C O M M U N I C A T I O N S
Table 2. Suzuki Couplings with Sulfophthalein Dyes with
XL-RC Pd
R
1
R
2
yielda (%)
Figure 3. (a) Three-phase test methodology and (b) HPLC traces of the
solid-phase Suzuki coupling products by Pd leached from the supported
catalysts.
bromophenol blue
bromocresol purple
bromothymol blue
Br
Me
i-Bu
H
H
Me
41 (33)
57 (56)
28 (25)
Table 1. Aqueous Suzuki Couplings with XL-RC Pd
a
Substrate (0.5 mmol), carboxyphenyl boronic acid (0.6 mmol), K3PO4
1.5 mmol), XL-RC Pd (10 mol % of aryl halide), water (5 mL), microwave,
20 °C, 10 min. b Based on the isolated yield of the monosubstituted product
(
1
and compared with yields obtained using (Pd(OAc)2) in parentheses.
supported catalysts are predominantly heterogeneous in nature and
could be recycled without loss of activity.
yieldb
(%)
yieldb
(%)
entryst
R
1
R
2
X
entry
R
1
R
2
X
1
2
3
4
5
6
4-CH3CO
4-CH3CO
4-NO2
4-CH3
2-CH3
H
H
H
H
H
H
Br 98
Br 99
Br 93
Br 83
Br 72
Br 94
7
8
9
2,4-diCH3O
4-CH3
2-CH3
H
Br 63
Acknowledgment. We thank the CCE partners: GSK, Astra-
Zeneca, Pfizer, Roche, Eli-Lilly, Organon, NovaBiochem /Merck,
Amersham/Nycomed Amersham, and Evotec OAI and Dr. Anton
Page in Southampton General Hospital for TEM images and Biotage
for the SmithSynthesiser.
c
CH3O Br 82
CH3O Br 62
CH3O Br 91
H
H
10 4-CH3O
11 4-CH3CO
12 4-CH3
Cl 25
Cl 14
4-CH3O
a
Aryl halide (0.5 mmol), boronic acid (0.75 mmol), K2CO3 (1.5 mmol),
Supporting Information Available: Detailed experimental pro-
cedures of TEM analysis, various tests, aqueous Suzuki coupling and
their characterization data, IR spectra, SEM, TEM of XL-RC Pd. This
material is available free of charge via the Internet at http://pubs.acs.org.
XL-RC Pd (10 mol % of aryl halide), water (2 mL), 80 °C, 4-16 h.
Isolated yield. Microwave, 120 °C, 10 min.
b
c
solution, with the resin cross-linking suppressing the leaching of
palladium from the support. This was confirmed by carrying out a
solid-phase Suzuki coupling reaction with each of the three catalysts
in a three-phase test (see Figure 3a).6a In this case reaction would
only be expected on the resin-bound 4-bromobenzamide 2 if
palladium was leached into solution during the solution-phase
reaction (to increase the robustness of this experiment reactions
were carried out for 16 h at 80 °C). Complete conversion occurred
with III, and 43% of the biaryl product 4 was obtained with II;
however, only 5% of 4 was generated with I (Figure 3b).
Aqueous Suzuki couplings between a range of aryl bromides
which are preferred to aryl iodides due to economic concerns
despite reduced reactivity) and aryl boronic acids were performed
with both activated and deactivated aryl bromides and afforded good
yields of products. Microwave conditions were also investigated
References
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(
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(
(
3471. (b) Jansson, A. M.; Groti, M.; Halkes, K. M.; Meldal, M. Org.
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(
120 °C, SmithSynthesier), and the former overnight reaction could
(
e) Okamoto, K.; Akiyama, R.; Yoshida, H.; Yoshida, T.; Kobayashi, S.
be accomplished within 10 min. However, the XL-RC Pd did not
have any reasonable activity with aryl chlorides under these
conditions (Table 1). The XL-RC Pd could be recycled six times
without loss of catalytic activity, with recovery by simple filtration
and washing, and gave excellent yields, with no special precautions
needed with respect to handling (in air). In particular, no noticeable
change in the size of Pd nanoparticles was observed by TEM after
recycling (Figure 1c and see Supporting Information).
The XL-RC Pd was employed in Suzuki reactions of sulfoph-
thalein dyes (required for sensor array-type applications) where
palladium contaminants can cause serious problems in the optical
properties of final product. Expectedly, the XL-RC Pd afforded
the desired products without contamination and with yields
comparable to those found under more conventional conditions
J. Am. Chem. Soc. 2005, 127, 2125-2135.
(6) (a) Davies, I. W.; Matty, L.; Hughes, D. L.; Reider, P. J. J. Am. Chem.
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Williams, M.; Shi, Y.-J.; Sun, Y. AdV. Synth. Catal. 2003, 345, 931-
9
2
35. (c) Yu, K.; Sommer, W.; Weck, M.; Jones, C. W. J. Catal. 2004,
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7) To test the possibility that terminal amino groups may play a role as
ligands, acetylated resins were used for capturing the palladium. Compared
with amino resins, similar amounts of palladium were captured by
acetylated resins, indicating most of palladium was captured by interaction
with the poly(ethylene glycol) and/or polystyrene backbone; prolonged
stirring in toluene at 80 °C can also afford reduced Pd(0), confirmed by
IR.
(
9
(8) (a) Sakurai, H.; Tsukuda, T.; Hirao, T. J. Org. Chem. 2002, 67, 2721-
2722. (b) Leadbeater, N. E.; Marco, M. Org. Lett. 2002, 4, 2973-2976.
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Comb. Chem. 2003, 5, 632-636. (b) Cho, J. K.; White, P. D.; Klute, W.;
Dean, T. W.; Bradley, M. Chem. Commun. 2004, 502-503. (c) Cho, J.
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Commun. 2004, 1470-1471.
(
Table 2).
In summary, cross-linked resin-captured palladium catalysts were
prepared and applied to Suzuki cross-couplings in water. These
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