Palladium catalysed cross-coupling of aryl bromides with functionalised arylboronic acids in the presence of a tetraphosphine ligand

Article abstract of DOI:10.1055/s-2002-34896

Cis,cis,cis-1,2,3,4-tetrakis(diphenylphosphinomethyl)cyclopentane/[PdCl(C ₃H₅)]₂ system catalyses efficiently the cross-coupling of aryl bromides with functionalised arylboronic acids. The electronic properties of the aryl

Full text of DOI:10.1055/s-2002-34896

LETTER
1807
Palladium Catalysed Cross-Coupling of Aryl Bromides with Functionalised
Arylboronic Acids in the Presence of a Tetraphosphine Ligand
Palladium Catalysed
C
a
ross-Coupli
r
ng of
A
r
yl Bro
e
mides Feuerstein, Florian Berthiol, Henri Doucet,* Maurice Santelli*
Laboratoire de Synthèse Organique associé au CNRS, Faculté des Sciences de Saint Jérôme, Avenue Escadrille Normandie-Niemen,
13397 Marseille Cedex 20, France
Fax +33(4)91983865; E-mail: henri.doucet@univ.u-3mrs.fr; E-mail: m.santelli@univ.u-3mrs.fr
Received 15 July 2002
The nature of phosphine ligand has an important effect
Abstract: Cis,cis,cis-1,2,3,4-tetrakis(diphenylphosphinomethyl)-
on the rate of transition-metal catalysed reactions. In order
cyclopentane/[PdCl(C3H5)]2 system catalyses efficiently the cross-
coupling of aryl bromides with functionalised arylboronic acids.
The electronic properties of the arylboronic acids seem to have a
to find more efficient palladium catalysts we have pre-
pared the tetrapodal5 phosphine ligand, cis,cis,cis-1,2,3,4-
minor influence on the reaction rate. Better results were generally tetrakis(diphenylphosphinomethyl)cyclopentane
or
Tedicyp6a (Figure 1). All four phosphines probably can-
not bind at the same time to the same palladium centre, but
the presence of these four phosphines close to the metal
centre seems to increase the coordination of the ligand to
the palladium complex and therefore increase the stability
of the catalyst. We have reported recently the first results
obtained for the reaction of electron poor aryl bromides associated
with electron rich arylboronic acids rather than the contrary.
Key words: catalysis, palladium, tetraphosphine, arylboronic
acids, aryl bromides
Biaryl compounds are fundamental building blocks in or- obtained in Suzuki cross-coupling7 using Tedicyp as
ganic synthesis and their preparation is an important in- ligand. For example, a TON (turnover number) of 96 000
dustrial goal.1 Palladium catalysed Suzuki cross-coupling 000 for the coupling of 4-bromoacetophenone with ben-
reaction is one of the most powerful methods for the syn- zeneboronic acid had been observed.7e Palladium catalyst
thesis of such compounds.2 In general, these palladium prepared with dppe as ligand is generally less active by a
catalysts are associated with triphenylphosphine ligand. factor of ten.7a,b We had also reported a few results using
Even if the catalyst formed by association of this ligand Tedicyp ligand with 4-methoxy- and 4-fluorobenzenebo-
with palladium complexes is efficient in terms of yield of ronic acids. Generally lower TONs were obtained with
adduct, the efficiency in terms of ratio substrate/catalyst is these substrates, but the reason of these results was not
generally low and 1 to 10% of the catalyst must be used. clear.7b Here, in order to further establish the requirements
In recent years, several more stable palladium catalysts for a successful Suzuki cross-coupling reaction, we wish
have been successfully used for Suzuki cross-coupling re- to report on the influence of several electron-donating and
action.3 However, most of the results which have been de- electron-withdrawing functions on the arylboronic acid
scribed with these catalysts, were obtained for the using Tedicyp as the ligand.
coupling of phenylboronic acid. Relatively few results
have been reported with functionalised arylboronic acids.4
One of the most active catalyst for such substrates has
Ph2P
PPh2
PPh2
Ph2P
Tedicyp
been prepared with the bulky ligand (o-biphenyl)P(t-
Bu)2.4c A resin-bound catalyst was also found to enable
Suzuki reaction with functionalised arylboronic acids in
high yields.4f An other efficient catalytic systems uses a
palladium–diazabutadiene complex.4i A palladium–car-
bene complex also efficiently promotes the cross-cou-
pling of methoxybenzeneboronic acids.4e However, to our
knowledge, the efficiency of tetraphosphine ligands for
the coupling of functionalised arylboronic acids has not
been reported.
Figure 1
First, we have investigated the Suzuki reaction of several
para substituted arylboronic acids with arylhalides in the
presence of the system [PdCl(C3H5)]2/2 Tedicyp in xy-
lenes at 130 °C (Scheme 1, Table 1). The results present-
ed in Table 1 unfold a strong influence of the substituents
of the arylboronic acids on the reaction rate.
R2
R1
R4
R3
R4
R2
[Pd(C3H5)Cl]2, tedicyp,
xylene, K2CO3, 130°C, 20 h
+
Br (HO)2B
R3
R1
Scheme 1
Synlett 2002, No. 11, Print: 29 10 2002.
Art Id.1437-2096,E;2002,0,11,1807,1810,ftx,en;G19802ST.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0936-5214

1808
M. Feuerstein et al.
LETTER
Table 1 Palladium–Tedicyp Catalysed Cross-Coupling (Scheme 1)8,a
Entry
R1
R2
R3
R4
Ratio
Yield (%)b
substrate/ catalyst
1
2
3
4-MeCO
4-MeO
2-Me
H
H
6-Me
2-Me
2-Me
2-Me
H
H
H
1 000 000
1 000 000
10 000
82 (78)
81 (76)
83 (76)
4
5
6
7
4-MeCO
4-MeCO
4-MeO
2-Me
H
H
H
6-Me
4-MeO
4-MeO
4-MeO
4-MeO
H
H
H
H
1 000 000
10 000 000
1 000 000
100 000
(80)
62
82 (74)
97 (95)
8
9
10
4-MeCO
4-MeO
2-Me
H
H
6-Me
2-MeO
2-MeO
2-MeO
H
H
H
1 000 000
1 000 000
10 000
91 (85)
53
66 (65)
11
12
13
4-MeCO
4-MeO
2-Me
H
H
6-Me
2-F
2-F
2-F
4-F
4-F
4-F
100 000
10 000
1 000
53
60
67 (60)
14
15
16
4-MeCO
4-MeO
2-Me
H
H
6-Me
4-CF3
4-CF3
4-CF3
H
H
H
1 000 000
100 000
10 000
60 (58)
75
98 (95)
17
18
19
4-MeCO
4-MeO
2-Me
H
H
6-Me
2-CF3
2-CF3
2-CF3
H
H
H
10 000
10 000
1 000
80 (78)
76
10
20
21
22
4-MeCO
4-MeO
2-Me
H
H
6-Me
3-CF3
3-CF3
3-CF3
5-CF3
5-CF3
5-CF3
100 000
100 000
10 000
100 (98)
92
97 (95)
23
24
25
4-MeCO
4-MeO
2-Me
H
H
6-Me
4-MeCO
4-MeCO
4-MeCO
H
H
H
100 000
250
250
66 (60)c
94 (90)
100 (90)
26
27
4-MeCO
4-MeO
H
H
2-MeCO
2-MeCO
H
H
10 000
10 000
100 (94)c
90 (88)c
28
29
4-MeCO
4-MeO
H
H
3-NO2
3-NO2
H
H
10 000
10 000
58
24c
30
31
4-F
4-F
H
H
4-MeO
2-Me
H
6-Me
100 000
10 000
80 (78)
48
32
33
2-F
2-F
4-F
4-F
4-MeO
2-Me
H
6-Me
100 000
1 000
65 (62)
22
34
35
36
4-CF3
4-CF3
4-CF3
H
H
H
4-MeO
4-MeO
2-Me
H
H
6-Me
100 000
1 000 000
10 000
100 (97)
72
25
37
38
2-CF3
2-CF3
H
H
4-MeO
4-MeO
H
H
100 000
1 000 000
100 (96)
28
39
40
41
3-CF3
3-CF3
3-CF3
5-CF3
5-CF3
5-CF3
4-MeO
4-MeO
2-Me
H
H
6-Me
1 000 000
10 000 000
10 000
99 (96)
35
33
42
43
2-MeCO
4-MeCO
H
H
4-MeO
2-Me
H
100 000
10 000
66
60
6-Me
44
45
3-NO2
3-NO2
H
H
4-MeO
4-MeCO
H
H
100 000
10 000
90 (86)c
75 (69)c
a Conditions: catalyst see ref.,6a ArBr (1 equiv), ArB(OH)2 (2 equiv), K2CO3 (2 equiv), xylene, 130 °C, 20 h, GC or NMR yields.
b Yields in brackets are isolated.
c Solvent: xylenes/DMF: 1/1 for solubility reasons.
Synlett 2002, No. 11, 1807–1810 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
Palladium Catalysed Cross-Coupling of Aryl Bromides with Functionalised Arylboronic Acids
1809
Electron-withdrawing groups in the arylboronic acid are Finally, the coupling in the presence of the sterically hin-
unfavourable in a few cases, while an electron-donation dered substrates 2,6-dimethylbromobenzene or 2,6-dime-
group is favourable. For example, a turnover number of 6 thylbenzeneboronic acid has been studied. The reactions
200 000 can be achieved with this catalyst for the reaction rates are much lower, however most of the reactions could
of 4-bromoacetophenone with 4-methoxybenzeneboronic be performed with substrate/catalyst ratios of 1 000–10
acid (entry 5) whereas the coupling of 4-bromoanisole 000. In general, better results were obtained for the cou-
with 4-acetylbenzeneboronic acid led to a much lower pling of 2,6-dimethylbromobenzene with functionalised
TON of 234 (entry 24). However, high TONs are obtained arylboronic acids (entries 3, 7, 10, 13, 16 and 22) than for
for the coupling of 4-trifluoromethylbenzeneboronic acid the coupling of functionalised arylbromides with 2,6-dim-
with 4-bromoacetophenone or 4-bromoanisole (entries 14 ethylbenzeneboronic acid (entries 31, 33, 36, 41 and 43).
and 15) indicating a minor electronic effect of the substit-
uents on the arylboronic acid on the reaction rate.
In summary, in the presence of the Tedicyp/palladium
complex, the Suzuki cross-coupling of several functiona-
Several reactions were also performed using 3-nitroben- lised arylboronic acids can be performed with as little as
zeneboronic acid (entries 28 and 29). With this substrate 0.00001% catalyst. A wide range of functions such as
low TONs were observed.
methoxy, fluoro, acetyl, nitro or trifluoromethyl is tolerat-
ed. In order to obtain high turnover numbers, electron-
withdrawing substituents of the substrates should be lo-
cated on the aryl bromide. If the functions and the purity
of the arylboronic acid have an influence on the catalyst,
their electronic properties have a minor influence on the
reaction rate. For this reason the electron-donating substit-
uents of the reaction should be located on the arylboronic
acid. When disappointing results are obtained with func-
tionalised arylboronic acids, they should be recrystallized.
To gain insight into the reason of such results, we under-
took a series of competitive reactions using an equimolar
mixture of 4-methoxybenzeneboronic acid and 3,5-bistri-
fluoromethylbenzene-boronic acid in the presence of aryl-
bromides (Scheme 2). We observed in both cases the
formation of a mixture of the coupling products. Ratios of
41/59 and 42/58 between the 4-methoxyphenylaryl ad-
duct a and the 3,5-bistrifluoromethylphenylaryl adduct b
were obtained. These results reveal that slightly higher re-
action rates can be obtained with electron-withdrawing
groups on the arylboronic acid. In fact, the lower reaction
rates observed in some cases with the arylboronic acids
bearing electron-withdrawing groups apparently does not
comes from the transmetallation rate of the arylboronic
acid with the palladium catalyst, but more likely from the
poisoning of the catalyst by the impurities or the functions
of the arylboronic acids. In order to confirm this, we have
recrystallized some of the arylboronic acids and better re-
sults were obtained in some cases. For example, a TON of
100 000 instead of 8 000 for the coupling of 3,5-bistriflu-
oromethylbenzeneboronic acid with 4-bromoacetophe-
none was obtained after recrystallization (entry 20).
Acknowledgement
M. F. is grateful to the Ministère de la Recherche for a grant. We
thank the CNRS for providing financial support.
References
(1) For reviews on biaryl synthesis: (a) Hassan, J.; Sévignon,
M.; Gozzi, C.; Schulz, E.; Lemaire, M. Chem. Rev. 2002,
102, 1359. (b) Stanforth, S. Tetrahedron 1998, 54, 263.
(2) For reviews on the cross-coupling of aryl halides with
arylboronic acids: (a) Suzuki, A. J. Organomet. Chem.
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576, 147. (c) Suzuki, A. Metal-Catalysed Cross-Coupling
Reaction; Diederich, F.; Stang, P. J., Eds.; Wiley: New York,
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Handbook of Palladium Catalysed Organic Reactions;
Academic Press: San Diego, 1997. (e) Miyaura, N.; Suzuki,
A. Chem. Rev. 1995, 95, 2457.
Then, we studied the influence of ortho substituents on the
arylboronic acid for the coupling with 4-bromoacetophe-
none or 4-bromoanisole. Higher TONs were obtained us-
ing a methyl or a methoxy substituent (entries 1, 2, 8 and
9) rather than a trifluoromethyl or an acetyl (entries 17,
18, 26 and 27). Here also the purity of the substrates seems
to be an important factor for a successful reaction.
(HO)2B
20 mmol
OMe
[Pd(C3H5)Cl]2, tedicyp,
R
R
OMe
a
+
Ratio S/C: 1000
R
Br
+
CF3
CF3
xylene, K2CO3, 130°C, 1h
10 mmol
(HO)2B
20 mmol
b
CF3
CF3
R = MeCO: conv. 100%, ratio a/b = 41/59
R = MeO: conv. 100%, ratio a/b = 42/58
Scheme 2
Synlett 2002, No. 11, 1807–1810 ISSN 0936-5214 © Thieme Stuttgart · New York

1810
M. Feuerstein et al.
LETTER
(3) For recent examples of efficient catalysts for Suzuki cross-
coupling: (a) Beller, M.; Fischer, H.; Herrmann, A.; Öfele,
K.; Brossmer, C. Angew. Chem., Int. Ed. Engl. 1995, 34,
1848. (b) Albisson, D. A.; Bedford, R. B.; Lawrence, S. E.;
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(e) Zapf, A.; Beller, M. Chem.–Eur. J. 2000, 6, 1830.
(f) Mc Guiness, D.; Cavell, K. Organometallics 2000, 19,
741. (g) Bedford, R.; Welch, S. Chem. Commun. 2001, 129.
(4) For recent examples of Suzuki cross-coupling with
functionalised arylboronic acids: (a) Badone, D.; Baroni,
M.; Cardamone, R.; Ielmini, A.; Guzzi, U. J. Org. Chem.
1997, 62, 7170. (b) Old, D.; Wolfe, J.; Buchwald, S. J. Am.
Chem. Soc. 1998, 120, 9722. (c) Wolfe, J.; Singer, R.; Yang,
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Chem. 1999, 64, 3885. (e) Zhang, C.; Huang, J.; Trudell,
M.; Nolan, S. J. Org. Chem. 1999, 64, 3804. (f) Zhang, T.;
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Dai, C.; Fu, G. J. Am. Chem. Soc. 2000, 122, 4020.
(h) Shaughnessy, K. H.; Booth, R. S. Org. Lett. 2001, 3,
2757. (i) Grasa, G.; Hillier, A.; Nolan, S. Org. Lett. 2001, 3,
1077.
(5) For a review on the synthesis of polypodal
diphenylphosphine ligands, see: Laurenti, D.; Santelli, M.
Org. Prep. Proced. Int. 1999, 31, 245.
(6) (a) Laurenti, D.; Feuerstein, M.; Pèpe, G.; Doucet, H.;
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(7) (a) Feuerstein, M.; Laurenti, D.; Bougeant, C.; Doucet, H.;
Santelli, M. Chem. Commun. 2001, 325. (b) Feuerstein, M.;
Doucet, H.; Santelli, M. Tetrahedron Lett. 2001, 42, 5659.
(c) Feuerstein, M.; Doucet, H.; Santelli, M. Tetrahedron
Lett. 2001, 42, 6667. (d) Feuerstein, M.; Doucet, H.;
Santelli, M. Synlett 2001, 1458. (e) Feuerstein, M.;
Laurenti, D.; Doucet, H.; Santelli, M. Synthesis 2001, 2320.
(8) As a typical experiment, the reaction of 4-bromoaceto
phenone (1.99 g, 10 mmol), 4-methoxybenzeneboronic acid
(3.04 g, 20 mmol) and K2CO3 (2.8 g, 20 mmol) at 130 °C
during 20 h in dry xylene (10 mL) in the presence of
cis,cis,cis-1,2,3,4-tetrakis(diphenylphosphinomethyl)cyclo-
pentane/[PdCl(C3H5)]2 complex (0.00001 mmol) under
argon affords the corresponding adduct after extraction with
dichloromethane, evaporation and filtration on silica gel
(dichloromethane/diethyl ether: 1/5) in 80% (1.81 g) isolated
yield. 1H NMR (300 MHz, CDCl3): = 8.00 (d, J = 8.5 Hz,
2 H), 7.64 (d, J = 8.5 Hz, 2 H), 7.56 (d, J = 8.7 Hz, 2 H), 6.99
(d, J = 8.7 Hz, 2 H), 3.85 (s, 3 H), 2.62 (s, 3 H).
Synlett 2002, No. 11, 1807–1810 ISSN 0936-5214 © Thieme Stuttgart · New York