Preparation of a PEG-Supported Ligand as Highly Stable Palladium Catalyst and Its Efficient Recyclability in the Heck Reaction

Article abstract of DOI:10.1080/00397910601031595

A reagent of NNN ligands immobilized on PEG has been prepared and coordinated to Pd(OAc)2 to provide a highly efficient and recyclable catalysis system for the Heck reaction. The reaction works very well with this catalysis system, and no palladium black is observed during the reaction. The reagent and palladium can be recycled easily and do not show significant activity decay after being reused 10 times.

Full text of DOI:10.1080/00397910601031595

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Preparation of a PEG‐Supported Ligand as
Highly Stable Palladium Catalyst and Its
Efficient Recyclability in the Heck Reaction
Hua‐Xing Zhang a , Cheng‐Cai Luo a , Ting Jin a & Xi‐Ping Luo b
a Key Laboratory for Molecular Design and Nutrition Engineering , Ningbo
Institute of Technology, Zhejiang University , Ningbo, China
b Zhejiang Forestry University , Linan, China
Published online: 25 Jul 2007.
To cite this article: Hua‐Xing Zhang , Cheng‐Cai Luo , Ting Jin & Xi‐Ping Luo (2007) Preparation of a
PEG‐Supported Ligand as Highly Stable Palladium Catalyst and Its Efficient Recyclability in the Heck Reaction,
Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
37:2, 191-197, DOI: 10.1080/00397910601031595
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Synthetic Communicationsw, 37: 191–197, 2007
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910601031595
Preparation of a PEG-Supported Ligand as
Highly Stable Palladium Catalyst and Its
Efficient Recyclability in the Heck Reaction
Hua-Xing Zhang, Cheng-Cai Luo, and Ting Jin
Key Laboratory for Molecular Design and Nutrition Engineering, Ningbo
Institute of Technology, Zhejiang University, Ningbo, China
Xi-Ping Luo
Zhejiang Forestry University, Linan, China
Abstract: A reagent of NNN ligands immobilized on PEG has been prepared and coor-
dinated to Pd(OAc)2 to provide a highly efficient and recyclable catalysis system for the
Heck reaction. The reaction works very well with this catalysis system, and no
palladium black is observed during the reaction. The reagent and palladium can be
recycled easily and do not show significant activity decay after being reused 10 times.
Keywords: Heck reaction, palladium, PEG, supported ligands
INTRODUCTION
The Heck reaction, the palladium-catalyzed coupling of aryl halides with
olefins, is an extremely valuable method for carbon–carbon bond
formation.[1–4] It is now widely used in the special chemical and pharma-
ceutical manufacturing industries, because it is simple, versatile, and rela-
tively mild.[5] However, palladium is not only expensive, but also the
residual metal in the product may pose environmental concerns, so
chemists have been trying to immobilize palladium metal to catalyze the
Heck reaction.
Received October 11, 2006
Address correspondence to Hua-Xing Zhang, Key Laboratory for Molecular Design
and Nutrition Engineering, Ningbo Institute of Technology, Zhejiang University,
Ningbo 315100, China. E-mail: zhhx@nit.net.cn
191

192
H.-X. Zhang et al.
Several catalyst-immobilization techniques have been mentioned
(or reported) in literatures. Pd on carbon and different metal oxides were
found to be good catalysts for the reaction,[6,7] and Pd supported on mesopo-
rous silica was also developed to catalyze the Heck reaction.[8,9] One dis-
advantage of immobilizing Pd on a solid substance is that Pd easily leaches
from the solid substance surface. More recently, polymer-supported ligands
containing Pd complexes were shown to be robust and easily recyclable
catalysts for the Heck reaction.[10,11] Hererin, we report an efficient and
recyclable catalyst, poly(ethyl glycol)–supported NNN tridentate ligand 1,
as a Pd-immobilizing reagent, used in Heck reaction.
RESULTS AND DISCUSSION
Our first objective was to synthesize the poly(ethyl glycol)–supported NNN
ligand 1 (Fig. 1). Compound 2 was the precursor. Compound 3 was
prepared from 2 with methyl benzyl amine in the presence of NaH.
Compound 3 was then deprotected with Pd(PPh3)4/K2CO3/MeOH to
remove allyl, followed by reacting with dibromoethan to get 4. Compound
1 was obtained by a coupling reaction of 10 equiv of 4 with 1 equiv of
PEG4000 in the presence of DBU (1,8-diazabicyclo[4.5.0]unolec-7-ene).
With compound 1 as reagent for Pd(OAc)2, the Heck reaction was carried
out, and the results are summarized in Table 1, whereas iodobenzene
couples smoothly with methyl acrylate and ethyl acrylate. Iodobenzene with
4-methyoxl as an electron-withdrawing substituent reacts with acrylate and
ethyl acrylat efficiently, too, but borombenzene shows low reactivity with
acrylate. There is no coupling activity between cholobenzene and acrylate.
In Table 1, the 1.3% and 0.06% Pd(OAc)2 catalyst loading was experimented.
It indicated that use of 0.6 mol% Pd(OAc)2 gives good yield too.
During the reaction, there is no Pd black observed on the glassware. After
the reaction, ether was poured into the reaction system. The mixture was kept
in a refrigerator for 10 min. PEG ligands and Pd(OAc)2 precipitated in the
glassware while the reaction product remained in the solvent. The precipi-
tation was obtained by filtering and then reused. Table 2 displayed the
reaction activity of phenyl iodide coupling with methyl acrylate catalyzed
Figure 1. (a) THF/NaH/Ph(CH3)NH, reflux, 8 h; (b) Pb(PPh3)4/K2CO3/MeOH, rt,
3 h; (c) K2CO3/BrCH2Ch2Br, DMF, 808C, 8 h; (d) PEG4000, toluene, DBU, rt, 8 h.

Table 1. Reagent 1 and Pd(OAc)2-catalyzed Heck Reactiona
Yield (%) with
Pd (OAc)2
(0.13 mmol)
Yield (%) with
Pd(OAc)2
(0.06 mmol)
Entry
1
Arylhalide
Olefin
Products
Methyl acrylate
Ethyl acrylate
Methyl cinnamate
Ethyl cinnamate
99
99
94
95
2
3
Methyl acrylate
Ethyl acrylate
4-methoxy methyl cinnamate
4-methoxy ethyl cinnamate
98
98
92
91
Methyl acrylate
Ethyl acrylate
Methyl cinnamate
Ethyl cinnamate
45
50
40
45
aReaction conductions: a mixture of aryl halides (10 mmol), alkene (10.5 mmol), TEA (10 mmol), DMF (5 ml), reagent 1
(0.056 mmol), and Pd(OAc)2 in air atmosphere, 1208C, 8 h. GC yield using glycol-n-butyl ether as internal standard.

194
H.-X. Zhang et al.
Table 2. Reuse of reagents 1 and Pd(OAc)2 in the
coupling of phenyl iodide and methyl acrylatea
Runb
Yield (%)c
1
2
99
99
98
99
97
96
97
98
95
95
3
4
5
6
7
8
9
10
aReaction conductions: a mixture of phenyl iodide
(10 mmol), methyl acrylate (10.5 mmol), TEA
(10 mmol), DMF (5 ml), reagent 1(0.056 mmol),
Pd(OAc)2 (0.13 mmol), in an air atmosphere, 120, 8 h.
bAfter reaction, the mixture was diluted with
diethyl ester and the reagent 1 with Pd(OAc)2 was
filtered off. The catalyst was reused after drying
under vacuum.
cGC yield using glycol-n-butyl ether as internal
standard.
by the recycled PEG ligands and Pd(OAc)2. It is obvious that the catalyst
system still exhibits high and stable activity after ten uses. Previous investi-
gations on the coordination and conformation in the PEG system containing
metal ions have revealed that PEG is wrapped around the metal ions,
forcing the ether oxygens to point inward and coordinate to metal ions,
mimicking crown ethers.[12,13] In the PEG–NNN ligands system, it is
possible that both the long chains of PEG and the tridentate NNN ligands coor-
dinate with Pd, which stabilizes the palladium catalytic system. After reaction,
the palladium catalyst wrapped by PEG long chains coprecipitates into the
ether, and thus the catalyst system is recycled and ready for reuse.
In conclusion, immobilization of NNN ligands on PEG has afforded a
highly efficient supported Pd(OAc)2 catalyst for the Heck reaction. The
yield of the reaction reached 99% with a fresh catalytic system. No
palladium black is observed during the reaction. The ligands and catalyst
have been reused at least 10 times with fairly stable activity.
EXPERIMENTAL
All reactions were monitored by thin-layer chromatography (TLC) on gel
F254 plates. 1H NMR spectra were recorded at 500 MHz on a Bruker

PEG-Supported Ligand
195
Avance 500 spectrometer, using CDCl3 as solvent and TMS as internal
standard. Mass spectroscopy data were obtained on a Bruker Esquire-LC
with electro-spray (ESI-MS) measurements.
4-Allyloxy-2,6-pyridinedimethyl ditosylate (2)
Compound 2 was prepared according to the literature.[14]
f4- Allyloxy-6-[(methyl-benzyl-amino)methyl]-pyridin-2-ylmethylg-
methyl-benzyl-amine (3)
A well-stirred NaH(1 g, 40 mmol) suspension was prepared in dry, freshly
distilled THF. This solution was added into methyl benzyl amine (4.1 g,
39.6 mmol) in an ice bath. Then the solution was stirred at room temperature
for 2 h. This solution was added to a solution of 2(5 g, 9.9 mmol) in 50 ml of
THF dropwise. The resulting solution was stirring at 508C for 8 h. After the
reaction, the solvent was removed under reduced pressure. This concentrated
solution was poured into 200 ml of water and 200 ml of CH2Cl2. The organic
phase was dried (MgSO4) and filtered, and the solvent was removed. The
residue was purified by column chromatography (HEX/EA 8 : 1) on silica
gel to give 1.6 g (87%) of 3. 1H NMR (500 MHz,CDCl3) d 7.21–7.25
(m, 4H), 6.72–6.74 (m, 6H), 6.58 (s, 2H), 5.82–5.87(m, 1H), 5.17–
5.24(q, 2H), 4.60 (s, 4H), 4.36–4.37 (d, J ¼ 5.5 Hz, 2H), 3.10 (s, 6H). 13C
NMR (500 MHz, CDCl3) d 116.8, 161.3, 149.5, 132.0, 129.4, 118.9, 116.9,
112.3, 105.6, 68.75, 59.0, 39.2. MS-ESI C24H27N3O 374.3(M þ Hþ),
396.2(M þ Naþ).
f4-(2-Bromo-ethoxy)-6-[(methyl-benzyl-amino)methyl]-pyridin-2-
ylmethyl)g-methyl-benzyl-amine (4)
A solution of 3 (1.6 g, 4.2 mmol) in 25 ml of methanol was prepared.
K2CO3(1.65 g, 12 mmol) and Pd(PPh3)4(0.046 g, 0.04 mmol) were added to
this solution. The solution was stirred at room temperature under nitrogen
for 1 h. Then the solvent was removed under reduced pressure. This residue
was added to 25 ml freshly distilled DMF and 7.7 g (42 mmol) dibro-
moethane. The mixture was stirred at 808C for 8 h. The reaction solution
was then concentrated under pressure to remove DMF and excessive dibro-
moethane. The residue was poured into 100 ml of water and 200 ml of
DCM. The organic phase was dried (MgSO4) and filtered, and the solvent
was removed. The residue was purified by column chromatography on
1
silica gel to give 1.75 g (95%) of 4. H NMR (500 MHz, CDCl3) d 7.21–
7.25(m, 4H), 6.72–6.73(m, 6H), 6.58(s, 2H), 4.59(s, 4H), 4.13(t, 2H),

196
H.-X. Zhang et al.
3.48(t, 2H), 3.10(s, 6H). 13C NMR (500 MHz, CDCl3) d 116.3, 161.6, 149.4,
129.3, 1116.9, 112.3, 105.2, 67.4, 59.0, 39.2, 28.46. MS-ESI C23H26BrN3O
441.3(M þ Hþ), 463.2 (M þ Naþ).
PEG4000-Supported NNN Ligands (1)
A solution of PEG4000 (4 g, 1.0 mmol) in 25 ml of freshly distilled toluene
was prepared. Compound 4 (1.5 g, 3.4 mmol) was added to the solution and
stirred 10 min at room temperature. Then 0.6 g of DBU (4 mmol) was
added to the solution. The reaction mixture was stirred at room temperature
for 24 h. After the reaction, the reaction solution was poured into 100 ml of
diethyl ether, then put into an icebox for 30 min, precipitating the product
as a slightly yellow solid. This material was isolated by filtering, recrystallized
from 2-propanol, and dried under vacuum. Yield 4.88 g of 1. IR 2882.9,
1
1602.7, 1457, 1357, 1273, 1114, 836 cm21. H NMR (500 MHz, CDCl3)
d 7.23 (m, 8H), 6.73 (m, 12H), 6.5 (s, 4H), 4.58 (s, 8H), 3.45–
3.81(m, 277H, PEG backbone 2OCH2CH2O-), 3.11 (s, 12H).
General Procedure for Using 1 in Homogeneous Heck Reaction
A solution of the aryl iodide (10 mmol), olefin (15 mmol), triethylamine
(15 mmol), Pd(OAc)2 (0.03 g, 0.13 mmol), and the ligands 1 (1.26 g,
0.056 mmol) in 8 ml of DMF was heated at 1208C under an air atmosphere.
The reaction progress was monitored by GC. After the reaction, the solution
was poured into 30 ml of diethyl ether, and then the solution was kept cool
in an icebox for 30 min to get a precipitation. The precipitation was washed
with further portions of diethyl ether and then was combined with the initial
filtrate. The precipitation was redissolved in DMF for use in the next cycle.
The combined ether was washed several times with water, then dried over
MgSO4. After filtration and removal of the solvent, the product was dried
under vacuum. Ten cycles were run for each reaction (Table 2).
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