Homocoupling of arylboronic acids and potassium aryltrifluoroborates catalyzed by protein-stabilized palladium nanoparticles under air in water

Article abstract of DOI:10.1016/j.tetlet.2010.03.015

Palladium nanoparticles stabilized primarily within the protein cavity of a highly thermostable Dps protein (DNA binding protein from starved cells) from the thermophilic bacterium Thermosynechoccus elongatus provide an efficient catalyst for the homocoupling of boronic acids and potassium aryltrifluoroborates in water under aerobic phosphine-free conditions. Symmetrical biaryls have been isolated in good to excellent yields. Potassium aryltrifluoroborates give similar or better results than the corresponding arylboronic acids.

Full text of DOI:10.1016/j.tetlet.2010.03.015

Tetrahedron Letters 51 (2010) 2550–2552
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Homocoupling of arylboronic acids and potassium aryltrifluoroborates
catalyzed by protein-stabilized palladium nanoparticles under air in water
Alessandro Prastaro a, Pierpaolo Ceci c, Emilia Chiancone b,c, Alberto Boffi b,c, Giancarlo Fabrizi a,
Sandro Cacchi a,
*
a Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza, Università di Roma, P.le A. Moro 5, 00185 Rome, Italy
b Dipartimento di Scienze Biochimiche, Sapienza, Università di Roma, P.le A. Moro 5, 00185 Rome, Italy
c Istituto di Biologia e Patologia Molecolari CNR, P.le A. Moro 5, 00185 Rome, Italy
a r t i c l e i n f o
a b s t r a c t
Article history:
Palladium nanoparticles stabilized primarily within the protein cavity of a highly thermostable Dps protein
(DNA binding protein from starved cells) from the thermophilic bacterium Thermosynechoccus elongatus
provide an efficient catalyst for the homocoupling of boronic acids and potassium aryltrifluoroborates in
water under aerobic phosphine-free conditions. Symmetrical biaryls have been isolated in good to excellent
yields. Potassium aryltrifluoroborates give similar or better results than the corresponding arylboronic
acids.
Received 27 January 2010
Revised 25 February 2010
Accepted 5 March 2010
Available online 11 March 2010
Keywords:
Ó 2010 Elsevier Ltd. All rights reserved.
Arylboronic acids
Potassium aryltrifluoroborates
Palladium nanoparticles
Water
Proteins
The symmetrical biaryl motif is diffused among a variety of
products exhibiting interesting properties. For example, symmetri-
cal biaryl systems are present in Crisamicin A, a natural product
that is active against B16 murine melanoma cells, the herpes
simplex, and vesicular stomatitis viruses,1 in polymers showing
conductive properties,2 and in ligands used in catalysis.3 Because
of their non-toxic nature, stability, broad tolerance of functional
groups, and ability to couple sterically demanding substrates, aryl-
boronic acids represent one of the most reliable substrates for the
synthesis of this class of compounds via palladium-catalyzed
homocoupling reactions. Symmetrical biaryls have been prepared
from arylboronic acids with homogeneous4 and heterogeneous4j,5
palladium catalysts under base-,4j,l,5a phosphine-free,4i,l,5,6, and
ultrasound5b conditions. Usually, the reactions have been carried
out using Pd(II) salts in the presence of oxidants,4d–g,i–m,6a,b,7,8
required to restore the active Pd(II) catalyst from the Pd(0) species
generated from bis(aryl)palladium(II) intermediates. Examples of
are only two reports of reactions carried out in water.6a,9 One
requires
phase transfer catalyst6a and the other uses
a
a
Pd(OAc)2/p-benzoquinone system under anaerobic electro-oxida-
tive conditions.9 There are no reports of homocoupling of arylbo-
ronic acids in the presence of palladium nanoparticles in water.
Herein we show that the palladium nanoparticles (Pdnp) stabi-
lized primarily within the protein cavity of a highly thermostable
Dps protein (DNA binding protein from starved cells) from the
thermophilic bacterium Thermosynechoccus elongatus (Te-Dps)
provide an efficient catalyst for the synthesis of symmetrical biar-
yls from arylboronic acids in water under aerobic and phosphine-
free conditions (Scheme 1). The procedure was also extended to
the less explored9 homocoupling of potassium aryltrifluoroborates.
Te-Dps-stabilized palladium nanoparticles (Pdnp/Te-Dps) were
prepared as described previously10 by the exposure of K2PdCl4 to
Te-Dps at room temperature and reduction with NaBH4.
homocoupling reactions performed in the presence of Pd(0) species
4h
such as Pd(PPh3)4
or Pd/C5 and oxidants have also been
described. Organic solvents have been typically employed, but
the reactions have also been carried out in supercritical carbon
Ar B(OH)2
Pdnp/Te-Dps
Ar Ar
or
dioxide7 and using water as
a
cosolvent,4k,5a,6b,8,9 including
H2O, air
Ar BF3K
water/ionic liquid mixtures.8a To the best of our knowledge, there
1
2
* Corresponding author. Tel.: +39 06 4991 2795; fax: +39 06 4991 2780.
E-mail address: sandro.cacchi@uniroma1.it (S. Cacchi).
Scheme 1. Homocoupling of boronic acids and potassium aryltrifluoroborates
catalyzed by Te-Dps-stabilized palladium nanoparticles.
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.03.015

A. Prastaro et al. / Tetrahedron Letters 51 (2010) 2550–2552
2551
Table 1
Table 2
The influence of Tris buffer concentration on the homocoupling of 4-tolylboronic acid
Homocoupling of arylboronic acids and potassium aryltrifluoroborates catalyzed by
catalyzed by protein-stabilized palladium nanoparticles (Pdnp/Te-Dps)a
protein-stabilized palladium nanoparticles (Pdnp/Te-Dps)a
Entry
1
Arylboronic acid 1
Time (h)
24
Yield% of 2b
Pdnp /Te-Dps
buffer
Me
Me
Me
B(OH)2
Me
B(OH)2
1a
1b
91
H2O, 100 °C, air
24 h
Me
1a
2a
2
24
85
B(OH)2
Entry
Tris buffer concentration (M)
Yield% of 2ab
3
4
PhB(OH)2
1c
24
48
92
67
1
2
3
4
5
6
7
0.10
0.25
0.50
0.75
1.00
1.50
2.00
78
82
80
85
91
51
33
B(OH)2
1d
B(OH)2
5
6
1e
1f
48
48
65
73
a
Reactions were carried out at 100 °C, under air, using 0.25 mmol 4-tolylboronic
acid, in 2 mL of Tris–HCl buffer at pH 8.9 for 24 h in the presence of 0.05 mol % of
[Pd].
Me
F
B(OH)2
b
Yields refer to single runs and are given for isolated products.
7
8
Cl
B(OH)2
B(OH)2
1g
1h
1i
24
24
24
48
82
78
63
81
The catalytic properties of water-soluble Pdnp/Te-Dps were
evaluated initially in the homocoupling of 4-tolylboronic acid at
100 °C for 24 h using a palladium loading down to 0.05 mol % in
the presence of a 0.1 M Tris [tris(hydroxymethyl)aminomethane]–
HCl buffer at pH 8.9 in water under air. Under these conditions, the
product 2a was isolated in 78% yield. No evidence of homocoupling
product formation was obtained when the reaction was carried out
under an argon atmosphere. Thereafter the influence of buffer con-
centration on the reaction outcome under air was explored. As
shown in Table 1, the yield of the homocoupling product increases
with increasing concentration of Tris, reaching the best result by
using a 1 M Tris–HCl buffer (Table 1, entry 5). A further increase of
the buffer concentration produced lower yields.
Using oxygen gas can accelerate the rate of the homocoupling
reaction. Compound 2a was isolated in 89% yield after 10 h under
a balloon of oxygen. However, for practical reasons, the optimized
conditions under air were used11 when we next explored the scope
and generality of the process. As shown by the results listed in
Table 2, homocoupling products were isolated in good to excellent
yields with a variety of arylboronic acids. Potassium aryltrifluorob-
orates were also investigated. At least with the examples that we
have examined, they have been found to give similar or better
results than the corresponding arylboronic acids in a shorter reac-
tion time (Table 2, compare entries 9, 10, and 14 with entries 15,
16, and 17, respectively). The methodology tolerates several useful
functional groups such as phenol, ether, keto, chloro, and bromo
Br
9
MeCO
B(OH)2
B(OH)2
10
MeO
MeO
1j
11
12
1k
1l
48
48
87
73
B(OH)2
OMe
B(OH)2
OMe
Me
B(OH)2
13
1m
17
80
Me
14
15
16
17
18
19
1n
1p
1q
1o
1r
10
10
24
7
85
82
87
80
60c
70
F3C
B(OH)2
BF3K
BF3K
BF3K
BF3K
BF3K
MeCO
MeO
F3C
MeO2C
HO
24
24
substituents as well as
a single or two ortho substituents
(Table 2, entries 2, 5, 12, 13). The ester 1r, however, undergoes a
hydrolytic process and the corresponding homocoupling product
was isolated as a dicarboxylic acid derivative.
1s
a
Reactions were carried out at 100 °C, under air, using 0.25 mmol arylboronic
As to the mechanism, the fact that no homocouplìng product
was observed in the absence of air supports the notion that the
reaction proceeds through the intermediacy of peroxo complexes
generated in the reaction of dioxygen with Pd(0) species.4j,12
In conclusion, we have shown that the palladium nanoparticles
stabilized primarily within the cage of a Dps protein from a
thermophilic protein (Pdnp/Te-Dps) can be used successfully in
the homocoupling of arylboronic acids and potassium aryltrifluo-
roborates under aerobic phosphine-free conditions in water.
Homocoupling products were isolated in good to excellent yields
in the presence of electron-donating and electron-withdrawing
groups. Single and two ortho substituents are also tolerated. Potas-
sium aryltrifluoroborates gave similar or better results than the
corresponding arylboronic acids.
acid or potassium aryltrifluoroborate in 2 mL of 1 M Tris–HCl buffer at pH 8.9 in the
presence of 0.05 mol % of [Pd] and monitored by HPLC.
b
Yields refer to single runs and are given for isolated products.
Isolated as dicarboxylic acid derivative.
c
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