Copper-catalyzed Suzuki cross-coupling using mixed nanocluster catalysts

Article abstract of DOI:10.1021/ja027716+

A small library of copper and noble metal nanoclusters is designed and synthesized. These clusters are tested as catalysts in the Suzuki cross-coupling of various aryl halides with phenylboronic acid. It is found that copper and copper/noble metal combination nanoclusters are active catalysts for this reaction, the most active being the combined copper/palladium clusters. Iodo-, bromo-, and chloroarenes can be used. In the case of p-nitrobromobenzene, a one-pot cross-coupling and selective hydrogenation is achieved. Copyright

Full text of DOI:10.1021/ja027716+

Published on Web 09/12/2002
Copper-Catalyzed Suzuki Cross-Coupling Using Mixed Nanocluster Catalysts
Mehul B. Thathagar, Jurriaan Beckers, and Gadi Rothenberg*
Chemical Engineering Department, UniVersiteit Van Amsterdam, Nieuwe Achtergracht 166,
1018 WV Amsterdam, The Netherlands
Received July 16, 2002
Cross-coupling of aryl halides with arylboronic acids (the
Suzuki-Miyaura reaction1) is one of the most useful synthetic
protocols in organic chemistry.2-5 It is used extensively in the
synthesis of polymers, agrochemicals, and pharmaceutical inter-
mediates. The catalyst of choice is almost invariably a palladium-
(0) complex, in the presence of (phosphorus) ligands, although for
aryl chlorides nickel6,7 catalysis has also been reported.
The accepted catalytic cycle begins with oxidative addition of
the aryl halide to a homogeneous Pd(0) complex, followed by
transmetalation and reductive elimination of the product. However,
investigations by Reetz et al.8,9 and Hyeon and co-workers10 have
shown that another reaction pathway is possible wherein the active
moieties are nanosized palladium colloids or hollow shells. We have
also shown that such palladium clusters can exhibit similar activity
in Ullmann-type reactions.11
The catalytic activity evidenced by monometallic12-19 and
bimetallic20 colloids prompted us to search for alternative colloid
catalysts for C-C cross-coupling reactions. Copper and copper-
Figure 1. Experimental design for preparing colloid catalyst mixtures of
copper, palladium, platinum, and ruthenium.
based alternatives are particularly attractive, being orders of
magnitude cheaper and also less harmful to the environment than
any noble metal. Moreover, Cu(I) salts and Cu2O have recently
been reported as co-reagents21-23 (albeit in stoichiometric amounts)
and cocatalysts24 in C-C and C-N25 coupling reactions.
Table 1. Biphenyl Yields and Second-Order Reaction Rate
Constants Obtained Using Various Nanocolloid Catalystsa
catalystb
(composition)
kobs
r2
c
entry
yield/%
(L/mol min-1
)
(five observations)
A mixture design26 assuming no prior knowledge was applied
to test the singular and the combined catalytic effects of copper
with three noble metals (palladium, platinum, and ruthenium, see
Figure 1). The fifteen cluster combinations 1-15 were prepared
by mixing predetermined quantities of the appropriate homogeneous
stock solutions of the metal chloride precursors, followed by
reduction with tetraoctylammonium formate (TOAF) in dimethyl-
formamide (DMF). XR diffraction analysis showed that the metal
cluster cores were between 1.6 and 2.1 nm in size, depending on
the metal precursors, with a distribution of (0.1 nm (see Supporting
Information for full experimental details).
1
2
3
4
5
6
7
8
9
10
1 (Cu)
2 (Pd)
3 (Ru)
5 (Cu/Pd)
8 (Pd/Pt)
9 (Pd/Ru)
11 (Cu/Pd/Pt)
12 (Cu/Pd/Ru)
14 (Pd/Pt/Ru)
15 (Cu/Pd/Pt/Ru)
62
100
40
100
94
3.2 × 10-3
5.9 × 10-2 d
2.0 × 10-3
6.1 × 10-2 d
9.7 × 10-3
2.9 × 10-2
2.5 × 10-2
3.8 × 10-2 d
7.3 × 10-3
2.8 × 10-3
0.985
0.990
0.938
0.992
0.934
0.985
0.991
0.996
0.923
0.992
100
92
100
81
62e
a Standard reaction conditions: 0.50 mmol iodobenzene, 0.75 mmol
phenylboronic acid, 1.5 mmol K2CO3, 0.01 mmol catalyst (2 mol % total
metal nanoclusters relative to PhI), 12.5 mL DMF, N2 atmosphere, 110
°C. b No conversion was observed with catalysts 4, 6, 7, 10, and 13. c GC
yield after 6 h, corrected for the presence of internal standard. d Value is
the average of two repeated experiments. e 100% yield obtained after 24 h.
The coupling of phenylboronic acid and iodobenzene to give
biphenyl (eq 1) was used as a model reaction. The results are shown
pure Pd 2 (cf. Table 1, entries 4 and 2). The activity trends continued
with the trimetallic clusters, with 12 > 11 > 14. The tetrametallic
combination 15 was less active but stable, reaching 100% conver-
sion after 24 h. The lower activity of 15 when compared to that of
the trimetallic catalysts 12, 11, and 14 may reflect structural
differences caused by the presence of Pt.
Repeated experiments (broken lines in Figure 2) confirmed that
the results are reproducible and that the nanoclusters retain their
activity for at least 4 weeks (all duplicate experiments were
performed using the same stock solution).
in Table 1 and in Figure 2. As expected, palladium 2 displayed the
highest activity of the monometallic catalysts, affording quantitative
yields after 4 h at 110 °C. No reaction was observed with the
platinum clusters, but ruthenium and, surprisingly, copper clusters
were found to be both active and stable (see Figure 2). Of the
bimetallic combinations, Cu/Pd 5 was the most active, on par with
* To whom correspondence should be addressed. Fax: +31 20 525 5604.
E-mail: gadi@science.uva.nl.
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J. AM. CHEM. SOC. 2002, 124, 11858-11859
10.1021/ja027716+ CCC: $22.00 © 2002 American Chemical Society

C O M M U N I C A T I O N S
the substrate. It is more likely that some homocoupling of
phenylboronic acid occurs in these cases.28,29 In the case of
p-nitrobromobenzene a remarkable one-pot cross-coupling followed
by reduction occurs, to yield first 100% 4-phenyl-nitrobenzene that
is subsequently hydrogenated to 4-phenyl-aminobenzene. This
surprising reaction may be due to the presence of the formate ions,
that can give H2 in the presence of palladium and water.30
We have shown here that designed copper and copper-based
nanocolloids can catalyze the Suzuki reaction, and may eventually
present an inexpensive and eco-friendly alternative to noble metal
catalysts. Further studies on the structure and activity scope of these
new materials are now in progress.
Acknowledgment. We thank Professors M. T. Reetz and H.
Bo¨nnemann for discussions and preprints, Dr. E. Eiser for perform-
ing the XR diffraction measurements, and Hans F. M. Boelens for
advice on experimental design.
Supporting Information Available: Detailed experimental pro-
cedures for the synthesis of catalysts 1-15; procedures for performing
the cross-coupling reactions; graphs showing time-resolved reaction
profiles and kinetic analysis (PDF). This material is available free of
charge via the Internet at http://pubs.acs.org.
Figure 2. Time-resolved reaction profiles observed for the Suzuki coupling
of phenylboronic acid and iodobenzene using various colloid catalysts.
Broken lines represent duplicate reactions. Standard reaction conditions:
0.50 mmol iodobenzene, 0.75 mmol phenyl boronic acid, 1.5 mmol K2-
CO3, 0.01 mmol catalyst (2 mol % total metal nanocluster relative to PhI),
12.5 mL of DMF, 110 °C, N2 atmosphere.
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a See Table 1 for reaction conditions. b GC yield, corrected for the
presence of an internal standard. Only the cross-coupling product was
observed, unless otherwise noted. c Biphenyl (12%) as byproduct. d 100%
conversion to 1,4-diphenylbenzene (terphenyl) was observed, plus 10-12%
biphenyl. e 4-Phenyl-1-nitrobenzene was formed in 100% yield after 4 h,
and then reduced in ca. 50% yield to 4-phenyl-aniline after a further 20 h.
f 2-Chlorobiphenyl (25%) and biphenyl (10%) were observed.
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Further reactions confirmed that these novel cross-coupling
catalysts are active over a range of aromatic substrates (see Table
2). In three of the experiments (Table 2, entries 3, 4, and 7), ca.
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