Table 2 Suzuki coupling reactions catalysed by new palladium complexesa
TON/mol
product (mol Pd)
Entry
Aryl halide
[5a](mol%)
T/°C
t/h
Yield (%)b
21
1
2
3
4
5
4-Bromoacetophenone
4-Bromoacetophenone
4-Bromoacetophenone
4-Chloroacetophenone
4-Chlorobenzaldehyde
0.002
0.001
0.0002
0.02
130
130
130
130
130
20
24
24
48
24
100
97
67
49 750
96 600
334 500
0
0
0.01c
27.2d
2 724
a
d
2 3
CO
, 150 cm o-xylene. b Determined by GC-MS. c Catalyst 5c.
3
Reaction conditions: 50 mmol aryl halide, 75 mmol phenylboronic acid, 100 mmol K
Conversion is 83.4%, other products are 1-(4-chlorophenyl)-1-phenylmethanol (37.4%) and 1-4-biphenyl-1-phenylmethanol (19%).
temperature (170 °C, entry 1) is required to achieve activity
norbornene to phenylnorbornane using 5a and bromobenzene in
12 h at 130 °C, 9500 turnovers).
comparable to the Herrmann system (1000 000 TON in 24 h at
5
1
30 °C), but no additive/promoting salts (e.g. NBu
4
Br) are
The Suzuki reaction is the coupling of aryl halides with
arylboronic acids (Scheme 2). It is mechanistically similar to the
Heck reaction, and both the Herrmann1b and Bedford com-
plexes have also been reported as active catalysts for this
reaction. Some results for the coupling of alkyl halides with
phenylboronic acid are displayed in Table 2.
required. In fact we have not observed any increase in activity
or catalyst stability when such salts are added to our system. As
the catalyst concentration is decreased, higher turnover num-
7
6
bers, in excess of 3 3 10 , are achieved at the expense of
product selectivity (entries 3 and 4). Indeed, when bromoaceto-
phenone was used as the substrate, Michael addition to the
alkene was a competing side reaction, which predominated with
higher temperatures and lower catalyst concentration. The
Michael addition is reversible so that the selectivity to the
coupled product increases with time (Fig. 1). Michael addition
was not observed when 4-bromobenzaldehyde was used (entry
Excellent conversions and selectivities are observed with
catalyst concentrations down to 0.001 mol% Pd, after which
longer reaction times are required. In contrast to the results of
Bedford and coworkers, little activity is observed when toluene
is used as the reaction solvent (Bedford obtains 1000 000 TON
7
in toluene in 2.25 h). No activity is observed with aryl chlorides
5
), as the aldehyde proton is less acidic than the a protons of the
when using complex 5a, but using the more electron donating
6
8
acetophenone, and a TON of 3.7 3 10 was achieved with good
selectivity. There is also evidence to suggest that complex 5a is
deactivated more quickly due to palladium metal aggregation
when higher catalyst concentrations are used, resulting in
incomplete reaction. Product decomposition at prolonged high
reaction temperatures has also proven a problem with certain
substrates.
5c activities higher than those reported by Fu and coworkers
using Pd/PBut
complexes (maximum TON = 200) or than
3
9
those recently reported by Beller and coworkers using
unmetallated monophosphine palladium complexes (maximum
TON < 2000) are obtained in the coupling of 4-chlor-
obenzaldehyde with phenylboronic acid. The major side
products of this reaction are 1-(4-chlorophenyl)-1-phenyl-
methanol and 1-(4-biphenyl)-1-phenylmethanol. Since the
latter arises from coupling of the Suzuki product to the boronic
acid, the overall turnovers to Suzuki products are ca. 4600,
which is similar to the best results obtained by Buchwald using
di-tert-butylphosphinobiphenyl.10 Other highly active catalysts
for Suzuki coupling, which have been reported since the
submission of this communication, show very low activities for
coupling of chloroaromatics with aryl boronic acids.1
1,12
In conclusion, we have developed an underligated palladium
catalyst system that shows comparable activity to existing
palladacycle systems but does not require promoting salts. By
making the P atom strongly electron donating (But
P groups), a
2
catalyst which shows very high activity for coupling of Suzuki
chloroaromatic compounds is obtained.
Fig. 1 Diagram of the concentration (C in mol%/100) vs. reaction time of the
Heck reaction of 4-bromoacetophenone ( < ) with n-butyl acrylate at 130 °C
to form n-butyl (E)-4-acetylcinnamate (-): catalyst 5a (0.0001 mol%,
0
.0002 mol% Pd). Michael addition by-products (Ω) and (8) are also
Notes and references
formed.
1
W. A. Herrmann, C. Brossmer, K. Ölefe, C.-P. Reisinger, T. Priermeier,
M. Beller and H. Fischer, Angew. Chem., Int. Ed. Engl., 1995, 34,
1844.
Non-activated and deactivated (electron donating) substrates,
such as bromobenzene, 4-bromoanisole and 4-bromo-N,N-
dimethylaniline (entries 6–8) require higher catalyst concentra-
tions and reaction times to obtain reasonable yields, but the
turnover numbers compare favourably with other palladacyclic
2 M. Beller, H. Fischer, W. A. Herrmann, K. Ölefe and C. Brossmer,
Angew. Chem., Int. Ed. Engl., 1995, 34, 1848.
M. Ohff, A. Ohff, M. E. van der Boom and D. Milstein, J. Am. Chem.
Soc., 1997, 119, 11687.
3
4
5
5
systems. Even 4-bromophenol reacted to give 20% of n-butyl-
D. A. Albisson, R. B. Bedford and P. N. Scully, Tetrahedron Lett., 1998,
(
E)-4-hydroxycinnamate, but 4-bromoaniline gave almost ex-
3
9, 9793.
clusively Michael addition products. The industrially important
reaction of ethene with 2-bromo-6-methoxynaphthalene also
occurs with excellent selectivity and good activity (entry 12).
Although the observations of Herrmann that aryl donating
groups on the phosphino moiety give higher activity than alkyl
groups have been confirmed, complex 5c catalyses the coupling
of 4-bromoacetophenone and n-butyl acrylate with excellent
selectivity when 0.02 mol% Pd is used (entry 13).
W. A. Herrmann, C. Brossmer, C.-P. Reisinger, T. H. Riermeier, K.
Ölefe and M. Beller, Chem. Eur. J., 1997, 3, 1357.
6 J. M. Brunel, A. Heumann and G. Buono, Angew. Chem., Int. Ed., 2000,
39, 1946
7 D. A. Albisson, R. B. Bedford, S. E. Lawrence and P. N. Scully, Chem.
Commun., 1998, 2095.
8
A. F. Littke, C. Y. Dai and G. C. Fu, J. Am. Chem. Soc., 2000, 122,
020.
M. G. Andreu, A. Zapf and M. Beller, Chem. Commun., 2000, 2475.
4
9
In addition to being an effective Heck catalyst, complex 5a
also exhibits catalytic activity towards the Suzuki coupling, and,
to a lesser extent, the Stille coupling (35% yield from
1
1
0 J. P. Wolfe, R. A. Singer, B. H. Young and S. L. Buchwald, J. Am.
Chem. Soc., 1999, 121, 9550.
1 R. B. Bedford and S. L. Welch, Chem. Commun, 2001, 129.
4
-bromoacetophenone and Me
turnovers) and the hydroarylation reaction (57% conversion of
3
PhSn in 6 h at 110 °C, 3528
12 M. Feuerstein, D. Laurenti, C. Bougeant, H. Doucet and M. Santelli,
6
Chem. Commun., 2001, 325.
780
Chem. Commun., 2001, 779–780
Gibson
