Efficient recycling in Suzuki-Miyaura reactions of aryl chlorides with arylboronic acids using polymer-supported aryldicyclohexylphosphine

Article abstract of DOI:10.1002/adsc.200606130

The synthesis of polymer-supported aryldicyclohexylphosphines has been developed. The catalytic performance of these ligands has been demonstrated in the Suzuki-Miyaura cross-coupling reaction of aryl chlorides with arylboronic acids. Concerning the recycling of the catalyst, the ligand based on copolymer polyethylene glycol/polystyrene showed a very high activity which was maintained during 6 runs.

Full text of DOI:10.1002/adsc.200606130

FULL PAPERS
DOI: 10.1002/adsc.200606130
Efficient Recycling in Suzuki–Miyaura Reactions of Aryl
Chlorides with Arylboronic Acids using Polymer-Supported
Aryldicyclohexylphosphine
Katarzyna Glegoła,a, b Eric Framery,a,* K. Michał Pietrusiewicz,b
and Denis Sinoua,*
a
Laboratoire de Synth›se AsymØtrique, UMR UCBL/CNRS 5181, ESCPE Lyon, UniversitØ Claude Bernard Lyon 1, 43
boulevard du 11 novembre 1918, 69622 Villeurbanne Cedex, France
Fax : (+33)-472-448-160; e-mail: framery@univ-lyon1.fr or sinou@univ-lyon1.fr
Department of Organic Chemistry, Maria Curie-Sklodowska University, ul. Gliniana 33, 20-614 Lublin Poland
b
Received: March 23, 2006; Accepted: May 15, 2006
Abstract: The synthesis of polymer-supported aryldi- showed a very high activity which was maintained
cyclohexylphosphines has been developed. The cata- during 6 runs.
lytic performance of these ligands has been demon-
strated in the Suzuki–Miyaura cross-coupling reac-
tion of aryl chlorides with arylboronic acids. Con- Keywords: aryl chlorides; catalyst recycling; cross-
cerning the recycling of the catalyst, the ligand based coupling; phosphane ligands; polymer supports;
on copolymer polyethylene glycol/polystyrene Suzuki–Miyaura reaction
Introduction
are higher than 90%. When aryl iodides or aryl bro-
mides were used, the catalyst could be recycled over
Biaryl derivatives constitute important building 10 and 5 times, respectively, without loss of activity.
blocks for the synthesis of pharmaceuticals, herbi- Due to their low cost and ready accessibility, aryl
cides, polymers, materials, liquid crystals and ligands, chlorides are more interesting substrates from the in-
with some applications being extended on an industri- dustrial point of view. However, their reactivities are
al scale.[1] One of the most important routes for the lower than those of aryl bromides, and the key to
preparation of biaryl compounds is certainly the pal- their successful coupling is the use of electron-rich
ladium-catalyzed cross-coupling reactions between and sterically hindered phosphines.[8] Only few exam-
aryl halides and arylboronic acids, the so-called ples of such phosphines based on an organic polymer
Suzuki–Miyaura reaction.[2] In recent years, the main are described in the literature. Miyaura[9] described
effort has been focused on the development of effi- one of the first cross-coupling reaction between acti-
cient recycling catalyst systems. In the industrial field, vated chloroarenes or chloropyridine derivatives and
one possibility is to use immobilized catalysts, which 4-tolylboronic acid using
a polystyrene-PPh2 as
offer more environmentally benign protocols, and ligand. Buchwald[10] presented Merrifield resin-sup-
simplified experimental parts can be considered using ported dicyclohexylphosphinobiphenyl ligands used in
heterogeneous catalysts. Many approaches to hetero- the Suzuki–Miyaura reactions between some aryl
genic a homogeneous catalyst have been published.[3] chlorides and arylboronic acids. However, in the
In heterogenised systems using organic or inorganic latter case, the catalyst recycling was studied using
supports, there are several ways for the binding of the only aryl bromides. The Suzuki–Miyaura coupling-re-
ligand: physisorption or entrapment, adsorption, ion cycling experiments using aryl chlorides has been de-
pair formation, or covalent binding. The last one scribed by Plenio,[11] who used soluble monomethyl
offers many advantages, the main one being in that of polyethylene glycol (MeOPEG)-tagged palladium
avoiding leaching.
phosphine complexes.
Many anchored Pd catalysts based on polymer-sup-
In this paper, we describe the synthesis of aryldicy-
ported mono- or diphosphine,[4] olefin,[5] salen[6] or clohexylphosphine supported on polystyrene (PS) or
N-heterocyclic carbene[7] have been described. Gener- on polyethylene glycol/polystyrene copolymer (PEG-
ally, the yields in the cross-coupling reactions between PS, TentaGelꢀ). This copolymer consists of a low
aryl iodides or aryl bromides with arylboronic acids cross-linked polystyrene matrix on which polyethy-
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Recycling in Suzuki–Miyaura Reactions of Aryl Chlorides with Arylboronic Acids
FULL PAPERS
lene glycol is grafted. The applications of these poly- PS-phosphine 1 or PEG-PS-phosphine 2, respectively.
mer-supported ligands in the cross-coupling reaction In order to assay the efficiency of coupling, the phos-
of aryl chlorides with arylboronic acids, as well as the phorus loading in PS-phosphine 1 and PEG-PS-phos-
experiments involving the recycling of the catalyst are phine 2 was determined for each condensation reac-
described.
tion. Concerning PS-phosphine 1, the synthesis was
performed three times, and the phosphorus analyses
were 1.89%, 2.00%, and 2.12% P, respectively. The
capacity of PS-NH2 is given by Fluka Company as
0.8–1.2 mmoles per gram, which approximates at
Results and Discussion
The synthesis of aryldicyclohexylphosphine based on 1.0 mmol per gram, thus, the percentage of coupling
polystyrene (PS) 1 or on copolymer polyethylene in PS-phosphine 1 was about 62%, 65%, and 68%,
glycol/polystyrene (PEG-PS) 2 is shown in Scheme 1. respectively. Concerning PEG-PS-phosphine 2, the
synthesis was performed four times, the phosphorus
analyses being 0.68%, 0.69%, 0.80%, and 0.89%, re-
spectively. The capacity of PEG-PS-NH2 is given as
0.4 mmole per gram, thus, the percentage of coupling
in PEG-PS-phosphine 2 was about 55%, 55%, 65%,
and 72%, respectively. The 31P{1H} NMR spectra of
resin-supported phosphines 1 and 2 were recorded
using standard solution-phase spectroscopic parame-
ters and equipment. Regardless of the solvent used
(chloroform, toluene, DMSO, water), the PS-phos-
phine 1 showed significantly broadened signals. Uozu-
mi[14c] observed also this phenomenon, and explained
it by the insolubility of the polymer in the used sol-
vents. From the PEG-PS-phosphine 2, a narrow signal
at d=À12.3 in chloroform was recorded.
Different cross-coupling reactions were investigated
using various aryl halides with two arylboronic acids:
phenylboronic acid and 4-methylphenylboronic acid.
The results are summarized in Table 1. Two reaction
media were used: toluene and a 3/2/2 toluene/EtOH/
H2O mixture. Water is known to influence favourably
the activity of the Suzuki–Miyaura catalyst.[15] Plen-
Scheme 1. Synthesis of solid-supported PS-phosphine 1 and
PEG-PS-phosphine 2. Reagents and conditions: (i) 4-cyano-
io[11c] found that addition of small amounts of water
phenylboronic acid, Pd(OAc)2/TPPTS, Et3N, CH3CN/H2O,
N
to the reaction medium increased significantly the ac-
tivity of the catalyst. Before testing the potential of
the two polymer-supported ligands 1 and 2, we stud-
ied the Suzuki–Miyaura cross-coupling of 1-bromo-4-
nitrobenzene (Table 1, entries 1 and 2) or 1-chloro-4-
nitrobenzene (Table 1, entries 3 and 4) with 1.1 equiv-
458C, 48 h; (ii) n-BuLi at À1008C during 1 h, then Cy2PCl
at À1008C and room temperature during 15 h; (iii) HCl,
1108C; (iv) PS-NH2 or PEG-PS-NH2 resin, EDC·HCl,
HOBT, DMF, room temperature, 24 h.
According to the procedure described in the literature alents of phenylboronic acid using a “ligandless” pal-
for 1,2-dibromobenzene,[12,13] the palladium-catalysed ladium catalyst. In the case of 1-bromo-4-nitroben-
coupling of 2-iodobromobenzene with 3-cyanophenyl- zene, the yields of the coupling reaction were 89%
boronic acid gave 2’-bromobiphenyl-4-carbonitrile 3 and 97% in toluene and in the mixture of solvents, re-
À
in 80% yield. A lithiation-phosphorylation of the C
spectively, while no reaction occurred in both media
Br bond of the biaryl derivative 3 afforded 2’-(dicy- when 1-chloro-4-nitrobenzene was used as the aryl
clohexylphosphino)biphenyl-4-carbonitrile 4 in 80% halide. It is well known that ligand-free Pd(OAc)2 is
G
yield. Acidic hydrolysis of this biaryl derivative 4 able to catalyse the coupling reaction of aryl iodides
gave 2’-(dicyclohexylphosphino)biphenyl-4-carboxylic and activated or deactivated aryl bromides;[1d,h,16] how-
acid 5 in 45% yield after purification. Following a ever, in the case of aryl chlorides, temperatures
standard method for the solid-phase amide bond for- higher than 1508C or microwave assistance are neces-
mation,[14] the condensation of carboxylic acid 5 with sary in order to perform efficiently this cross-coupling
PS-NH2 or PEG-PS-NH2 in DMF solution in the pres- reaction.[17]
ence of 1-[3-dimethylaminopropyl]-3-ethylcarbodi-
In the presence of polymer-supported ligands 1 and
imide hydrochloride (EDC·HCl), and 1-hydroxyben- 2 (Table 1, entries 5–20), the reactions were carried
zotriazole (HOBT), afforded the polymer-supported out in the two media (toluene or a 3/2/2 toluene/
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Table 1. Suzuki–Miyaura cross-coupling of aryl halides and boronic acids with Pd
(OAc)2/1 or 2.[a]
A
[b]
Entry
Ar-X
Ar’-B(OH)2
LSolvent
Yield [%][c]
89
97
0
1
2
3
4
5
6
7
8
1-Bromo-4-nitrobenzene
Phenylboronic acid
no
no
no
no
1
1
2
2
1
1
2
1
1
2
1
1
2
1
1
Toluene
Toluene/EtOH/H2O
Toluene
Toluene/EtOH/H2O
Toluene
Toluene/EtOH/H2O
Toluene
Toluene/EtOH/H2O
Toluene
Toluene/EtOH/H2O
Toluene/EtOH/H2O
Toluene
Toluene/EtOH/H2O
Toluene/EtOH/H2O
Toluene
Toluene/EtOH/H2O
Toluene/EtOH/H2O
Toluene
1-Chloro-4-nitrobenzene
Phenylboronic acid
0
60
20
86
96
90
20
65
91
15
92
30
0
9
4-Chlorobenzonitrile
Phenylboronic acid
10
11
12
13
14
15
16
17
18
19
20
4-Chlorobenzaldehyde
1-Chloro-4-methylbenzene
1-Chloro-4-nitrobenzene
Phenylboronic acid
Phenylboronic acid
0
4-Methylphenylboronic acid
90
18
0
Toluene/EtOH/H2O
Toluene/EtOH/H2O
2
[a]
Reaction conditions: [aryl halide]=0.07m; [aryl halide]/[boronic acid]/
G
N
action time was 20 h.
[b]
[c]
In the case of toluene, the base was K3PO4 and the reaction temperature was 1008C; in the case of toluene/EtOH/H2O
(3/2/2), the base was Na2CO3 and the reaction temperature was 808C.
Isolated chemical yield after column chromatography.
EtOH/H2O mixture) in the presence of the catalyst (90%) and a very low yield in the other medium
formed in situ from 0.2% M of Pd(OAc)2 and 0.6% (18%) (Table 1, entries 18 and 19). Generally, elevat-
AHCTREUNG
M of polymer-supported ligand, in the presence of ed temperature is necessary in order to obtain good
K3PO4 (3 equivs.) or Na2CO3 (3 equivs.) as the base, yields.[8] The difference in the efficiency of the studied
and with an aryl chloride/arylboronic acid ratio of 1 coupling in the two media could be explained by the
to 1.1. When the reaction was performed in toluene, difference in their polarity. In fact, the polystyrene
K3PO4 was used as the base and the applied tempera- support presents hydrophobic properties, and for the
ture was 1008C, whereas in a 3/2/2 toluene/EtOH/ same volume of solvent and for the same quantity of
H2O mixture, Na2CO3 was used as the base and the PS-phosphine 1, the resin swells more in toluene than
applied temperature was 808C. It is to be noticed that in a 3/2/2 toluene/EtOH/H2O mixture. The better
the presence of EtOH did not allow us to perform the swelling of polymer should give a better accessibility
Suzuki–Miyaura reaction at a temperature higher of the reagents to the palladium complexes, and so a
than 808C.
higher conversion.
Using PS-phosphine 1 as the ligand, aryl chlorides
In the case of PEG-PS-phosphine 2, the organic
bearing electron-withdrawing groups reacted with resin presents hydrophobic and hydrophilic proper-
phenylboronic acid affording the corresponding biaryl ties. In comparison to polystyrene, the swelling vol-
compounds in low yields (15–20%) when the reaction umes of this copolymer in water and in EtOH are not
was performed in the 3/2/2 toluene/EtOH/H2O mix- negligible. And so, the swelling of the copolymer in
ture (Table 1, entries 6, 10 and 13). However, moving both media should be similar; consequently, the yields
to toluene as the solvent gave quite good yields (60– in cross-coupling products in toluene or in a 3/2/2 tol-
91%) of the biaryl derivatives (Table 1, entries 5, 9 uene/EtOH/H2O mixture should be very close. In the
and 12). 1-Chloro-4-methylbenzene bearing an elec- case of reaction between 1-chloro-4-nitrobenzene and
tron-donating group gave a very low yield in toluene phenylboronic acid (Table 1, entries 7 and 8), the
(30%) and no reaction at all in the mixture of sol- yields in biaryl compounds were 86% in toluene and
vents (Table 1, entries 15 and 16). Reaction of 4-meth- 96% in the mixture of solvents, in agreement with
ylphenylboronic acid with 1-chloro-4-nitrobenzene these properties. Two other aryl chlorides bearing
gave a high yield of coupling product in toluene electron-withdrawing groups, namely 4-chlorobenzo-
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Recycling in Suzuki–Miyaura Reactions of Aryl Chlorides with Arylboronic Acids
FULL PAPERS
nitrile and 4-chlorobenzaldehyde, were used in the polyethylene glycol/polystyrene (PEG-PS-phosphine)
cross-coupling reaction with phenylboronic acid. With via a dicyclohexylphosphinobenzoic acid has been de-
the first aryl chloride, the yield in biaryl derivative scribed. The efficiency of these polymer-supported li-
was 65% (Table 1, entry 11), and with the second gands has been demonstrated in palladium-catalyzed
one, the yield was 92% (Table 1, entry 14). Using 1- coupling reactions between aryl chlorides and arylbor-
chloro-4-methylbenzene, bearing an electron-donating onic acids under smooth conditions. With only 1.1
group with phenylboronic acid, or 1-chloro-4-nitro- equivalents of arylboronic acid in relation to aryl
benzene with 4-methylphenylboronic acid gave no re- chloride, the chemical yields are generally high using
action at all (Table 1, entries 17 and 20).
The recycling of the catalysts derived from poly- solvent, or PEG-PS-phosphine-palladium complexes
mer-supported ligands 1 or 2 and Pd(OAc)2 was then in a 3/2/2 toluene/EtOH/H2O mixture. We have
PS-phosphine-palladium complexes in toluene as the
AHCTREUNG
studied in this reaction. The main results of the recy- shown the high efficiency of PEG-PS-phosphine in
cling experiments are summarized in Table 2. After the 3/2/2 toluene/EtOH/H2O mixture for recycling
the first run performed under the same conditions as palladium in the cross-coupling reaction of 1-chloro-
reported before, the polymer-supported palladium 4-nitrobenzene with 1.1 equivalent of phenylboronic
complex was filtered, and washed with CH2Cl2 when acid. This study is currently being extended to other
K3PO4 was used as the base, or with ethyl acetate and aryl chlorides, as well as to the binding of the phos-
water when Na2CO3 was used as the base. Then the phinocarboxylic acid to other natural aminopolymers.
complex was used in the next Suzuki–Miyaura reac-
tion without any addition of palladium catalyst. Using
the PS-phosphine 1 in toluene, the yields of coupling Experimental Section
between 4-chlorobenzaldehyde and phenylboronic
acid, or 1-chloro-4-nitrobenzene and 4-methylphenyl- General Remarks
boronic acid, decreased drastically for the second run
Solvents were purified by standard methods and dried if
from 91% to 50%, or from 90% to 46%, respectively
necessary. All commercially available reagents were used as
(Table 2, entries 1 and 2). Using the PEG-PS-phos-
received. All manipulations involving palladium catalyst
phine 2 in toluene, the yield of the coupling product
of 1-chloro-4-nitrobenzene and phenylboronic acid
decreased from 86% to 30% for the third run
(Table 2, entry 3). However, when the 3/2/2 toluene/
EtOH/H2O mixture was used as the solvent, the
chemical yield remained the same (91–100%) during
four runs, and decreased slightly in the fifth and the
sixth run to 80% and 79% yield, respectively
(Table 2, entry 4). Apparently, the efficiency of the
studied recycling-coupling reaction is strongly influ-
enced by the nature of the used solvent and the base.
were performed under the usual inert atmosphere techni-
ques in Schlenk tubes. Conversion was determined by GC
using a Quadrex OV1 column (30 m ” 0.25 mm). Column
chromatography was performed on silica gel 60 (230–240
mesh, Merck). NMR spectra were recorded with a Bruker
AC 300 spectrometer and referenced as follows: 1H
(300 MHz), internal SiMe4 at d=0.00 ppm, 13C (75 MHz),
internal CDCl3 at d=77.2 ppm, and 31P (121 MHz), external
85% H3PO4 at d=0.00 ppm.
Preparation of 2’-Bromobiphenyl-4-carbonitrile (3)
A mixture of Pd(OAc)2 (16.8 mg, 0.075 mmol) and trisodium
A
salt of trisulfonated triphenylphosphine (TPPTS, 90 mg,
0.15 mmol) in water (1.50 mL) was stirred at room tempera-
ture for 30 min. A mixture of 2-iodobromobenzene (849 mg,
3 mmol), 4-cyanophenylboronic acid (534 mg, 3.63 mmol),
Conclusions
The synthesis of an aryldicyclohexylphosphine based
on polystyrene (PS-phosphine) and on a copolymer triethylamine (1.05 mL, 759 mg, 7.5 mmol), and acetonitrile
Table 2. Recycling experiments for Suzuki–Miyaura cross-coupling.[a]
Entry
Ar-Cl
Ar’-B(OH)2
LYield (%)
1
[b] – Run
3
2
4
5
6
1[c]
2[c]
3[c]
4[d]
4-Chlorobenzaldehyde
1-Chloro-4-nitrobenzene
1-Chloro-4-nitrobenzene
1-Chloro-4-nitrobenzene
Phenylboronic acid
4-Methylphenylboronic acid
Phenylboronic acid
1
1
2
2
91
90
86
96
50
46
76
94
30
91
Phenylboronic acid
100
80
79
[a]
Reaction conditions: [aryl halide]=0.07m; [aryl halide]/[boronic acid]/
action time was 20 h.
Isolated chemical yield after column chromatography.
Toluene, K3PO4, 1008C; after each run the polymer was washed with CH2Cl2.
Toluene/EtOH/H2O (3/2/2), Na2CO3, 808C; after each run the polymer was washed with EtOAc and water.
A
G
[b]
[c]
[d]
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Katarzyna Glegoła et al.
FULL PAPERS
(7.5 mL) was then added. The resulting mixture was stirred
at 458C for 48 h, then the reaction mixture was cooled at
room temperature and filtered on Celite. After evaporation
of the solvent, the crude mixture was purified by flash chro-
matography on silica gel [petroleum ether (PE)/ethyl ace-
tate (EA), 10/1] to give compound 3 as a white solid; yield:
Preparation of Solid-Supported PS-Phosphine (1) or
PEG-PS-Phosphine (2)
A mixture of resin (0.3 mmol of NH2 group), carboxylic acid
5 (118 mg, 0.3 mmol), EDC·HCl (93 mg, 0.48 mmol), HOBT
(87 mg, 0.6 mmol), and DMF (5 mL), was stirred at room
temperature for 24 h. Then the polymer was filtered, and
washed with DMF (3”2 mL) and CH2Cl2 (4”2 mL). The
resin was dried under reduced pressure to give PS-phos-
phine 1 or PEG-PS-phosphine 2, respectively.
1
620 mg (80%). Rf =0.45 (PE/EA, 10/1); H NMR (CDCl3):
d=7.75 (d, J=8.0 Hz, 2H), 7.72 (d, J=8.0 Hz, 1H), 7.54 (d,
J=8.0 Hz, 2H), 7.43 (dd, J=8.0, 8.0 Hz, 1H), 7.35–7.25 (m,
2H), in agreement with the literature.[12]
Solid-supported PS-phosphine 1: Analysis:
P 1.89%,
2.00%, or 2.12%.
Preparation of 2’-(Dicyclohexylphosphino)-
biphenyl-4-carbonitrile (4)
Solid-supported PEG-PS-phosphine 2: 31P NMR (CDCl3):
d=À12.3; Analysis: P 0.68%, 0.69%, 0.80%, or 0.89%.
A solution of 3 (353.5 mg, 1.37 mmol) in THF (7 mL) was
cooled at À1008C. A solution of n-BuLi (1 mL, 1.6 mmol)
at 1.6m in hexane was added drop by drop, and the reaction
mixture was stirred at À1008C for 1 hour. Then a solution
of Cy2PCl (0.31 mL, 326 mg, 1.4 mmol) in THF (1 mL) was
slowly added. The reaction mixture was stirred for 1 hour at
À1008C, then at room temperature for 15 h. After evapora-
tion of the solvents, ethyl acetate (20 mL) and a 1/1 mixture
of water and brine (12 mL) were added. After separation,
the aqueous phase was washed with ethyl acetate. The or-
ganic phases were dried over MgSO4, and after evaporation
of the solvent, the residue was purified by flash-chromatog-
raphy on silica gel (PE/EA, 15/1) to give compound 4 as a
white solid; yield: 410 mg (80%). Rf =0.65 (PE/EA, 10/1);
1H NMR (CDCl3): d=7.66 (d, J=8.1 Hz, 2H, Harom), 7.65–
7.59 (m, 1H, Harom), 7.50–7.35 (m, 4H, Harom), 7.28–7.18 (m,
1H, Harom), 1.92–1.79 (m, 2H, PCH), 1.75–1.45 (m, 10H,
CH2), 1.36–0.97 (m, 10H, CH2); 31P NMR (CDCl3): d À12.2.
These data are in agreement with the literature.[12]
Typical Cross-Coupling Procedure in Toluene
Pd(OAc)2 (1.3 mg, 6 mmol), polymer-supported ligand (18
R
mmol of phosphine), K3PO4 (1.91 g, 9.0 mmol) and toluene
(12 mL) were placed in a flask under argon. The solution
was stirred for 30 min. A mixture of aryl halide (3.0 mmol),
and arylboronic acid (3.3 mmol) in toluene (30 mL) was
then added. The resulting mixture was stirred at 1008C for
20 h. The mixture was cooled at room temperature, the het-
erogeneous solution was filtered, and the filtrate was con-
centrated under reduced pressure to give the corresponding
crude biaryl compound, which was purified by flash chroma-
tography on silica gel to afford the pure coupling product.
Typical Cross-Coupling Procedure in a 3/2/2
Toluene/EtOH/H2O Mixture
Pd(OAc)2 (1.3 mg, 6 mmol), polymer-supported ligand (18
N
mmol of phosphine), and toluene (6 mL), were placed in a
flask under argon. The solution was stirred for 30 min. Aryl
halide (3 mmol) and arylboronic acid (3.3 mmol) in a mix-
ture of toluene (6 mL) and EtOH (12 mL) were then added
in the flask, followed by Na2CO3 (0.95 g, 9 mmol) in water
(12 mL). The resulting mixture was stirred at 808C for 20 h.
After being cooled at room temperature, the heterogeneous
solution was filtered, and the two phases were separated.
The EtOH/H2O layer was washed twice with toluene, and
the organic phases were dried over MgSO4. Evaporation of
the solvents under reduced pressure gives the corresponding
crude biaryl compound, which was purified by flash chroma-
tography on silica gel to afford the pure coupling product.
Preparation of 2’-(Dicyclohexylphosphino)-
biphenyl-4-carboxylic Acid (5)
A mixture of 4 (400 mg, 1.06 mmol) and HCl 33% (7.5 mL)
was heated at 1108C for 4 h. After concentration at 808C
under reduced pressure, the residue was dissolved in CH2Cl2
(30 mL) and Et3N (0.15 mL, 107.3 mg, 1.2 mmol), and the
mixture was stirred at room temperature. The organic phase
was washed with brine (2”10 mL), dried over MgSO4 and
then concentrated under reduced pressure. The crude prod-
uct was purified by flash chromatography on silica gel using
ethyl acetate as the eluent to give compound 5 as a white
solid; yield: 190 mg (45%). Rf =0.43 (CH2Cl2/MeOH, 10/1);
1H NMR (CDCl3): d=8.12 (d, J=8.1 Hz, 2H, Harom), 7.67–
7.57 (m, 1H, Harom), 7.48–7.36 (m, 4H, Harom), 7.35–7.20 (m,
1H, Harom), 1.95–1.80 (m, 2H, PCH), 1.80–1.50 (m, 10H,
CH2), 1.47–0.92 (m, 10H, CH2); 13C NMR (CDCl3): d=
172.4, 150.4 (d, J=28.5 Hz), 149.5 (d, J=6.2 Hz), 134.7 (d,
J=21.7 Hz), 133.9 (d, J=2.5 Hz), 131.6 (d, J=4.3 Hz), 130.6
(d, J=5.6 Hz), 130.2, 129.2, 128.5, 127.9, 35.4 (d, J=
13.6 Hz), 31.2 (d, J=17.4 Hz), 30.0 (d, J=8.7 Hz), 28.0 (d,
J=12.4 Hz), 27.9 (d, J=7.4 Hz), 27.2; 31P NMR (CDCl3): d
=À12.0; HR-MS: m/z=395.2150, calcd. for C25H32O2P [M+
H]+: 395.2140.
Recycling Cross-Coupling Procedure
For the first run, the same experimental conditions than de-
scribed above were used. After filtration, the polymer-sup-
ported complex was washed with CH2Cl2 (2”5 mL) when
K3PO4 was used as the base, and with ethyl acetate (2”
5 mL), with water (2”5 mL), and then ethyl acetate (2”
5 mL) when Na2CO3 was used as the base. After drying the
polymer under vacuum, a mixture of aryl halide (3 mmol),
arylboronic acid (3.3 mmol), base (9 mmol), and 14 mLof
solvent, was added to this polymer.
1732
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ꢁ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2006, 348, 1728 – 1733

Recycling in Suzuki–Miyaura Reactions of Aryl Chlorides with Arylboronic Acids
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Acknowledgements
One of us (K. G.) thanks the French Ministry of Education
for a fellowship.
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