Palladium-tetraphosphine catalysed cross coupling of aryl bromides with arylboronic acids: Remarkable influence of the nature of the ligand

Article abstract of DOI:10.1039/b009520f

The cis, cis, cis-1,2,3,4-Tetrakis(diphenylphosphinomethyl)cyclopentane- [PdCl(C₃H₅)]₂ system catalyses the cross coupling of aryl bromides with arylboronic acids with very high substrate-catalyst ratios in good yields; a turnover number of 28 000 000 can be obtained for the addition of 4-bromobenzophenone to benzeneboronic acid in the presence of this catalyst.

Full text of DOI:10.1039/b009520f

Palladium–tetraphosphine catalysed cross coupling of aryl bromides with
arylboronic acids: remarkable influence of the nature of the ligand
Marie Feuerstein, Dorothe´e Laurenti, Ce´line Bougeant, Henri Doucet* and Maurice Santelli*
Laboratoire de Synthe`se Organique associe´ au CNRS, Faculte´ des Sciences de Saint Je´roˆme, Avenue Escardrille
Normandie-Niemen, 13397 Marseille Cedex 20, France. E-mail: henri.doucet@lso.u-3mrs.fr,
m.santelli@lso.u-3mrs.fr; Fax: 04 91 98 38 65
Received (in Cambridge, UK) 27th November 2000, Accepted 12th January 2001
First published as an Advance Article on the web 31st January 2001
The cis,cis,cis-1,2,3,4-Tetrakis(diphenylphosphinomethyl)-
cyclopentane–[PdCl(C3H5)]2 system catalyses the cross cou-
pling of aryl bromides with arylboronic acids with very high
substrate–catalyst ratios in good yields; a turnover number
of 28 000 000 can be obtained for the addition of 4-bromo-
benzophenone to benzeneboronic acid in the presence of this
catalyst.
diarylphosphines in the cross coupling of arylboronic acid with
aryl bromides.
First, we tried to evaluate the importance of the presence of
phosphine ligands on the complex. So we performed the
reaction with [PdCl(C3H5)]2 as catalyst in the absence of ligand.
We observed that the coupling of 2,4-dimethoxybromobenzene
2 or 3-bromothiophene 3 with benzeneboronic acid 12 in the
presence of 4% catalyst led to the biaryl adducts in low yield
(Scheme 1 and 2) (Table 1, entries 1 and 2). Next, we tried to
evaluate the difference of efficiency between mono, di and
polydentate ligands bearing diphenylphosphino groups for this
reaction. For this we compared the rate of the reaction in the
presence of a monophosphine PPh3, a diphosphine dppe, and
with our tetraphosphine.9 Addition of 3-bromothiophene 3 to
benzeneboronic acid 12 in the presence of 0.0002% catalyst, led
to the addition product in 2% conversion when PPh3 was used
as ligand and 61% conversion with dppe (Table 1, entries 3 and
5). With Tedicyp the yield was 91% in the presence of
0.00002% catalyst (substrate–catalyst ratio of 5 000 000) (Table
1 entry 7) and 16% in the presence of 0.0000002% catalyst
(Table 1, entry 9). A similar tendency was observed for the
addition of 2,4-dimethoxybromobenzene 2 to benzeneboronic
acid 12. In the presence of 0.0002% catalyst, only 2%
conversion was observed with PPh3 (Table 1, entry 4). With
Tedicyp, in the presence of 0.00002% catalyst, the conversion
was 28% (Table 1, entry 6).
The electronic properties of the ligand are certainly of
importance for this reaction, as most triarylphosphines are not
sufficiently electron-rich to promote a fast oxidative addition of
aryl bromides.2 However, previous studies have shown that
electron-rich trialkylphosphines such as PCy3 are also rather
inefficient ligands for this reaction.10 In contrast t-Bu2P(biphe-
nyl) is an effective ligand for the Suzuki coupling.6 Although
electron-rich ligands such as P(Cy)3 facilitate oxidative addi-
tion, they also decrease the rate of the reductive elimination
process. These observations indicate that the combination of
both steric bulk and electronics is important. The complex
formed by association of Tedicyp and [PdCl(C3H5)]2 seems to
possess a fine balance of steric and electronic properties, which
allow a fast catalytic process.
Biaryl compounds are fundamental building blocks in organic
synthesis and their preparation is an important industrial goal.1
The cross coupling reaction is an efficient method for the
synthesis of these compounds.2 The classical method of
performing this reaction is to employ aryl halides and
organometals containing zinc, magnesium or boron in the
presence of palladium catalysts. These palladium complexes are
generally associated with the triphenylphosphine ligand.2 Even
if the catalyst formed by association of this ligand with
palladium complexes is efficient in terms of yield of adduct, the
efficiency in terms of substrate–catalyst ratio is usually low. In
general 1–10% of the catalyst must be used. Recently a few
bulky monodentate ligands have been successfully used for this
reaction.3 One of the most efficient catalytic systems uses a
palladium–phosphite complex. The nature of the phosphite
ligand has an important effect on the yield of the reaction, and
only hindered phosphites such as P(O-2,4-tBu2C6H3)3 or P(O-
iPr)3 are useful ligands.4 A carbene ligand also leads to the
formation of palladium catalysts that are more efficient than
those of triphenylphosphine for this reaction. With this complex
the reaction can be performed with as little as 0.0004%
catalyst.5 Finally, a very efficient catalyst for this reaction has
been prepared with the bulky ligand (o-biphenyl)P(t-Bu)2.6 If
bulky monodentate ligands have been successfully used for this
reaction, to our knowledge, the efficiency of bulky polydentate
ligands has not yet been demonstrated.
The nature of the phosphine ligand on complexes has a
tremendous influence on the rate of catalysed reactons.7 In order
to find more efficient palladium catalysts we have prepared a
new tetrapodal phosphine ligand, cis,cis,cis-1,2,3,4-tetrakis(di-
phenylphosphinomethyl)cyclopentane or Tedicyp 18 (Fig. 1) in
which the four diphenylphosphino groups are stereospecifically
bound to the same face of the cyclopentane ring. The presence
of four phosphines close to the metal centre should increase the
coordination of the ligand to the metal centre and therefore
increase the stability of the catalyst. We have reported recently
the first results obtained in allylic substitution using 1 as
ligand.8 For example, a TON of 680 000 for the addition of
dipropylamine to allyl acetate had been observed. In this paper,
we wish to report on the superiority of Tedicyp 1 over other
Next we tried to evaluate the scope and limitations of the
Tedicyp–palladium complex for this reaction. A survey of
Scheme 1
Fig. 1
Scheme 2
DOI: 10.1039/b009520f
Chem. Commun., 2001, 325–326
This journal is © The Royal Society of Chemistry 2001
325

Table 1 Palladium-catalysed cross-coupling with 12: influence of the ligand
Substrate–catalyst
Entry
Substrate
Ligand
T/h
ratio
Yield (%)
1
2
3
4
5
6
7
8
9
3-Bromothiophene
2,4-Dimethoxybromobenzene
3-Bromothiophene
2,4-Dimethoxybromobenzene
3-Bromothiophene
2,4-Dimethoxybromobenzene
3-Bromothiophene
No ligand
No ligand
PPh3
PPh3
dppe
1
1
1
1
24
48
96
24
24
20
24
20
24
25
25
500 000
500 000
500 000
33
16
2
2
61
28
91
34
16
5 000 000
5 000 000
100 000 000
500 000 000
3-Bromothiophene
3-Bromothiophene
Conditions: catalyst [Pd(C3H5)Cl]2/ligand 1/1; 3-bromothiophene 1 eq.; benzeneboronic acid 12 1.5 eq.; K2CO3 2 eq.; 130 °C; xylene.
Table 2 Tedicyp–Pd catalysed cross-coupling11
catalytic cross coupling of aryl bromides with arylboronic acids
is provided in Table 2. A wide variety of functional groups are
Aryl
bromide
Boronic
acid
Substrate–catalyst
ratio
tolerated. Coupling of 4-bromoanisole 4, 4-bromophenol 5,
4-bromobenzaldehyde 6, 4-bromoacetophenone and
Product
17
Yield (%)
7
4-bromobenzophenone 8 with benzeneboronic acid 12 in the
presence of 0.00001% of Tedicyp–palladium complex led to the
coupling products in 25, 74, 15, 96 and 98% yields, re-
spectively. A turnover number of 28 000 000 has been obtained
for the addition of 4-bromobenzophenone 8 to benzeneboronic
acid 12. Lower TON were observed in the course of the
coupling of 1-bromo-4-nitrobenzene 9 and 4-bromo-N,N-
dimethylaniline 10 with 12. Coupling of 4-bromoacetophenone
7 with the substituted 4-fluorobenzeneboronic acid 13 and
4-methoxybenzeneboronic acid 14, in the presence of 0.0001%
catalyst, led to the coupling products 25 and 26 in 97% and 80%
yield (Scheme 3). When we used 3-bromopyridine 11 in the
presence of 0.0001% catalyst a complete conversion was
observed for the coupling with benzeneboronic acid 12.
Turnover numbers of 75 000 and 96 000 have also been
obtained for the coupling of 3-bromopyridine 11 with 4-me-
thoxybenzeneboronic acid 14 and 4-fluorobenzeneboronic acid
13 respectively (Scheme 4). These results seem to indicate that
in general electron-poor aryl bromides can be reacted at higher
TON than electron-rich aryl bromides. In contrast, substituents
on the arylboronic acid seem to have a minor effect. In all cases,
only traces ( < 1%) of homocoupling products were observed
with this catalyst. The best results were usually obtained with
K2CO3 as base in toluene or xylene as solvents. Use of biphasic
solvent systems generally gave inferior results compared to
reactions run without added water.
4
5
12
12
100 000
10 000 000
1 000 000
10 000 000
10 000 000
10 000 000
10 000 000
100 000 000
100 000
93a
25f
98b
74a
15d
96f
98c
28a
26b
92a
95a
97e
80a
98e
96d
75d
18
6
7
8
12
12
12
19
20
21
9
10
5
7
7
11
11
11
12
12
13
13
14
12
13
14
22
23
24
25
26
27
28
29
100 000
20 000 000
1 000 000
1 000 000
1 000 000
100 000
100 000
Conditions: catalyst see ref. 9; ArX 1 eq; ArB(OH)2 1.5 eq.; K2CO3 2 eq.;
xylene; 130 °C.
a 24 h, b 48 h, c 72 h, d 90 h, e 115 h, f 135 h.
0.000005% catalyst without further optimisation of the reaction
conditions. These results represent an inexpensive, efficient,
and environmentally friendly synthesis.
We thank the CNRS for providing financial support.
Notes and references
1 For a review on biaryl synthesis: S. Stanforth, Tetrahedron, 1998, 54,
263.
2 For reviews on the cross coupling of aryl bromides with arylboronic
acids: (a) A. Suzuki, Metal-catalysed cross-coupling reaction, ed. F.
Diederich and P. J. Stang, Wiley, New York, 1998; (b) J.-L. Malleron,
J.-C. Fiaud and J.-Y. Legros, Handbook of palladium catalysed organic
reactions, Academic Press, San Diego, 1997; (c) N. Miyaura and A.
Suzuki, Chem. Rev., 1995, 95, 2457.
Scheme 3
ˆ
3 (a) M. Beller, H. Fischer, A. Herrmann, K. Ofele and C. Brossmer,
Angew. Chem., Int. Ed. Engl., 1995, 34, 1848; (b) D. A. Albisson, R. B.
Bedford, S. E. Lawrence and P. N. Scully, Chem. Commun., 1998,
2095.
4 A. Zapf and M. Beller, Chem. Eur. J., 2000, 6, 1830.
5 D. McGuiness and K. Cavell, Organometallics, 2000, 19, 741.
6 (a) J. Wolfe, R. Singer, B. Yang and S. Buchwald, J. Am. Chem. Soc.,
1999, 121, 9550; (b) J. Wolfe and S. Buchwald, Angew. Chem., Int. Ed.,
1999, 38, 2413.
Scheme 4
7 C. Bianchini, H. M. Lee, A. Meli, W. Oberhauser, F. Vizza, P.
Bru¨ggeller, R. Haid and C. Langes, Chem. Commun., 2000, 777.
8 M. Feuerstein, D. Laurenti, H. Doucet and M. Santelli, Chem. Commun.,
2001, 43.
9 For the preparation of the catalyst see D. Laurenti, M. Feurstein, G.
Pe`pe, H. Doucet and M. Santelli, J. Org. Chem., in press.
10 W. Shen, Tetrahedron Lett., 1997, 38, 5575.
11 As a typical experiment, the reaction of 4-bromoacetophenone 7 (1.03 g,
5.2 mmol), benzeneboronic acid 12 (0.92 g, 7.6 mmol) and K2CO3 (1.38
g, 10 mmol) at 130 °C for 24 h in dry xylene (10 mL) in the presence of
cis,cis,cis-1,2,3,4-tetrakis(diphenylphosphinomethyl)cyclopentane–
[PdCl(C3H5)]2 complex (5.2 1027 mmol) under argon affords the
corresponding biaryl adduct 20 after evaporation and filtration on silica
gel in 96% (0.98 g) isolated yield.
In conclusion, the use of the tetradentate ligand Tedicyp
associated with a palladium complex provides a convenient
catalyst for the cross coupling of aryl bromides with arylboronic
acids. This catalyst is much more efficient than the complex
formed with the triphenylphosphine ligand. This efficiency
probably comes from the presence of the four diphenylphos-
phinoalkyl groups stereospecifically bound to the same face of
the cyclopentane ring which probably increases the coordina-
tion of the ligand to the metal and presents precipitation of the
catalyst. The complex seems also to possess a fine balance of
steric and electronic properties which allow a fast catalytic
process. The reaction can be performed with as little as
326
Chem. Commun., 2001, 325–326