Size controlled synthesis of Pd nanoparticles in water and their catalytic application in C-C coupling reactions

Article abstract of DOI:10.1016/j.tet.2009.03.062

Catalytically active Pd nanoparticles have been synthesized in water by a novel reduction of Pd(II) with a Fischer carbene complex where polyethylene glycol (PEG) was used as stabilizer. PEG molecules wrap around the nanoparticles to impart stability and prevent agglomeration, yet leave enough surface area available on the nanoparticle for catalytic activity. Our method is superior to others in terms of rapid generation and stabilization of Pd nanoparticles in water with a cheap, readily available PEG stabilizer. The size of the nanoparticles generated can be controlled by the concentration of PEG in water medium. The size decreased with the increase in the PEG: Pd ratio. This aqueous nano-sized Pd is a highly efficient catalyst for Suzuki, Heck, Sonogashira, and Stille reaction. Water is used as the only solvent for the coupling reactions.

Full text of DOI:10.1016/j.tet.2009.03.062

Tetrahedron 65 (2009) 4367–4374
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Size controlled synthesis of Pd nanoparticles in water and their catalytic
application in C–C coupling reactions
*
Sudeshna Sawoo, Dipankar Srimani, Piyali Dutta, Rima Lahiri, Amitabha Sarkar
Department of Organic Chemistry, Indian Association for the Cultivation of Science, Kolkata 700032, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Catalytically active Pd nanoparticles have been synthesized in water by a novel reduction of Pd(II) with
a Fischer carbene complex where polyethylene glycol (PEG) was used as stabilizer. PEG molecules wrap
around the nanoparticles to impart stability and prevent agglomeration, yet leave enough surface area
available on the nanoparticle for catalytic activity. Our method is superior to others in terms of rapid
generation and stabilization of Pd nanoparticles in water with a cheap, readily available PEG stabilizer.
The size of the nanoparticles generated can be controlled by the concentration of PEG in water medium.
The size decreased with the increase in the PEG: Pd ratio. This aqueous nano-sized Pd is a highly efficient
catalyst for Suzuki, Heck, Sonogashira, and Stille reaction. Water is used as the only solvent for the
coupling reactions.
Received 3 February 2009
Received in revised form 20 March 2009
Accepted 23 March 2009
Available online 27 March 2009
Keywords:
Pd nanoparticle
Fischer carbene complex
PEG
Ó 2009 Elsevier Ltd. All rights reserved.
Water
C–C coupling
1. Introduction
solvents,6 but they are not devoid of toxicity. Efforts have been
made, therefore, to develop a Pd catalytic system free of organic
Organic synthesis is routinely performed in non-aqueous sol-
vents, be it in academic research laboratories or industrial pro-
duction units. Lack of solubility of generally lipophilic organic or
organometallic compounds in water compelled chemists to employ
non-aqueous solvents. In contrast, nature, in its unique way, utilizes
water for enzymatic transformations of all organic substrates. The
use of water, the most abundant and non-toxic solvent for reactions
is reclaiming its importance due to pressing environmental, eco-
nomical, and safety concerns.1 Current emphasis on green chem-
istry underscores the need for developing catalytic reactions,
especially with involving precious metals as mediators, in aqueous
medium.2
Palladium catalyzed carbon–carbon and carbon–heteroatom
coupling reactions are extensively used in the synthesis of complex
organic molecules.3 In these reactions, either preformed Pd com-
plexes like (PPh3)4Pd are used where ligands are P and/or N donors
or active Pd complexes are generated in situ.4 Many of these ligands
are expensive, toxic, and sensitive to air and a major challenge lies
in the separation of product from expensive catalyst, much to the
dismay of large-scale producers. As an alternative, solid supported
Pd catalysts have been developed for several reactions.5 Ionic liq-
uids are said to provide a green alternative to conventional organic
solvent for such reactions. Water-soluble, phosphine based ligands,7
and phase-transfer catalysts8 have been used in an aqueous–or-
ganic biphasic reaction, but they operate under rather harsh
conditions.
Nanoparticle catalysis in water squarely addresses the issue of
carrying out efficient reactions under environmentally benign
conditions associated with green chemistry and also facilitates
separation of products9 from Pd colloids dispersed in water. Since
catalysis takes place on metal surface, nanoparticles are much more
reactive than the particulate metal counterpart due to their high
surface to volume ratio.10 In this paper, we report a combination of
both these facets use of water as solvent and use of Pd nano-
particles, which are synthesized and stabilized in water11 as cata-
lyst for a variety of coupling reactions where predominantly
lipophilic organic reactants provide high yield of products in water
as the only solvent.
2. Experimental
2.1. General
All chemicals were purchased as reagent grade from commercial
suppliers and used without further purification, unless otherwise
noted. Reactions were monitored by thin layer chromatography
(TLC). All 1H NMR (300 MHz), 13C NMR (75 MHz) spectra were
recorded on a Bruker-Avance DPX300 for a CDCl3 solution and
* Corresponding author. Tel.: þ913324734971; fax: þ913324732805.
E-mail address: ocas@iacs.res.in (A. Sarkar).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.03.062

4368
S. Sawoo et al. / Tetrahedron 65 (2009) 4367–4374
reported in parts per million (
d
). UV–vis spectra were recorded on
water was added. The reaction mixture was then stirred at the
specified temperatures for 10 min to 8 h (see Table 1). After cooling
to room temperature, the reaction mixture was extracted thrice
with diethyl ether (15 mL) and washed with water (10 mL). Then
the organic phase was dried over Na2SO4, filtered, and concentrated
in vacuum. The products were purified by flash column chroma-
tography using either petroleum ether or ether (10–15%)/petro-
leum ether.
Evolution 300 (Thermo). TEM pictures were taken on a JEM-2011
(JEOL). Flash Column chromatography was performed with silica
gel (230–400 mesh). All cross-coupling reactions were carried in
water under air.
2.2. Preparation and characterization of Pd nanoparticles
The acyl metal salt12 (CO)5W]C(Me)ONEt4 (0.002 g, 0.004 mmol)
was dispersed into 4 mL of distilled water and added slowly in a drop
wise manner into a well-stirred aqueous solution (6 mL) of K2PdCl4
(0.0032 g, 0.01 mmol) and polyethylene glycol (PEG 6000, 0.06 g,
0.01 mmol) (Scheme 1). This affords 1 mol % catalyst solution (Pd/PEG
6000 molar ratio¼1:1) that has been used throughout the study.
The yellow color of the Pd(II) solution (lmax 415 nm) immedi-
ately changed into dark brown indicating formation of Pd nano-
particles as characterized by UV–vis spectrum (Fig. 1).
The absorption peak (lmax 415 nm) gradually flattened with
incremental addition of Fischer carbene complex with concomitant
increase in the intensity of absorption (Fig. 1, curve A to K). After
complete addition of the Fischer carbene salt, a broad band de-
veloped without any peak, which is characteristic of colloidal pal-
ladium (Fig. 1). Transmission Electron Microscopy (TEM) pictures
were taken with different concentration of PEG 6000, which con-
firmed the generation Pd nanoparticles with a spherical shape and
an average diameter of 7–10 nm (Fig. 2).
The selected area electron diffraction (SAED) pattern (Fig. 3b),
exhibited four diffused rings, which were assigned to the (111),
(200), (220), and (311) reflections of fcc Pd and confirms the crys-
talline nature of nanoparticles. The lattice spacing value of
0.224 nm in the high-resolution transmission electron microscopy
(HRTEM) image (Fig. 3a) matched very well with the (111) lattice
plane of palladium metal. The colloidal Pd was stable in aqueous
medium and no precipitate was observed for months.
2.4.2. Heck reaction of aryl halides
The catalyst solution (2 mol %) in water was added to an RB flask
containing the aryl bromide (1 mmol), alkene (1.2 mmol), and
K2CO3 (2 mmol). The reaction mixture was stirred at 100 ꢀC for 12–
14 h. After cooling to room temperature, the reaction mixture was
extracted with ether (3ꢁ15 mL) and washed with water (10 mL),
and then the organic phase was dried over Na2SO4, filtered, and
concentrated in vacuum. The products were purified by flash
column chromatography using either petroleum ether or acetone
(2–4%)/petroleum ether.
2.4.3. Sonogashira reaction of aryl halides
The catalyst solution in water (1 mol %) was added to the aryl
iodide (1 mmol), acetylene (1.2 mmol), and K2CO3 (2 mmol) in an
RB flask. The reaction mixture was stirred at 55–65 ꢀC for 2–3.5 h.
After cooling to room temperature, the reaction mixture was
extracted with ethyl acetate (3ꢁ15 mL) and washed with water
(10 mL), and then the organic phase was dried over Na2SO4, filtered,
and concentrated in vacuum. The products were purified by flash
column chromatography using either petroleum ether or ethyl
acetate (5–15%)/petroleum ether.
2.4.4. Stille reaction of aryl halides
The catalyst solution (10 mL, 1 mol %) in water was added to
a
mixture of aryl bromide (1 mmol), phenyltributylstannane
(1.2 mmol), and K2CO3 (2 mmol). The reaction mixture was stirred
at 80 ꢀC for 2–3 h. After cooling to room temperature, the reaction
mixture was extracted thrice with diethyl ether (15 mL) and
washed with water (10 mL). Then the organic phase was dried over
Na2SO4, filtered, and concentrated in vacuum. The products were
purified by flash column chromatography using either petroleum
ether or ether (10–15%)/petroleum ether.
2.3. Size control of Pd nanoparticles by variation of amount
of PEG
Earlier we have shown that the size of Au nanoparticles gener-
ated by this method can be controlled by varying the chain length
of OEG or PEG.13 In the case of palladium, we used PEG in different
concentrations with respect to K2PdCl4 like 1:1,1:2,1:3,1:4, and 1:5
to see if it affected the size of Pd nanoparticle. The gradual variation
in size of nanoparticles with different PEG 6000 molar concentra-
tion is revealed clearly in the TEM pictures (Fig. 2A–E). The hy-
perbolic nature of the curve obtained from the plot of the size of Pd
nanoparticle against PEG concentration (Fig. 4), implies that size of
the nanoparticle decreased gradually with the increase in PEG
concentration and a limiting value is reached as the surface of the
particles get saturated with the capping agent.
1.50
1.35
1.20
1.05
0.90
K
J
I
H
G
0.75
2.4. Pd nanoparticle catalyzed reactions in water
F
E
D
0.60
2.4.1. Suzuki reaction of aryl halides
c
B
To a mixture of aryl halide (1 mmol), boronic acid (1.2 mmol),
and K2CO3 (2 mmol), 10 mL of the catalyst solution (1 mol %) in
0.45
A
0.30
0.15
0.00
O
O
O
O
n
O
ONEt4
OC CO
O
O
Water, PEG
OC
W
OC CO
1
K2PdCl4
+
Room Temperature
O
300
350
400 450
Wavelength (nm)
500
550
600
Me
n
Figure 1. UV–vis spectrum taken after each addition of Fischer carbene salt suspen-
sion (0.1 mM) by 100 L amount to K2PdCl4 solution (0.1 mM) (curve A) and gradual
formation of Pd nanoparticles indicated from the curves B to K.
Scheme 1. Preparation of Pd nanoparticles in water with acyl metal carbene salt 1,
(CO)5W]C(CH3)ONEt4 and K2PdCl4 using PEG 6000 as stabilizer.
m

S. Sawoo et al. / Tetrahedron 65 (2009) 4367–4374
4369
A
A1
12
Pd:PEG-6000=1:1
10
8
6
4
2
0
7
8
9
Diameter / nm
10
11
12
B1
B
80
70
60
50
40
30
20
10
0
Pd:PEG-6000 = 1:2
4
5
6
7
8
9
Diameter / nm
10 11 12 13
C
D
E
16
14
12
10
8
C1
Pd:PEG-6000 = 1:3
6
4
2
0
5
6
7
Diameter / nm
8
9
10
18
16
14
12
10
8
D1
Pd:PEG-6000 = 1:4
6
4
2
0
4
5
6
7
8
Diameter / nm
9
10
E1
20
15
10
5
Pd:PEG-6000 = 1:5
0
5
6
7
Diameter / nm
8
9
Figure 2. TEM pictures of Pd nanoparticles with varying Pd/PEG molar ratio (A) 1:1, (B) 1:2, (C) 1:3, (D) 1:4, (E) 1:5 and their corresponding size distribution graphs in A1, B1, C1, D1, E1.

4370
S. Sawoo et al. / Tetrahedron 65 (2009) 4367–4374
(a)
(b)
(111)
(200)
(220)
(311)
Figure 3. (a) High-resolution TEM of a single Pd nanoparticle and (b) SAED pattern of crystalline Pd nanoparticles.
3. Results and discussions
which serves as the stabilizing agent for the nanoparticles.13 This
protocol is extremely mild yet reliable for controlled generation of
stable Pd nanoparticles in water at room temperature (Scheme 1).
The Fischer carbene complex features tungsten metal in zero oxi-
dation state and thus provides a source of soluble W(0) species. It
transfers electrons to reduce other metals like Pd, Pt, Au or Ag and
itself gets converted to W(III) state in this process.y PEG has shown
its ability to stabilize due to its special molecular structure. Unlike
in many reported instances of Pd nanoparticle catalysis where PEG
has been used as a solvent23 we limited the quantity of PEG to a few
mol % and those Pd nanoparticles stabilized by PEG are highly ef-
fective as catalyst. Usually the dendritic polymer-bound Pd com-
plexes execute low reactivity as catalyst because catalytic centers
are rendered inaccessible by encapsulating polymer or surfac-
tants24 but, in our case PEG wrapping does not appear to adversely
affect the reactivity of Pd nanoparticles.
We have already reported that such catalytic system is effective
for Hiyama coupling reaction in water and that the rate of the
reaction varies according to the size of the nanopartricles.13 We
have now extended this study to cover Suzuki, Heck, Stille, and
Sonogashira couplings in order to extend their utility. We report
herein the usefulness of Pd nanoparticles as catalyst for different
cross-coupling reactions in water alone as solvent and without
exclusion of air.
Palladium nanoparticle catalyzed coupling was pioneered by
Reetz using surfactants as stabilizing agents.14 Recently, EI-Sayed et
al. reported the use of PVP stabilized Pd nanoparticles as efficient
catalysts15 for the Suzuki reaction in aqueous medium (40% EtOH or
CH3CN/H2O), but this approach was to aryl iodides. Use of triblock
copolymer in synthesis and stabilization of Pd nanoparticles re-
cently reported by Hyeon and his group.11b Such polymer, den-
drimer,16 organic ligands,17 and surfactant stabilized Pd
nanoparticles18 are being widely used for various coupling re-
actions but most of them use organic or ionic liquid as solvent, high
temperature or microwave irradiation.18,19 Recently it has been
suspected in several ‘ligand-modified’ as well as ‘ligandless’ Pd
systems,20,21 the active catalytic species might be Pd nanoparticles
formed in situ under the given reaction condition. Schmidt and
Vries et al. have shown that Pd(OAc)2 as catalyst precursor in very
dilute solution gives good result at high temperature in Heck re-
action with activated aryl halides.22 But the scope of ‘ligandless’
catalyst recycle is limited by the fact that Pd nanoparticles even-
tually aggregate to form Pd black; hence it falls short of general
implementation. Thus, it is still very challenging to develop a user-
friendly process to synthesize metal nanoparticles that are stable in
aqueous phase and use them for catalysis under mild conditions.
We established that the Fischer carbene complex is effective for
generation of metal nanoparticles like Au and Pd in water in
presence of an oligo or polyethylene glycol (OEG or PEG) additive,
3.1. Suzuki reaction
The Suzuki reaction25 in aqueous medium is known from a long
time and it also has been used for sensitive substrates like un-
protected halonucleosides.26 Homogeneous Pd based catalysts
were used in these instances. Use of Pd nanoparticle in Suzuki
coupling in aqueous phase, on the other hand, has only a few
precedents till date.27 A nanoparticle suspension (0.01 mmol)
prepared in 10 mL water was added drop wise to the reaction
mixture by constant stirring using a magnetic stirrer at room
temperature to check its catalytic activity for the reaction of phe-
nylboronic acid with p-bromoacetophenone in DME/water (1:5
v/v). Gratifyingly, the reactants were fully converted into desired
product (isolated yield 95% after purification) at room temperature
within 3 h. In subsequent runs, use of DME as co-solvent was dis-
pensed with and the reaction was performed in pure water with
equally impressive yield and the reaction was complete within 2 h.
A yield of 98% was obtained within 2 h when the reaction was
10.0
9.5
9.0
8.5
8.0
7.5
7.0
1:1
1:2
1:3
Pd:PEG
1:4
1:5
y
The oxidation state of W(III) was not experimentally determined, but the
stoichiometry of carbene complex and metal salt [for Pd(II), Pd/W 2:3, for Au(III),
Au/W 1:1 etc.] suggests formation of W(III).
Figure 4. The graph obtained from average particle size with varying Pd/PEG ratio.

S. Sawoo et al. / Tetrahedron 65 (2009) 4367–4374
4371
carried out at room temperature, establishing the superior catalytic
efficiency of the nanoparticles in aqueous medium (Table 1).
A variety of substituted aryl bromides featuring either an elec-
tron-releasing or an electron-withdrawing group were then ex-
amined (Table 1). The electron-rich substrates like bromoanisole
(entry 7) required 2 h for complete conversion at 25 ꢀC. However,
reaction of 1-chloro-4-nitrobenzene with phenylboronic acid did
not afford any coupled product. An ortho substitution offers steric
hindrance and requires elevated temperature for useful conversion
(entries 3 and 9). For activated substrate like p-bromoacetophe-
none, the rapid reaction rate was insensitive to the base used. Less
activated substrate like 4-bromoanisole was sensitive to the nature
of base. Among the bases screened, K2CO3 was found to be more
effective than triethylamine, NaOAc, CsCO3, CsF, or CsOAc. After
extraction of the product from p-bromoacetophenone and
phenylboronic acid with ether (entry 4), the aqueous extract was
recycled, albeit with gradual loss of catalytic efficiency (yield
dropped from 90% to 40%).
3.2. Heck reaction
One of the most important Pd catalyzed coupling reaction is
vinylation of aryl halides, known as the Heck reaction.28
It has been demonstrated that Pd nanoparticles catalyze Heck
reactions with activated esters and aryl iodides either at elevated
temperatures under ligand free condition14f or in presence of
tetraalkylammonium bromide as stabilizer.29 In our experiments,
palladium nanoparticles stabilized by PEG displayed high catalytic
activity in Heck arylation. For iodo- and bromoarenes, 2 mol % of
Pd nanoparticle was adequate for a relatively unactivated partner
like tert-butylstyrene (Table 2) in water under reflux. The re-
quirement of a higher catalyst loading is compensated by the
efficiency of the reaction and avoidance of organic solvent for the
reaction (Table 2).
Table 1
Pd nanoparticles catalyzed Suzuki coupling reaction with aryl halide and phenyl-
boronic acida
Ar
B(OH)2
3.3. Copper-free Sonogashira reaction
Pd nanoparticle, H2O
K2CO3
Ar-X
+
The alkynylation of aryl halides, frequently called Sonogashira–
Hagihara reaction30 is another synthetically useful coupling
reaction catalyzed by palladium(0). Application of this reaction
(between a terminal alkyne and aryl halide) is to be found in
Entry
Substrate
Product
Temp Time
(ꢀC)
% Yieldb
1
2
25
10 min 98
O2N
I
O2N
Table 2
25
60
30 min 98
I
Pd nanoparticles catalyzed Heck coupling reaction with aryl halide and alkenea
R/Ar
Pd nanoparticle, H2O
K2CO3
R/Ar
I
Ph
Ar
Ar-X
+
OCH3
OCH3
3
3 h
91
Entry
1
Aryl handle
Alkene
Temp (ꢀC) Time (h) % Yieldb
4
5
25
25
2 h
2 h
98
90
H3COC
H3C
Br H3COC
CO2Me
80
100
100
100
100
100
6
10
10
14
12
12
92
92
90
70
80
75
O2N
O2N
I
I
Br
H3C
2
3
4
5
6
Br
H3COC
H3CO
OHC
Br
6
25
3 h
92
H3C
H3C
H3CO
Br
Br
Br
7
8
25
40
2 h
4 h
98
90
H3CO
Br
Br
OHC
H3CO
H3CO
Br
7
8
100
100
12
12
5
Br
CHO
9
60
8 h
85
OHC
OHC
CHO
74
Br
Br
10
11
60
60
60
4 h
8 h
4 h
95
87
92
OHC
OHC
OHC
OHC
Br
9
100
100
12
12
80
72
Br
CHO
Br
Br
Ph
12
10
CHO
a
a
Reaction conditions: aryl halide (1.0 equiv), boronic acid (1.2 equiv), K2CO3 (2 equiv),
water (4 mL), Pd nanoparticle inwater (0.01 equiv, 6 mL) with PEG 6000 (1.0 equiv, 60 mg).
Aryl bromide (1 mmol), alkene (1.2 mmol), K2CO3 (2 mmol), water (4 mL), Pd
nanoparticle in water (0.02 equiv with PEG 6000 2.0 equiv 120 mg).
b
b
Isolated yield after purification by flash column chromatography (eluent: pe-
Isolated yield after purification by flash column chromatography (eluent:
troleum ether or ether/petroleum ether).
petroleum ether or acetone/petroleum ether).

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S. Sawoo et al. / Tetrahedron 65 (2009) 4367–4374
Table 3
Pd nanoparticles catalyzed Sonogashira coupling reaction with aryl halide and alkynea
R1
Pd nanoparticle, H2O
R1
Ar
Ar-X
+
K2CO3
Entry
Aryl iodide
O2N
Alkyne
Product
Time (h)
2c
% Yieldb
95
I
I
I
O2N
1
2
3
OH
3.5c
2c
95
92
OH
O2N
O2N
O2N
O2N
CH3
OH
CH3
OH
5d
94
88
90
H3CO
H3CO
H3CO
I
I
I
4
H3CO
H3CO
5d
OH
OH
5
6
CH3
OH
CH3
OH
3.5d
H3CO
O2N
3.5d
90
OH
OH
O2N
I
7
C2H5
C2H5
a
Aryl bromide (1 mmol), alkyne (1.2 mmol), K2CO3 (2 mmol), water (4 mL), Pd nanoparticle in water (0.01 equiv with PEG 6000 1.0 equiv).
Isolated yield after purification by flash column chromatography (eluent: petroleum ether or ethyl acetate/petroleum ether).
Reaction temperature is 55 ꢀC.
Reaction temperature is 65 ꢀC.
b
c
d
synthesis of numerous natural products including enediyne anti-
increase in the quantity of catalyst to match the efficiency ach-
ieved with iodoarenes. With our catalytic system, we were able
to obtain biaryls even from moderately activated bromo sub-
strates and phenyltributylstannane in aqueous medium at 80 ꢀC
with K2CO3 as base. There was no need for careful exclusion of air
(Table 4).
biotics.31 Although copper(I) has been initially used as co-catalyst
with an amine as solvent as well as base, a few copper-free pro-
cedures were subsequently developed32 but they usually required
ultrasound or microwave activation.
The only report for Sonogashira reaction carried out in water
alone33 prescribes phosphine ligands for palladium as catalyst and
use of Cu(I).
Our catalytic system is a unique and operationally simple
procedure that is conducted in pure water without Cu(I) salt,
phosphine or amine ligand for palladium and any precaution to
exclude air. No surfactant or organic co-solvent was required. High
yields were obtained at 55–65 ꢀC for iodoarenes (Table 3). Since
no copper salt was used, the undesired formation of oxidative
homocoupling product, a diyne, was also avoided. Although the
reaction proceeded well with aryl iodides, it was a disappoint-
ment that no coupling product was formed with activated bro-
mides like 4-bromoacetophenone even at elevated temperature
under a wide range of conditions varying the solvent and the base
(Table 3).
4. Conclusion
The generation and stabilization of catalytically active nano-
particles in water have several important advantages over both
traditional homogeneous and supported transition-metal catalysts
in terms of lower cost, absence of expensive ligands and organic
solvents. It combines high activity of the homogeneous system
with potential of recovery and recycling as practiced with het-
erogeneous catalysts. Here, PEG act as stabilizer, which absorb to
the particle surface, control particle size, and prevent agglomer-
ation. Water is an excellent solvent for this PEG capped nano-
particles in catalytic system. Possibly the polar capping agent
forms a more open structure in water, so that reactants could
easily get into contact with the metal surface. This is a favorable
situation for catalysis since strong encapsulation could lead to loss
of catalytic activity.
In conclusion, we have successfully illustrated that PEG stabi-
lized Pd nanoparticles (obtained from reaction of a Fischer carbene
complex of tungsten with K2PdCl4 at room temperature) have
a narrow size distribution and the size can be controlled varying the
PEG concentration in water. Those nanoparticles displayed high
catalytic activities toward Suzuki, Heck, Sonogashira, and Stille
reactions in water alone as solvent under mild condition. No care to
exclude air was necessary. We are currently looking forward to
utilize this catalytic system for biological applications in water. We
also plan to investigate synthesis and utility of chiral PEG scaffold in
3.4. Stille reaction
In this coupling reaction the organometallic coupling partner is
an organostannane that is air and moisture stable, which reacts
with aryl halides.34
In majority of instances, Stille reaction with bromo or
iodoarenes has been performed in aqueous solvent using
RSnCl3.35 A few articles that report on Stille reactions catalyzed
by Pd nanoparticles, describe the use of quaternary ammonium
salts as stabilizer and solvent36,16e or ionic liquid as solvent for Pd
nanoparticles generated in situ.37 Crook et al. used dendrimer
bound Pd nanoparticles in water as catalyst at room temperature
for this reaction;16e the bromoarenes required about 10-fold

S. Sawoo et al. / Tetrahedron 65 (2009) 4367–4374
4373
Table 4
Media; John Wiley & Sons: New York, NY, 2007; (d) Li, C. J. In Organic Synthesis
in Water; Lindstrom, U. M., Ed.; Blackwell: New York, NY, 2007.
Pd nanoparticles catalyzed Stille coupling reaction with aryl halide and
phenyltributylstannanea
2. (a) Cornils, B. J. Mol. Catal. A: Chem. 1999, 143, 1; (b) Genet, J. P.; Savignac, M.
J. Organomet. Chem. 1999, 576, 305; (c) Li, C.-J. Acc. Chem. Res. 2002, 35, 533; (d)
Cornils, B.; Venkatraman, S.; Huang, T.; Li, C.-J. Adv. Synth. Catal. 2002, 344, 399;
(e) Li, C.-J. In Aqueous-Phase Organometallic Catalysis: Concepts and Applications;
Herrmann, W. A., Cornils, B., Eds.; Wiley-VCH: Weinheim, New York, NY, 1998.
3. (a) Metal-Catalyzed Cross-Coupling Reactions; Diederich, F., Stang, P. J., Eds.;
Wiley-VCH: Weinheim, 1998; (b) Metal-Catalyzed Cross-Coupling Reactions; de
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Ar
SnBu3
Pd nanoparticle, H2O
K2CO3, 80 °C
Ar-X
+
Entry
1
Substrate
Product
Time (h) % Yieldb
2
2
95
98
O2N
Br
Br
O2N
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and the references therein.
2
O2N
O2N
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Br
CHO
3
4
2
2
95
95
CHO
Br
OHC
OHC
5
6
7
2
2
3
95
90
88
H3COC
Br H3COC
Br
H3C
Br
Br
H3C
8
9
3
3
3
95
92
98
H3C
H3C
H3CO
H3CO
Br
Br
10
H3CO
H3CO
a
Aryl bromide (1 mmol), phenyltributylstannane (1.2 mmol), K2CO3 (2 mmol),
water (4 mL), Pd nanoparticle in water (0.02 equiv with PEG 6000 1.0 equiv). All
reactions are performed at 80 ꢀC.
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Fujihara, H. J. Am. Chem. Soc. 2003, 125, 15742.
b
Isolated yield after purification by flash column chromatography (eluent:
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3885.
petroleum ether or ether/petroleum ether).
asymmetric synthesis involving Pd nanoparticle-mediated cou-
pling reactions.
Acknowledgements
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We thank CSIR, India, and Syngene International Ltd., Bangalore,
India, for financial support. S.S, D.S, and P.D. are thankful to CSIR,
India, for Research Fellowships. Mr. Sadhucharan Mallick is thanked
for assistance with some preliminary experiments.
Supplementary data
Supplementary data (contains copies of 1H and 13C NMR spectra
of all products listed in the tables) associated with this article
provided as a separate file. Supplementary data associated with this
article can be found in the online version, at doi:10.1016/
j.tet.2009.03.062.
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