Ligand- and copper-free Sonogashira and Heck couplings of (Het)aryl chlorides and bromides catalyzed by palladium nanoparticles supported on in situ generated Al(OH)3

Article abstract of DOI:10.1039/c6ra25416k

The ligand- and copper-free Sonogashira reaction of (Het)aryl halides (Br and Cl) with various terminal alkynes and the Heck coupling of (Het)aryl halides (Br and Cl) with a series of olefins, catalyzed by palladium nanoparticles supported on newly generated Al(OH)₃, were developed. The catalyst can be readily recovered and reused 6 times without significant loss of activity and palladium leaching.

Full text of DOI:10.1039/c6ra25416k

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Ligand- and copper-free Sonogashira and Heck
couplings of (Het)aryl chlorides and bromides
catalyzed by palladium nanoparticles supported on
in situ generated Al(OH)3†
Cite this: RSC Adv., 2017, 7, 2475
*
Xing Li, Xiaolei Gong, Zhipeng Li, Honghong Chang, Wenchao Gao
*
and Wenlong Wei
Received 18th October 2016
Accepted 26th November 2016
The ligand- and copper-free Sonogashira reaction of (Het)aryl halides (Br and Cl) with various terminal
alkynes and the Heck coupling of (Het)aryl halides (Br and Cl) with a series of olefins, catalyzed by
palladium nanoparticles supported on newly generated Al(OH)3, were developed. The catalyst can be
readily recovered and reused 6 times without significant loss of activity and palladium leaching.
DOI: 10.1039/c6ra25416k
www.rsc.org/advances
The efficiency of heterogeneous catalysis in organic synthesis elimination of copper and phosphorus ligands, as well as
can be improved by employing nanosized catalysts because of affording recovery and reuse of costly palladium catalyst.
their extremely small size and large surface-to-volume ratio.1 Although several notable examples of truly green conditions for
Recently, it has been demonstrated that palladium nano- the Sonogashira10 and Heck11 reactions were reported, the
particles (PdNPs) as catalysts offer signicant potential for substrate scope is still limited and successful examples for het-
a wide range of applications in organic synthesis.2 The surface eroaryl halides remain rare because the corresponding reactions
properties of these PdNPs and their catalytic activity are mainly of heteroaryl bromides proved to be more challenging.12,13 From
decided by the nature of catalyst supports and the methods for the viewpoint of synthetic cost, developing a generally applicable
their preparation. PdNPs are usually prepared by chemical catalytic system with broader substrate scope has received
vapor deposition from Pd precursors in the presence of considerable attention and is highly desirable. Herein, we will
hydrogen gas or by classical methods like impregnation or co- report the application of such a palladium nanoparticles cata-
precipitation. To improve their catalytic activity, however, lyst14 supported on Al(OH)3 which was in situ formed (see Scheme
some improved methods for their preparation are required.
1) in ligand- and copper-free Sonogashira and Heck cross-
Palladium-catalyzed cross-coupling reactions have become coupling reactions of (Het)aryl bromides and chlorides. The
one of the most prominent and powerful methods for the catalyst has exhibited obviously higher catalytic activity than that
formation of carbon–carbon bonds.3 Among them, the Sonoga- prepared by co-precipitation, which demonstrate that the prep-
shira4 and Heck5 reactions have been found useful in the aration methods of the catalyst exerted an important impact.14d
synthesis of a variety of target compounds with applications
We rst investigated the Sonogashira reaction between 4-
ranging from natural products and pharmaceuticals to organic methoxybromobenzene (1o) with phenylacetylene (2a) to opti-
functional materials. Signicant progress has been achieved by mize reaction conditions (Table 1). Screening of common
using palladium salts6,7 or homogeneous palladium complexes8,9 solvents showed that DMSO was the best choice over DMF, and
as catalysts in the absence of copper co-catalysts. However, these H2O (entry 2 vs. 1 and 3). Bases have a strong effect on the yield,
two reactions still suffer from some limitations about the envi- and NaOAc was the best among the bases screened, including
ronmental and economical sustainability. In most cases, cata- K2CO3, K3PO4 and KOAc (entries 7 vs. 2, 4, 5). The reaction did
lysts failed to be recycled and reused, and phosphorus ligands
were also employed. To address these challenges, intense
research efforts have been devoted to nd suitable heteroge-
neous Pd catalysts of broad scope, capable of allowing the
Department of Chemistry and Chemical Engineering, Taiyuan University of
Technology, 79 West Yingze Street, Taiyuan 030024, People's Republic of China.
E-mail: lixing@tyut.edu.cn; weiwenlong@tyut.edu.cn
† Electronic supplementary information (ESI) available. See DOI:
Scheme 1 Preparation of Pd nanoparticles catalyst 1.
10.1039/c6ra25416k
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Table 1 Optimization of reaction conditions for the Sonogashira Table 2 The scope of aryl halides with phenylacetylenea,b
reactiona
Entry
Solvent
Base
Yieldb (%)
1
2
3
4
5
6
7
8d
DMF
DMSO
H2O
DMSO
DMSO
DMSO
DMSO
DMSO
K2CO3
K2CO3
K2CO3
K3PO4
KOAc
KOH
NaOAc
NaOAc
21
36
Trace
13
37
N.D.c
62
91
a
Reactions were performed with 4-methoxybromobenzene (0.2 mmol)
b
c
under N2 atmosphere at 120 ꢀC for 40 h. Isolated yield. N.D. ¼ Not
d
detected. Reaction conditions: 4-methoxybromobenzene (0.2 mmol),
phenylacetylene (1.5 equiv.), Pd catalyst 1 (8.8 mg, 0.2 mol%), NaOAc
(1.5 equiv.), TBAB (0.5 equiv.), DMSO (1.0 mL), N2, 120 ꢀC.
not give 3o at all when KOH was used (entry 6). It was note-
worthy that the addition of TBAB improved the result further,
providing 3o in 91% yield (entry 8).
With the optimized protocol in hand, the scope of this
catalytic system was next explored. Aryl halides in reaction with
2a were investigated rst (Table 2). The reaction worked very
well for a range of aryl bromides with various substituents at
the phenyl ring, and the products were isolated in good to
excellent yields. Aryl bromides with electron-withdrawing
substituents at the phenyl ring afforded the desired 1,3-diynes
in high yields (3b–3j), whereas aryl bromides bearing electron-
donating substituents provided the desired 1,3-diynes in 81–
91% yields (3k–3o). The experimental results indicated that a-,
and b-bromide substituted naphthalene afforded similarly
good yields (3p and 3q). Sterically hindered 1-bromo-3,4-
diuorobenzene was also suitable for this transformation (3r).
Moreover, the arene ring is not limited to benzene rings. Het-
eroaryl bromides derived from pyridines, thiophenes, quino-
lines, and pyrimidines could be converted to the corresponding
cross-coupled products in modest to high yields (3s–3zb). NO2-
substituted aryl chlorides were also deemed to be suitable cross-
coupling partners (3b–3d). Unfortunately, 1-chloronaphthalene
and 4-methylchlorobenzene gave only 53% and 41% yields,
respectively (3p and 3m).
Consequently, the scope of the arylacetylenes was examined
in the coupling with bromobenzene. Phenylacetylene bearing
electron-donating and electron-withdrawing groups in the
benzene ring furnished the products in good to excellent yields,
respectively (Table 3, 3e–3m, 3zc). The reactions of 4-ethynylto-
luene and 1-ethynyl-4-uorobenzene with 4-nitrobromobenzene
were smoothly carried out to furnish the desired products (Table
3, 3zd and 3ze). In addition, 2-ethynylpyridine and 3-ethynylth-
iophene, heteroaryl alkynes, were also viable partners, providing
74% and 31% yields, respectively (Table 3, 3s and 3zf).
a
Reaction conditions: (hetero)aryl halide (0.2 mmol), phenylacetylene
(34 mL, 1.5 equiv.), Pd catalyst 1 (8.8 mg, 0.2 mol%), NaOAc (24.5 mg,
1.5 equiv.), TBAB (32.3 mg, 0.5 equiv.), DMSO (1.0 mL), N2, 120 ꢀC.
b
c
d
Isolated yield. 110 ꢀC was used. 90 ꢀC was used in the absence of
TBAB.
acrylate 4a was chosen for initial study. Different solvents were
explored in an effort to optimize the yield of 5a. As shown in
Table 4, TBAB gave 5a in the highest yield and only poor to
moderate yields were obtained with other solvents like dioxane,
DMF, NMP, and acetonitrile (Table 4, entry 5 vs. 1–4). Among
the bases evaluated, K3PO4 was found to be optimal. Lower
yields were provided with K2CO3, TBAA, Et3N and NaOAc
(Table 4, entry 5 vs. 6–9). Further optimization clearly indicated
To test the effect of this nano-Pd catalyst in the Heck
coupling reaction, the coupling of bromobenzene 1a and butyl
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Table 3 The scope of (hetero)arylacetylenes with bromobenzenea,b
Table
5
Substrate scope of (hetero)aryl halides for the Heck
couplinga,b
a
Reaction conditions: bromobenzene or 4-nitrobromobenzene (0.2
mmol), (hetero)aryl acetylene (1.5 equiv.), Pd catalyst 1 (0.2 mol% Pd),
NaOAc (1.5 equiv.), TBAB (0.5 equiv.), DMSO (1.0 mL), N2, 120 ꢀC.
b
Isolated yield.
Table 4 Optimization of reaction conditions for the Heck reaction of
bromobenzene with butyl acrylatea
Cat. 1
(mol% Pd)
T
(ꢀC)
Yieldb
(%)
Entry
Solvent
Base
a
Reaction conditions: (hetero)aryl bromide (0.2 mmol), butyl acrylate
(0.26 mmol), catalyst 1 (0.1 mol% Pd), K3PO4 (0.2 mmol), TBAB
1
2
3
4
5
6
7
8
DMF (0.5 mL)
NMP (0.5 mL)
CH3CN (0.5 mL)
Dioxane (0.5 mL)
TBAB (0.3 g)
TBAB (0.3 g)
TBAB (0.3 g)
TBAB (0.3 g)
TBAB (0.3 g)
TBAB (0.3 g)
TBAB (0.3 g)
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K2CO3
TBAA
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.07
0.1
130
130
130
130
130
130
130
130
130
130
120
78
74
61
Trace
99
48
86
61
79
b
(0.3 g), N2, 130 ꢀC. Isolated yield. c Reaction conditions: aryl chloride
(0.2 mmol), butyl acrylate (0.26 mmol), catalyst 1 (0.1 mol% Pd),
K3PO4 (0.2 mmol), TBAB (0.3 g), DMF (0.2 mL), N2, 130 ꢀC.
also be obtained when NO2- and Me-substituted chloroben-
zenes were used as substrates with longer reaction time and
more catalyst loading (Table 5, 5b–5d and 5i–5k). Furthermore,
a series of functional groups, including Me-, F-, and diMe-
substituted styrenes could smoothly couple with bromo-
benzene to provide good results (Table 6, 5t–5za).
We further turned our attention to the recovery and reuse of
the nano-Pd catalyst 1 through the Sonogashira reaction
between 4-methoxybromobenzene (1o) with phenylacetylene
(2a) and the results are shown in Table 7. The catalyst could
be recovered through membrane ltration and reused in the
next reaction. The experimental results showed that the cata-
lytic activity and reaction yield did not obviously decrease aer
the sixth consecutive cycles. Moreover, the palladium leaching
during the recovery process was not obviously observed which
was determined by inductively coupled plasma atomic emission
spectroscopy (ICP-AES) (Table 7, runs 1–6 vs. 0).
Et3N
9
10
11
NaOAc
K3PO4
K3PO4
82
89
a
Reaction conditions: bromobenzene (0.2 mmol), butyl acrylate
(0.26 mmol, 1.3 equiv.), catalyst 1, base (0.2 mmol), solvent, N2 for
b
19 h. Isolated yield.
that lower catalyst loading and temperature resulted in bad
results (Table 4, entries 10–11 vs. 5).
To demonstrate the generality of this nanoparticles pd
catalyst 1, our attention was next focused on investigating the
substrate scope for Heck cross-coupling using a variety of aryl
halides.15 In all of our cases, both electron-rich and electron-
poor groups and some heteroaryl rings substituted aryl
bromides reacted with butyl acrylate to give the desired prod-
ucts in moderate to high yields, exhibiting a good efficiency
(Table 5, 5a–5s). It was found that moderate to good yields could
In conclusion, we have developed efficient, practical and
general copper-free Sonogashira and Heck cross-coupling
reactions using a nanoparticles pd catalyst supported on in
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Table
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