A novel fluorous palladium catalyst for Suzuki reaction in fluorous media

Article abstract of DOI:10.1016/j.jfluchem.2007.07.008

Palladium(II) perfluorooctanesulfonate [Pd(OSO₂R_f8)₂] catalyses the highly efficient Suzuki reaction in the presence of a catalytic amount of perfluoroalkylated-pyridine as a ligand in a fluorous biphase system (FBS). The fluorous phase containing the active palladium species is easily separated and can be reused several times without a significant loss of catalytic activity.

Full text of DOI:10.1016/j.jfluchem.2007.07.008

Journal of Fluorine Chemistry 128 (2007) 1421–1424
www.elsevier.com/locate/fluor
Short communication
A novel fluorous palladium catalyst for Suzuki reaction
in fluorous media
*
Ming-Gui Shen, Chun Cai , Wen-Bin Yi
Chemical Engineering College, Nanjing University of Science & Technology, Nanjing 210094, China
Received 3 June 2007; received in revised form 19 July 2007; accepted 24 July 2007
Available online 31 July 2007
Abstract
Palladium(II) perfluorooctanesulfonate [Pd(OSO2Rf8)2] catalyses the highly efficient Suzuki reaction in the presence of a catalytic amount of
perfluoroalkylated-pyridine as a ligand in a fluorous biphase system (FBS). The fluorous phase containing the active palladium species is easily
separated and can be reused several times without a significant loss of catalytic activity.
# 2007 Elsevier B.V. All rights reserved.
Keywords: Suzuki reaction; Palladium(II) perfluorooctanesulfonate; Perfluorinated ligand; Fluorous biphasic catalysis
1. Introduction
investigate the application of a novel fluorous palladium
catalyst, palladium(II) perfluorooctanesulfonate [Pd(O-
SO2Rf8)2] with perfluoroalkylated-pyridine ligand (Scheme
1). We prepared a novel fluorous palladium catalyst with
perfluoroalkylated-pyridine as ligand, for using in the Suzuki
reaction. The perfluoroalkylated-pyridine ligand was prepared
according to the method described by Uemura (Scheme 2) [9].
´
´
Horvath and Rabai introduced the concept of fluorous
biphase system (FBS) in 1994 [1]. As a new kind of phase-
separation and catalyst immobilization technique, FBS has
been used for many organic syntheses [2].
The Suzuki reaction has been regarded as one of the most
important tools to create C–C bonds [3]. Many efficient and
selective catalytic systems were developed for the reaction [4].
However, Suzuki reactions remain a tough challenge for
chemists in designing recyclable systems because the catalytic
cycle is unstable, responsive to various factors [5]. Schneider
and Bannwarth applied fluorous bis(triphenylphosphine)palla-
dium dichloride complexes as catalyst precursors to Suzuki
reactions [6]. It could be shown in one example that the amount
of catalyst could be reduced from 1.5 mol% to 0.1 mol% still
resulting in a high yield (>86%) in first run. However, in
repetitive cycles, considerable loss of activity of catalyst was
found. Rocaboy and Gladysz used the soluble fluorous
palladacycle complexes as the catalyst in Suzuki reactions
[7]. Nevertheless, under fluorous recycling conditions
decreased activities of the catalysts were observed. As a part
of our studies to explore the utility of transition metal perflates
catalyzed reactions in fluorous solvents [8], we decided to
2. Results and discussion
First, we prepared Pd(OSO2Rf8)2 from palladium carbonate
(PdCO3) by stirring it with heptadecafluorooctanesulfonic acid
(Rf8SO3H, PfOH) (Scheme 3). Then, the influences of bases
and solvents on catalytic property of the Pd(OSO2Rf8)2-ligand 1
were investigated by using coupling reaction of bromobenzene
with phenylboronic acid. The results were shown in Table 1. It
was found that among the bases tested (K3PO4, Na2CO3, and
NEt3), K3PO4 proved to be the most efficient. Among the
solvents used (DMF, dioxane, and H2O), DMF was the best
choice. Taken together, excellent result was obtained when the
coupling reaction was carried out using K3PO4 as the base and
DMF as the solvent (Table 1, entry 1).
We next examined whether Pd(OSO2Rf8)2 could be used
directly, without any other ligand, to catalyze the suzuki
reactions. To begin our study, we performed the Suzuki reaction
between bromobenzene and phenylboronic acid. It was found
that the reaction using Pd(OSO2Rf8)2 as catalyst alone could
* Corresponding author. Fax: +86 25 84315030.
E-mail address: c.cai@mail.njust.edu.cn (C. Cai).
0022-1139/$ – see front matter # 2007 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2007.07.008

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M.-G. Shen et al. / Journal of Fluorine Chemistry 128 (2007) 1421–1424
Table 2
Pd(OSO2Rf8)2-1 catalyzed Suzuki reactions in FBS
a
Scheme 1.
Entry
Aryl halide
Time (h)
Yield (%)b
1c
2d
3
PhBr
6
4
4
4
4
4
4
6
6
6
6
6
6
6
8
8
8
6
92, 25, 9
PhI
99, 97, 96, 94
2-CH3C6H4I
3-CH3C6H4I
4-CH3C6H4I
2-NO2C6H4I
4-NO2C6H4I
PhBr
98
4
99
5
97
Scheme 2.
6
98
7
8d
99
98, 96, 94, 92
9
4-NO2C6H4Br
4-CH3C6H4Br
4-CH3COC6H4Br
4-CH3OC6H4Br
4-CHOC6H4Br
2-CH3OC6H4Br
PhCl
97
96
98
98
95
98
53
45
52
97
10
11
12
13
14
15
16
17
18e
Scheme 3.
catalyze the Suzuki reaction in successful yield, however, great
decrease of the catalytic activity was observed in the recycles
(Table 2, entry 1).
4-CH3C6H4Cl
4-CH3COC6H4Cl
PhBr
Using the perfluoroalkylated-pyridine ligand, the Suzuki
reaction of iodobenzene with phenylboronic acid was then
examined. After a typical experiment, the course of the reaction
was followed by GC. Thus, in the presence of Pd(OSO2Rf8)2
and ligand 1, the coupling product was obtained in 99% GC
yield after 4 h (Table 2, entry 2). Using the same reaction
conditions, we next examined the application of Pd(OSO2Rf8)2-
ligand 1 to the cross coupling of a variety of aryl iodides. Both
the electron-rich and electron-poor aryl iodides could be
efficiently converted to the desirable products in high yields
(entries 3–7). Besides aryl iodides, aryl bromides could also
be successfully transformed to the desired Suzuki coupling
products under a longer reaction times (entries 8–14). But, it
was not active enough to handle an aryl chloride (entries 15–17)
even under much longer reaction times. It provided a much
lower yield between 45% and 53%. When the reaction was run
in 10 mmol scale (halobenzene), the present catalyst precursor
system was robust enough and the yield do not drop at larger
scales (entry 18).
a
Reaction conditions: Halobenzene (0.5 mmol), PhB(OH)2 (0.75 mmol),
Pd(OSO2Rf8)2 (0.001 mmol), Ligand (0.004 mmol), K3PO4 (1 mmol), Water
(1.00 mL), DMF (1.5 mL).
b
GC yield based on halobenzene.
c
The coupling reaction performed with no ligand, the fluorous phase was run
for three consecutive cycle.
d
The fluorous phase was run for four consecutive cycle.
e
The reaction was run under 10 mmol scale (halobenzene).
(entries 2 and 8). It may be caused by the lost of the
perfluoroalkylated-pyridine ligand in the recycle procedure.
The amount of palladium which had leached into the product
phase (DMF-H2O) after the reaction was determined by ICP.
Notably, the Pd-content was not detectable (<1 ppm). This
result suggests the robustness of the catalytic system for recycle
use.
In conclusion, the novel fluorous biphase system consist of
Pd(OSO2Rf8)2 and perfluoroalkylated-pyridine 1 showed a high
catalytic activity for Suzuki reaction. The fluorous phase
containing the active palladium species was easily separated
and could be reused several times without a significant loss of
catalytic activity when the perfluoroalkylated-pyridine ligand
was used.
We next sought to probe whether the catalytically active
species or a precursor could be recycled. Only a slight decrease
of the catalytic activity was observed even after three recycles
Table 1
Coupling reaction of bromobenzene with phenylboronic acid in the presence of
several bases and solvents
3. Experimental
Entry
Base
Solvent
Yield (%)a
3.1. General
1
2
3
4
5
6
7
8
9
K3PO4
K3PO4
K3PO4
Na2CO3
Na2CO3
Na2CO3
NEt3
DMF
98
95
38
78
70
35
18
20
26
Dioxane
H2O
Chemicals used were obtained from commercial suppliers
and used without further purifications. Melting points were
determined on a Shimadzu DSC-50 thermal analyzer. IR
spectra were recorded on a Bomem MB154S infrared analyzer.
DMF
Dioxane
H2O
1
UV–vis spectra were obtained with a UV-1601 apparatus. H
DMF
NMR and 19F NMR spectra were recorded with a Bruker
Advance RX500 spectrometer. Mass spectra were recorded on a
Saturn 2000GC/MS instrument. Inductively coupled plasma
NEt3
Dioxane
H2O
NEt3
aGC yield based on bromobenzene.

M.-G. Shen et al. / Journal of Fluorine Chemistry 128 (2007) 1421–1424
1423
(ICP) spectra were measured on an Ultima2C apparatus.
Elemental analyses were performed on
MT3CHN recorder.
4-Methylbiphenyl (Lit. [11]) A white solid; mp 45–48 8C.
1H NMR (500 MHz, CDCl3) d = 2.36 (s, 3H), 7.22 (d,
J = 8.1 Hz, 2H), 7.30 (m, 1H), 7.39 (t, J = 7.5 Hz, 2H), 7.46
(d, J = 8.1 Hz, 2H), 7.54 (d, J = 7.5 Hz, 2H). MS (EI) m/z 168
(M+).
a Yanagimoto
3.2. Preparation of Pd(OSO2Rf8)2
2-Nitrobiphenyl (Lit. [13]) Ayellow solid; mp 36–38 8C. 1H
NMR (500 MHz, CDCl3) d = 7.32–7.36 (m, 2H), 7.40–7.50 (m,
5H), 7.59–7.62 (m, 1H), 7.84–7.88 (m, 1H). MS (EI) m/z 199
(M+).
Palladium carbonate (0.17 g, 1.0 mmol) and a solution of
Rf8SO3H (1.23 g, 1.5 mmol) in water (5 mL) was stirred at
refluxing temperature for 4 h. The resulting gelatin-like solid
was collected, washed with H2O and dried at 160 8C for 24 h in
vacuum to give a brown solid (0.84 g, 76%), which does not
have a clear melting point up to 500 8C, but shrinks around
330 8C and 410 8C. IR (KBr) y1230 (CF3), 1148 (CF2), 1080
(SO2), 1061 (SO2), 752 (S–O) and 640 (C–S) cmÀ1. ICP:
calculated for C16O6F34S2Pd: Pd, 9.63; found: Pd, 9.61. Anal.
calculated for C16O6F34S2Pd: C, 17.38; found: C, 17.29. 19F
NMR (500 MHz, CF3C6H5): d À126.2, À121.2, À114.2,
À81.4.
4-Nitrobiphenyl (Lit. [11]) A yellow solid; mp 113–114 8C.
1H NMR (500 MHz, CDCl3) d = 7.42–7.50 (m, 3H), 7.59 (m,
2H), 7.73 (d, J = 8.9 Hz, 2H), 8.28 (d, J = 8.9 Hz, 2H). MS (EI)
m/z 199 (M+).
4-Acetylbiphenyl (Lit. [10]) A white solid; mp 121–122 8C.
1H NMR (500 MHz, CDCl3) d = 2.67 (s, 3H), 7.43 (t,
J = 7.3 Hz, 1H), 7.50 (t, J = 7.5 Hz, 2H), 7.66 (d, J = 7.7Hz,
2H), 7.72 (d, J = 8.2 Hz, 2H), 8.06 (d, J = 8.2 Hz, 2H). MS (EI)
m/z 196 (M+).
4-Methoxybiphenyl (Lit. [11]) A white solid; mp 90–91 8C.
1H NMR (500 MHz, CDCl3) d = 3.82 (s, 3H), 6.97 (m, 2H),
7.30 (d, J = 7.2 Hz, 1H), 7.39 (t, J = 7.5 Hz, 2H), 7.52 (m, 4H).
MS (EI) m/z 184 (M+).
3.3. Typical procedure for Suzuki reaction in a FBS
To a mixture of Pd(OSO2Rf8)2 (1.06 mg, 0.001 mmol) and
DMF (1.5 mL) in a flask, ligand 1 (2.3 mg, 0.004 mmol) was
added under vigorous stirring. After 10 min, perfluorodecalin
(2 mL), iodobenzene (0.102 g, 0.5 mmol), PhB(OH)2 (0.092 g,
0.75 mmol), and a solution of K3PO4 (0.266 g, 1 mmol) in
water (1.00 mL) were added. The samples were vigorously
stirred at 80 8C for 4 h. The resulting mixture was cooled with
ice bath. Then, the fluorous layer on the bottom was separated
for the next reaction. The reaction mixture (organic phase) was
diluted with an aqueous KOH (10 mL, 1 M) and extracted with
ether (2 Â 10 mL). The combined organic extracts were dried
over Na2SO4 for GC analysis. After GC analysis, the solvent
was removed under reduced pressure and the residue was
purified by a silica gel column chromatograph (eluent:
petroleum ether/EtOAC = 25/1) to give a white solid. The
4-Phenylbenzaldehyde (Lit. [14]) A yellow solid; mp 57–
1
59 8C. H NMR (500 MHz, CDCl3) d = 7.71–7.34 (m, 5H),
7.73 (m, 2H), 7.92 (m, 2H), 10.04 (m, 1H). MS (EI) m/z 182
(M+).
2-Methoxybiphenyl (Lit. [11]) A white solid; mp 30–31 8C.
1H NMR (500 MHz, CDCl3) d = 3.80 (s, 3H), 7.97–8.02 (m,
2H), 7.29–7.34 (m, 3H), 7.39 (m, 2H), 7.50 (d, J = 6.9 Hz, 2H).
MS (EI) m/z 184 (M+).
References
[1] I.T. Horvath, J. Rabai Sci. 266 (1994) 72–75.
´
[2] J.A. Gladysz, D.P. Curran, I.T. Horvath (Eds.), Handbook of Fluorous
Chemistry, Willey Press, New York, 2004 , pp. 175–365 (chapter 10).
[3] W. Herz, H. Falk, G.W. Kirby, R.E. Moore (Eds.), Progress in the
Chemistry of Organic Natural Products, vol. 82, Springer, New York,
2001, pp. 1–293.
1
product was characterized by GC/MS and H NMR.
3.4. Typical procedure for catalyst recycling
[4] (a) N. Miyara, A. Suzuki, Chem. Rev. 95 (1995) 2457–2483;
(b) K. Okamoto, R. Akiyama, S. Kobayashi, Org. Lett. 6 (2004) 1987–
1990;
After the reaction as described above, the mixture was
allowed to stand for ca. 5 min without stirring, and then the
organic phase was separated using a pipette. The resulting
fluorous phase was ready for further runs: that is, iodobenzene
(0.5 mmol), DMF (1.5 mL), PhB(OH)2 (0.75 mmol) and a
solution of K3PO4 (0.266 g, 1 mmol) in water (1.00 mL) were
added to the fluorous phase and the mixture was stirred at 80 8C.
(c) P.G. Steel, C.W.T. Teasdale, Tetrahedron Lett. 45 (2004) 8977–8980;
(d) N.T.S. Phan, D.H. Brown, P. Styring, Tetrahedron Lett. 45 (2004)
7915–7919;
´ ´
(e) J. Gil-Molto, S. Karlstrom, C. Najera, Tetrahedron 61 (2005) 12168–
12176;
(f) K.M. Dwood, A. Kirschning, Tetrahedron 61 (2005) 12121–
12130;
1
(g) J.-H. Li, X.-C. Hu, Y.-X. Xie, Tetrahedron Lett. 47 (2006) 7239–
7243.
Biphenyl (Lit. [10]) A white solid; mp 69–70 8C. H NMR
(500 MHz, CDCl3) d = 7.35 (tt, J = 7.4Hz, J = 1.4 Hz, 2H),
7.44 (t, J = 7.7 Hz, 4H), 7.59 (dd, J = 8.5Hz, J = 1.2Hz, 4H).
MS (EI) m/z 154 (M+).
[5] (a) V. Farina, Adv. Synth. Catal. 346 (2004) 1553–1582;
(b) N.T.S. Phan, M. Van Der Sluys, C.W. Jones, Adv. Synth. Catal. 348
(2006) 609–679.
2-Methylbiphenyl (Lit. [11]) A yellow liquid; 1H NMR
(500 MHz, CDCl3) d = 2.25 (s, 3H), 7.21–7.24 (m, 4H), 7.28–
7.33 (m, 3H), 7.36–7.39 (m, 2H). MS (EI) m/z 168 (M+).
3-Methylbiphenyl (Lit. [12]) A yellow liquid; 1H NMR
(500 MHz, CDCl3) d = 2.37 (s, 3H), 7.12 (m, 1H), 7.29 (m, 2H),
7.36–7.38 (m, 4H), 7.55 (m, 2H). MS (EI) m/z 168 (M+).
[6] S. Schneider, W. Bannwarth, Helv. Chim. Acta 84 (2001) 735–
742.
[7] C. Rocaboy, J.A. Gladysz, Tetrahedron 58 (2002) 4007–4014;
C. Rocaboy, J.A. Gladysz, New J. Chem. 27 (2003) 39–49.
[8] (a) W.-B. Yi, C. Cai, J. Fluorine Chem. 127 (2006) 1515–1521;
(b) W.-B. Yi, C. Cai, Aust. J. Chem. 59 (2006) 349–353;
(c) W.-B. Yi, C. Cai, Synth. Commun. 36 (2006) 2957–2961;

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M.-G. Shen et al. / Journal of Fluorine Chemistry 128 (2007) 1421–1424
(d) M.-G. Shen, C. Cai, J. Fluorine Chem. 3 (2007) 232–235;
(e) M.-G. Shen, C. Cai, Catal. Commun. 6 (2007) 871–875.
[11] X. Cui, T. Qin, J.-R. Wang, L. Liu, Q.-X. Guo, Synthesis 3 (2007) 393–399.
[12] M.S.C. Rao, G.S.K. Rao, Synthesis (1987) 231–233.
[13] M.-J. Dai, B. Liang, C.-H. Wang, J.-H. Chen, Z. Yang, Org. Lett. 6 (2004)
221–224.
[9] For preparation of ligand 1 see: T. Nishimura, Y. Maeda, N. Kakiuchi, S.
Uemura, J. Chem. Soc. Perkin Trans. 1 (2000) 4301–4305.
[10] K.A. Riina, E.L. Nicholas, Org. Lett. 7 (2005) 2101–2104.
[14] C.J. Dahl, K.G. Lewis, Aust. J. Chem. 18 (1965) 1307–1308.