1
458
LETTER
Palladium Catalysed Cross-Coupling of Aryl Chlorides with Arylboronic
Acids in the Presence of a New Tetraphosphine Ligand
Marie Feuerstein, Henri Doucet,* Maurice Santelli*
Laboratoire de Synthèse Organique associé au CNRS, Faculté des Sciences de Saint Jérôme, Avenue Escadrille Normandie-Niemen,
1
3397 Marseille Cedex 20, France
Fax (33) 4 91 98 38 65; E-mail: henri.doucet@lso.u-3mrs.fr; m.santelli@lso.u-3mrs.fr
Received 14 June 2001
crease the stability of the catalyst. We have reported
Abstract: Cis,cis,cis-1,2,3,4-tetrakis(diphenylphosphinomethyl)-
8
recently the first results obtained in allylic substitution
cyclo pentane/[PdCl(C H )] system catalyses the cross-coupling of
3
5
2
9
and in Suzuki cross-coupling using 1 as ligand. For ex-
aryl chlorides with arylboronic acids with high ratios substrate/cat-
alyst. A turnover number of 6800000 has been obtained for the ad-
ample, a TON of 28000000 for the coupling of 4-bro-
dition of the activated 2-chloro-5-(trifluoromethyl)nitrobenzene to mobenzaldehyde with benzeneboronic acid had been
benzeneboronic acid in the presence of this catalyst.
observed. Here, we wish to report on the catalysed cross-
Key words: catalysis, palladium, tetraphosphine, arylboronic acids, coupling of arylchlorides with Tedicyp 1 as ligand.
aryl chlorides
Ph2P
PPh2
Ph2P
Biaryl compounds are fundamental building blocks in or-
ganic synthesis and their preparation is an important in-
dustrial goal. The Suzuki cross-coupling reaction is one
PPh2
1
Tedicyp 1
of the most efficient methods for the synthesis of these
2
compounds. The general procedure to perform this reac- Figure
tion is to employ aryl iodides or bromides and a boronic
acid in the presence of palladium catalysts. However,
First, we have investigated the Suzuki reaction of several
para substituted aryl chlorides with benzeneboronic acid
in the presence of the system [PdCl(C H )] / 2 tedicyp in
xylene at 130 °C. The results presented in the Table un-
fold a strong substituent effect on the reaction rate. Elec-
tron-withdrawing groups in the aryl chloride support the
Suzuki reaction, while electron-donating groups are un-
favourable. Turnover numbers of 2500-13000 can be
achieved with this catalyst for activated substrates such as
from an industrial point of view, the use of cheaper aryl
3
chlorides is important. Since a few years several ligands
have been tested for the coupling of these relatively inert
3
5
2
4
−6
substrates. The nature of the ligand has an important ef-
fect on the yield of the reaction, and only hindered elec-
tron rich ligands led to the coupling adducts in good
yields. The most efficient catalytic systems use bulky
4
b,c
monodentate ligands such as (o-biphenyl)P(t-Bu) ,
2
4
g
4h
P(O-2,4-tBu C H ) or P(t-Bu) . To our knowledge the
2
6
3 3
3
4
-chloroacetophenone, 4-chlorobenzaldehyde, 4-chlo-
robenzonitrile, 1-chloro-4-(trifluoromethyl)benzene and
-chloronitrobenzene (Scheme, Table). In the presence
most efficient ligand for this reaction is PBu(adaman-
4
i
tyl)2. With this ligand a TON (turnover number) of
9000 has been obtained for the coupling of 2-chloroben-
4
6
6
of the very activated substrate 2-chloro-5-(trifluoro-
methyl)nitrobenzene an extremely high TON has been
obtained: 6800000. On the other hand, with deactivated
zonitrile with benzeneboronic acid. A few bidentate
ligands such as dppp,
aminophosphine or a bis carbene have also been used,
however they seem in general less efficient than bulky
5
c
5a
5b
dppb,
P(o-tolyl)3,
an
5
d
5e
4
-chloroanisole we obtained a TON of 21.
monodentate ligands. If monodentate or bidentate ligands Next we studied the influence of an ortho substituent on
have been used for the coupling of aryl chlorides, to our the aryl chloride, but no significant steric effect was ob-
knowledge, the efficiency of tetradentate ligands has not served on the rate of the reaction. 2-Chloroacetophenone,
yet been demonstrated.
2-chlorobenzaldehyde, 2-chlorobenzonitrile and 1-chlo-
ro-2-(trifluoromethyl)benzene led to similar TON’s than
para substituted aryl chlorides.
The nature of the phosphine ligand has an important effect
on the rate of transition-metal catalysed reactions. In order
to find more efficient palladium catalysts we have pre- We also tried to evaluate the importance of the presence
7
pared a new tetrapodal phosphine ligand, cis,cis,cis- of a tetradentate phosphine ligand on the complex. For
1
,2,3,4-tetrakis(diphenylphosphino-methyl)cyclopentane
this we compared the rate of the reaction in the presence
8
a
or Tedicyp 1 (Figure) in which the four diphenylphos- of electronically similar ligands: PPh , dppe, dppb. For
3
phino groups are stereospecifically bound to the same face the coupling of 4-chloroacetophenone in the presence of
of the cyclopentane ring. The presence of four phosphines 0.1% [PdCl(C H )] / 4 PPh only traces of product were
3
5
2
3
close to the metal centre seems to increase the coordina- observed. The same reaction performed with dppe or dppb
tion of the ligand to the metal centre and therefore in- led to higher TON’s: 220 and 260, respectively. With 1
Synlett 2001, No. 9, 1458–1460 ISSN 0936-5214 © Thieme Stuttgart · New York