Fluorous-silica-supported perfluoro-tagged palladium complexes catalyze Suzuki couplings in water

Article abstract of DOI:10.1002/hlca.200490260

Different Pd-complexes (see 2a-d and 3) with and without perfluoroalkyl tags were deposited on fluorous reversed-phase silica 1 and unmodified silica gel. These supported complexes were successfully used as precatalysts for the Suzuki reaction in H₂O. H₂O-Soluble aryl bromides were easily converted to the corresponding biphenyls. Although none of the complexes is H₂O-soluble, the active catalyst is most likely homogeneously dissolved. Nevertheless, the Pd-leaching into the product was low.

Full text of DOI:10.1002/hlca.200490260

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Fluorous-Silica-Supported Perfluoro-Tagged Palladium Complexes Catalyze
Suzuki Couplings in Water
by Carl Christoph Tzschucke and Willi Bannwarth*
Institut f¸r Organische Chemie und Biochemie, Albert-Ludwigs-Universit‰t Freiburg, Albertstrasse 21,
D-79104 Freiburg
(phone: ‡ 497612036073; fax: ‡ 497612038705; e-mail: willi.bannwarth@organik.chemie.uni-freiburg.de)
Different Pd-complexes (see 2a d and 3) with and without perfluoroalkyl tags were deposited on fluorous
reversed-phase silica 1 and unmodified silica gel. These supported complexes were successfully used as
precatalysts for the Suzuki reaction in H2O. H2O-Soluble aryl bromides were easily converted to the
corresponding biphenyls. Although none of the complexes is H2O-soluble, the active catalyst is most likely
homogeneously dissolved. Nevertheless, the Pd-leaching into the product was low.
Introduction.
In catalytic chemistry, there is an increasing requirement to
optimize reactions in terms of environmental and process safety as well as in terms of
economic viability. Important aspects are the reduction of waste, straightforward
isolation of products, recycling of catalysts, and the use of environmentally benign
reaction media [1]. Water is in these regards a suitable solvent, since it is cheap,
nonflammable and nontoxic. However, it is important to remove products and catalyst
efficiently to allow for easy disposal of H2O.
Solid-supported catalysts have become valuable tools for simplified product
isolation and catalyst recycling. For immobilization, catalysts can be linked covalently
to different supports, such as polymer resins or inorganic solids. Polar catalysts can be
adsorbed on silica gel [2], or immobilized in a thin layer of H2O [3], ethylene glycol [4],
or ionic liquids [5][6] on a silica support. The reaction is carried out in an apolar
organic solvent. These applications usually require suitable derivatization of the
catalyst with polar functionalities. The system can be reversed in such a way that a
lipophilic catalyst is physisorbed on reversed-phase silica gel [7] or fluorous reversed-
phase silica gel (FRPSG) [8][9] and applied to reactions in polar solvents.
In this context, we reported the use of fluorous reversed-phase silica gel (FRPSG)
as solid support for the noncovalent immobilization of perfluoro-tagged Pd-catalysts
[8]. These supported Pd-complexes were applied to Suzuki couplings and to
Sonogashira reactions. The FRPSG-supported catalyst was removed by simple
decantation or filtration, and the catalyst could be reused several times without
significant loss of efficiency. The same strategy was used in a solventless approach by
Biffis et al. for the immobilization of dirhodium(II) perfluorocarboxylates as catalyst
for the alcoholysis of silanes [9]. Attempts of Pozzi et al. to immobilize perfluoro-
tagged [CoIII(salen)] complexes on FRPSG did not lead to active catalysts [10]. In a
similiar context, Gladysz et al. employed the thermomorphic behavior of certain
perfluoro-tagged compounds together with Teflon shavings as solid-support material
¹ 2004 Verlag Helvetica Chimica Acta AG, Z¸rich

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[11 13]. In combinatorial chemistry, FRPSG has been used as a solid support for
multistep organic synthesis [14]. FRPSG has found numerous applications as material
for solid-phase extractions and chromatography [15][16].
While, in our previous experiments in 1,2-dimethoxyethane (ˆ glyme), the Pd-
leaching was already low [8], we thought that it could be further reduced by the use of
H2O as the reaction solvent, because of the pronounced hydrophobicity of perfluoro-
tagged compounds. But this hydrophobicity also presents a challenge, since FRPSG is
usually not wetted by H2O as demonstrated by the high contact angle (Fig. 1) [17], and
the question was whether the reaction could occur at all. Herein, we report the first
application of a precatalyst supported on FRPSG in H2O as the sole reaction solvent,
and data suggesting a homogeneous nature of the actual catalytic species.
Fig. 1. Photographs of solvent drops on the perfluorinated silicium dioxide surface of a silicon wafer,
demonstrating the large difference in polarity: left: water drop with a contact angle of 116.48, and right: 1,2-
dimethoxyethane drop with a contact angle of 62.58. Due to the lower interfacial energy, 1,2-dimethoxyethane
can wet FRPSG much better than H2O [17].
Results and Discussion. The FRPSG 1 and the perfluoro-tagged Pd-complexes
2a d were prepared by our reported procedures [14][18]. For the immobilization of
the complexes, FRPSG 1 was shaken with a solution of perfluoro-tagged bis(triar-
ylphosphine)palladium complexes 2a d in Et2O, and the solvent was evaporated. The
thus immobilized precatalyst is an air-stable, free-flowing powder. These catalyst-
loaded FRPSGs were employed in different Suzuki cross-coupling reactions in H2O.

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Initially, between 0.001 mol-% and 1 mol-% of 2a on FRPSG was tested as
precatalyst for the Suzuki coupling of phenylboronic acid and p-bromomandelic acid
(ˆ4-bromo-a-hydroxybenzeneacetic acid) in H2O (see Scheme 1 and Table 1). The
product was separated by filtration, and the supported catalyst was reused up to five
times. For the higher catalyst loadings (Entries 1 and 2), nearly complete conversion
was observed in the first run. Up to the sixth run, the conversion decreased only to 87%
and 76%, respectively. With the lower catalyst loadings (Entries 3 and 4), the
conversion was low in the first run but increased significantly in the second run. It must
be noted, however, that the yields deviate more from the average in the first runs than
in the following runs. This might be due to insufficient wetting of the support during the
first run. The conversions remained on a fairly high level with 0.01 mol-% of catalyst.
Only with 0.001 mol-% of catalyst, the conversions decreased from the third to the sixth
run, still leading to cumulated turn-over numbers (TON) of more than 200000.
Scheme 1. Suzuki Reactions Performed with 0.01 1 mol-% of 2a Immobilized on Support 1
Table 1. Suzuki Reactions with Complexes 2a d and 3. Yields are determined by HPLC and are the average of
at least two independent experiments. TON ˆ turn-over number.
Entry
Catalyst/Support
Catalyst loading [mol-%]
Yield [%]
TON
1
2
3
4
5
6
7
8
2a/FRPSG
2a/FRPSG
2a/FRPSG
2a/FRPSG
2b/FRPSG
2c/FRPSG
2d/FRPSG
3/silica gel
1.0
0.1
0.01
0.001
0.1
0.1
0.1
0.1
98 (98, 95, 90, 83, 87)
99 (91, 88, 79, 80, 76)
6 (74, 86, 86, 85, 70)
27 (71, 54, 37, 22, 7)
88 (62, 83, 84, 86, 82)
94 (76, 83, 82, 74, 73)
85 (90, 89, 88, 85, 75)
52 (95, 95, 91, 85, 77)
551
5130
40600
217000
4850
4820
5120
4950
To examine the influence of the perfluoro tags and the support, Pd-complexes 2b d
and 3 on FRPSG 1 were used as precatalysts. Like in complex 2a, in 2b an ethylene
spacer isolates the aryl ring from the electron-withdrawing perfluoroalkyl chain. In 2c
the perfluoro tag is directly attached to the phenyl ring, while, in 2d, an electron-
donating CH2O spacer is employed. In these experiments, the loading of the support
was 10 mg of complex per g FRPSG, and the catalyst loading was 0.1 mol-%. In the first
run, the yields obtained with 2b d were slightly lower than with 2a, but in recycling
experiments, all four complexes behaved similarly, giving cumulated TONs in the range
of 5000 (Table 1, Entries 5 7). Thus, neither the spacer between the perfluoroalkyl
chain and the phenyl ring nor the point of attachment of the perfluoro tag exerts a

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detectable influence on the catalyst performance. To our surprise, complex 2a on
FRPSG and the nontagged complex 3 on normal silica gel behaved quite similiarly
(Table 1, Entries 2 and 8).
To assess the catalyst leaching, the coupling of phenylboronic acid and p-
bromomandelic acid was carried out with 0.1 mol-% of 2a on FRPSG 1 and 0.1 mol-
% of 3 on unmodified silica gel. After reaction, the support was filtered off and washed
with H2O. The combined filtrates were evaporated, and the Pd-content was determined
by inductively coupled plasma (ICP) MS. For 2a on FRPSG, the amount of Pd in the
crude product was 2.2 ppm, corresponding to 0.8% of the Pd, whereas, for 3 on silica
gel, we observed 14.0 ppm in the crude product, corresponding to 7.4% of the Pd.
Despite the low leaching of Pd, the question still remained whether the catalytic
process proceeded in a heterogeneous or a homogeneous fashion. To shed more light
on this problem, we carried out a three-phase test (cf. Ley and co-workers [19]) in
which a solid-phase-bound aryl iodide was subjected to the reaction conditions
(Scheme 2). If the catalyst is truly immobilized, the spatial separation from the iodide
prevents any conversion, while a soluble catalyst can reach the substrate by diffusion,
and thus, effect conversion. We carried out the experiment with complex 2a supported
on FRPSG 1 in the presence and in the absence of bromomandelic acid as a soluble
substrate. Similarly, control experiments were carried out with complex 3 on
unmodified silica gel. In all four experiments, over 80% conversion of the solid-
phase-bound iodide was observed. These results suggest that the catalyst is operating by
a homogeneous mechanism and does not depend on a soluble aryl halide for generation
of the active species from the precatalyst.
Scheme 2. Three-Phase Test: Behavior of a Solid-Phase-Bound Aryl Iodide under Suzuki Coupling Conditions.
Upon cleavage from the support, the conversion was determined by HPLC.
The assumption of a homogeneous catalyst is supported further by the finding that
the reaction continues after filtration of the reaction mixture and leads to the same
conversions (Fig. 2). Upon completion of the reaction and cooling to room temper-
ature, the Pd-species are possibly recaptured by the solid phase, which would be in
accordance with the low Pd-leaching. Such a −release and capture× mechanism has been
invoked recently for a catalyst based on Pd-containing perovskites [19]. But it is also
conceivable that the support acts as a reservoir, and only a small fraction of active

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Fig. 2. Formation of phenylmandelic acid vs. reaction time. Reaction conditions: 0.1 mol-% 2a/FRPSG,
Na2CO3, H2O, 808, 16 h. a) Fresh catalyst, b) reused catalyst, c) second reuse. The dashed line denotes the
filtration of the reaction mixture.
catalyst is released into the solution. That very small catalyst amounts can lead to high
conversion, was already shown above (Table 1, Entry 4).
Furthermore, Pd-complex 2a was evaluated in the Suzuki coupling of different
substrates (see Scheme 3 and Table 2). The reaction proceeded well with a range of
H2O-soluble substrates, and the catalyst could be recycled. Only in the case of 2-
bromobenzoic acid, the yield was low and recycling of the catalyst was not successful
(Table 2, Entry 4). This is probably due to steric hindrance of the o-carboxyl group. On
the other hand, in the boronic acid, small o-substituents were well tolerated, as the
comparison of (4-methoxyphenyl)boronic acid (Table 2, Entries 8 and 9) and (2-
methoxyphenyl)boronic acid (Table 2, Entries 10 and 11) shows. In the coupling of 4-
bromophenylacetic acid with (4-formylphenyl)boronic acid, less than 5% conversion
was observed in the first run (not shown). Upon recycling of the catalyst, slightly
increased activity was observed, with 15% conversion of the bromide. With less H2O-
soluble substrates like 4-bromoacetophenone or 4-bromobutylbenzene, no significant
consumption of boronic acid could be observed. It is possible that, in these cases, the
Scheme 3. Suzuki Reactions with Different Substrates in the Presence of 0.1 mol-% 2a on Support 1

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Table 2. Suzuki Reactions with Different Substrates in the Presence of 0.1 mol-% 2a on Support 1 (Scheme 3)
Entry
R1
R2
Yield [%]
1
2
3
H
H
H
H
4-CH(OH)CO2H
4-CO2H
3-CO2H
100 (94, 93)
100 (97, 93)
99 (93, 90)
30 (6, 8)
4
2-CO2H
5
6
7
8
9
10
11
H
H
H
4-MeO
4-MeO
2-MeO
2-MeO
4-CH2CO2H
100 (82, 88)
94 (98)
76 (97)
99 (88, 99)
89 (99)
98 (99, 99)
78 (95)
4-CONHCH2CO2H
3-CONHCH2CO2H
4-CH(OH)CO2H
4-CH2CO2H
4-CH(OH)CO2H
4-CH2CO2H
hydrophobic substrate covers the solid support and mechanically prevents the contact
between the solution and the precatalyst.
Conclusions.
In summary, we could demonstrate that perfluoro-tagged Pd-
complexes immobilized on FRPSG 1 are useful as precatalysts for the Suzuki reaction
in H2O, despite their pronounced hydrophobicity. There is conclusive evidence that the
actual catalysis proceeds via a homogeneously dissolved Pd-species. H2O-Soluble
substrates were easily converted to the corresponding biphenyls. The supported
complexes were separated by simple filtration and could be reused several times. With
low catalyst loadings, TONs as high as 200000 were achieved.
Financial support from Fluka, Buchs (CH), is gratefully acknowledged.
Experimental Part
General. All reagents and solvents were obtained from either Fluka or Aldrich and were used without
further purification. HPLC: Agilent-1100 system with binary pump, sample changer, column oven, and diode-
array detector. M.p.: IA9000 apparatus from Electrothermal Engineering Ltd.; uncorrected. NMR Spectra:
1
chemical shifts d in ppm rel. to SiMe4 (ˆ0 ppm) for H- and rel. to CHCl3 (ˆ 77 ppm) for 13C. MS: Finnigan
MAT8200 (EI), MAT312 (CI), and TSQ7000 (ESI) spectrometer; APCI ˆ atmospheric-pressure chemical
ionization, ICP ˆ inductively coupled plasma; in m/z (rel. %).
Typical Procedure for Recycling Experiments. To FRPSG-supported catalyst (100 mg) under Ar, an aq.
stock soln. of the substrates (3 ml, containing 0.3 mmol of 4-bromomandelic acid, 0.33 mmol of phenylboronic
acid, and 0.6 mmol of Na2CO3) was added. The mixture was shaken at 808 for 16 h. An aliquot (20 ml) of the soln.
was withdrawn, and the yield was measured by HPLC analysis. The mixture was cooled to 208 and filtered. The
FRPSG was washed with 1m HCl in MeOH/H2O 11:1 (2 Â 1 ml), MeOH (2 Â 1 ml), and H2O (2 Â 1 ml). The
immobilized catalyst was reused as such in further experiments. All manipulations were carried out
automatically (Automated Synthesis Workstation ASW 2000, Chemspeed Ltd., Augst, Switzerland). HPLC
analysis: C-18 column (Zorbax SB, 3 mm, 4.6 Â 50 mm); isocratic eluent H2O/MeCN/HCOOH 70 :30 :0.2 (v/v);
detection at 210 nm; conversions calculated from the ratio of the peak areas of 4-bromomandelic acid and 4-
phenylmandelic acid corrected for the extinction coefficients.
General Procedure (G. P.) for Preparative Experiments: 4-Phenylmandelic Acid (ˆa-Hydroxy[1,1'-
biphenyl]-4-acetic Acid): A 13-ml glass reactor was charged with FRPSG-supported catalyst (100 mg), solid
4-bromomandelic acid (69 mg, 0.3 mmol), and phenylboronic acid (40 mg, 0.33 mmol). Under Ar, 2m aq.
Na2CO3 (3 ml, 0.6 mmol) was added. The mixture was shaken at 808 for 16 h. Aliquots (20 ml) of the soln. were
withdrawn at the beginning of the reaction and after 16 h, and the conversion was estimated by HPLC. The
mixture was cooled to 208 and filtered. The FRPSG was washed with H2O (4 Â 1 ml). The immobilized catalyst

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was reused as such in further experiments. Up to this point, all manipulations were carried out automatically by
Chemspeed ASW 2000. The aq. product soln. was acidified with conc. HCl soln. (1 ml) and extracted with Et2O
(3 Â 5 ml) and the combined extract evaporated to give the product. An anal. sample was crystallized from
AcOEt. M.p. 1998 ([20]: 202 2048). 1H-NMR ((D6)DMSO, 400 MHz): 7.62 7.66 (m, 4 arom. H); 7.50
(m(AA'BB'), Japp ˆ 8.2, 2 arom. H); 7.45 (−t×, Japp ˆ 7.7, 2 arom. H); 7.35 (−t×, Japp ˆ 7.5, 1 arom. H); 5.08 (s, CH).
13C-NMR ((D6)DMSO, 100.6 MHz): 174.0; 139.8; 139.5; 139.3; 128.9; 127.4; 127.2; 126.6; 126.4; 72.1. EI-MS: 228
‡
‡
(52, M ), 183 (100, [M À CO2H] ), 155 (41).
[1,1'-Biphenyl]-4-carboxylic Acid. According to the G. P., but with a different workup procedure: Upon
completion of the reaction, the mixture was filtered and the FRPSG washed with 1m HCl in MeOH/H2O 11:1
(2 Â 1 ml), MeOH (2 Â 1 ml), and H2O (2 Â 1 ml). The combined filtrate was diluted with sat. aq. NaCl soln.
(30 ml) and extracted with Et2O (3 Â 20 ml). The combined extracts were evaporated to give the product. An
anal. sample was crystallized from MeOH. M.p. 223 2268 (dec.) ([21]: 226 2288). 1H-NMR ((D6)DMSO,
400 MHz): 8.01 (m(AA'BB'), Japp ˆ 8.2, 2 arom. H); 7.79 (m(AA'BB'), Japp ˆ 8.2, 2 arom. H); 7.72
(m(AA'BB'), Japp ˆ 7.3, 2 arom. H); 7.49 (−t×, Japp ˆ 7.5, 2 arom. H); 7.41 (−t×, Japp ˆ 7.3, 1 arom. H). 13C-NMR
‡
((D6)DMSO, 100.6 MHz): 167.0; 144.2; 139.0; 129.9; 129.6; 129.0; 128.2; 126.9; 126.7. EI-MS : 198 (100, M ), 181
‡
(63, [M À OH] ).
[1,1'-Biphenyl]-3-carboxylic Acid. According to the G. P. M.p. 1688 ([22]: 169 1708). 1H-NMR
((D6)DMSO, 400 MHz): 13.0 (br., OH); 8.17 (t, J ˆ 1.7 Hz, 1 arom. H); 7.89 7.95 (m, 2 arom. H); 7.69
(m(AA'BB'), Japp ˆ 7.3, 2 arom. H); 7.59 (t, J ˆ 7.7, 1 arom. H); 7.49 (−t×, Japp ˆ 7.7, 2 arom. H); 7.40 (−t×, Japp
ˆ
7.3, 1 arom. H). 13C-NMR ((D6)DMSO, 100.6 MHz): 167.1; 140.5; 139.2; 131.4; 131.0; 129.3; 129.0; 128.2; 127.8;
‡
‡
127.2; 126.7. EI-MS: 198 (100, M ), 181 (29, [M À OH] ), 152 (34).
[1,1'Biphenyl]-4-acetic Acid. According to the G. P. M.p. 1658 ([20]: 161 1628). 1H-NMR (CDCl3,
400 MHz): 7.54 7.59 (m, 4 arom. H); 7.42 (−t×, Japp ˆ 8.0, 2 arom. H); 7.31 7.37 (m, 3 arom. H); 3.69 (s, CH2).
13C-NMR (CDCl3, 100.6 MHz): 177.4; 140.8; 140.5; 132.4; 129.9; 128.9; 127.5; 127.4; 127.2; 40.7. EI-MS: 212 (53,
‡
‡
M ), 167 (100, [M À CHO2] ).
4-Phenylhippuric Acid. (ˆ N-([1,1'-Biphenyl]-4-ylcarbonyl)glycine). According to the G. P., but extraction
with AcOEt instead of Et2O. M.p. 218 2198 (dec.) ([23]: 2118). 1H-NMR ((D6)DMSO, CD3OD, 500 MHz): 7.94
(m(AA'BB'), Japp ˆ 8.6, 2 arom. H); 7.75 (m(AA'BB'), Japp ˆ 8.6, 2 arom. H); 7.70 (m, Japp ˆ 8.2, 2 arom. H); 7.46
(−t×, Japp ˆ 7.6, 2 arom. H); 7.38 (m, 1 arom. H); 3.95 (s, CH2). 13C-NMR ((D6)DMSO, CD3OD, 125.7 MHz):
‡
171.6; 166.7; 143.5; 139.6; 132.9; 131.7; 129.3; 128.2; 127.1; 126.8; 41.3. EI-MS: 255 (15, M ), 211 (51, [M À
‡
‡
CO2] ), 181 (100, C13H9O ), 152 (44).
3-Phenylhippuric Acid (ˆ N-([1,1'-Biphenyl]-3-ylcarbonyl)glycine). According to the G. P., but extraction
with AcOEt instead of Et2O. M.p. 212 2138 ([24]: 2198). 1H-NMR (CD3OD, 500 MHz): 8.12 (t, J ˆ 1.9,
1 arom. H); 7.83 (ddd, J ˆ 7.7, 1.8, 1.1, 1 arom. H); 7.80 (ddd, J ˆ 7.8, 1.9, 1.1, 1 arom. H); 7.65 7.67 (m, 2 ar-
om. H); 7.54 (t, J ˆ 7.8, 1 arom. H); 7.45 (−t×, Japp ˆ 7.9, 2 arom. H); 7.34 (−t×, Japp ˆ 7.4, 1 arom. H); 4.12 (s, CH2).
13C-NMR (CD3OD, 125.7 MHz): 173.2; 170.4; 142.9; 141.5; 135.7; 131.4; 130.2; 130.0; 128.8; 128.1; 127.2; 127.0;
‡
‡
‡
25.6. EI-MS: 255 (27, M ), 211 (37, [M À CO2] ), 181 (100, C13H9O ), 152 (58).
4-(4-Methoxyphenyl)mandelic Acid (ˆa-Hydroxy-4'-methoxy[1,1'-biphenyl]-4-acetic Acid). According to
the G. P., but workup as described above for [1,1'-biphenyl]-4-carboxylic acid. 1H-NMR (CD3OD, 400 MHz;
* ˆ overlapping): 7.55* (m(AA'BB'), Japp ˆ 8.6, 2 arom. H); 7.53* (m(AA'BB'), Japp ˆ 9.0, 2 arom. H); 7.46
(m(AA'BB'), Japp ˆ 8.2, 2 arom. H); 6.97 (m(AA'BB'), Japp ˆ 9.0, 2 arom. H); 5.21 (s, CH); 3.81 (s, MeO).
13C-NMR (CD3OD, 100.6 MHz): 174.9; 160.9; 142.2; 138.7; 134.3; 129.0; 127.6; 115.3; 74.1; 55.8. APCI-MS
(neg.): 257 (100, [M À H]À), 213 (14, [M À CO2H]À).
4-(4-Methoxyphenyl)phenylacetic Acid (ˆ4'-Methoxy[1,1'-biphenyl]-4-acetic Acid). According to the G. P.,
1
but workup as described above for [1,1'-biphenyl]-4-carboxylic acid. H-NMR (CD3OD, 400 MHz): 7.49 7.53
(m, 4 arom. H); 7.32 (m(AA'BB'), Japp ˆ 8.2, 2 arom. H); 6.97 (m(AA'BB'), Japp ˆ 9.0, 2 arom. H); 3.81
(s, MeO); 3.60 (s, CH2). 13C-NMR (CD3OD, 100.6 MHz): 176.0; 160.7; 140.7; 134.7; 134.6; 130.8; 128.9; 127.6;
‡
‡
115.3; 55.8; 41.9. EI-MS: 242 (80, M ), 197 (100, [M À CO2H] ), 182 (15), 154 (31).
4-(2-Methoxyphenyl)mandelic Acid (ˆa-Hydroxy-2'-methoxy[1,1'-biphenyl]-4-acetic Acid). According to
the G. P. 1H-NMR (CD3OD, 400 MHz): 7.44 7.48 (m(AA'BB'), 4 arom. H); 7.24 7.31 (m, 2 arom. H); 7.04
(d, J ˆ 8.2, 1 arom. H); 6.98 (t, J ˆ 7.5, 1 arom. H); 5.15 (s, CHOH); 3.76 (s, MeO). 13C-NMR (CD3OD,
100.6 MHz): 176.4; 158.0; 140.0; 139.4; 131.7; 131.6; 130.5; 129.9; 127.4; 121.9; 112.7; 74.2; 56.0. APCI-MS (neg.):
257 (100, [M À H]À), 213 (44, [M À CO2H]À).
4-(2-Methoxyphenyl)phenylacetic Acid (ˆ2'-Methoxy[1,1'-biphenyl]-4-acetic Acid). According to the G. P.
1H-NMR (CD3OD, 500 MHz; * ˆ overlapped): 7.40 (m(AA'BB'), Japp ˆ 8.5, 2 arom. H); 7.22 7.29* (m, 2ar-
om. H); 7.25* (m(AA'BB'), Japp ˆ 7.8, 2 arom. H); 7.01 (dd, J ˆ 8.2, 1.0, 1 arom. H); 6.97 (td, J ˆ 7.5, 1.1,

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1 arom. H); 3.73 (s, MeO); 3.63 (s, CH2). 13C-NMR (CD3OD, 125.7 MHz): 175.7; 158.0; 138.8; 134.5; 132.4;
‡
‡
131.6; 130.6; 129.9; 129.7; 121.9; 112.6; 56.0; 41.7. EI-MS: 242 (100, M ), 197 (94, [M À CO2H] ), 181(54).
O1-([1,1'-Biphenyl-4-ylmethyl)glycerol (ˆ 3-([1,1'-Biphenyl]-4-ylmethoxy)propane-1,2-diol). According to
the G. P., but extraction with AcOEt instead of Et2O. 1H-NMR (CDCl3, 500 MHz): 7.55 7.57 (m, 4 arom. H);
7.42 (t, J ˆ 7.77, 2 arom. H); 7.37 (d, J ˆ 8.2, 2 arom. H); 7.33 (−t×, J ˆ 7.5, 1 arom. H); 4.57 (s, ArCH2); 3.91
(m, 1 H); 3.68 3.72 (m, 1 H), 3.60 3.64 (m, 1 H); 3.52 3.59 (m, 2 H); 2.9 (br., 2 OH). 13C-NMR (CDCl3,
‡
125.7 MHz): 140.9; 140.7; 136.7; 128.8; 128.3; 127.4; 127.2; 127.1; 73.3; 71.8; 70.7; 64.1. EI-MS: 258 (7, M ), 183
‡
‡
‡
(48, C13H11O ); 167 (100, C13H11 ), 152 (33, C12H8 ).
Typical Procedure for the Determination of Pd Leaching on Preparation of 4-Phenylmandelic Acid. To
supported catalyst (500 mg, 1.5 mmol of Pd-complex 2a or 3 on either FRPSG or silica gel), an aq. stock soln. of
the substrates (15 ml, containing 1.5 mmol of 4-bromomandelic acid, 1.65 mmol of phenylboronic acid, and
3.0 mmol of Na2CO3) was added under Ar. The mixture was shaken at 808 for 16 h. The mixture was cooled to
r.t. and filtered. The FRPSG was washed with H2O (4 Â 5 ml). The combined filtrate was evaporated, and the
Pd-content of the solid residue was determined by ICP-MS (Solvias, Basel, Switzerland).
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Received August 13,2004