Remarkably facile Heck and Suzuki reactions in water using a simple cationic surfactant and ligand-free palladium catalysts

Article abstract of DOI:10.1016/j.tetlet.2005.03.118

A facile surfactant mediated Heck and Suzuki coupling procedure in water has been developed using ligand-free Pd-catalysts. The procedure which involves nanometric palladium colloids, is operationally simple, environmentally benign and synthetically as efficient as conventional procedures using organic solvents.

Full text of DOI:10.1016/j.tetlet.2005.03.118

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 3557–3560
Remarkably facile Heck and Suzuki reactions in water using a
simple cationic surfactant and ligand-free palladium catalysts
Santanu Bhattacharya,a,* Aasheesh Srivastavaa and Saumitra Senguptab,*
aDepartment of Organic Chemistry, Indian Institute of Science, Bangalore 560 012, India
bDepartment of Chemistry, Jadavpur University, Kolkata 700 032, India
Received 10 January 2005; revised 4 March 2005; accepted 11 March 2005
Available online 6 April 2005
Abstract—A facile surfactant mediated Heck and Suzuki coupling procedure in water has been developed using ligand-free Pd-
catalysts. The procedure which involves nanometric palladium colloids, is operationally simple, environmentally benign and
synthetically as efficient as conventional procedures using organic solvents.
Ó 2005 Published by Elsevier Ltd.
Palladium catalyzed arylation of olefins, the Heck reac-
1
cles, pincers and NHC ligated catalysts and are thought
to be responsible for their superior reactivity.5
tion, is a powerfultoolin organic synthesis.
It has
found widespread use in the synthesis of naturalprod-
ucts, polymers, dendrimers and various conjugated
architectures of materials science interest. The Heck
reaction also holds much promise in many industrial
processes, especially in the synthesis of fine chemicals
However, despite all these developments on catalyst
design, polar aprotic solvents (CH3CN, DMF, DMA,
NMP) still remain the preferred medium for carrying
out Heck reactions. Driven by environmentalconcerns,
recently, much effort has been directed towards using
water as solvent for organic and organometallic reac-
tions.6 Although there are some reports on the Heck
reaction in mixed aqueous organic solvents in the pres-
ence of PTCs or Pd-catalysts having water soluble phos-
phine ligands,6d studies directed towards the Heck
reaction in water alone are less common.7 The latter
are mostly confined to reactions with water soluble sub-
strates using specialadditives and hence, al ck a general
synthetic appeal. We now report a facile surfactant-
mediated Heck reaction in water catalyzed
by ligand-free palladium catalysts which, while being
environmentally benign, rival conventional Heck
reaction procedures in synthetic efficacy and opera-
tionalsimpilcity.
2
and active pharmaceuticalintermediates. In view of
these, much attention has been paid in recent years to
develop milder and operationally simpler procedures
for the Heck reaction. Some important developments in-
clude the use of ligand-free Pd-catalysts in combination
with tetraalkylammonium salts (Jeffery conditions), the
use of palladacycles, pincer and supported palladium
catalysts and more recently, the bulky electron rich
phosphine and the N-heterocyclic carbene (NHC)
ligands for palladium.3 Additives such as tetra-
butylammonium bromide have led to remarkable rate
enhancements in the Heck reactions of aryliodides in
organic solvents3a whereas by using the pincer catalysts
or electron rich phosphine or NHC ligands, the Heck
reaction can now be carried out with the cheap, but
otherwise unreactive, chloroarenes.3f–j Recently, Reetz
et al. have shown that Pd(OAc)2 in combination with
tetrabutylammonium bromide gives rise to nanometric
Pd-colloids which are the actual catalysts under the
so-called Jeffery conditions.4 Pd-nanoparticles were also
shown to be involved in Heck reactions with palladacy-
As a model, the Heck reaction of PhI with methyl acry-
late (MA) in water (1% PdCl2, NaHCO3) at 80 °C was
examined under a variety of conditions (Table 1). In
the absence of any surfactant, only 30% conversion
was obtained after 2 h (entry 1). Addition of cetyltrime-
thylammonium bromide (CTAB) led to a gradual in-
crease in the conversion rate reaching a maximum of
95% after 2 h when 50 mol% of CTAB was used (entries
2–4). On the other hand, the use of SDS, Brij 56 or
*
Corresponding authors. Fax: +91 33 24146266; e-mailaddresses:
sb@orgchem.iisc.ernet.in; jusaumitra@yahoo.co.uk
0040-4039/$ - see front matter Ó 2005 Published by Elsevier Ltd.
doi:10.1016/j.tetlet.2005.03.118

3558
S. Bhattacharya et al. / Tetrahedron Letters 46 (2005) 3557–3560
Table 1. Effect of additives on the Heck reaction of PhI in water
the formation of Pd-nanoparticles having an average
diameter of 5 nm (Fig. 1b).
1% PdCl2, NaHCO3,
I
CO2Me
H2O, 80 oC, 2 h
"Additive"
CO2Me
+
In a controlexperiment, the reaction components with-
out CTAB were heated in water at 80 °C for 2 h which
gave a nearly clear solution with some Pd-black form-
ation (30% conversion, cf. entry 1, Table 1). Addition of
CTAB (50 mol%) immediately led to the formation of a
brown black emulsion attesting to the stabilizing role
of CTAB towards Pd-nanocluster formation. Further
heating at 80 °C for 2 h produced methylcinnamate in
67% yield. Thus, CTAB performs a dual role in these
aqueous Heck reactions. First, it provides a strong
miceller effect and second, it acts as a stabilizer for Pd-
nanocluster formation.9 Perhaps, SDS and Brij 56 are
not capable of stabilizing Pd-nanoclusters under the
above conditions and Bu4NBr, while being able to stabi-
lize Pd-nanoparticles,4c,9 cannot provide a miceller effect
to the extent CTAB is capable of, thus explaining the
decisive advantage of using CTAB over the other addi-
tives in these aqueous Heck reactions. Organic reactants
are usually partitioned into micelles by hydrophobic
interactions. CTAB with its C16-hydrocarbon chain pro-
vides a strong hydrophobic force that can solubilize the
organic reactants much more efficiently than Bu4NBr
can do with its shorter C4-chains. The rate enhancing
micellar effect may be due to the increased localization
of the reactants in micelles together with the typical
physicochemicalproperties of its environment which
are significantly different from those of the bulk
solvents.10
Entry
Additive (mol%)
Yield (%)
1
2
3
4
5
6
7
CTAB (0)
CTAB (7)
CTAB (25)
CTAB (50)
SDS (50)
30
50
80
95
40
30
50
Brij 56 (50)
Bu4NBr (50)
Bu4NBr (50 mol% each) gave only marginalincreases in
conversion rates over those obtained in water alone (en-
tries 5–7). It appears from these results that only cat-
ionic surfactants are capable of enhancing the rate of
the Heck reaction through miceller effects. That CTAB
is more efficient than Bu4NBr is also noteworthy since
the latter has been shown to greatly enhance the rate
3a
of Heck reactions in conventionalorganic sovl ents.
In order to understand the superiority of CTAB over
other surfactant types in this aqueous Heck reaction,
further physicalstudies were undertaken. The UV–Vis
spectra of PdCl2 in water and that of a mixture of PdCl2
and CTAB in water at room temperature are shown in
Figure 1a. The marked difference in their spectra indi-
cates a strong interaction between PdCl2 and CTAB in
water. Addition of MA to this mixture and heating to
80 °C led to a color change from golden yellow to choc-
olate brown. The fine structures in the spectra disap-
peared and a new structureless band with increased
intensity in the visible region appeared, indicating that
Pd-nanoparticles had been formed.8 Pd-nanoparticles
prepared authentically via EtOH reduction8c of PdCl2
showed an identicalstructureelss UV–Vis band ( Fig.
1a). Notably, addition of PhI to the mixture of PdCl2
and CTAB in water and heating to 80 °C did not lead
to any color change or any difference in the UV–Vis
spectra (not shown). These results clearly showed that
MA acted as the reducing agent for PdCl2 to produce
the CTAB-stabilized Pd-nanoparticles. A transmission
electron microscopic (TEM) image clearly indicated
The synthetic efficacy of this surfactant mediated aque-
ous Heck reaction was then studied with a number of
different aryl halides and olefins (Scheme 1) and the re-
sults shown in Table 2. Heck reaction of iodobenzene
(1a) with MA, styrene and acrylonitrile gave good yields
of the corresponding products 2a–c within 2–3 h at
80 °C (entries 1–3). Pd(OAc)2 can also be used as a cat-
alyst in these reactions with equal efficacy. A lower cat-
alytic loading (0.1% PdCl2) can be used with no loss in
product yield (entry 2). As expected, iodoarenes with
an ortho-substituent (1b) or an electron donating substi-
tuent (1c) considerably lowered the reaction rate. In
these cases, a full equivalent of CTAB, a higher temper-
ature (100 °C) and prolonged reaction times were
required to obtain good yields of the products 2d–f
(entries 4–6). NaOAc was found to be a superior base
over NaHCO3 for these latter reactions. Nevertheless,
the reaction times and product yields are comparable,
if not better, than those reported in organic solvents un-
der conventionalHeck reaction conditions. Less reactive
bromoarenes such as 1d required an even higher reac-
X
Y
1% PdCl2, NaHCO3 or NaOAc
Y
R
R
+
0.5-1.0 equiv. CTAB, H2O
80-130oC
X = I , Br
Y = CO2Me, CO2Et, CN, Ph
Figure 1. (a) UV–Vis changes during Pd-nanoparticle formation in
water with MA and CTAB; (b) TEM image of the Pd-nanoparticles
formed.
Scheme 1.

S. Bhattacharya et al. / Tetrahedron Letters 46 (2005) 3557–3560
Table 2. CTAB-mediated Heck Reaction in watera
3559
Entry
ArX
Olefin
T (°C/h)
Product
Yield (%)
CO2Me
I
1
MA
80/2
95
89
2a
1a
2
3
4
1a
S
80/3
2b
CN
1a
AN
EA
80/2
83
2c
I
CO2Et
2d
100/13
87b
Me
Me
1b
5
1b
S
100/20
80b
Me
2e
I
CO2Et
6
7
EA
S
100/10
130/12
82b
80b
MeO
MeO
2f
1c
Br
MeC(O)
MeC(O)
1d
2g
a 1 mmolArX, 2 mmoloelfin, 0.5 mmolCTAB, 2 mmolNaHCO
and 0.01 mmolof PdCl in water (3 mL).
2
3
b 1 equiv CTAB and 2 equiv NaOAc were used. MA = methyl acrylate, S = styrene, AN = acrylonitrile, EA = ethyl acrylate.
tion temperature (130 °C), the corresponding Heck
product 2g being obtained in 80% yield after 12 h (entry
7). It may be noted that even in traditionalorganic
solvents, the Heck reactions of bromoarenes usually
require higher reaction temperatures (ca. 130–
140 °C)4d,5c and hence, our aqueous Heck reaction pro-
tocolcompares favorabyl with conventionalconditions.
Notably, in contrast to the findings of Reetz and de
Vries,4d lowering of the Pd-loading (0.1% PdCl2 or
Pd(OAc)2) did not improve the Heck reaction profile
of the bromoarene 1d.
ligand-free Pd-catalysts.14 The procedure is operation-
ally simple, environmentally benign and is comparable,
if not better, in synthetic efficacy to conventionalPd-cat-
alyzed coupling protocols in organic solvents. The use of
an aqueous reaction medium and colloidal Pd-catalysts
promise further opportunities in batch processing and
catalyst recycling.15
Acknowledgements
A.S. acknowledges CSIR, New Delhi for a Senior
Research Fellowship. S.S. thanks the Department of
Organic Chemistry, Indian Institute of Science,
Bangalore for an OC-ICOS Visiting Fellowship.
The Suzuki cross coupling reaction is a powerful Pd-cat-
alyzed regime for the synthesis of unsymmetrical biaryls
from arylboronic acids and haloarenes. 11 Pd-nanoparti-
cle catalyzed Suzuki coupling in organic solvents has
also been described.4a,d,12 However, there are no reports
on Suzuki coupling reactions with ligand-free Pd-cata-
lysts in water alone, except for one example that
involved high reaction temperatures (>150 °C) under
microwave irradiation.13 The above success with the
Heck reaction in water prompted us to explore such a
possibility. In the event, PhB(OH)2 3 was smoothly cou-
pled with haloarenes 1c,d in water in the presence of
CTAB and 1% Pd(OAc)2 at 100 °C to give the biaryls
4a,b in excellent yields (Scheme 2). The reactions are
remarkably fast (1–3 h) with high turnover frequencies.
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Scheme 2.

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screw cap was charged with the arylhiadle
(1.0 mmol), olefin (2.0 mmol), CTAB (0.5 mmol for 1a;
1.0 mmolfor 1b–d), PdCl2 (0.01 mmol), NaHCO3
1a–d
(2.0 mmolfor 1a) or NaOAc (2.0 mmolfor 1b–d) in water
(3 mL). The mixture was then heated with vigorous
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