Heterogenized gold(I), gold(III), and palladium(II) complexes for C-C bond reactions

Article abstract of DOI:10.1055/s-2007-984500

Recycling of heterogenized gold(I), gold(III), and palladium(II) complexes could be achieved for Suzuki and Sonogashira cross-coupling reaction between iodo benzene and arylboronic acids or alkynes. Au(I) and Pd(II) afford selectively nonsymmetrical biaryl compounds, while gold(III) complexes can only catalyze the arylboronic or alkynes homocoupling. Recycling occurs without loss of the catalytic activity after several reaction cycles. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2007-984500

CLUSTER
1771
Heterogenized Gold(I), Gold(III), and Palladium(II) Complexes for C–C Bond
Reactions
Heterogenized
G
ol
v
d(I),
G
old(II
e
I), and
P
all
l
adium(
i
I
I) Com
n
plexes o Corma,*a Camino González-Arellano,b,c Marta Iglesias,b Susana Pérez-Ferreras,b,c Félix Sánchezc
a
Instituto de Tecnología Química, CSIC-UPV, Avda. de los Naranjos s/n, 46022 Valencia, Spain
Fax +34(96)3877809; E-mail: acorma@itq.upv.es
b
c
Instituto de Ciencia de Materiales de Madrid, CSIC, C/ Sor Juana Inés de la Cruz 3, Cantoblanco 28049 Madrid, Spain
Instituto de Química Orgánica, CSIC, C/ Juan de la Cierva 3, 28006 Madrid, Spain
Received 8 March 2007
g–1) = 830, micropore surface (t-plot m2 g–1) = 130, exter-
nal (or mesoporous) surface area (m2 g–1) = 700],11 be-
cause the resulting materials are stable to the reaction
conditions and can be recycled without loss of activity.
Abstract: Recycling of heterogenized gold(I), gold(III), and palla-
dium(II) complexes could be achieved for Suzuki and Sonogashira
cross-coupling reaction between iodo benzene and arylboronic
acids or alkynes. Au(I) and Pd(II) afford selectively nonsymmetri-
cal biaryl compounds, while gold(III) complexes can only catalyze
the arylboronic or alkynes homocoupling. Recycling occurs without
loss of the catalytic activity after several reaction cycles.
Immobilization of gold and palladium complexes onto the
inorganic matrices to generate heterogenized catalysts
[Au, Pd-(support)] was achieved by refluxing a mixture of
the precursor 1/2M (M = Pd, Au) and the support, in tolu-
ene, for 16 hours. These materials were characterized by
microanalysis, FT-IR, DFTR, and 13C NMR spectrosco-
py.12 The catalysts prepared in this way presented metal
loading of 0.20–0.30 mmol metal/g support, as deter-
mined by atomic absorption analysis.
Key words: C–C coupling, gold, Suzuki, Sonogashira, homoge-
neous catalysis, heterogenized
The use of gold compounds in homogeneous and hetero-
geneous catalytic organic reactions has been undervalued
for many years due to the preconceived idea that gold is
chemically inert. However, recent reports have changed
this assessment and gold compounds are known to display
high catalytic activity.1 Indeed, Au(III) can act as a Lewis
acid catalyst for a large variety of reactions,2,3 solid gold
catalysts on the other hand can be recycled, and when
prepared in the form of gold nanoparticles they are highly
active and selective for reactions such as CO oxidation,4
chemoselective reduction of substituted nitroaromatics by
H2,5 selective oxidation of alcohols,6 and some C–C bond-
forming reactions.7 Moreover, the use of Au complexes in
homogeneous catalysis has undergone a renaissance and
spectacular achievements have recently been reported.8
Supported gold and palladium complexes were tested for
catalyzing three types of carbon–carbon bond-formation
reactions: Suzuki (Table 1 and Table 2), homocoupling
(Table 3), and Sonogashira (Table 4); gold complexes
were inactive for the Heck reaction. Firstly, reaction vari-
ables such as solvent, base, temperature, and reaction
were optimized. For example, our Suzuki reactions
typically involved iodobenzene and arylboronic acid
(aryl = Ph, 3- and 4-BrPh, 4-MeOPh, 4-MePh, 4-CHOPh)
in xylene in the presence of a catalyst (homogeneous or
supported; 10–20%) at 130 °C for 6–24 hours.13 In our ex-
periments, we have found that K3PO4 is the most effective
base because with K2CO3 longer reaction times were nec-
essary in order to obtain reasonable conversions. Reaction
solutions were removed from the flask and then subjected
to GC analysis. The products were purified via flash chro-
matography and characterized by spectroscopic methods.
The isolated supported gold and palladium catalysts were
washed with various solvents several times and air-dried.
In this paper, we report the use of MCM-41, ITQ-2 and
silica gel matrices for supporting catalytic homogeneous
gold and palladium Suzuki, Sonogashira cross-coupling,
and homocoupling reactions. These Pd-catalyzed C–C
coupling reactions rank today amongst the most general
transformations in organic synthesis, with great industrial
potential for the synthesis of chemicals, therapeutic drugs,
and their intermediates.9 The complexes of gold and pal-
ladium with Schiff bases and unsymmetrical carbene
(NHC) were chosen to be heterogenized on supports such
as silica gel (Merck silica, average pore diameter 40 Å),
ordered mesoporous silica MCM-41 [BET surface area
(m2 g–1) = 1030, micropore surface (t-plot m2 g–1) = 0, ex-
ternal (or mesoporous) surface area (m2 g–1) = 1030],10
and delaminated zeolite ITQ-2 [BET surface area (m2
The effect of electron-donating and electron-withdrawing
substituents in the boronic acid on reactivity can be seen
in Table 1 and Table 2. In general, moderate yields (cal-
culated with respect to PhI) and 100% selectivity towards
the cross-coupling product were found with Au(I)–car-
bene complexes (homogeneous and heterogenized; only
traces for boronic homocoupling were detected). Pd(II)
complexes have also been tested under the same reaction
conditions (Table 2). Results show that activity and selec-
tivity of Au(I) and Pd(II) complexes are similar, though
the Pd complex is slightly less active. Nevertheless, it is
interesting to see that Au(I) which has the same d10 elec-
tronic structure as Pd(0) is able to catalyze the cross-cou-
SYNLETT 2007, No. 11, pp 1771–1774
0
3
.0
7
.2
0
0
7
Advanced online publication: 25.06.2007
DOI: 10.1055/s-2007-984500; Art ID: Y01107ST
© Georg Thieme Verlag Stuttgart · New York

1772
A. Corma et al.
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N
O
N
O
M
Ph
O
Si
O
OAc
O
NH
NH
1Au,1Pd-(Sil, MCM-41, ITQ-2)
HO
HO
O
O
N
N
Si(OEt)3
N
Si
N
Au
Cl
HO
O
Au
Cl
toluene
2Au
2Au-(Sil, MCM-41, ITQ-2)
HO
HO
O
O
Si(OEt)3
N
N
Si
N
Cl Pd Cl
L
N
HO
O
Cl Pd Cl
toluene
L
2Pd
2Pd-(Sil, MCM-41, ITQ-2)
Figure 1 Selected catalysts for C–C coupling reactions
pling reaction with high selectivity. On the other hand, by catalysts were re-used (to test their recyclability) and the
changing the charge of the gold atom [1Au(III)] it is pos- results show that reproducibility is high. Hot filtration ex-
sible to selectively catalyze the homocoupling reaction periments and ICP measurements were independently
(Table 3), the respective 1Pd(II) complexes catalyze carried out to rule out the possibility of leaching. In order
selectively the cross-coupling reaction.
to check the stability of metal complexes supported on the
solid matrix, we have characterized the solid before and
after reaction. As can be deduced from FT-IR, 13C NMR,
and UV/Vis spectra the nature of supported species is very
similar and the most important signals for Schiff base
ligands appear in the same position after reaction. No sig-
nificant loss of the catalytic activity was observed for
2Au, 2Pd-(MCM-41) in Suzuki and Sonogashira reac-
The homogeneous and heterogenized complexes were
also studied for Sonogashira14 cross-coupling of IPh with
a series of alkynes containing electron-donating and elec-
tron-withdrawing substituents in the alkyne (R–CC,
R = Ph, COOEt). In the case of Au(I) complex moderate
to excellent yields with high selectivities (99%) to the
cross-coupling Sonogashira reaction were obtained
(Table 4). On the other hand, when Au(III) complexes
were used as catalyst for several of the reactions, the prod- Table 2 Pd(II)-Catalyzed Suzuki Cross-Coupling Reactions
between Iodobenzene and Aryl Boronic Acidsa
uct observed was 10% of alkyne homocoupling with a
very small amount of iodobenzene homocoupling. Results
Aryl
2Pd
2Pd-
2Pd-
2Pd-
(Sil)
show that activity of Pd catalysts is similar to gold, with
the selectivity for the Sonogashira reaction also being
high.
(MCM-41) (ITQ-2)
Conv. (%) Conv. (%) Conv. (%) Conv. (%)
Ph
100
40
100
50
75
70
70
100
60
100
35
The feasibility of repeated use of supported gold and
palladium catalysts was also examined. In Table 5, we
present results from the investigation of recycling of Au,
Pd-supported for four consecutive runs of the same reac-
tion. After each run, the heterogenized catalysts were fil-
tered and washed, then fresh substrate and solvent were
added, without further addition of catalyst, for several
consecutive experiments and have found that both yield
and activity are retained. After each experiment a fraction
of supported catalyst was analyzed and the concentration
4-OMePh
3-BrPh
4-MePh
4-CHOPh
65
55
40
60
60
a Conditions: aryl boronic acid (15 mmol), aryl halide (10 mmol),
catalyst (10 mol%), and K3PO4 (20 mmol) in xylene at 130 °C.
Yields were determined by GC analysis of the crude reaction
of metal on the support did not change. Filtrate was used mixtures at 24 h and by isolated samples of the reaction.
in a new reaction and did not catalyze the reaction. The
Synlett 2007, No. 11, 1771–1774 © Thieme Stuttgart · New York

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Heterogenized Gold(I), Gold(III), and Palladium(II) Complexes
1773
tions as we show in Table 5. 1Au-(MCM-41) was also re-
cycled 3 times for the homocoupling reaction.
Table 3 Yields for Au(III)-Catalyzed Homocoupling of Aryl
Boronic Acids under Suzuki Reaction Conditionsa
In summary, gold(III) homogeneous or heterogenized
complexes catalyze the homocoupling of arylboronic ac-
ids or alkynes to afford symmetrical biaryls whereas the
respective gold(I) and palladium(II) complexes catalyze
the corresponding cross-coupling reaction product. The
facts that no inert atmosphere and no additional ligands or
cocatalysts are necessary, the easy separation, and the
easy availability make the supported catalysts an interest-
ing alternative to homogeneous catalysts. We have shown
that by choosing metal, ligand, and support, it is possible
to obtain a selective catalytic system for a specific reac-
tion. No significant loss of the catalytic activity of the im-
mobilized catalysts was observed after several reaction
cycles.
Aryl
1Au(III)
95/97
1Au(III)-(MCM-41)
Ph
97/99
94/97
92/95
4-OMePh
3-BrPh
90/96
93/95
a Conditions: aryl boronic acid (15 mmol), catalyst (20 mol%), and
K3PO4 (20 mmol) in xylene at 130 °C. Yields were determined by GC
analysis of the crude reaction mixtures at 24 h and by isolated samples
of the reaction.
Table 4 Pd(II) and Au(I)-Catalyzed Cross-Coupling in Sonogashira
Reactiona (IPh + R–CC → Ph–CCR)
Catalyst
R = Ph
17
R = CH2CH(CO2Me)2
2Au
15
10
25
35
Synthesis of Metal Complexes
1Au, 1Au-(support), 1Pd, 1Pd-(support), 2Au, 2Au-(support) were
obtained in high yields following the general method as we de-
scribed previously.12
2Au-(MCM-41)
2Pd
34
30
2Pd-(MCM-41)
40
Synthesis of 2Pd
A mixture of 100 mg of the imidazolium salt and 0.17 mmol of sil-
ver(I) oxide was taken up in 20 mL of CH2Cl2 and stirred for 3 h.
The suspension was filtered and [Pd(COD)Cl2] (1 mmol) was added
to the filtrate. After 12 h, the reaction mixture was filtered through
Celite®. The solvent was removed in vacuum until ca. 5 mL re-
mained and hexane was added, causing a precipitate to form bis[1-
(2,4,6-trimehylphenyl)-3-propyl-2,3-dihydro-1H-imidazol-2-yl]–
palladium(II) dichloride.
a Conditions: alkyne (15 mmol), aryl halide (10 mmol), catalyst (20
mol%), and K3PO4 (20 mmol) in xylene at 130 °C. Yields were deter-
mined by GC analysis of the crude reaction mixtures at 24 h.
Table 1 Au(I)-Catalyzed Suzuki Cross-Coupling Reactions
between Iodobenzene and Aryl Boronic Acidsa
2Pd: yield 82%. Anal. Calcd (%) for C40H65Cl2N4O6PdSi (677.1):
1
C, 51.4; H, 7.3; N, 6.0. Found: C, 51.3; H, 7.5; N, 6.0. H NMR
Aryl
2Au
2Au-
2Au-
2Au-
(Sil)
(CDCl3): d = 6.91–6.87 (m, 4 Him), 6.75–6.72 (m, 4 Harom), 4.81 (br,
4 H, CH2N), 3.88 (c, 12 H, OCH2CH3, J = 6.51 Hz), 2.43 (s, 6 H,
CH3p-), 2.38 (s, 12 H, CH3o-), 1.85 (s, 4 H, CH2), 1.26 (t, 18 H,
OCH2CH3, J = 6.51 Hz), 0.86–0.82 (m, 2 H, CH2Si) ppm. 13C NMR
(CDCl3): d = 172.11 (NCN), 139.34 (CaromN), 134.67 (CaromCH3o-),
129.83 (CaromCH3p-), 129.23 (CHarom), 122.49 (=CHaliph), 121.99
(=CHarom), 58.22 (OCH2CH3), 53.41 (CH2N), 29.59 (CH2), 21.01
(CH3o-), 18.32 (OCH2CH3), 17.81 (CH3p-), 17.26 (CH2Si) ppm. IR
(KBr): n = 3155–3010 (=CH), 3000–2850 (CH), 1608 (C=C), 1541
(C=N), 1465 (=CN), 1022 (CN), 1076 (SiO), 782 (SiC). Cm–1. UV/
Vis (l): 291, 340, 415 nm. MS (ES): m/z (%) = 933 (13) [M + 1].
(MCM-41) (ITQ-2)
Conv. (%) Conv. (%) Conv. (%) Conv. (%)
Ph
100
53
100
65
100
70
100
45
4-MeOC6H4
3-BrC6H4
4-MeC6H4
4-CHOC6H4
65
70
70
50
70
70
80
85 (6)
2Pd-(support)
a Conditions: aryl boronic acid (15 mmol), aryl halide (10 mmol),
catalyst (20 mol%), and K3PO4 (20 mmol) in xylene at 130 °C.
Yields were determined by GC analysis of the crude reaction
mixtures at 24 h and by isolated samples of the reaction.
To a suspension of the support in toluene (20 mL), at r.t., was added
a CH2Cl2 solution of [1-(2,4,6-trimehylphenyl)-3-(3-triethoxysi-
lyl)propyl-2,3-dihydro-1H-imidazol-2-yl]–palladium(II) chloride
complex (20% in weight). The resulting mixture was stirred under
reflux for 4 h (12 h at reflux for heterogenized), cooled to r.t., and
Table 5 Repeated Uses of Recovered 2Au-(MCM-41), 2Pd-(MCM-41) for Catalyzing Suzuki and Sonogashira Reactionsa
Reagents
2Au-(MCM-41)
2Pd-(MCM-41)
1
2
3
4
1
2
3
4
IPh/RPhB(OH)2
IPh/RPhCC
65
34
55
25
60
30
65
40
50
40
40
50
55
50
50
55
a Yields were determined by GC analysis.
Synlett 2007, No. 11, 1771–1774 © Thieme Stuttgart · New York

1774
A. Corma et al.
CLUSTER
then concentrated under vacuum. The residue was washed several
times with Et2O, dried and filtered to afford the respective complex-
es in almost quantitative yields.
(7) (a) Carrettin, S.; Guzmán, J.; Corma, A. Angew. Chem. Int.
Ed. 2005, 44, 2242. (b) Hashmi, A. S. K.; Schwarz, L.;
Choi, J.-H.; Frost, T. M. Angew. Chem. Int. Ed. 2000, 39,
2285.
2Pd-(MCM-41)
(8) (a) Hashmi, A. S. K. Angew. Chem. Int. Ed. 2005, 44, 6990.
(b) Arcadi, A.; Di Giuseppe, S. Curr. Org. Chem. 2004, 8,
795. (c) Hoffmann-Röder, A.; Krause, N. Org. Biomol.
Chem. 2005, 3, 387. (d) Hashmi, A. S. K. Gold Bull. 2003,
36, 3. (e) Hashmi, A. S. K. Gold Bull. 2004, 37, 51.
(f) González-Arellano, C.; Corma, A.; Iglesias, M.; Sánchez,
F. Chem. Commun. 2005, 3451. (g) Hashmi, A. S. K.;
Salatte, R.; Frey, W. Chem. Eur. J. 2006, 12, 6991.
(h) Hashmi, A. S. K.; Weyrauch, J. P.; Rudolph, M.;
Kurpejovic, E. Angew. Chem. Int. Ed. 2004, 43, 6545.
(9) (a) Metal-Catalyzed Cross-Coupling Reactions; Diederich,
F.; Stang, P. G., Eds.; Wiley-VCH: Weinheim, 1997.
(b) Transition Metals for Organic Synthesis, Building Blocks
and Fine Chemicals; Beller, M., Ed.; Wiley-VCH:
Weinheim, 2004.
(10) (a) Kresge, C. T.; Leonowicz, M. E.; Roth, W. J.; Vartuli, J.
C.; Beck, J. S. Nature (London) 1992, 359, 710. (b)Beck, J.
S.; Roth, W. J.; Leonowicz, M. E.; Kresge, C. T.; Schmitt,
K. D.; Chu, C. T.-W.; Olson, K. H.; Sheppard, E.; McCullen,
S. B.; Higgins, J. B.; Schlenk, J. L. J. Am. Chem. Soc. 1992,
114, 10834.
(11) (a) Corma, A.; Fornés, V.; Pergher, S. B. Nature (London)
1998, 396, 353. (b) Corma, A.; Fornés, V.; Martínez-
Triguero, J.; Pergher, S. B. J. Catal. 1999, 186, 57.
(c) Corma, A.; Fornés, V.; Guil, J. M.; Pergher, S. B.;
Maesen, Th. L. M.; Buglass, J. G. Microporous Mesoporous
Mater. 2000, 38, 301.
Anal. Found (%): C, 10.4; H, 2.9; N, 0.5; Pd, 0.6 (0.19 mmol/g). 13
C
NMR (solid): d = 175.61 (CPd), 137.26 (CaromN), 133.26
(CaromCH3o-), 129.28 (CaromCH3p-), 128.84 (CHarom), 126.52 (=CHa-
liph), 123.16 (=CHarom), 58.27 (OCH2CH3), 55.31 (CH2N), 30.02
(CH2), 23.17 (CH3o-), 19.61 (OCH2CH3), 17.82 (CH3p-), 16.62
(CH2Si) ppm. IR (KBr): n = 1609 (C=N), 1481 (=CN), 1080 cm–1.
UV/Vis (l): 341, 417 nm.
2Pd-(ITQ-2)
Anal. Found (%): C, 9.7; H, 2.4; N, 0.6; Pd, 0.6 (0.19 mmol/g). 13
C
NMR (solid): d = 175.61 (CPd), 139.71 (CaromN), 135.57 (CaromCH3
o-), 130.93 (CaromCH3p-), 130.44 (CHarom), 122.91 (=CHaliph),
122.16 (=CHarom), 60.48 (OCH2CH3), 59.83 (CH2N), 32.32 (CH2),
24.58 (CH3o-), 19.91 (OCH2CH3), 18.04 (CH3p-), 17.14 (CH2Si)
ppm. IR (KBr): n = 1608 (C=N), 1482 (=CN), 1085(CN) cm–1. UV/
Vis (l): 342, 418 nm.
2Pd-(Sil)
Anal. Found (%): C, 9.5; H, 2.7; N, 0.7; Pd, 0.7 (0.21 mmol/g). 13
C
NMR (solid): d = 175.52 (CPd), 139.69 (CaromN), 135.38
(CaromCH3o-), 131.23 (CaromCH3p-), 130.90 (CHarom), 123.65 (=CHa-
liph), 122.87 (=CHarom), 61.02 (OCH2CH3), 58.33 (CH2N), 31.87
(CH2), 25.05 (CH3o-), 19.72 (OCH2CH3), 18.51 (CH3p-), 18.05
(CH2Si) ppm. IR (KBr): n = 1609 (C=N), 1483 (=CN), 1084 (CN)
cm–1. UV/Vis (l): 340, 416 nm.
(12) (a) González-Arellano, C.; Gutiérrez-Puebla, E.; Iglesias,
M.; Sánchez, F. Eur. J. Inorg. Chem. 2004, 1955.
(b) Corma, A.; Gutiérrez-Puebla, E.; Iglesias, M.; Monge,
A.; Pérez-Ferreras, S.; Sánchez, F. Adv. Synth. Catal. 2006,
348, 1899.
Acknowledgment
Financial support by the Dirección General de Investigación
Científica y Técnica of Spain (Project MAT2006-14274-C02-01
and 02) is gratefully acknowledged. C. González-Arellano thanks
the I3P program for financial support.
(13) Suzuki: the reaction was carried out in a 25 mL vessel, at
130 °C in a time range of 3–24 h. In a typical run, a mixture
of aryl halide (10 mmol), boronic acid (15 mmol), aq K3PO4
(20 mmol), and catalyst (10–20 mol%) in 3 mL of o-xylene
was stirred for the desired time. The solution was allowed to
cool, and a 1:1 mixture of Et2O–H2O (20 mL) was added.
The organic layer was washed, separated, further washed
with another 10 mL portion of Et2O, dried with anhyd
MgSO4, and filtered. The solvent and volatiles were
completely removed under vacuum to give the crude product
which subjected to column chromatographic separation
resulted in pure compounds. The reaction was followed by
GC-MS. At the end of the process, the mixture of reaction
was filtered; the residue of support-containing catalyst
washed to completely remove the remains of products and/
or reactants and used again.
(14) Sonogashira: The reaction was carried out in a 25 mL vessel,
at 130 °C during 24 h. In a typical run, a mixture of aryl
halide (10 mmol), alkyne (15 mmol), aq K2CO3 or K3PO4
(20 mmol) and catalyst (10–20 mol%) in 3 mL of o-xylene
was stirred for the desired time. The reaction was followed
by GC-MS. At the end of the process, the mixture of reaction
was filtered; the residue of support-containing catalyst
washed to completely remove the remains of products and/
or reactants, and used again.
References and Notes
(1) (a) Hashmi, A. S. K.; Hutchings, G. J. Angew. Chem. Int. Ed.
2006, 45, 7896. (b) Bond, G. C.; Louis, C.; Thompson, D. T.
In Catalysis by Gold; Imperial College Press: London,
2006. (c) Dyker, G. Angew. Chem. Int. Ed. 2000, 39, 4237;
and references therein.
(2) Corma, A.; García, H. Chem. Rev. 2003, 103, 4307.
(3) (a) Yao, X.; Li, Ch.-J. J. Am. Chem. Soc. 2004, 126, 6884.
(b) Wei, Ch.; Li, Ch.-J. J. Am. Chem. Soc. 2003, 125, 9584.
(4) (a) Haruta, M.; Yamada, N.; Kobayashi, T.; Iijima, S. J.
Catal. 1989, 115, 301. (b) Guzman, J.; Gates, B. C. J. Am.
Chem. Soc. 2004, 126, 2672. (c) Daniel, M. C.; Astruc, D.
Chem. Rev. 2004, 104, 293. (d) Lemire, C.; Meyer, R.;
Shaikhutdino, S.; Freund, H. J. Angew. Chem. Int. Ed. 2004,
43, 118.
(5) Corma, A.; Serna, P. Science 2006, 313, 332.
(6) (a) Prati, L.; Rossi, M. J. Catal. 1998, 176, 552. (b) Abad,
A.; Concepción, P.; Corma, A.; García, H. Angew. Chem.
Int. Ed. 2005, 44, 4066. (c) Enache, D. I.; Edwards, J. K.;
Landon, P.; Solsona-Espriu, B.; Carley, A. F.; Herzing, A.
A.; Watanabe, M.; Kiely, C. J.; Knight, D. W.; Hutchings, G.
J. Science 2006, 311, 362.
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