Application of dimeric cyclopalladated complex of tribenzylamine as an efficient catalyst in the Heck cross-coupling reaction

Article abstract of DOI:10.1016/j.jorganchem.2011.03.023

The activity of [Pd{C₆H₄(CH₂N(CH ₂Ph)₂)} (μ-Br)]₂ complex was investigated in the Heck-Mizoroki C-C cross-coupling reaction. This complex is an active and efficient catalyst for the Heck reaction of aryl iodides, bromides and even chlorides and also arenesulfonyl chlorides. The cross-coupled products were produced in excellent yields in short reaction time using a catalytic amount of [Pd{C₆H₄(CH₂N(CH₂Ph)₂) (μ-Br)]₂ complex in NMP at 130 °C.

Full text of DOI:10.1016/j.jorganchem.2011.03.023

Journal of Organometallic Chemistry 696 (2011) 2669e2675
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Note
Application of dimeric cyclopalladated complex of tribenzylamine as an efficient
catalyst in the Heck cross-coupling reaction
,
b
,
a
Abdol R. Hajipour a , Fatemeh Rafiee
*
a Pharmaceutical Research Laboratory, Department of Chemistry, Isfahan University of Technology, Isfahan 84156, Islamic Republic of Iran
b Department of Pharmacology, University of Wisconsin, Medical School, 1300 University Avenue, Madison, WI 53706-1532, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
The activity of [Pd{C6H4(CH2N(CH2Ph)2)} (m-Br)]2 complex was investigated in the HeckeMizoroki CeC
Received 5 February 2011
Received in revised form
20 March 2011
cross-coupling reaction. This complex is an active and efficient catalyst for the Heck reaction of aryl
iodides, bromides and even chlorides and also arenesulfonyl chlorides. The cross-coupled products were
produced in excellent yields in short reaction time using a catalytic amount of [Pd{C6H4(CH2N(CH2Ph)2)
(m
-Br)]2 complex in NMP at 130 ꢀC.
Accepted 23 March 2011
Ó 2011 Elsevier B.V. All rights reserved.
Keywords:
Cyclopalladated complex
Catalyst
Tribenzylamine
Heck reaction
1. Introduction
Cyclopalladated complexes are important starting materials in
organometallic chemistry [13,14]. Palladacycles have been known
for over 30 years [15e20] and have been acquiring great interest
due to their applications in many areas, including organic
synthesis [21e24], material science [25], biologically active
compounds [26] and as building blocks in macromolecular
chemistry [27e29]. Cyclopalladated complexes exhibit a superior
catalytic efficiency in cross-coupling reactions. In particular, the
phospa-palladacycles introduced by Herrmann have found
application in a wide variety of palladium-catalyzed reactions [1].
Phosphine ligands, especially the electron-rich phosphines, are
often toxic and sensitive to air and moisture. Bedford et al. also
showed that phosphinite palladacycles exhibited better activity
than structurally similar phosphite and phosphine complexes
[22]. Consequently, the search for easy handling, active, thermally
stable and low-cost catalysts caused the development of
phosphine-free palladium catalysts such as palladium complexes
bearing nitrogen-donor ligands [30]. For several years only aryl
iodides and aryl bromides were employed in Heck reaction.
Different efforts have been down to find better catalysts for
coupling aryl chlorides as readily available and industrially
important compounds by Heck reaction. The aryl chlorides react
very slowly by palladium catalysts [31,32] due to the strength of
the CeCl bond which delays the oxidation addition to Pd(II)
complexes [33,34]. Heck reaction of aryl chlorides with olefins
was carried out by using additives containing tetraalkylammo-
nium or tetraalkylphosphonium salts at higher temperature and
The formation of carbonecarbon bonds is a fundamental reac-
tion in organic synthesis due to many vast applications in the areas
of bioactive compounds, natural products and high performance
materials. The Heck coupling, one of the most important palla-
dium-catalyzed CeC bond formation reactions, is a process also
described as olefin arylation. The Heck reaction has received
considerable attention, primarily due to the enormous synthetic
potential to generate sp2esp2 carbonecarbon bonds [1]. However,
the reaction suffers from limitations that have so far precluded
many industrial applications [2]. Typically,
a relatively large
amount of catalyst (1e5 mol%) is needed for reasonable conver-
sions and often catalyst recycling is hampered. Various approaches
towards catalyst improvement have been described [3]. Most effort
was reported to be achieved with activated, electron-poor chlor-
oarenes using highly basic, sterically hindered phosphanes [4], the
use of a large excess of coordinating ligands, for example, triphe-
nylphosphane [5] or tris(2,4-di-tert-butylphenyl)phosphate (tbp)
[6], the use of heterogeneous Pd/C [7] or Pd/MgO [8], or the use of
nanostructured palladium clusters [9], the use of N-heterocyclic
carbenes (NHC) [10] and the use of palladacycles [11,12].
* Corresponding author. Pharmaceutical Research Laboratory, Department of
Chemistry, Isfahan University of Technology, Isfahan 84156, Islamic Republic of Iran.
Tel.: þ98 311 391 3262; fax: þ98 311 391 2350.
E-mail address: haji@cc.iut.ac.ir (A.R. Hajipour).
0022-328X/$ e see front matter Ó 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2011.03.023

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A.R. Hajipour, F. Rafiee / Journal of Organometallic Chemistry 696 (2011) 2669e2675
Table 2
Optimization of catalyst concentration under conventional heating.a
Entry
Catalyst (mol%)
Time (min)
Temperature (ꢀC)
Conversion (%)
1
2
3
4
5
6
None
0.01
0.03
0.05
0.1
120
120
120
120
40
130
130
130
130
130
130
0
40
60
90
100
100
0.2
40
a
Reaction conditions: 1 mmol 4-bromoacetophenon, 2.2 mmol methylacrylate,
1.1 mmol K2CO3, 3 ml NMP and palladacycle.
Scheme 1. The HeckeMizoroki cross-coupling reaction of aryl halides with olefins by
a cyclopalladated complex A.
different olefins under conventional heating at 130 ꢀC, as shown in
Table 3.
The results showed that aryl halides with either electron-
withdrawing or electron-donating substituents reacted with
olefins rapidly and generated the coupled products with excellent
yields. The coupling reactions with acrylates as the olefin were
faster than styrene and methylstyrene.
high loadings of complex in long reaction times [10]. The activity
with aryl chloride substrates can be greatly improved using
cyclopalladated complexes as thermally stable catalyst [35e40].
In a continuation of our recent investigations on the application
of the palladacycle systems in Heck reactions [41e43] and cyana-
tion reactions [44,45], we now wish to report the extension of
[Pd{C6H4(CH2N(CH2Ph)2) (m-Br)]2 complex, as an efficient, ther-
The ideal substrates for coupling reactions are aryl chlorides,
since they tend to be cheaper and more widely available than
their bromide or iodide counterparts. Unfortunately, the high
CeCl bond strength compared with CeBr and CeI bonds dis-
favour oxidative addition, the first step in catalytic coupling
reactions. The most reported catalyst needed to be used in high
loadings, and they show little or no activity with aryl chloride
substrates.
Furthermore, as shown in Table 3 (entries 13e15, 32e34) the
catalytic amount of palladacyclic complex A can be used in the Heck
coupling of even less reactive aryl chloride derivatives with olefins
in good yields.
Although this procedure could active CeCl, however in the
compounds containing both Br and Cl substituent, by using
a stoichiometric amount of olefins only the Br was substituted,
which may be due to the higher activity of Br compared
with Cl.
mally stable and non-sensitive to air and moisture catalyst for Heck
coupling reaction of various types of aryl halides under traditional
heating (Scheme 1).
2. Results and discussion
Cyclopalladation of tribenzylamine proceeds in benzene at
80 ꢀC when the amine is heated with an equimolar amount of
palladium(II) acetate. Tribenzylamine did not produce isolable
bis-amine complex owing to the three bulky benzyl groups on
the nitrogen atom, whereas less sterically demanding amines, for
example, monobenzylamine coordinated palladium much more
tightly, preventing the conversion of the bis-amine adduct to the
cyclopalladated complex. [Pd{C6H4(CH2N(CH2Ph)2)} (m-Br)]2 (A)
as a palladacycle complex was prepared according to the litera-
ture [46] and its application in Heck coupling reaction was
studied.
The application of palladacycle A as a catalyst for the Heck cross-
coupling reaction was examined by optimizing both base and
solvent effects. The reaction of 4-bromoacetophenone with meth-
ylacrylate using palladacycle A as the catalyst was carried out in
various solvents and organic and inorganic bases under conven-
tional heating at 130 ꢀC, as shown in Table 1.
We found that K2CO3 as base and N-methyl-2-pyrrolidone
(NMP) as solvent gave the best results (Table 1, entry 4). Various
catalyst concentrations were also tested (Table 2, entry 5) and
0.1 mol% gave the best result.
These optimized reaction conditions were applied in the Heck
cross-coupling reaction of different types of aryl halides with
Arenesulfonyl chlorides could be used as electrophilic partners
under desulfinylation conditions in place of aryl halides (Table 3,
entries 16, 35, 36 and 40). Arenesulfonyl chlorides are inexpensive
and readily available compounds and more reactive than corre-
sponding bromides and chlorides. The reactive Pd0 catalyst
undergoes oxidative addition of the SO2eCl bond to give first
a chloro palladiumII sulfinate (AreSO2ePdIIeCl). Desulfinylation
occurs rapidly at high temperature (130 ꢀC) and RePdeCl complex
forms, which is followed by the reversible coordination of the olefin
to it. The Pd0 formed in the main catalytic cycle, after
reductive elimination steps [47].
b-hydride and
Production of exclusively the trans isomers and complete
conversions by this method are great advantages of the presented
catalyst.
Table 1
3. Experimental
Optimization of base and solvent under conventional heating in an oil bath.a
3.1. General
Entry
Solvent
Base
Temperature
(ꢀC)
Time (min)
Conversion
(%)
1H NMR spectra were recorded at 500 and 400 MHz in CDCl3
solutions at room temperature on a Bruker, Avance 500 instrument
(Rheinstetten, Germany) and Varian 400 NMR (TMS was used as an
internal standard). The FT-IR spectra were recorded on a spectro-
photometer (Jasco-680, Japan). Furthermore, we used GC (BEIFIN
3420 Gas Chromatograph equipped a Varian CP SIL 5CB column e
30 m, 0.32 mm, 0.25 mm) for examination of reaction completion
and yields. All chemical materials were purchased from Merck and
Aldrich and were used as received.
1
2
3
4
5
6
7
8
NMP
NMP
NMP
NMP
NMP
DMF
CH3CN
Toluene
Et3N
130
130
130
130
130
130
80
120
120
120
40
0
30
40
100
90
90
0
Cs2CO3
Na2CO3
K2CO3
CH3COONa
K2CO3
40
120
120
3
K2CO3
K2CO3
110
0
a
Reaction conditions: 1 mmol 4-bromoacetophenon, 2.2 mmol methylacrylate,
1.1 mmol base, 0.1 mol% palladacycle.

A.R. Hajipour, F. Rafiee / Journal of Organometallic Chemistry 696 (2011) 2669e2675
2671
Table 3
Heck reaction of aryl halides under conventional heating conditions in an oil bath.
Entry ArX
R0CH]CH2
Product
Time (min)
Yield (%)
20
35
110
50
96
94
80
93
1
2
3
4
5
6
7
60
25
90
96
95
90
87
95
35
40
100
35
40
80
93
85
8
9
70
87
(continued on next page)

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A.R. Hajipour, F. Rafiee / Journal of Organometallic Chemistry 696 (2011) 2669e2675
Table 3 (continued )
Entry
ArX
R0CH]CH2
Product
Time (min)
Yield (%)
10
180
75
11
130
85
12
13
14
15
16
17
90
50
80
91
87
78
130
90
50
70
130
80
95
94
78
90
85
96
130
140
85
80
18

A.R. Hajipour, F. Rafiee / Journal of Organometallic Chemistry 696 (2011) 2669e2675
2673
Table 3 (continued)
Entry
ArX
R0CH]CH2
Product
Time (min)
Yield (%)
19
45
92
90
20
60
65
110
91
83
21
22
23
24
25
120
200
70
80
67
92
85
140
26
27
200
110
87
90
(continued on next page)

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A.R. Hajipour, F. Rafiee / Journal of Organometallic Chemistry 696 (2011) 2669e2675
Table 3 (continued )
Entry
ArX
R0CH]CH2
Product
Time (min)
Yield (%)
80
100
86
85
28
29
180
78
30
70
82
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In a round-bottom flask equipped with a magnetic stirring bar to
a mixture of K2CO3 (1.1 mmol), olefin (2.2 mmol) and aryl halide
(1 mmol) in NMP (3 ml) were added 0.1 mol% of palladacycle
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mixture was heated at 130 ꢀC in an oil bath. The reaction’s progress
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raphy (GC). After completion of the reaction the mixture was diluted
with n-hexane and water. The organic layer was washed with brine,
dried over Na2SO4, and concentrated under reduced pressure. The
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4. Conclusion
Using
dimeric
orthopalladate
-Br)]2 as an efficient catalyst for Heck
complex
[Pd
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m
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Isfahan Science & Technology Town (ISTT), IR, Iran. Further financial
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