Heck coupling reaction catalyzed by [(C3H5)PdCl] 2-N,N,N′,N′-tetra(diphenylphosphinomethyl)-1, 2-ethylenediamine

Article abstract of DOI:10.1016/j.catcom.2010.07.007

Pd-N,N,N′,N′-tetra(diphenylphosphinomethyl)-1,2-ethylenediamine was used for Heck coupling reaction and showed a good activity. When the molar ratio of substrate to palladium was 1000, the yield of the coupling product was up to 99% for activated aryl bromides and 58% for aryl chloride. ³¹P NMR in situ indicated that the good activity of this system results from the active palladium species stabilized effectively by this tetraphosphine.

Full text of DOI:10.1016/j.catcom.2010.07.007

Catalysis Communications 12 (2010) 222–225
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Catalysis Communications
journal homepage: www.elsevier.com/locate/catcom
Short Communication
Heck coupling reaction catalyzed by [(C H )PdCl] -N,N,N′,N′-tetra
3
5
2
(diphenylphosphinomethyl)-1,2-ethylenediamine
Xiao-Jun Yu, Rong Zhou, Yu Zhang, Hai-Yan Fu, Rui-Xiang Li ⁎, Hua Chen, Xian-Jun Li
Key Lab of Green Chemistry and Technology, Ministry of Education, College of Chemistry, Sichuan University, 610064, Chengdu, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Pd-N,N,N′,N′-tetra(diphenylphosphinomethyl)-1,2-ethylenediamine was used for Heck coupling reaction
Received 3 March 2010
Received in revised form 30 June 2010
Accepted 7 July 2010
and showed a good activity. When the molar ratio of substrate to palladium was 1000, the yield of the
coupling product was up to 99% for activated aryl bromides and 58% for aryl chloride. P NMR in situ
indicated that the good activity of this system results from the active palladium species stabilized effectively
by this tetraphosphine.
31
Available online 16 July 2010
©
2010 Elsevier B.V. All rights reserved.
Keywords:
Heck coupling reaction
Arylchloride
Arylbromide
Tetraphosphine
Palladium
1
. Introduction
and its application in Heck reaction are promoted. The typical
tetraphosphine, which was derived from ferrocene, gave a TON of
65,000 for the coupling reaction of 4-bromoanisole with styrene
[16,17]. The most successful tetraphosphine Tedicyp, reported by M.
Santelli [18], gave a high TON of 210,000,000 in Heck coupling
reaction of acrylate with aryl bromide [3,19–23].
However, the difficulties in synthesis of the mentioned tetrapho-
sphines and their inefficiency in the coupling reaction of aryl chloride
limit their applications. Interestingly, a bidentate phosphine contain-
ing nitrogen, N,N-bis(diphenylphosphinomethyl)amine, could facili-
tate Heck reaction and gave a good yield with PhCl as substrate
[11,24,25]. This result encourages us to study on tetraphosphines
containing nitrogen for Heck coupling. Herein, we originally use a
tetraphosphine N,N,N′,N′-tetra(diphenylphosphinomethyl)-1,2-ethy-
lenediamine to investigate the Heck coupling reaction of aryl halide
with styrene. It is found that the reaction proceeds smoothly with aryl
chloride and gives medium conversion in the condition of low catalyst
loading of 0.1 mol%.
Construction of carbon–carbon bonding between aryl halide and
alkene catalyzed by palladium is one of the most important methods
in synthetic chemistry [1–3]. In the past decades, many natural
products, key intermediates, pharmaceuticals and others useful
compounds are successfully synthesized in the different kinds of
palladium catalytic systems. This cross-coupling reaction was origi-
nally developed by Mozoriki and Heck in the presence of Pd(OAc)
4,5]. While PPh was added, the selectivity and yield of the coupling
2
[
3
product were obviously improved [6]. Consequently, a great number
of triaryl phosphines were used in this reaction. For example, a yield
of 95% was observed with PhBr as a substrate in the presence of o-
3
Tol P [7,8]. It was also found that the palladium complexes with bulky
and strong electron-donating trialkylphosphines are favorable to C–C
coupling between aryl halide and styrene [9,10]. In spite of this, the
catalyst loading is generally over 1% because monophosphines could
not efficiently stabilize Pd species under the reaction conditions.
However, a diphosphine generally shows better coordination ability
to stabilize active Pd species in catalytic cycle due to its chelating
effect. Even if the catalytic activity of stable Pd-diphosphine systems is
lower [2,11–15], their long lifetime causes a higher TON [2,3]. Based
on these findings, the design and synthesis of polydentate phosphine
2. Experimental
2.1. General
All chemicals were purchased from commercial suppliers. Except
for some liquid reagents being sensitive to light and moisture that
⁎
Corresponding author. College of Chemistry, Sichuan University, Chengdu, Sichuan
3 5 2
were redistilled, there is no further treatment. [PdCl(C H )] [26] and
6
1
10064, PR China. Tel./fax: +86 28 85412904.
E-mail address: liruixiang@scu.edu.cn (R.-X. Li).
N,N,N′,N′-tetra(diphenylphosphinomethyl)-1,2-ethylenediamine [27]
566-7367/$ – see front matter © 2010 Elsevier B.V. All rights reserved.
doi:10.1016/j.catcom.2010.07.007

X.-J. Yu et al. / Catalysis Communications 12 (2010) 222–225
223
were prepared with the reported methods. H NMR, 13C NMR and 31
1
P
Table 1
a
Heck coupling in different conditions.
NMR spectra were recorded on Bruker AV II-400 MHz.
Entry
Substrate
Substrate/catalyst
Time (h)
Yield (%)
(E)-Sel (%)
2
.2. General procedure of Heck coupling reaction
b,c
1
2
3
4
5
6
7
8
9
1
1
1
1
PhI
PhI
PhI
PhI
PhI
PhI
PhBr
PhBr
PhBr
PhBr
PhBr
PhBr
PhBr
PhBr
100
100
100
100
100
100
100
100
20
20
20
20
4
84
90
N99 (86)
N99 (99)
95
84
58
65
71
65
58
54
41
90
88
89
90
88
89
92
92
90
91
92
92
95
92
b
NaOH (160 mg, 4 mmol) or K
2
CO
3
(4 mmol), PhBr (211 μL,
d
2
mmol) and styrene (461 μL, 4 mmol) were added successively into
a dried Schlenk tube with a magnetic bar. Then DMA (2 mL) and DMF
solution of tetraphosphine-[PdCl(C )] (1 mL, 0.02 mmol), which
was formed at 120 °C for 30 min, were added into it, respectively. The
solution was stirred at 120 °C for 30 h. At the end of reaction, the
solution was cooled to room temperature and water (4 mL) was
added into it. The mixture solution was extracted with ethyl acetate
d
4
3
H
5
2
16
24
30
10
30
30
30
30
100
100
0e
1
2
3
14
100 (M=PdCl
100 (L/M=4)
100 (M=Pd(OAc)
1000
2
)
(
4
3×5 mL) and organic layer was dried over MgSO . The dried solution
2
)
was filtered and purified with silica gel chromatography (petroleum
60
ether) to give a corresponding product with an isolation yield of 94%
a
Reaction condition: ArX 2 mmol, styrene 4 mmol,
2 3
K CO 4 mmol, 1/[PdCl
(
340 mg) or GC yield of 97%.
3 5 2
(C H )] =2/1, DMF as solvent (3 mL), yield analyzed by GC, temperature 120 °C,
yields in parentheses correspond to isolated yield.
b
Temperature 100 °C.
Styrene 1.1 equivalent.
Phosphine free.
Temperature 140 °C.
3
. Results and discussion
c
d
3
.1. Coupling reaction of aryl halide with styrene
e
To evaluate the catalytic activity of Pd-tetraphosphine (1,
Scheme 1) in Heck coupling reaction, we investigated first the
2
increased to 4 with PdCl as a precursor, its activity was still lower. So
reaction of styrene with PhI in the presence of 1 mol% tetraphosphine
[PdCl(C )] was chosen as the catalyst precursor in the following
3
H
5
2
(
1)-[PdCl(C
3
H
5
)]
2
and a good yield was obtained at 100 °C (Table 1,
research. A similar result, in which 1:1 (molar ratio) of tetraphosphine
to Pd gave the best conversion of Heck coupling, was reported by
Semeril et al. [28]. Interestingly, after the ratio of substrate to catalyst
was increased to 1000, the conversion only decreased a little under a
similar reaction condition (Table 1, entry 14).
entry 1). Then, we increased the ratio of styrene to PhI to 2 equiv., and
a yield of 90% was achieved with slight loss in (E)-isomer selectivity
(
reaction, reaction temperature was increased to 120 °C, and a
complete conversion of PhI was observed whether tetraphosphine
Table 1, entry 2). In order to improve the conversion of the coupling
Due to the great effect of base on Heck reaction, the effect of
(
1) existed or not (Table 1, entries 3 and 4). When reaction time was
3 3 4 2 3 3
NaHCO , K PO , K CO , NEt , NaOH, KOH, DMAP (N,N-dimethylami-
t
shortened to 4 h, palladium–phosphine system gave a higher yield
than phosphine-free system (Table 1, entries 5 and 6). It is well
known that ArI was an active substrate for Heck reaction due to weak
C–I bond. So phenyl bromide was used as a substrate and 71%
conversion was obtained at 120 °C for 30 h (Table 1, entries 7–9). It is
noteworthy that the yield of the coupling reaction increased gradually
with the extension of reaction time. Obviously, the catalyst did not
deactivate during this long period and showed a good stability. After
reaction temperature was further increased to 140 °C, at which Heck
coupling is generally performed, the activity of the catalyst system
was obviously improved and a conversion of 65% was obtained in 10 h
mopyridine) and NaO Bu (Table 2) were investigated. As a result, the
highest conversion was given with NaOH. Although a complete
conversion of PhBr was observed with KOH, the signal of desired
product was almost not detected on GC signal. Probably, the strong
basicity of KOH caused the serious side reactions. Similarly, when
some activated substrates, such as 4-bromo-phenylacetone and 4-
CF
3
C
6
H
4
Br were used, the existence of NaOH was disfavorable to the
CO could effectively
formation of desired products and a weak base K
2
3
promote the formation of the desired products (Table 3, entries 2 and
3). It is well known that DMF is a good solvent for Heck reaction, but
DMF will decompose in the presence of NaOH at 120 °C. Considering
the difference of polarity and chemical properties between DMA and
DMF, we used a mixed solvent (2 mL DMA and 1 mL DMF) for the
coupling reaction of PhBr. To our delight, a yield of 97% was achieved
(Table 3, entry 4).
(
Table 1, entry 10). When [PdCl(C
3
H
5
)]
2
was replaced with the
, the lower
conventional catalytic precursor PdCl
2
and Pd(OAc)
2
conversions were given under the same reaction conditions
Table 1, entries 11 and 13). If the molar ratio of ligand to metal
(
Scheme 1. Possible formation process of catalyst.

224
X.-J. Yu et al. / Catalysis Communications 12 (2010) 222–225
Table 2
the formation of complexes 2 and 3 (Scheme 1) was fast undoubtedly.
a
Effect of different bases on the Heck coupling reaction.
2
31
We had prepared η complex, and it showed a singlet at 2.9 ppm on
P
Entry
Base
Conv. (%)
Sel. (%)
NMR spectra. So it was reasonable to assign that the signal A was from
2
η -Pd complex. Moreover, when B, E and F signals disappeared, the A
1
2
3
4
5
6
7
8
NaHCO
3
41
60
60
15
38
93 (89)
53
N99
93
92
92
90
91
93
93
–
2
t
signal still existed. This result also proved the good stability of η -Pd
NaO Bu
3
1
K
2
CO
3
complex. According to the change of B and E signal intensities on
P
1
NEt
3
NMR spectra, we speculated that B and E signals should come from η -Pd
complex (2) because the coordination of phosphorus atom with Pd did
not obviously affect the chemical shifts of other phosphorus atoms
which were far from the coordinated phosphorus atom. As stated
DMAP
NaOH
K
3
PO
4
KOH
4
a
previously [16,17], η -phosphine–Pd complex was always in rapid
Reaction condition: PhBr 2 mmol, styrene 4 mmol, base 4 mmol, 1/[PdCl
)] =2/1, DMF as solvent (3 mL), substrate/catalyst=1000, temperature 120 °C,
equilibrium of dissociation and association, which would result in
(
C
3
H
5
2
31
time 30 h, conversion analyzed by GC.
broadened signals on P NMR spectra. Also, Hierso et al. [17] disclosed
that the 31P NMR signal of η -tetraphosphine (derived from ferrocene)–
4
So the optimum conditions were the reaction temperature of
20 °C, molar ratio 1000 of substrate to the catalyst, a mixture of DMA
Table 3
a
1
Heck coupling of different aryl halides.
and DMF as solvent and NaOH as a base (except for some activated
substrates). The catalytic performance of this system for a series of aryl
halides were tested at these conditions. The coupling reaction of PhI
and aryl bromide bearing 4-acetyl, 4-trifloromethyl and 4-methoxy
substituent showed an excellent yield (Table 3, entries 1–5). For the
aromatic chloride substrate, which is the most difficult to occur the
coupling reaction, this system gave a good yield of 58% for an
activated ArCl (Table 3, entry 6). Furthermore, we investigated
the Heck coupling of aromatic chloride substrates with acrylate
Yield (%)b
Entry
Substrate
1
90 (N99)
2c
3c
4
89 (N99)
85
(Table 3, entries 10–12). When ethyl acrylate and the inactivated
chlorobenzene were used as the starting materials, a yield of 35% was
given (Table 3, entry 10). If ethyl acrylate reacted with the activated
substrate 4-nitrochlorobenzene, the yield was up to 96% (Table 3, entry
94 (97)
1
1). In addition, the reaction of a bulky butyl acrylate with 4-
nitrochlorobenzene also gave a satisfying yield of 69% (Table 3, entry
2). To the best of our knowledge, this is the best result in the Heck
coupling of aryl chloride in the presence of 0.1 mol% catalyst at 120 °C
3,16] as the reported best yield of the Heck coupling reaction between
-nitrochlorobenzene and butyl acrylate was only 32% with Pd-Tedicyp
1
5
6
83 (89)
58
[
4
of 0.2 mol% at the higher temperature of 130 °C [18]. Although some
bulky alkylphosphines and palladacyles [29,30] could catalyze this
coupling efficiently, a high reaction temperature and catalyst loading
are required. Similarly, Keles et al. [24,25] reported that Heck reaction
of PhCl with acrylate was carried out in the presence of 3 mol% Pd
to give 70% conversion, but the conversion was not more than 90% to
PhBr with 3.3% catalyst loading. Obviously, this tetraphosphine (1)
showed a higher activity than diphosphine N,N-bis(diphenylpho-
sphinomethyl)amine.
7
43
8d
(3)
3
.2. Possible Pd–P species in this system
Recently, it was proposed that P–Pd bond in η -palladium complexes
9d
(39)
35
4
bearing tetraphosphine was weak [16,17]. For tetraphosphine (1), the
reported single crystal structure of its η -Pd complex showed that the P–
10e
2
Pd bond was strong and no interaction between N atoms of tetrapho-
sphine (1) and Pd was observed [31,32]. We considered that the
2
4
11e
formation of η -Pd complex was easy and η -Pd complex was difficult
due to its linear structure. In order to illustrate this question in detail and
obtain some useful information of the active species, 31P NMR signals of
96
the mixture of phosphine (1) and [Pd(C
3 5 2 3
H )Cl] in CDCl at different
1 f
2
69
time intervals were recorded at room temperature (Fig. 1). It was found
31
that new P NMR signals (A, B, and E) appeared very quickly, and signal
intensity of A at 2.9 ppm, B at 2.7 ppm, E at −28.2 ppm and F at
a
Reaction condition: ArX 2 mmol, styrene 3 mmol, NaOH 3 mmol, 1/[PdCl
3 5 2
(C H )] =2/1, DMF:DMA=1:2 as solvent (3 mL), substrate/catalyst=1000, temperature
−
28.4 ppm gradually decreased with the extension of time, while some
new signals appeared at −15.7 ppm (C) and −10.7 ppm (D) 20 h later.
120 °C, time 30 h.
b
Isolated yield. Yields in parentheses correspond to GC yield. All GC yield's (E)-isomer
selectivity is more than 90%.
Santalli reported that tetraphosphine Tedicyp reacted with palladium
precursor to form η -palladium complex in 20 min or less as all P atoms
c
4
K
2
CO
3
as base.
d
e
f
S/C: 100 (entry 8); 10000 (entry 9).
NaHCO
NaHCO
in Tedicyp were in cis position [3,17]. Although tetraphosphine 1 was
3
as base, ethyl acrylate as olefin, time 20 h.
3
as base, butyl acrylate as olefin, time 20 h.
4
difficult to form η complex for a short time due to its linear backbone,

X.-J. Yu et al. / Catalysis Communications 12 (2010) 222–225
225
Fig. 1. 31P NMR spectra of [(C
H
)PdCl]
2
3
5
2
-N,N,N′,N′-tetra(diphenylphosphinomethyl)-1,2-ethylenediamine in situ.
Pd appeared at 8.9 and 3.5 ppm, respectively, and η -P–Pd complex
good to perfect conversion of aryl bromide in a low ratio of catalyst to
substrate. Moreover, the coupling reaction between arylchloride and
styrene proceeded smoothly with medium yield in a low catalyst
loading. 31P NMR in situ indicated that tetraphosphine (1) could
enhance the stability of the formed Pd complex.
showed two signals at 39.2 and 41.7 ppm. So it is reasonable to attribute
31
4
the signals C and D on P NMR to be η -palladium complex (5). This
complex (5) could be formed in 20 h at room temperature and its
4
concentration increased with the extension of time. Until 96 h later, η -
palladium complex (5) was completely formed. Furthermore, the
catalyst, which was prepared in situ in 120 °C in DMF for 20 min,
presented two feature signals at −16.3 ppm and −10.5 ppm (broad-
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dissociated in 107 h [17]. Why can the existence of N atom in ligand 1
cause the much better stability of Pd-tetraphosphine complex in Heck
coupling reaction? To date, we are not clear and our research is
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in the presence of the η2 complex (4) and a yield of 80% was given.
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[
[
[
[
[
[
[
transformed into complex 5 at room temperature, NMR signal of A
could be maintained after 96 h (Fig. 1). However, 31P NMR of the
[
catalyst, which was prepared in situ in the temperature of 120 °C for
4
[
[
[
2
0 min, demonstrated that η -palladium complex was fast formed in
the reaction condition. In other words, the complexes 2, 3 and 4 were
4
completely converted into η -palladium complex for a short time and
they were not the active ingredient, and the really active species for
4
Heck reaction was η -palladium complex (5).
[
[
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. Conclusion
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In summary, we used an easily synthesized tetraphosphine (1) to
develop a new system for Heck coupling. This system could give a