride.
1
2
3
4
5
H O
95
95
96
97
96
6
5
2
2
p-CH C H B(OH)
H O
3
6
4
2
2
p-FC H B(OH)
H O
6
4
2
2
p-ClC H B(OH)
H O
6
4
2
2
p-BrC H B(OH)
H O–C H OH
6
4
2
2
2
5
(
1/1)
6
7
8
9
p-CH C H B(OH)
H O–C H OH
92
95
96
94
90
93
56
3
6
4
2
2
2
5
Acknowledgements
(
1/1)
C H CHꢀCHB(OH)
H O–C H OH
6
5
2
2
2
5
(
1/1)
We wish to thank the Department of Energy and the
Robert H. Cole Foundation for support of this
research.
p-CH COC H B(OH) H O–C H OH
3
6
4
2
2
2
5
(
1/1)
p-CH SC H B(OH)
H O–C H OH
3
6
4
2
2
2
5
(
1/1)
10
11
12
m-CHOC H B(OH)
H O–C H OH
6
4
2
2
2
5
(
1/1)
References
Naphthalene-1-boronic H O–C H OH
acid
2
2
5
(1/1)
1
. (a) Suzuki, A. J. Organomet. Chem. 1999, 576, 147; (b)
Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457; (c)
Suzuki, A. In Metal-catalysed Cross-coupling Reactions;
Diederich, F.; Stang, P. T., Eds. Cross coupling reaction of
organoboron compounds with organic halides; Wiley-VCH:
Weinheim, 1998; pp. 49–97.
o-CH C H B(OH)
H O–C H OH
3
6
4
2
2
2
5
(
1/1)
a
Reaction conditions: arylboronic acid (1.0 mmol), PdCl2 (0.03
mmol), Na CO (2.0 mmol), p-toluenesulfonyl chloride (0.5 mmol),
2
3
solvent (20 mL) room temperature for 12 h.
Isolated yield.
b
2. Miyaura, N.; Suzuki, A. Main Group Met. Chem. 1987, 10,
95.
2
Very good yields are observed for arylboronic acids
containing both electron donating and electron with-
drawing groups. It is noteworthy that substituents at
the ortho-position lead to decreased yields (entry 12,
Table 2). Functional groups such as halide, methoxy,
and acetyl are not affected. Vinyl boronic acids also
homo-couple under the reaction conditions (81% yield,
3. Song, Z. Z.; Wong, H. N. C. J. Org. Chem. 1994, 59, 33.
4. Yamaguchi, S.; Ohno, S.; Tamao, K. Synlett 1997, 1199.
5. O’Keefe, D. F.; Dannock, M. C.; Marcuccio, S. M. Tetra-
hedron Lett. 1992, 34, 6679.
6. Smith, K. A.; Campi, E. M.; Jackson, W. R.; Marcuccio,
S.; Naeslund, C. G. M.; Deacon, G. B. Synlett 1997, 131.
7. Wong, M. S.; Zhang, X. L. Tetrahedron Lett. 2001, 42, 4087.
PdCl (3 mole %)
2
Na CO (2 eq.)
2
3
Cl
Cl
B(OH)2
Cl
p-Toluenesulfonyl chloride
H O-C H OH (V/V, 1/1)
Mixture of stereoisomers
2
2 5
Scheme 2.