Phosphine-free perfluoro-tagged palladium nanoparticles supported on fluorous silica gel: Application to the heck reaction

Article abstract of DOI:10.1021/ol7024845

The immobilization of phosphine-free perfluoro-tagged palladium nanoparticles Pd-1 on fluorous silica gel (FSG) and their utilization in the Heck reaction have been investigated. High yields of vinylic substitution products have been obtained. Recycling s

Full text of DOI:10.1021/ol7024845

ORGANIC
LETTERS
2008
Vol. 10, No. 4
561-564
Phosphine-Free Perfluoro-Tagged
Palladium Nanoparticles Supported on
Fluorous Silica Gel: Application to the
Heck Reaction†
|
Roberta Bernini,‡ Sandro Cacchi,*,§ Giancarlo Fabrizi,§ Giovanni Forte,
Sandra Niembro, Francesco Petrucci, Roser Pleixats, Alessandro Prastaro,‡
|
Rosa Maria Sebastia´n, Roger Soler, Mar Tristany, and Adelina Vallribera*,
Dipartimento A.B.A.C., UniVersita` della Tuscia e Consorzio UniVersitario “La
Chimica per l’Ambiente”, Via S. Camillo De Lellis, 01100 Viterbo, Italy, Dipartimento
di Studi di Chimica e Tecnologia delle Sostanze Biologicamente AttiVe, UniVersita`
degli Studi “La Sapienza”, P.le A. Moro 5, 00185 Rome, Italy, Istituto Superiore di
Sanita`, Viale Regina Elena 299, 00161 Rome, Italy, and Department of Chemistry,
UniVersitat Auto`noma de Barcelona, Cerdanyola 08193, Spain
sandro.cacchi@uniroma1.it; adelina.Vallribera@uab.es
Received October 25, 2007
ABSTRACT
The immobilization of phosphine-free perfluoro-tagged palladium nanoparticles Pd-1 on fluorous silica gel (FSG) and their utilization in the
Heck reaction have been investigated. High yields of vinylic substitution products have been obtained. Recycling studies have shown that the
solid-supported palladium catalyst can be readily recovered and reused several times without significant loss of activity. Reactions and
recovery of the solid-supported palladium catalyst system can be carried out in the presence of air, without any particular precaution.
Solid-supported palladium-catalyzed reactions have become
a valuable tool for facilitating the separation, recovery, and
reuse of expensive palladium catalysts and for reducing
palladium contamination of the isolated products. Both of
these problems are in fact of primary importance for the
pharmaceutical industry which has to transfer laboratory-
scale methods to large-scale cost-effective processes and limit
the presence of heavy metal impurities in active substances.
A large number of materials have been used to support
palladium, including activated carbon, silica gel, polymers
containing covalently bound ligands, metal oxides, porous
aluminosilicates, clays and other inorganic materials, and
microporous and mesoporous supports.1 Palladium has
also been microencapsulated in polymeric coating,2 and
aerogels3 have been used to prepare heterogeneous palladium
catalysts.
Recently, some of us found that palladium nanoparticles
can be stabilized by entrapment in perfluoro-tagged phos-
phine-free compounds,4 although heavily fluorinated com-
pounds are not expected to be the best constituents of
protecting shields for nanoparticles (perfluorinated chains are
† Dedicated to the memory of Prof. Marcial Moreno-Man˜as, a colleague
and a friend.
‡ Universita` della Tuscia e Consorzio Universitario “La Chimica per
l’Ambiente”.
§ Universita` degli Studi “La Sapienza”.
(1) For an excellent recent review on the use of heterogeneous palladium
catalysts in C-C bond-forming reactions, see: Yin, L.; Liebscher, J. Chem.
ReV. 2007, 107, 133.
| Istituto Superiore di Sanita`.
Universitat Auto`noma de Barcelona.
10.1021/ol7024845 CCC: $40.75
© 2008 American Chemical Society
Published on Web 01/19/2008

indeed known to exhibit very small attractive interactions
toward other materials and among themselves5). Thus, we
were intrigued by the idea of immobilizing phosphine-free
perfluoro-tagged palladium nanoparticles on fluorous6 silica
gel (FSG) and evaluating the utilization of the immobilized
catalyst in the Heck reaction.
Herein we report the results of our study.
A previous attractive example of immobilization of pal-
ladium on FSG is due to Bannwarth et al.7 who prepared
several catalysts via adsorption of palladium(II) complexes
containing perfluoro-tagged phosphine ligands and showed
the advantages of their utilization (separation and recovery
of perfluoro-tagged catalysts) compared with fluorous bi-
phasic catalysis approaches using expensive and environ-
mentally persistent perfluorinated solvents.8
Phosphine-free perfluoro-tagged palladium nanoparticles
Pd-1 (diameter 2.3 ( 0.7 nm; 13.4% palladium) were
prepared as described previously for similar systems4e by
reduction of PdCl2 with methanol at 60 °C in the presence
of sodium chloride and compound 1, a stabilizing agent
featuring long perfluorinated chains, followed by the addition
of AcONa (Scheme 1 and Figure 1a). The electron diffraction
Figure 1. TEM images (Pd-1 and Pd-1/FSG) and electron
diffraction (Pd-1). (a) TEM image of Pd-1. (b) TEM image of Pd-
1/FSG. (c) TEM image of recovered Pd-1/FSG after 15 runs. (d)
Electron diffraction of Pd-1.
Scheme 1
To prepare the immobilized precatalyst, nanoparticles Pd-1
were dissolved in perfluorooctane, commercially available
FSG (C8; 35-70 µm) was added to the solution, and the
solvent was evaporated. The immobilized precatalyst (Pd-
1/FSG) was obtained as an air-stable powder. Transmission
electron microscopy (TEM) of Pd-1/FSG was carried out. It
showed well-defined spherical particles dispersed in the silica
matrix (Figure 1b). The mean diameter of the nanoparticles
was about 1.5 ( 0.7 nm.
A silica gel containing 100 mg of Pd-1 per g of FSG and
a 0.6 mol % palladium loading was initially evaluated in
the Heck reaction of methyl acrylate with iodobenzene in
DMF at 80 °C for 24 h. The reaction could be carried out in
the presence of air, and methyl cinnamate was obtained in
almost quantitative yield in the first run as well in the second
one. However, a loss of activity was observed in the third
run (85% yield) which became even more substantial in the
patterns of this sample were obtained, and the diffraction
rings can be ascribed to the (111), (200), (220), and (311)
crystallographic planes of the fcc-Pd (Figure 1d).
(2) (a) For some recent references, see: Akiyama, R.; Kobayashi, S.
Angew. Chem., Int. Ed. 2001, 40, 3469. (b) Ramarao, C.; Ley, S. V.; Smith,
S. C.; Shirley, I. M.; DeAlmeida, N. Chem. Commun. 2002, 1132. (c) Ley,
S. V.; Ramarao, C.; Gordon, R. S.; Holmes, A. B.; Morrison, A. J.;
McConvey, I. F.; Shirley, I. M.; Smith, S. C.; Smith, M. D. Chem. Commun.
2002, 1134. (d) Bremeyer, N.; Ley, S. V.; Ramarao, C.; Shirley, I. M.;
Smith, S. C. Synlett 2002, 1843. (e) Ley, S. V.; Mitchell, C.; Pears, D.;
Ramarao, C.; Yu, J.-Q.; Zhou, W. Org. Lett. 2003, 5, 4665.
(3) (a) Martinez, S.; Vallribera, A.; Cotet, C. L.; Popovici, M.; Martin,
L.; Roig, A.; Moreno-Man˜as, M.; Molins, E. New J. Chem. 2005, 29, 1342.
(b) Cotet, L. C.; Gich, M.; Roig, A.; Popescu, I. C.; Cosoveanu, V.; Molins,
E.; Danciu, V. J. Non-Cryst. Solids 2006, 352, 2772. (c) Cacchi, S.; Cotet,
C. L.; Fabrizi, G.; Forte, G.; Goggiamani, A.; Martin, L.; Martinez, S.;
Molins, E.; Moreno-Man˜as, M.; Petrucci, F.; Roig, A.; Vallribera, A.
Tetrahedron 2007, 63, 2519. (d) Soler, R.; Cacchi, S.; Fabrizi, G.; Forte,
G.; Mart´ın, L.; Mart´ınez, S.; Molins, E.; Moreno-Man˜as, M.; Petrucci, F.;
Roig, A.; Sebastia´n, R. M.; Vallribera, A. Synthesis 2007, 3068.
(4) (a) Moreno-Man˜as, M.; Pleixats, R.; Villarroya, S. Organometallics
2001, 20, 4524-4528. (b) Moreno-Man˜as, M.; Pleixats, R.; Villarroya, S.
Chem. Commun. 2002, 60-61 (c) Tristany, M.; Courmarcel, J.; Dieudonne,
P.; Moreno-Man˜as, M.; Pleixats, R.; Rimola, A.; Sodupe, M.; Villarroya,
S. Chem. Mater. 2006, 18, 716. (d) Serra-Muns, A.; Soler, R.; Badetti, E.;
de Mendoza, P.; Moreno-Man˜as, M.; Pleixats, R.; Sebastia´n, R. M.;
Vallribera, A. New J. Chem. 2006, 30, 1584. (e) Niembro, S.; Vallribera,
A.; Moreno-Man˜as, M. New J. Chem. 2008, 32, 94.
(5) (a) Banks, R. E., Smart, B. E., Tatlow, J. C., Eds. Organofluorine
Chemistry. Principles and Commercial Applications; Plenum: New York,
1994 (b) Kirsch, P. Ed. Moden Fluoroorganic Chemistry; Wiley-VCH:
Weinheim, 2004.
(6) For some recent reviews on fluorous catalysts, see: (a) Gladysz, J.
A.; Correa de Costa, R. In The Handbook of Fluorous Chemistry; Gladysz,
J. A., Curran, D. P., Horvath, I. T., Eds.; Wiley-VCH: Weinheim, 2004,
pp 24-40, see especially sections 4.6-4.9. (b) Curran, D. P. In The
Handbook of Fluorous Chemistry; Gladysz, J. A., Curran, D. P., Horvath,
I. T., Eds.; Wiley-VCH: Weinheim, 2004, pp 101-127, see section 7.6.
(c) Schneider, S.; Tzschucke, C. C.; Bannwarth, W. In The Handbook of
Fluorous Chemistry; Gladysz, J. A., Curran, D. P., Horvath, I. T., Eds.;
Wiley-VCH: Weinheim, 2004, pp 257-272. (d) Curran, D. P.; Fischer,
K.; Moura-Letts, G. Synlett 2004, 1379.
(7) (a) Tzschucke, C. C.; Markert, C.; Glatz, H.; Bannwarth, W. Angew.
Chem., Int. Ed. 2002, 41, 4500. (b) Tzschucke, C. C.; Bannwarth, W. HelV.
Chim. Acta 2004, 87, 2882.
(8) Ravishankara, A. R.; Solomon, S .; Turnipseed, A. A.; Warren, R.
F. Science 1993, 259, 194.
562
Org. Lett., Vol. 10, No. 4, 2008

fourth run (75% yield). Assuming that these results might
be due to the leaching of palladium in DMF, we switched
to using MeCN. After some experimentation we found that
complete conversion could be obtained in MeCN at 100 °C
after 24 h using 20 mg of Pd-1 per g of FSG and a catalyst
loading down to 0.1 mol %.
Recycling studies were then performed which showed that
the supported catalyst system can be reused several times
without significant loss of activity (Table 1). The recovery
Methyl cinnamate was obtained in 93% yield in the first run.
However, a remarkable loss of activity was observed in the
second run, the Heck product being isolated only in 59%
yield.
We then evaluated the efficiency of Pd-1/FSG with other
aryl iodides (Scheme 2). Our preparative results are sum-
marized in Table 2.
Table 2. Reaction of aryl iodides with methyl acrylate
catalyzed by Pd-1/FSG (0.1 mol %)a
Table 1. Recycling studies for the reaction of iodobenzene
with methyl acrylate catalyzed by Pd-1/FSG (0.1 mol %)a
aryl iodide 2
entry
time (h)
yield % of 3b,c
1
2
3
4
5
6
7
8
9
p-MeCO-C6H4-I
p-MeO-C6H4-I
p-Me-C6H4-I
p-NO2-C6H4-I
m-CF3-C6H4-I
p-EtOCO-C6H4-I
m-Me, p-NO2-C6H3-I
o-NH2-C6H4-I
b
c
d
e
f
g
h
i
5
23
23
48
6
89 (90)
90 (70)
90
74 (65)
93 (90)
98
96
84
89
run
yield % of 3a
run
yield % of 3a
1
2
3
4
5
6
7
8
90 (91)
96 (90)
96 (90)
93 (86)
87 (88)
89 (95)
97 (100)
96 (99)
9
10
11
12
13
14
15
95 (94)
98 (95)
97
90
90
5
23
48
7
84
80
o-MeOCO-C6H4-I
j
a Reactions were carried out using 1 mmol of aryl iodide, 2 mmol of
methyl acrylate, 3 mmol of Et3N at 100 °C in the presence of 0.1 mol %
of Pd-1/FSG in 2 mL of MeCN. b Yields are given for isolated products.
c Yields in parentheses are for the second run carried out with the recovered
catalyst.
a Reactions were carried out using 1 mmol of iodobenzene, 2 mmol of
methyl acrylate, 3 mmol of Et3N at 100 °C for 24 h in the presence of
0.1 mol % of Pd-1/FSG in 2 mL of MeCN. b Yields in parentheses refer to
a second set of experiments.
of the supported palladium involves centrifugation and
decanting the solution in the presence of air, without any
particular precaution. The resistance of Pd-1/FSG to leaching
was assessed for the same reaction (iodobenzene and methyl
acrylate). Sector field inductively coupled plasma mass
Recycling studies were also performed using 10 mg of
Pd-1 per 3 g of FSG and a palladium loading down to 0.001
mol % (Table 3). The cumulated turn-over number (TON)
over three runs is 265000.
Table 3. Recycling studies with 0.001 mol % of Pd-1/FSGa
Scheme 2
run
yield % of 3a
1
2
3
100
82
83
a Reactions were carried out using 1 mmol of iodobenzene, 2 mmol of
methyl acrylate, 3 mmol of Et3N at 140 °C for 24 h in the presence of
0.001 mol % of catalyst in 2 mL of MeCN.
spectrometry (SF-ICP-MS) analysis indicated the level of
palladium in the crude mixtures to be in the 2-7 ppm range.
Agglomeration of nanoparticles was not observed upon
recycling. The recovered material after the 15th run was
examined by TEM showing nanoparticles of about 1.9 (
0.3 nm (Figure 1c). Control experiments were also carried
out to assess whether leaching of nanoparticle support may
take place under reaction conditions. 19F NMR analysis of
the crude mixture derived from the reaction of methyl
acrylate with m-(trifluoromethyl)iodobenzene after filtration
revealed the presence of small amounts of 1, corresponding
to an original nanoparticle support loss of about 5%. No
evidence of fluorine was attained in the isolated vinylic
substitution product. The crucial role of fluorous-fluorous
interactions was assessed by immobilizing Pd-1 on standard
reversed-phase silica gel and using the resultant precatalyst
in our model reaction (methyl acrylate and iodobenzene).
We have not investigated in detail whether the nanopar-
ticles on the solid surface are the actual catalyst or just a
source that leaches active catalyst species.9 Nevertheless,
when methyl acrylate, p-iodoanisole, and Et3N were added
to the crude mixture derived from the reaction of methyl
acrylate with iodobenzene (after separation of the solid
material), the corresponding vinylic substitution derivative
was isolated in 40% yield after 23 h at 100 °C, showing
that palladium species leached from the solid surface are, at
least in part, responsible for the catalytic activity.
(9) For a recent review on solid precatalysts and on evidence for and
against catalysis by solid surfaces vs soluble species, see: (a) Phan, N. T.
S.; Van Der Sluys, M.; Jones, C. W. AdV. Synth. Catal. 2006, 348, 609.
See also: refs 6a and (b) Thathagar, M. B.; ten Elshof, J. E.; Rothenberg,
G. Angew. Chem., Int. Ed. 2006, 45, 2886.
Org. Lett., Vol. 10, No. 4, 2008
563

In conclusion, we have demonstrated that phosphine-free
perfluoro-tagged palladium nanoparticles can be immobilized
on fluorous silica gel to give a precatalyst which can be
successfully used in the Heck reaction. The utilization of
Pd-1/FRG does not require an inert atmosphere. Reactions
and recovery of the catalyst system can be carried out in the
presence of air without any particular precaution. The catalyst
system can be easily recovered and reused several times
without any appreciable loss of activity in many cases. It is
also conceivable that the characteristics of this type of
precatalyst can be adjusted by using different heavily
fluorinated compounds. In general, the immobilized pal-
ladium nanoparticles described herein holds promise as the
first example of a new class of solid-supported precatalysts.
Further studies on this immobilization strategy are currently
underway.
Acknowledgment. Work carried out in the framework
of the National Projects FIRB 2003 and “Stereoselezione in
Sintesi Organica. Metodologie ed Applicazioni” supported
by the Ministero dell’Universita` e della Ricerca Scientifica
e Tecnologica and by the University “La Sapienza. Financial
support from Ministerio de Educacio´n y Ciencia (Projects
CTQ2005-04968-C02-01 and CTQ2006-04204 and Con-
solider Ingenio 2010 (CSD2007-00006)) and DURSI-Gen-
eralitat de Catalunya (SGR 2005-00305) is gratefully ac-
knowledged.
Supporting Information Available: Complete descrip-
tion of experimental details and product characterization. This
material is available free of charge via the Internet at
http://pubs.acs.org.
OL7024845
564
Org. Lett., Vol. 10, No. 4, 2008