Suzuki-Miyaura cross-coupling of arenediazonium salts catalyzed by alginate/gellan-stabilized palladium nanoparticles under aerobic conditions in water

Article abstract of DOI:10.1039/c2gc15679b

The use of palladium nanoparticles stabilized by natural beads made of an alginate/gellan mixture in the Suzuki-Miyaura cross-coupling reaction of arenediazonium tetrafluoroborates with potassium aryltrifluoroborates (1:1 molar ratio) with loading as low as 0.01-0.002 mol% under aerobic, phosphine-, and base-free conditions in water is described. The catalyst system can be reused several times without significant loss of activity.

Full text of DOI:10.1039/c2gc15679b

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COMMUNICATION
Suzuki-Miyaura cross-coupling of arenediazonium salts catalyzed by
alginate/gellan-stabilized palladium nanoparticles under aerobic conditions
in water†
Sandro Cacchi,*a Eugenio Caponetti,b,c Maria Antonietta Casadei,a Andrea Di Giulio,d Giancarlo Fabrizi,a
Giovanni Forte,e Antonella Goggiamani,a Sandra Moreno,d Patrizia Paolicelli,a Francesco Petrucci,e
Alessandro Prastaroa and Maria Luisa Saladinob
Received 9th June 2011, Accepted 21st November 2011
DOI: 10.1039/c2gc15679b
The use of palladium nanoparticles stabilized by nat-
ural beads made of an alginate/gellan mixture in the
Suzuki-Miyaura cross-coupling reaction of arenediazo-
nium tetrafluoroborates with potassium aryltrifluorobo-
rates (1 : 1 molar ratio) with loading as low as 0.01–0.002
mol% under aerobic, phosphine-, and base-free conditions
in water is described. The catalyst system can be reused
several times without significant loss of activity.
could not be recycled).4b These studies are in line with the current
trend of the modern sustainable chemistry, which requires to
develop new processes that minimize pollution in chemical
synthesis. In this context, heterogeneous catalysis is on the rise
because of its potential in reducing contamination of the isolated
products as well as in facilitating the removal, recovery, and
reutilization of transition metals.5 Particularly, biodegradable
natural polymers are attracting growing interest as substitutes
for classical inorganic and petrochemical-based supports for
environmentally friendly catalysts. Among them, widely diffused
polysaccharides represent an attractive and promising mate-
rial. Palladium/polysaccharides such as Pd/arabinogalactan,6
Pd/chitosan,7 and Pd/starch8 have been prepared. Recently,
a heterogeneous catalyst based on palladium chelated in the
framework of alginate biopolymer (a polymer of mannuronic
and guluronic acids) has been shown to be active in the Suzuki-
Miyaura cross-coupling reaction of iodobenzene or neutral and
electron-poor aryl bromides with phenylboronic acid (DMF,
Since the pioneering studies reported by Matsuda et al. in
1977,1 arenediazonium salts have emerged as an attractive
alternative to aryl halides or triflates. This is due to their higher
reactivity at room temperature or slightly higher temperature,
their availability from anilines, considerably cheaper than most
of the corresponding aryl halides or triflates, the use of aqueous
conditions, and the absence of added bases and phopshine
ligands in several applications. They have been used in a variety
of palladium-catalyzed reactions2 including the Suzuki-Miyaura
cross-coupling,3 one of the most convenient and powerful tools
in the arsenal of the practising organic chemist for the formation
of carbon-carbon bonds.
◦
K2CO3, 70 C).9 High to excellent conversions and excellent
selectivity was observed with the substrates investigated. The
catalyst, tested for the reaction of bromobenzene, could be used
three times. However, a decrease of the conversion from 95 to
70% was observed.
Recently, Suzuki-Miyaura cross-couplings of arenediazonium
salts with arylboronic acids have also been performed under
heterogeneous conditions.4 Best results have been obtained using
Herein, we report that palladium nanoparticles stabilized by
an alginate/gellan mixture (Fig. 1) can be successfully used in
the Suzuki-Miyaura cross-coupling reaction of arenediazonium
tetrafluoroborates with potassium aryltrifluoroborates with a
loading as low as 0.01–0.002 mol% in water. Potassium aryltriflu-
oroborates have been selected as coupling partners because they
are known to circumvent many of the drawbacks associated with
the use of arylboronic acids such as the tendency of the latter
to give protodeborination10 or homocoupling in the Suzuki-
Miyaura process11 and to form trimeric anhydrides (boroxines),
which creates difficulties in their purification and some structural
ambiguity.12
◦
0.1–0.9 mol% Pd/C in MeOH at 25 C (the catalyst, however,
aDipartimento di Chimica e Tecnologie del Farmaco, Sapienza,
Universita` di Roma, P.le A. Moro 5, 00185, Rome, Italy.
E-mail: sandro.cacchi@uniroma1.it; Fax: +39 (06) 4991-2780; Tel: +39
(06) 4991-2795
bDipartimento di Chimica “S. Cannizzaro”, Universita` degli Studi di
Palermo, Parco D’Orleans II - Viale delle Scienze pad.17, 90128,
Palermo, Italy
cCentro Grandi Apparecchiature – UniNetLab, Universita` degli Studi di
Palermo, Via F. Marini 14, 90128, Palermo, Italy
dDipartimenti di Biologia e di Biologia Ambientale - LIME, Viale
Marconi 446, 00146, Rome, Italy
Palladium nanoparticles stabilized by alginate (Pdnp/A), pre-
pared as described in literature,9 were initially tested when the
study of the reaction of 4-acetyldiazobenzene tetrafluoroborate
1a and potassium 4-methoxyphenyltrifluoroborate 2a as the
eIstituto Superiore di Sanita`, Viale Regina Elena 299, 00161, Rome, Italy
† Electronic supplementary information (ESI) available. See DOI:
10.1039/c2gc15679b
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Table 1 Optimization studiesa
Fig. 1 Chemical structure of alginate (A) and gellan (G).
Entry
Pd-polysaccharide
Solvent
Yield % of 3ab
model system began. Reactions were performed using 1a and
2a in a 1 : 1 molar ratio and Pdnp/A (0.01 mol% palladium
loading) in water at 40 ◦C for 24 h under aerobic conditions
in the absence of bases. Under these conditions, 3a was isolated
in a satisfactory 70% yield (Table 1, entry 1). Unfortunately, after
the first run, the reused catalyst showed a significant deactivation
leading to a modest yield of the desired cross-coupling product.
Compound 3a was isolated in 60% yield. Most probably, the
loss of activity is due to the leaching of palladium, in turn
dependent on the instability of the alginate scaffold under the
reaction conditions (shrinking of beads is clearly visible). Worse
results were obtained switching to palladium nanoparticles
stabilized by gellan, a natural polymer of glucose, rhamnose,
and glucuronic acid. Using this catalyst system (Pdnp/G; 0.01
mol% palladium loading), prepared in the same manner,9 the
cross-coupling product 3a was formed only in trace amounts
(Table 1, entry 2). The reasons of this lack of activity are unclear
at the moment. Interestingly, 3a was isolated in 62% yield when
the same reaction was carried out in MeCN.
1
2
3
4
5
6
7
8
9
Pdnp/A
H2O
H2O
H2O
MeOH
EtOH
H2O/EtOH (50/50)
MeCN
DMF
H2O/MeCN (95/5)
70
traces
90
—
—
85
70
63
92
Pdnp/G
Pdnp/A-G
Pdnp/A-G
Pdnp/A-G
Pdnp/A-G
Pdnp/A-G
Pdnp/A-G
Pdnp/A-G
a Reactions were carried out using 1 mmol of 1a and 1 mmol of 2a in
2 mL of solvent at 40 ◦C in the presence of Pdnp/polysaccharide (14 mg;
0.01 mol% palladium loading) for 24 h. b Yields are given for isolated
products.
Table 2 Recycling studies on the reaction of 4-acetyldiazobenzene
tetrafluoroborate 1a with potassium 4-methoxyphenyltrifluoroborate 2a
using Pdnp/A-Ga
Entry
Pd loading
Yield % of 3ab
TON
1
2
0.01 mol (%)
0.002 mol (%)
90, 85, 87, 83, 80, 84, 87, 88
85, 82, 80, 78, 61
68400
193000
Searching further for an efficient and reusable catalyst system
based on a polysaccharide scaffold and with the idea of
taking advantage of the synergic interactions described in the
literature when mixing different biopolymers,13 we decided to
investigate the activity of palladium nanoparticles stabilized
by an alginate/gellan mixture (Pdnp/A-G). To our delight, this
catalyst system (0.01 mol% palladium loading) could afford
the desired coupling product 3a in 90% yield under the same
conditions (Table 1, entry 3). More importantly, it could be
reused several times without significant loss of activity (Table
2, entry 1). The cumulated turnover number‡ (TON) over
eight runs is 68 400. The recovery of the supported palladium
involves filtration and washing with methanol in the presence
of air, without any particular precaution. Further recycling
studies were performed using lower palladium loading. With
a palladium loading down to 0.002 mol%, the cumulated turn-
over number over five runs is 193 000 (Table 2, entry 2).
a Reactions were carried out at 40 ◦C under aerobic conditions in 2 mL of
water using 1 mmol of 1a and 1 mmol of 2a in the presence of Pdnp/A-G
for 24 h. b Yields are given for isolated products.
Scheme 1 Preparation of Pdnp/A-G.
Palladium nanoparticles stabilized by alginate/gellan beads
(Pdnp/A-G; 0.00141% palladium) were prepared dropping an
alginate/gellan (50 : 50) solution into a CaCl2 solution. Hydrogel
beads were soaked for 48 h in a Na2PdCl4 solution and
then dehydrated in a series of successive ethanol-water baths
of increasing alcohol concentration. Reduction of palladium
occurs during the dehydratation step with ethanol (Scheme 1,
Fig. 2 and 3).
When observed under a stereomicroscope, hydrogel beads
generally show a subspherical shape and a diameter of 1–3 mm
(Fig. 2a). SEM analysis, performed prior to catalysis (Fig. 2b)
demonstrate a homogeneously smooth surface of beads, which,
at higher magnification, displays aggregated nanoparticles (Fig.
2c). FIB/SEM cross sections of the alginate/gellan beads,
performed through the ion beam milling process (Fig. 2d),
show several nanoparticles even under the superficial layer (Fig.
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Fig. 3 TEM image and particle size distribution of Pdnp/A-G (0.01
mol% palladium loading) (particle size 3.4 1.4 nm). (b) TEM image
and particle size distribution of Pdnp/A-G recovered after 8 runs (particle
size 3.6 1.7 nm). In these calculations only the isolated particles have
been taken into account.
Table 3 Reaction of arenediazonium tetrafluoroborates 1 with potas-
sium aryltrifluoroborates 2 catalyzed by Pdnp/A–Ga
Fig. 2 (a) Stereomicrograph of hydrogel beads (Pdnp/A-G; 0.01 mol%
palladium loading) showing homogeneous morphology. (b–f) FIB/SEM
images of alginate/gellan beads, prior to catalysis. (b) External view of
a representative bead showing regular shape and smooth surface. (c)
Close-up of the external surface with aggregated nanoparticles. (d) View
of the site of ion-beam milling process. (e, f) Details of cross sections,
showing both outer and inner bead composition. Note the spongy
appearance and the highly porous scaffold containing electron dense
nanoparticles (whitish structures).
Entry Ar1 1
Ar2 2
Time (h) Yield % of 3b
1
2
3
4
5
6
7
8
4-MeCOC6H4
4-MeOC6H4 24
4-ClC6H4 48
4-CF3C6H4 24
90
77
86
80
66
86
78
77
86
88
85
83
87
77
67
73c
90
40
51
traces
3a
3b
3c
3d
3e
3f
2-BrC6H4
Ph
48
48
2e,f). This powerful procedure, avoiding artifact generation also
allows study of the inner structure of hydrogel beads, which
appear to contain a highly porous scaffold (Fig. 2d–f).
Transmission Electron Microscopy (TEM) measurements
indicate that the catalyst system before use contains palladium
spheroidal nanoparticles, whose average size is 3.4 1.4 nm (Fig.
3a). The material recovered after 8 runs showed nanoparticles
of about 3.6 1.7 nm in diameter (Fig. 3b).
For the sake of comparison, the use of other solvents in
the Suzuki-Miyaura cross-coupling was explored. No coupling
product was formed in MeOH or EtOH (Table 1, entries 4
and 5) and MeCN or DMF led to the isolation of 3a in lower
yields (Table 1, entries 7 and 8). Furthermore, solubilization of
the microbeads was observed in DMF. Only with H2O/MeOH
and H2O/MeCN mixtures did the reaction afford 3a in yields
similar to those obtained in water (Table 1, entries 6 and 9).
However, water is particularly attractive as reaction medium. It is
inexpensive, nontoxic, and nonflammable, and is easily separated
from organic products.14 Therefore, reactions were conducted in
water when we next explored the efficiency of Pdnp/A-G with
other arenediazonium tetrafluoroborates and potassium aryltri-
fluoroborates. As shown in Table 3, good to high yields were
obtained with arenediazonium tetrafluoroborates and potas-
4-MeOC6H4
4-MeOC6H4 10
4-ClC6H4 24
4-CF3C6H4 24
Ph 48
4-MeOC6H4 24
4-ClC6H4 24
3g
3h
3i
9
10
11
12
13
14
15
16
17
18
19
20
4-CNC6H4
Ph
4-ClC6H4
4-CF3C6H4 24
2-Me, 4-MeOC6H3 4-CF3C6H4 48
4-ClC6H4
4-ClC6H4
2-ClC6H4
2-ClC6H4
3j
3k
3l
4-CF3C6H4 24
4-MeOC6H4 48
3i
24
3m
3n
3o
3p
3q
3r
—
4-BrC6H4
2-BrC6H4
4-BrC6H4
2-BrC6H4
24
36
36
48
a Reactions were carried out in 2 mL of H2O using 1 mmol of 1 and 1
mmol of 2 at 40 ◦C in the presence of Pdnp/A–G (0.01 mol% palladium
loading). b Yields are given for isolated products. c The homocoupling
product derived from potassium aryl trifluoroborate was isolated in
23%.
sium aryltrifluoroborates containing both electron-donating
and electron-withdrawing substituents. ortho substituents are
tolerated in the arenediazonium tetrafluoroborate (Table 3, entry
16 and 19) or the potassium aryltrifluoroborate (Table 3, entry 4
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stabilized by alginate/gellan aerogel beads can be successfully
used in the Suzuki-Miyaura cross-coupling reaction of arenedia-
zonium tetrafluoroborates with potassium aryltrifluoroborates
under aerobic, phosphine-, and base-free conditions in water
with loading as low as 0.01–0.002 mol%. The catalyst system
can be reused several times without significant loss of activity.
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Acknowledgements
Work carried out in the framework of the National Projects
funded by Ministero dell’Universita` e della Ricerca Scientifica
“Stereoselezione in Sintesi Organica. Metodologie ed Appli-
cazioni”.
Notes and references
‡ Cumulated turnover number: cumulated overall yields divided by their
catalyst loading.
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320 | Green Chem., 2012, 14, 317–320
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The Royal Society of Chemistry 2012
©