Aerobic ligand-free Suzuki coupling catalyzed by in situ-generated palladium nanoparticles in water

Article abstract of DOI:10.1016/j.tetlet.2008.12.063

A simple and efficient procedure for Suzuki coupling of aryl bromides/iodides with aryl- and alkylboronic acids catalyzed by in situ-generated palladium(0) nanoparticles in water without any ligand in open air to produce a variety of functionalized biaryls and alkyl-aryls has been developed. The boronic acids act here as the reducing agent for the formation of Pd nanoparticles. The reactions are remarkably fast (5 min) and high yielding. The catalyst is recyclable up to three runs without loss of efficiency.

Full text of DOI:10.1016/j.tetlet.2008.12.063

Tetrahedron Letters 50 (2009) 1003–1006
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Aerobic ligand-free Suzuki coupling catalyzed by in situ-generated
palladium nanoparticles in water
Debasree Saha, Kalicharan Chattopadhyay, Brindaban C. Ranu *
Department of Organic Chemistry, Indian Association for the Cultivation of Science, Jadavpur, Kolkata 700 032, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A simple and efficient procedure for Suzuki coupling of aryl bromides/iodides with aryl- and alkylboronic
acids catalyzed by in situ-generated palladium(0) nanoparticles in water without any ligand in open air
to produce a variety of functionalized biaryls and alkyl-aryls has been developed. The boronic acids act
here as the reducing agent for the formation of Pd nanoparticles. The reactions are remarkably fast
Received 19 September 2008
Revised 8 December 2008
Accepted 11 December 2008
Available online 24 December 2008
(5 min) and high yielding. The catalyst is recyclable up to three runs without loss of efficiency.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords:
Suzuki coupling
Palladium nanoparticles
Biaryl
Alkyl–aryl
Reaction in water
Since the first report of palladium-catalyzed Suzuki coupling of
aryl halides with arylboronic acids, this reaction has undergone a
catalyzed by in situ-generated Pd(0) nanoparticles in water with-
out a conventional ligand (Scheme 1).
1
tremendous growth, and is considered one of the most powerful
tools for the construction of an aryl–aryl bond, in particular for
the formation of biaryls, structural units found in natural products,
pharmaceuticals, and advanced materials.2 The catalysis by metal
nanoparticles is of considerable current interest as these semi-het-
erogeneous catalysts usually show enhanced catalytic efficiency
because of their better ability to transfer electrons and large sur-
To optimize the reaction conditions, a series of experiments
under varied conditions in terms of surfactants, base, reaction tem-
perature, and reaction time for a model coupling reaction of
4-bromoanisole and phenylboronic acid were carried out as illus-
trated in Table 1. It was found that the best results in terms of
yields and reaction time were obtained using sodium dodecyl
sulfate (SDS)/K
3 4 3 4
PO at 100 °C in water (Table 1, entry 5), K PO acts
3
8
face area-to-volume ratio. In addition, they also offer the general
here as a base as well as a stabilizer.
advantages of heterogeneous catalysts of easy recovery and recy-
clability. A variety of palladium nanoparticles-catalyzed Suzuki
We also found that a representative coupling of 4-bromoaceto-
phenone and phenylboronic acid in water at 100 °C furnished the
best yield (96%) compared to other organic solvents such as DMF,
toluene, and THF under identical conditions (Table 2).
Thus, in a general experimental procedure under optimized
conditions, arylboronic acid (1.2 mmol) was added to a stirred
solution of Na PdCl (2.5 mol %), K PO (1.5 mmol), and SDS
2 4 3 4
(0.5 mmol) in water followed by aryl bromide (1 mmol) at room
temperature in the open air. The reaction mixture was heated at
3
reactions, such as naphthidine di(radical cations)-stabilized palla-
dium nanoparticles in dioxane,4a in situ-generated palladium
4b
nanoparticles in PEG-400 without any ligand, dendrimer-stabi-
lized Pd nanoparticles in H
2
O/EtOH,4 and Pd nanoparticles sup-
c
4d
ported on polyaniline nanofibers in water, have been developed
4
among others. However, many of these procedures used expen-
sive and complex ligands or supports, and with a few exceptions,
most reactions involved hazardous organic solvents. Also several
of these reactions are sluggish requiring at least 24 h for comple-
tion. The use of an eco-friendly reaction medium, minimization
of steps, better yields, and faster reaction remained constant chal-
SDS , Na PdCl
1
2
2
4
1
R -R2
R -X
+
R -B(OH)
2
K PO , H O
3
4
2
lenges in the context of green chemistry.5,6 As a part of our pro-
gram to explore palladium nanoparticles for carbon–carbon bond
100 ºC
1
2
R = aryl , heteroaryl; R = aryl , alkyl
7
formation, we report here a one-pot Suzuki coupling reaction
X = I , Br
*
Corresponding author. Tel.: +91 3324734971; fax: +91 24732805.
E-mail address: ocbcr@iacs.res.in (B.C. Ranu).
Scheme 1.
0
040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.12.063

1
004
D. Saha et al. / Tetrahedron Letters 50 (2009) 1003–1006
Table 1
Table 3
Standardization of reaction conditions
Pd nanoparticles-catalyzed cross coupling of arylhalides and aryl or alkyl boronic
acids
Surfactant
Na PdCl ,SDS
Aq. Na PdCl
R2
2
4
2
4
R1
R1
R2
X + (HO) B
MeO
Br+
B(OH)2
OMe
2
Base
K PO H O
3
4
,
2
100
ºC
X = Br, I
Entry
Surfactant
Base
Temp (°C)
Time
Yield (%)
1
2
3
4
5
6
7
8
SDS
SDS
SDS
SDS
SDS
—
K
K
2
CO
PO
3
27
25
28
25
100
100
25
5 h
5 h
5 h
5 h
5 min
20 min
5 h
37
72
20
21
95
75
63
85
Entry
R1
R2
Time (min)
Yielda (%)
Ref.
3
4
*
1
H
H
H
H
H
H
H
3-CH
H
4-CH
H
H
3-CH
4-CHO
H
4-CHO
H
H
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
96
92
92
94
95
96
96
92
92
94
95
95
94
92
96
95
94
94
4c
4c
4d
4a
4f
9
4f
10
4f
14
12
13
4e
14
15
4f
KF
NaOAc
PO
2
3
4
5
6
7
8
9
10
11
2-OCH
3-OCH
4-OCH
4-OCH
4-CH
4-CH
4-F
4-Cl
4-Cl
4-Cl
3-CHO
2-CHO
2-COH
4-CN
3
3
3
3
K
3
4
K
K
K
3
PO
3
PO
3
PO
4
—
TBAB
4
3
3
4
100
5 min
3
3
Table 2
Standardization of solvent for Suzuki cross-coupling
3
12
Na PdCl , SDS
2
4
13
MeOC
Br+
B(OH)2
COMe
14
15
16
K PO , solvent
3
4
3
Entry
Solvent
Temp (°C)
Time (min)
Yield (%)
17
4-NO2
3-CF
3
3-CH3
H
16
17
*
18
1
2
3
4
DMF
Toluene
THF
100
100
100
100
5
5
5
5
52
52
30
96
Br
Br
19
3-CH
3
5
96
12
2
H O
2
0
1
4-CHO
5
90
18
1
00 °C (oil bath) for 5 min. Extraction with ethyl acetate and
purification (recrystallization/chromatography) provided the pure
product. All of these products are known compounds, and were
easily identified by comparison of their spectroscopic ( H NMR
and C NMR) data with those reported (see references in Table 3).
To confirm the formation of Pd nanoparticles and determine
their properties, an extract from the reaction of 4-bromoanisole
and phenylboronic acid in the presence of SDS (100 °C) after
5
8
2
4-HO
4-F
4-CH
3-CH
3-Cl
4-COCH
3
5
5
5
92
84
88
19
20
21
22
23
1
3
3
1
3
I
*
4
2
H
5
92
22
N
S
4-COCH
4-CHO
4-CN
2
2
5
6
H
10
88
23
min showed the formation of nanoparticles of the size of 6–
nm by a TEM (transmission electron microscope) image (Fig. 1)
Br
n
3
Bu–B(OH)
2
5
15
25
86
75
70
24
25
25
and EDS (energy dispersive X-ray spectroscopy) confirmed the
presence of Pd nanoparticles (Fig. 2). The UV spectra showed the
presence of a peak at 425 nm corresponding to Pd(II) of aqueous
27
CH
CH
3
–B(OH)
–B(OH)
2
28
3
2
a
Yields refer to those of purified isolated products characterized by spectroscopic
1
13
solution of Na
2
PdCl
4
before the start of the reaction and the disap-
data (IR, H NMR, and C NMR).
*
pearance of this peak with the progress of the reaction after 2 min
indicating complete formation of Pd(0) nanoparticles, and their
presence till the end of the reaction (Fig. 3).
Indicates X = I.
A wide range of aryl bromides and iodides with varied substit-
uents underwent cross coupling with several diversely substituted
phenylboronic acids and alkylboronic acids by this procedure to
produce the corresponding biaryls and alkyl–aryls. The results
are summarized in Table 3. Most of these reactions were very fast
being completed in 5 min. The presence of an electron-withdraw-
ing or electron-donating group on the aromatic ring of aryl halides
did not affect the reactivity and yields of products. Aryl iodides (Ta-
ble 3, entries 1, 18, and 24) and aryl bromides participated in this
reaction leaving chlorides and fluorides unreactive (Table 3, entries
such as OCH , Cl, F, CHO, COCH , CN, NO , CF , and OH were com-
patible in this reaction, and thus this procedure provided an easy
access to functionalized biaryls. Particularly, the biphenyls con-
3
3
2
3
3
taining highly manipulable groups such as CHO, COCH , CN, and
NO (Table 3, entries 14–17, 20, 23, and 26) in either one or both
2
rings are very useful in organic synthesis.
In general, the reactions are very clean and high yielding. The
aqueous layer containing the catalyst after work up was recycled
for three subsequent runs without an appreciable loss of efficiency.
As indicated by UV studies, Pd(II) was reduced to Pd(0) by phen-
ylboronic acid during the reaction. It was also confirmed by a blank
9
–12, and 22). The substituted phenylboronic acids (Table 3, en-
tries 6, 8, 11, 12, 14, 17, 19, and 23) also coupled with aryl halides
readily. The alkylboronic acids (Table 3, entries 26–28) underwent
reactions by this procedure to produce the corresponding alkyl–ar-
yls without any difficulty. The sensitive heteroaryl halides (Table 3,
entries 24 and 25) bearing pyridyl and thienyl moieties produced
the corresponding aryl-heteroaryl-coupled products in high yields.
The position (o, m, and p) of substituents on the aromatic rings of
aryl halides and phenylboronic acids did not have any appreciable
effect on the progress of the reaction. Several functional groups
2 4
experiment adding phenylboronic acid to a solution of Na PdCl in
water without using SDS and aryl halide, where the solution turned
black immediately indicating the formation of Pd(0). A similar
reduction of palladium(II) acetate by phenylboronic acid was also
4
b
observed by Jin. It is believed that Pd(0) is the catalytic species
and that the reaction proceeds through the usual interaction of aryl
halide and Pd(0) to form the aryl-palladiumhalide complex 1,
which then couples with arylboronic acid to give the aryl-Pd(II)
intermediate 2, and finally provides the biaryl product via the

D. Saha et al. / Tetrahedron Letters 50 (2009) 1003–1006
1005
2
R B(OH)2 + K PO4
3
Pd(II)
Pd (0)
1
R -R2
1
R X
R Pd(II)R2
1
1
R Pd(II)X
2
R B(OH) , K PO
2
3
4
2
1
Scheme 2. Plausible mechanism of Suzuki coupling.
reductive elimination of Pd(II) to Pd(0) as outlined in Scheme 2. It
was also found that the reaction did not proceed at all in the ab-
sence of Pd nanoparticles.
7
c
Recently, we have reported Pd nanoparticles-catalyzed Hiy-
ama coupling using Na PdCl /SDS/NaOH/H O. Although the pres-
ent procedure used a similar reagent system, Na PdCl /SDS/
PO /H O, there are marked differences in the formation and
reactivity of Pd nanoparticles. In Hiyama Coupling, Pd nanoparti-
cles are formed by the reduction of Pd-salt by SDS, whereas in this
reaction, the reduction of Pd(II) was done by phenyl/alkylboronic
acid, this being a much faster process. All the reactions (Suzuki)
proceeded well in the absence of SDS in reasonably good yields
2
4
2
2
4
Figure 1. TEM image Pd nanoparticles.
K
3
4
2
7
c
(
10–15% lower than those in the presence of SDS), and thus SDS
is not an essential part of this process. SDS was used to stabilize
the Pd nanoparticles and to improve the recyclability of Pd nano-
particles. Tetrabutylammonium bromide, a different stabilizer,
was also found to provide results similar to SDS (Table 1, entry
8
). On the contrary, in the Hiyama coupling the reaction did not
proceed at all in the absence of SDS, which acts as a reducing as
well as a stabilizing agent. Moreover, we have been able to success-
fully use alkylboronic acid forming an aryl–alkyl bond in Suzuki
coupling, whereas in the case of the earlier Hiyama coupling,7c this
reaction did not go with alkylboronic acid. In general, alkylboronic
acids are less reactive than arylboronic acids, and thus it is very
difficult to achieve aryl–alkyls. Our procedure is efficient and has
accomplished these reactions (Table 3, entries 26–28) and pro-
vided improved yields in a shorter reaction time (10–25 min com-
2
4
pared to 7.5–72 h by a reported procedure ).
On comparison of our results with those in some of the recently
published procedures using Pd nanoparticles for Suzuki coupling,4
we find that this procedure provides significant advantages in
terms of reaction time, simplicity of operation, and yields of prod-
ucts. In addition, this procedure provides a one-pot operation using
in situ-generated Pd nanoparticles, whereas, with one exception,4b
others use preformed nanoparticles thus making the process two-
step.
In conclusion, we have developed a convenient and efficient
one-pot procedure for Suzuki coupling of aryl halides and aryl-
and alkylboronic acids catalyzed by in situ-generated Pd(0) nano-
particles in water under aerobic and ligand-free conditions. The
significant advantages of this procedure are simple operation, rea-
sonably high yields, very fast (5 min) reaction time, easy recovery
of the catalyst, and reusability up to three runs without any appre-
ciable loss of efficiency and environment-friendly reaction condi-
tions. Suzuki coupling in the absence of any conventional ligand
is also of much significance.
Figure 2. EDX spectra of PdNP on Cu grid.
4
3
2
1
0
Reaction mixture after 2 min.
Aq. Na PdCl4
2
Reaction mixture after 5 min.
Acknowledgments
2
00
400
600
800
This investigation has enjoyed financial support from CSIR, New
Delhi by a Grant [01(1936)/04-EMR-II]. D.S. and K.C. are thankful to
CSIR for their fellowships.
Wavelength
Figure 3. UV spectra of Pd at different stages (0–5 min) of the reaction.

1
006
D. Saha et al. / Tetrahedron Letters 50 (2009) 1003–1006
6
7
.
.
Anastas, P. T.; Warner, J. C. Green Chemistry: Theory and Practice; Oxford
University Press: New York, 1998.
(a) Ranu, B. C.; Chattopadhyay, K. Org. Lett. 2007, 9, 2409–2412; (b) Ranu, B. C.;
Chattopadhyay, K.; Adak, L. Org. Lett. 2007, 9, 4595–4598; (c) Ranu, B. C.; Dey,
R.; Chattopadhyay, K. Tetrahedron Lett. 2008, 49, 3430–3432.
Supplementary data
Supplementary data (Copies of 1H and 13C NMR spectra of all
products listed in Table 3) associated with this article can be found,
in the online version, at doi:10.1016/j.tetlet.2008.12.063.
8.
.
Kapoor, S.; Joshi, R.; Mukherjee, T. Chem. Phys. Lett. 2002, 354, 443–448.
Yamada, Y. M. A.; Maeda, Y.; Uozumi, Y. Org. Lett. 2006, 8, 4259–4262.
9
10. Rammial, T.; Taylor, S. A.; Bender, M. L.; Gorodetski, B.; Lee, P. T. K.; Walsby, C.
J.; Clyburne, J. A. C. J. Org. Chem. 2008, 73, 801–812.
1. Srimani, D.; Sawoo, S.; Sarkar, A. Org. Lett. 2007, 9, 3639–3642.
2. Uozumi, Y.; Nakai, Y. Org. Lett. 2002, 4, 2997–3000.
References and notes
1
1
1
2
.
.
Miyaura, N.; Yanada, K.; Suzuki, A. Tetrahedron Lett. 1979, 20, 3437–3440.
(a) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457–2483; (b) Hassan, J.;
Sevignon, M.; Gozzi, C.; Schulz, E.; Lemaire, M. Chem. Rev. 2002, 102, 1359–
13. Kataoka, N.; Shelby, Q.; Stambuli, J. P.; Hartwig, J. F. J. Org. Chem. 2002, 67,
5553–5566.
14. Tanaka, M.; Souma, Y. Chem. Commun. 1991, 1551–1553.
15. Baruwati, B.; Guin, D.; Manorama, S. B. Org. Lett. 2007, 9, 5377–5380.
16. Masllorens, J.; Roglam, A.; Moreno-Manas, N.; Parella, T. Organometallics 2004,
23, 2533–2540.
1
469; (c) Farina, V. Adv. Synth. Catal. 2004, 346, 1553–1582; (d) Nakamura, I.;
Yamamoto, Y. Chem. Rev. 2004, 104, 2127–2198; (e) Phan, N. T. S.; Vander Sluys,
M.; Jones, C. W. Adv. Synth. Catal. 2006, 348, 609–679.
3
.
.
(a) Roucoux, A.; Schulz, J.; Patin, H. Chem. Rev. 2002, 102, 3757–3778; (b)
Astruc, D.; Lu, F.; Aranzaes, J. R. Angew. Chem., Int. Ed. 2005, 44, 7852–7872; (c)
Astruc, D. Inorg. Chem. 2007, 46, 1884–1894.
(a) Desmarets, C.; Omar-Amrani, R.; Walcarius, A.; Lambert, J.; Champagne, B.;
Fort, Y.; Schneider, R. Tetrahedron 2008, 64, 372–381. and references cited
therein; (b) Han, W.; Liu, C.; Jin, Z. Adv. Synth. Catal. 2008, 350, 501–508. and
references cited therein; (c) Diallo, A. K.; Ornelas, C.; Salmon, L.; Aranzaes, J. R.;
Astruc, D. Angew. Chem., Int. Ed. 2007, 46, 8644–8648; (d) Gallon, B. J.; Kojima,
R. W.; Kaner, R. B.; Diaconescu, P. L. Angew. Chem., Int. Ed. 2007, 46, 7251–7254;
17. Fuchibe, K.; Ohshima, Y.; Mitomi, K.; Akiyama, T. Org. Lett. 2007, 9, 1497–1499.
18. Goodman, S. L.; Holzemann, G.; Sulyok, G. A. G.; Kessler, H. J. Med. Chem. 2002,
45, 1045–1051.
19. Edsall, R. J., Jr.; Harris, H. A.; Manas, E. S.; Mewshaw, R. E. Biorg. Med. Chem.
2003, 11, 3457–3474.
4
20. Antelo Miguez, J. M.; Adrio, L. A.; Sousa-Pedrares, A.; Vila, J. M.; Hii, K. K. J. Org.
Chem. 2007, 72, 7771–7774.
21. Li, F.; Bai, S.; Hor, T. S. A. Organometallics 2008, 27, 672–677.
22. Proch, S.; Kempe, R. Angew. Chem., Int. Ed 2007, 46, 3135–3138.
23. Gong, J. F.; Zhang, Y. H.; Song, M. P. Organometallics 2007, 26, 6487–6492.
24. Najera, C.; Gil-Molto, J.; Karlstrom, S. Adv. Synth. Catal. 2004, 346, 1798–1811.
25. Pouchert, C. J., II ed.. In The Aldrich Library of NMR Spectra; Aldrich Chemical:
Milwaukee, USA, 1983; Vol. 1.
(
2
e) Wu, L.; Li, B. L.; Huang, Y.-Y.; Zhou, H.-F.; He, Y.-M.; Fan, Q.-H. Org. Lett.
006, 8, 3605–3608. and references cited therein; (f) Wei, W.; Qin, Y.; Luo, M.;
Xia, P.; Wong, M. S. Organometallics 2008, 27, 2268–2272.
Shaughnessy, K. H.; DeVasher, R. B. Curr. Org. Chem. 2005, 9, 585–604.
5
.