Applications of a monomeric orthopalladate complex containing mixed phosphorus-nitrogen donors in the Heck reaction

Article abstract of DOI:10.1016/j.tetlet.2011.07.036

The [Pd{C₆H₂(CH₂CH₂NH ₂)-(OMe)₂,3,4}Br(PPh₃)] monomeric orthopalladate complex of homoveratrylamine and triphenylphosphine was synthesized and its application in Heck coupling reactions was investigated. This complex had been demonstrated to be more active than the corresponding dimeric catalyst for Heck reactions of aryl iodides, bromides and even chlorides and also arenesulfonyl chlorides. The cross-coupled products were produced in excellent yields using catalytic amounts of [Pd{C₆H ₂(CH₂CH₂NH₂)-(OMe) ₂,3,4}Br(PPh₃)] as a thermally stable and oxygen insensitive complex in NMP at 130 °C.

Full text of DOI:10.1016/j.tetlet.2011.07.036

Tetrahedron Letters 52 (2011) 4782–4787
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Applications of a monomeric orthopalladate complex containing mixed
phosphorus–nitrogen donors in the Heck reaction
Abdol Reza Hajipour a,b, , Fatemeh Rafiee a, Arnold E. Rouho b
⇑
a Pharmaceutical Research Laboratory, Department of Chemistry, Isfahan University of Technology, Isfahan 84156, Iran
b Department of Pharmacology, University of Wisconsin, Medical School, 1300 University Avenue, Madison, 53706-1532 WI, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
The [Pd{C6H2(CH2CH2NH2)-(OMe)2,3,4}Br(PPh3)] monomeric orthopalladate complex of homoveratryl-
amine and triphenylphosphine was synthesized and its application in Heck coupling reactions was
investigated. This complex had been demonstrated to be more active than the corresponding dimeric
catalyst for Heck reactions of aryl iodides, bromides and even chlorides and also arenesulfonyl chlorides.
Received 27 February 2011
Revised 26 June 2011
Accepted 11 July 2011
Available online 19 July 2011
The cross-coupled products were produced in excellent yields using catalytic amounts of [Pd{C6H2
-
(CH2CH2NH2)-(OMe)2,3,4}Br(PPh3)] as a thermally stable and oxygen insensitive complex in NMP at
130 °C.
Keywords:
Cyclopalladated complex
Palladium catalyst
Triphenylphosphine
Heck reaction
Ó 2011 Elsevier Ltd. All rights reserved.
The Heck coupling is an important palladium-catalyzed reaction
in organic synthesis.1 Due to the many applications of Heck reac-
tions in the synthesis of monomers, pharmaceuticals and bioactive
compounds, natural products, sunscreen agents, herbicides and
high performance materials, considerable efforts have been made
to find new catalytic systems and methodologies to improve this
reaction.2 A relatively large amount of catalyst (1–5 mol %) is often
needed for reasonable conversions in these coupling reactions.3
Various approaches toward catalyst improvement have been
described including the use of highly basic, sterically hindered
phosphanes,4 the use of a large excess of coordinating ligands, for
example triphenylphosphine5 or tris(2,4-di-tert-butylphenyl)phos-
phate (tbp),6 the use of heterogeneous Pd/C7 or Pd/MgO,8 the use of
nanostructured palladium clusters,9 the use of N-heterocyclic carb-
enes (NHC)10 and the use of palladacycles.11,12 Palladacycle-con-
Scheme 1. The synthesis of the monomeric orthopalladate complex 2.
taining catalysts are
a very important class of catalyst in
organometallic chemistry.13,14 They have been known for over 30
years15–20 and have been used as very efficient catalysts in very
low concentrations for the synthesis of materials,21–25 biologically
active compounds26 and macromolecules.27–29
with a dimeric [Pd{C6H2(CH2CH2NH2)-(OMe)2,3,4}(l-Br)]2 palla-
dacycle.
The palladacycle [Pd{C6H2(CH2CH2NH2)-(OMe)2,3,4}(
l-Br)]2
1
In continuation of our investigations on the synthesis and
applications of palladacycles in Heck reactions,30–32 Suzuki33
and cyanation reactions,34,35 we report herein the synthesis of
the monomeric orthopalladate complex [Pd{C6H2(CH2CH2NH2)-
(OMe)2,3,4}Br(PPh3)] 2. The activity of this complex was investi-
gated in the Heck–Mizoroki C–C cross-coupling and compared
was prepared according to our previous work.30 The acetate-bridged
orthopalladate complex was obtained from homoveratrylamine by
addition of Pd(OAc)2 in acetonitrile as a binuclear complex. The hal-
ogen-bridged orthopalladate complex was prepared by the addition
of NaBr to a solution of the acetate-bridged complex in acetone.
Addition of triphenylphosphine to this dimeric orthopalladate com-
plex [Pd{C6H2(CH2CH2NH2)-(OMe)2,3,4}(l-Br)]2 1 in dichlorometh-
⇑
ane gave the monomeric orthopalladate complex 2 [Pd{C6H2(CH2
CH2NH2)-(OMe)2,3,4}Br(PPh3)] as a yellow powder (Scheme 1).
Corresponding author. Tel.: +98 311 391 3262; fax: +98 311 391 2350.
E-mail address: haji@cc.iut.ac.ir (A.R. Hajipour).
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.07.036

A. R. Hajipour et al. / Tetrahedron Letters 52 (2011) 4782–4787
4783
Table 1
The structure of this palladacycle was determined by elemental
analysis and 1H NMR spectroscopy.
Optimization of the reaction conditions for the Heck reaction of 4-bromobenzalde-
hyde with methyl acrylate
The activity of this complex was investigated in Heck–Mizoroki
C–C cross-coupling reactions and compared with the dimeric pal-
ladacycle 1. The monomeric complex contains mixed phospho-
rus–nitrogen (P–N) donors and was found to be more active in
Heck reactions (Scheme 2) than the dimer, which contains only a
single nitrogen donor.
In order to optimize the conditions, preliminary experiments
were carried out on the vinylation of 4-bromobenzaldehyde with
methyl acrylate using palladacycle 2. With the intention of study-
ing the effects of various parameters on the reaction time and
yield, the reaction was carried out in various solvents with organic
and inorganic bases and conventional heating at 130 °C, as shown
in Table 1.
Entry
Solvent
Base
Temp (°C)
Time (min)
Conversion (%)
1
2
3
4
5
6
7
8
NMP
NMP
NMP
NMP
NMP
DMF
DMF
DMF
DMF
CH3CN
Toluene
Et3N
130
130
130
130
130
130
130
130
130
80
180
180
180
40
0
Na2CO3
Cs2CO3
K2CO3
NaOAc
Et3N
Cs2CO3
NaOAc
K2CO3
K2CO3
K2CO3
30
40
100
90
0
Trace
60
70
0
60
180
180
180
180
180
180
9
10
11
110
0
As demonstrated in Table 1 (entry 4), the use of K2CO3 as the
base and N-methyl-2-pyrrolidone (NMP) as the solvent gave the
best results. As the catalyst is thermally stable and not sensitive
to oxygen and moisture, the reactions were carried out under air.
After optimization of the base and solvent, various catalyst con-
centrations were tested. The results in Table 2 show that 0.4 mol %
of the catalyst gave the best results.
We applied the optimized conditions to the Heck cross-coupling
reactions of different aryl halides with methyl acrylate, methyl
methacrylate, styrene and methylstyrene using conventional heat-
ing at 130 °C (Table 3). The results showed that aryl halides with
either electron-withdrawing or electron-donating substituents re-
act with olefins and generate the coupled products in excellent
yields. Also the results listed in Table 3 clearly show that the cou-
pling reactions with methyl acrylate and methyl methacrylate as
the olefin were faster than those of styrene and methylstyrene.
In the case of 1-bromo-3-chlorobenzene (Table 3, entries 5, 20
and 27), this procedure activated the C–Cl bond. However, by using
a stoichiometric amount of olefin, only the Br was substituted in
each case. In all of the reactions, only the E-isomers of the products
were produced.
Table 2
Optimization of the catalyst concentration on the Heck reaction of 4-bromobenzal-
dehyde with methyl acrylate at 130 °C
Entry
Cat. (mol%)
Time (min)
Conversion (%)
1
2
3
4
5
6
7
8
None
0.02
0.05
0.1
0.2
0.3
120
120
120
120
100
60
0
40
60
85
95
100
100
100
0.4
0.5
40
40
tertiary phosphines, usually triphenylphosphine, are required to
drive the reaction.37,38
Pd(OAc)2 in combination with tertiary phosphine ligands as the
catalytic system is generally reduced to the catalytically active pal-
ladium(0) species in the presence of a base.39 The monomeric com-
plexes are easier to reduce to the active Pd(0) species compared
with the dimeric catalyst.37
In conclusion, the monomeric orthopalladate complex
[Pd{C6H2(CH2CH2-NH2)-(OMe)2,3,4}Br(PPh3)] 2 is an efficient cata-
lyst for Heck reactions of aryl bromides, aryl iodides, aryl chlorides
and arenesulfonyl chlorides. This monomeric complex contains
mixed phosphorus–nitrogen (P–N) donors and was found to be
more reactive than the corresponding dimeric complex which con-
tains only a single nitrogen donor.
Because of the availability of aryl chlorides, they are the best
substrates for coupling reactions in comparison with their bromide
or iodide analogs. This method can be used for Heck reactions of
even less reactive aryl chlorides, albeit with longer reaction times
(Table 3, entries 11, 12, 13 and 23).
Arenesulfonyl chlorides could also be used as the electrophilic
partners in place of aryl halides under desulfinylation conditions
(Table 3, entries 14, 24 and 25). Arenesulfonyl chlorides are inex-
pensive readily available compounds and are more reactive than
the corresponding bromides and chlorides. The reactive Pd(0)
catalyst undergoes oxidative addition of the SO2–Cl bond of the
sulfonyl chloride to give a chloro palladium(II) sulfinate (Ar-SO2-
PdII-Cl). At high temperature (130 °C) desulfinylation occurs
rapidly and an Ar–Pd–Cl complex forms, followed by reversible
coordination of the olefin. Pd(0) is formed in the main catalytic
cycle, after b-hydride and reductive elimination steps.36
As demonstrated in Table 4, the monomeric complex 2 was
more active than the dimeric complex 1. In many Heck reactions,
Synthesis of the monomeric orthopalladate complex 2
The dimeric palladacycle complex 1 was prepared according to
our previous work.30 A 50 mL round-bottom flask was charged
with homoveratrylamine (1.1 mmol), Pd(OAc)2 (1.1 mmol) and
acetonitrile (20 mL) and the contents refluxed for 4 h. The resulting
suspension was filtered through a plug of MgSO4. The solvent was
removed under reduced pressure, and CH2Cl2 (2 mL) and n-hexane
(15 mL) were added to give the acetato-bridged cyclopalladated
complex as a yellow precipitate which was filtered, washed with
H2O and air-dried. Yield: 47%. To a solution of this complex
(0.2 mmol) in acetone (25 mL) was added NaBr (1.94 mmol) and
the suspension was stirred for 8 h. Acetone was evaporated, CH2Cl2
(10 mL) was added and the mixture filtered through a plug of
MgSO4. The filtrate was concentrated to 2 mL under reduced pres-
sure using a rotary evaporator, and n-hexane (15 mL) was added.
The suspension produced was filtered and air-dried to afford the
dimeric complex 1 as an orange solid. PPh3 (0.22 mmol) was added
to the dimeric complex 1 (0.11 mmol) in CH2Cl2 (10 mL). After stir-
ring at room temperature for 2 h the reaction mixture was concen-
trated. Addition of n-hexane afforded the monomeric complex 2 as
Scheme 2. The Heck cross-coupling reaction of aryl halides with olefins using the
monomeric orthopalladate complex 2.

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A. R. Hajipour et al. / Tetrahedron Letters 52 (2011) 4782–4787
Table 3
Heck reactions of aryl halides under conventional heating conditions in an oil batha
Entry
1
ArX
R0CH@CH2
Product
Time (min)
20
Yieldb (%)
95
2
3
30
40
94
96
4
5
6
25
95
94
92
30
150
7
8
20
35
95
96
9
50
87
10
11
12
120
70
80
85
87
60
13
50
89
14
15
50
20
90
96

A. R. Hajipour et al. / Tetrahedron Letters 52 (2011) 4782–4787
4785
Table 3 (continued)
Entry
ArX
R0CH@CH2
Product
Time (min)
20
Yieldb (%)
16
97
17
18
60
80
92
94
19
20
21
120
20
92
92
93
150
22
23
100
180
92
83
24
25
80
90
90
130
26
80
95
95
27
100
a
Reaction conditions: aryl halide (1 mmol), olefin (2.2 mmol), K2CO3 (1.1 mmol), catalyst 2 (0.4 mol %), NMP; 130 °C.
Isolated yield.
b
a yellow solid. 1H NMR (500 MHz, CDCl3, ppm): d, 7.77–7.74 (m,
6H, PPh3), 7.30–7.15 (m, 9H, PPh3), 6.83 (br d, 1H, J = 7.30 Hz,
C6H2), 6.81 (br d, 1H, J = 6.85 Hz, C6H2), 3.90 (s, 3H, OMe), 3.89 (s,
3H, OMe), 3.17–3.07 (m, 2H, NH2), 2.93–2.80 (m, 2H, CH2), 2.65–
2.45 (br m, 2H, CH2) ppm. 31P NMR: 30 ppm. IR (KBr, cmꢀ1):
3298–3152 (N–H). Decomp: 180 °C. Color: yellow. Yield: 66%. Anal.
Calcd for C28H29BrNPO2Pd: C, 53.48; H, 4.66; N, 2.23. Found: C,
53.31; H, 4.71; N, 2.45.
General procedure for Heck reactions of aryl halides with
olefins
To a round-bottom flask equipped with a magnetic stirring bar
were added monomeric palladacycle
2 (0.4 mol %), K2CO3
(1.1 mmol), olefin (2.2 mmol) and aryl halide (1 mmol) in NMP
(3 mL). The mixture was heated at 130 °C using an oil bath and
the progress was monitored by TLC (hexane/EtOAc, 80:20) and

4786
A. R. Hajipour et al. / Tetrahedron Letters 52 (2011) 4782–4787
Table 4
Comparison of the efficiencies of the dimeric and monomeric orthopalladated complexes 1 and 2 in Heck reactionsa
Entry
1
ArX
R0CH@CH2
Product
Catalyst
Time (min)
Yieldb (%)
1
2
80
20
92
95
1
2
240
40
80
96
2
3
1
2
420
150
90
92
1
2
120
20
90
97
4
5
6
1
2
120
20
92
96
1
2
180
120
87
92
1
2
600
150
80
93
7
1
2
480
100
85
92
8
9
1
2
180
80
96
95
a
Reaction conditions: aryl halide (1 mmol), olefin (2.2 mmol), K2CO3 (1.1 mmol), catalyst (0.4 mol %), NMP; 130 °C.
Isolated yield.
b
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We gratefully acknowledge the funding support received for
this project from the Isfahan University of Technology (IUT), IR Iran
and Isfahan Science & Technology Town (ISTT), IR, Iran. Further
financial support from the Center of Excellence in Sensor and
Green Chemistry Research (IUT) is gratefully acknowledged.
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