Nanocrystalline magnesium oxide-stabilized palladium(0): The Heck reaction of heteroaryl bromides in the absence of additional ligands and base

Article abstract of DOI:10.1039/c3cy00404j

An efficient and user-friendly protocol has been realized for the Heck reaction of heteroaryl bromides by using a reusable nanocrystalline magnesium oxide-stabilized palladium(0) catalyst without the aid of additional ligands and base. Dimethylamine generated under in situ conditions by the decomposition of DMF serves as the base in this reaction. The catalyst was reused with consistent activity up to four cycles.

Full text of DOI:10.1039/c3cy00404j

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Nanocrystalline magnesium oxide-stabilized
palladium(0): the Heck reaction of heteroaryl bromides
Cite this: DOI: 10.1039/c3cy00404j
in the absence of additional ligands and base†
Received 12th June 2013,
Accepted 3rd July 2013
Mannepalli Lakshmi Kantam,*a Police Vishnuvardhan Redddy,a
Pottabathula Srinivas,a Akula Venugopal,a Suresh Bhargavab and Yuta Nishinac
DOI: 10.1039/c3cy00404j
www.rsc.org/catalysis
An efficient and user-friendly protocol has been realized for the
Nanocrystalline metal oxides have recently received much
Heck reaction of heteroaryl bromides by using a reusable nano- attention in view of their potential usefulness as materials9 and
crystalline magnesium oxide-stabilized palladium(0) catalyst with- more importantly as catalysts.10 Nanocrystalline magnesium
out the aid of additional ligands and base. Dimethylamine oxide (NAP-MgO) possesses a high concentration of reactive
generated under in situ conditions by the decomposition of DMF sites on the surface, such as Lewis acid Mg2+ and Lewis base
serves as the base in this reaction. The catalyst was reused with O2À, lattice bound and isolated hydroxyl groups and anionic
consistent activity up to four cycles.
and cationic vacancies. Earlier, we reported the effective C–C
bond forming reactions using Mg–Al layered hydroxide and
The palladium-catalyzed Heck reaction has become one of the NAP-MgO-supported palladium catalysts.11 Moreover, the
most important C–C bond forming reactions due to its func- enhanced activity of NAP-MgO-stabilized osmate, palladate
tional group tolerance and its application to a broad range of and tungstate systems over their homogeneous counterparts
endeavors, ranging from synthetic organic chemistry to materials has also been reported.12 Herein, we report a convenient and
science.1 In particular, the Heck reaction of heteroaryl halides reusable NAP-MgO–Pd(0) catalyst for the Heck coupling of
has received considerable attention as heteroaryl derivatives are heteroaryl bromides with olefins in the absence of additional
present in a variety of biologically active compounds and ligands and base (Scheme 1).
pharmaceuticals.2 In recent years, palladium catalysts, in
For optimization of the reaction conditions, a simple repre-
conjunction with tertiary aryl or alkyl phosphine ligands,3 sentative model system consisting of 3-bromopyridine and
N-heterocyclic,4 and carbocyclic carbenes,5 have been used styrene was chosen and the results of this optimization study
for the Heck reaction of aryl and heteroaryl halides in the are summarized in Table 1. For this study, based on our
presence of a base. Further progress has been made by per- previous results,8 DMF was chosen as the solvent. This reaction
forming the reactions under ligand-free conditions6 or using was carried out using NAP-Mg–Pd(0) (0.020 g, 9 wt%) as the
reusable catalysts.7 There are few examples3f,g of palladium- catalyst at 130 1C for 8 hours to give an 86% yield of the desired
catalyzed Heck reactions in the presence of a ligand and base C–C coupled product (Table 1, entry 1). As it is always advisable
for the synthesis of heteroaryl derivatives. Very recently, an to compare the activity with commercially available and reusable
economical method for the Heck reaction of heteroaryl bro- Pd-catalysts,6,7 the reaction was repeated under the same
mides was developed by us under both ligand- and base-free conditions using Pd/C, LDH–Pd(0) and Mg–La–Pd(0) catalysts,
conditions using a homogeneous palladium catalyst.8 It is however there was no evidence for the formation of the desired
highly desirable to develop
a recoverable and reusable C–C coupled product (Table 1, entries 2 and 3), but in the case
palladium catalytic system from an industrial and environ- of Mg–La–Pd(0) 20% yield of the C–C coupled product was
mental point of view.
obtained (Table 1, entry 4). Although DMF was initially chosen
as the solvent, the reaction was also performed in a variety of
a I & PC Division, CSIR-Indian Institute of Chemical Technology, Hyderabad – 500 607,
India. E-mail: mlakshmi@iict.res.in; Fax: +91-40-27193510; Tel: +91-40-27193510
b Advanced Materials & Industrial Chemistry Group, School of Applied Sciences,
RMIT University, Melbourne, Australia
c Research Core for Interdisciplinary Sciences, Okayama University, Tsushima,
Kita-ku, Okayama 700-8530, Japan
† Electronic supplementary information (ESI) available. See DOI: 10.1039/
c3cy00404j
Scheme 1 The Heck reaction of styrene with 3-bromopyridine.
c
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Table 1 Optimization of reaction conditions
Table
2
The Heck reaction of different heteroaryl bromides catalyzed by
NAP-Mg–Pd(0)
Entrya
1
Het-ArBr
Product
Yieldb (%)
74
Entrya
Catalyst
Solvent
Yieldb (%)
1
2
3
4
5
6
7
8
9
10
NAP-Mg–Pd(0)
Pd–C
LDH–Pd(0)
Mg-La–Pd(0)
NAP-Mg–Pd(0)
NAP-Mg–Pd(0)
NAP-Mg–Pd(0)
NAP-Mg–Pd(0)
NAP-Mg–Pd(0)
NAP-Mg–Pd(0)
DMF
DMF
DMF
DMF
DMA
DMSO
Toluene
DMF
DMF
DMF
86
0
0c
20d
20
0
o5
55e
40f
20g
2
86
a
The reactions were carried out with 3-bromopyridine (1 mmol),
styrene (2 mmol) and catalyst (0.020 g) in 2.5 mL of solvent at
3
4
5
85
82
87
b
c
130 1C for 8 h. Isolated yields. Reaction with the catalyst (0.030 g).
d
e
f
Reaction with the catalyst (0.030 g). Reaction at 110 1C. Reaction
g
with the catalyst (0.015 g). Reaction with the catalyst (0.010 g).
solvents; however only poor yields of the C–C coupled products
were obtained when DMA, DMSO and toluene were employed
(Table 1, entries 5–7). The reaction was also carried out at low
temperature (Table 1, entry 8) and with low catalyst loadings
(Table 1, entries 9 and 10), but in these cases only moderate
yields of the C–C coupled products were obtained. From the
above results, the following optimized reaction conditions were
established with respect to the heteroaryl halide: 20 mg of
NAP-Mg–Pd(0) as the catalyst in 2.5 mL of DMF as the solvent at
130 1C for 8 h.
A variety of heteroaryl bromides were reacted using the
above optimized reaction conditions and the results are pre-
sented in Table 2. The Heck reaction of p-electron deficient
heteroaryl bromides, such as 3-bromopyridine, 2-bromo-
pyridine, 3-bromoquinoline and 4-bromoisoquinoline, with
styrene afforded high yields of the C–C coupled products
(Table 2, entries 1–4). As shown in our previous report,8 the
position of the bromo-substituent on pyridine can influence
the yield of the product (entries 1 vs. 2). In the case of
p-electron-rich heteroaryl halides, such as 2-and 3-bromothio-
phenes and 3-bromofuran, the yield of the products under the
optimized conditions are nearly the same as in the cases of
p-electron-deficient heteroaryl halides (Table 2, entries 5–7).
6
7
8
9
75
83
81
90
60
10
a
The reactions (entries 1–10) were carried out with heteroaryl bromides
Similarly, comparable yields were obtained from the reaction of (1 mmol), styrene (2 mmol) and catalyst (0.020 g) in 2.5 mL of solvent at
b
130 1C for 8 h. Isolated yields.
styrene with 5-methoxy-3-bromopyridine and 2-nitro-5-bromo-
pyridine (Table 2, entries 8 and 9). The reaction of electron-rich
6-methyl-2-bromopyridine gave the Heck coupled product in
60% yield under the same reaction conditions (Table 2, 4-chlorostyrene and 2-naphthylstyrene with the p-electron-
entry 10); this was one of the first compounds to be developed deficient heterocycles such as 3-bromopyridine and 3-bromo-
that acts as a selective antagonist for the metabotropic glutamate quinoline afforded good yields (85–91%) of the coupled
receptor.13
products (Table 3, entries 1–3 and 7). Only 65% of the desired
Next, we investigated the use of NAP-Mg–Pd(0) to catalyze product was obtained from the reaction of the activated olefin
the reaction between various heteroaryl bromides and substi- n-butylacrylate and phenylacrylate with 3-bromopyridine
tuted styrenes, n-butylacrylates and phenylacrylates, and the (Table 3, entries 4 and 5). Slightly lower yields were observed in
results are presented in Table 3. The reaction of 4-methylstyrene, the case of p-electron-rich 3-bromothiophene with 4-methylstyrene
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Table 3 The NAP-Mg–Pd(0) catalyzed Heck reaction of heteroaryl bromides and
olefins
Entrya
1
Het-ArBr
R
Product
Yieldb (%)
91
Fig. 1 Transmission electron micrographs of fresh (a) and used (b) NAP-Mg–Pd(0),
4-Me-C6H4
and the catalyst after the 5th cycle (c).
Therefore, it is assumed that presence of heteroatoms in aryl
halides is essential for the success of the reaction.
2
4-Cl-C6H4
88
The C–C coupled products were isolated from the catalyst by
simple filtration after completion of the reaction. The catalyst
was washed first with water and then with diethyl ether to
remove any organic material. It was dried at room temperature
and used for reusability studies. It was observed that the
catalyst shows almost consistent activity up to four cycles
(Table 4). The TEM image of the used catalyst did not show
any change in the shape and size of the support or active Pd(0)
centers. The slight decrease in the observed activity in the
subsequent cycles may be attributed to a decrease in the surface
area due to hydration of the catalyst by water formed in the
reaction.14 No quantifiable amount of leached palladium was
detected in the filtrate by AAS.
The TEM images of the fresh and used NAP-Mg–Pd(0)
catalysts are shown in Fig. 1. It appears that there is not much
change in the shape and size of the Pd particles in both fresh
and used catalysts. TEM analysis indicated that the nano Pd
particles had a mean diameter of 10 and 12 nm for fresh and
used catalysts. The morphology of the catalyst remains the
same even after 4 recycles.
3
4
5
C10H7
89
65
75
nBu-CO2
Ph-CO2
6
7
4-Me-C6H4
75
4-Cl-C6H4
C10H7
76
85
8
a
The reactions (entries 1–10) were carried out with heteroaryl bromides
(1 mmol), styrene (2 mmol) and catalyst (0.020 g) in 2.5 mL of solvent at
The proposed mechanism involves the initial oxidative
addition of heteroaryl halides to the palladium(0) catalyst
(Scheme 2). In the second step, the palladium(II) catalyst forms
a p complex with olefin followed by insertion of alkene into the
b
130 1C for 8 h. Isolated yields.
and 4-chlorostyrene when compared to p-electron-deficient
3-bromopyridine (Table 3, entries 5 and 6). It is clear from
these results that regardless of the electron-withdrawing or
donating groups on the aromatic ring of the substituted
styrenes, both p-electron-rich and p-electron-deficient hetero-
cycles showed similar activity in the Heck reaction (Table 3,
entries 1 vs. 2 and 5 vs. 6). However, the reaction of aryl halides
that lack a heteroatom, for example, 4-bromoanisole and
4-chloronitrobenzene failed under the standard conditions.
Table 4 Recyclability test of the catalyst with different substrates
Yieldb
Substratea
Fresh
Run 1
Run 2
Run 3
Run 4
3-Bromopyridine
3-Bromothiophene
3-Bromoquinoline
86
84
87
85
84
85
83
84
84
80
83
83
80
80
83
a
Scheme 2 A plausible mechanism for the Nap-MgO–Pd(0) catalyzed Heck
reaction of heteroaryl bromides (for the sake of convenience only one palladium
nano particle is shown on the support).
The reactions were carried out with heteroaryl bromides (1 mmol),
styrene (2 mmol) and catalyst (0.020 g) in 2.5 mL of solvent at 130 1C for
8 h. Isolated yields.
b
c
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product by a beta elimination step. Subsequently, palladium(0)
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The Heck reaction of heteroaryl bromides with olefins had been
accomplished by using a reusable heterogeneous NAP-Mg–Pd(0)
catalyst. The catalyst was recovered and reused up to four cycles
with almost consistent activity. The simple procedure, easy
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