Aqueous-phase, palladium-catalyzed heck reaction: The significant role of cn-containing counter anion

Article abstract of DOI:10.1002/cjoc.201200675

Water-soluble diol-functionalized imidazolium ionic liquid 1, prepared from 2,2-bis(1-methyl-methyl-imidazolium)propane-1,3-diol bromide, potassium hydroxide, and malononitrile, was used as an efficient phosphine-free ligand for palladium-catalyzed arylation of aryl halides with acrylates in aqueous phase under mild conditions. It was found that the synergistic coordinating action of diol-functionalized imidazolium cation with CN-containing anion played the key role in improving the activity and stability of the catalyst. Water-soluble diol-functionalized imidazolium ionic liquid 1, prepared from 2,2-bis(1-methyl-methylimidazolium)propane-1,3-diol bromide, potassium hydroxide, and malononitrile, was used as an efficient phosphine-free ligand for palladium-catalyzed arylation of aryl halides with acrylates in aqueous phase under mild conditions. Copyright

Full text of DOI:10.1002/cjoc.201200675

FULL PAPER
DOI: 10.1002/cjoc.201200675
Aqueous-Phase, Palladium-Catalyzed Heck Reaction: The
Significant Role of CN-containing Counter Anion†
Cai, Yueqina(蔡月琴)
Song, Gonghua*,b(宋恭华)
Zhou, Xiaoyingb(周晓英)
a School of Chemistry and Molecular Engineering, East China University of Science and Technology, Shanghai
200237, China
b Shanghai Key Laboratory of Chemical Biology, Institute of Pesticides & Pharmaceuticals, East China
University of Science and Technology, Shanghai 200237, China
Water-soluble diol-functionalized imidazolium ionic liquid 1, prepared from 2,2-bis(1-methyl-methyl-imida-
zolium)propane-1,3-diol bromide, potassium hydroxide, and malononitrile, was used as an efficient phosphine-free
ligand for palladium-catalyzed arylation of aryl halides with acrylates in aqueous phase under mild conditions. It
was found that the synergistic coordinating action of diol-functionalized imidazolium cation with CN-containing
anion played the key role in improving the activity and stability of the catalyst.
Keywords homogeneous catalysis, acylation, Heck reaction, phosphine-free ligand, nitrile group
Introduction
catalyzed Heck reaction in recent years. Among them,
most of the reactions were carried out in organic sol-
vents like DMF or NMP.
It has been estimated that about 80% of chemical
waste resulted from use of flammable, toxic, and non-
renewable organic solvents.[1] Thus, replacing organic
solvents with more environmentally acceptable alterna-
tives becomes one of the major tasks of green chemis-
try.[2] Among the efforts on this subject, using water as a
reaction medium has received great attention since wa-
ter has the advantages of low cost, nontoxicity, non-
flammability, and being a renewable resource.[3] The
palladium-catalyzed Heck reaction has now become a
widely used synthetic methodology for forming carbon-
carbon bonds and been found numerous applications in
synthetic organic chemistry.[4-7] However, most of the
previously reported Heck reactions were carried out in
organic solvents.[4] As amendments following the first
report of cross-coupling reactions catalyzed by
Pd(TPPMS)3,[8] several examples of Pd-catalyzed Heck
cross-coupling reactions in aqueous solvents have been
demonstrated by using water-soluble phosphine
ligands.[9-13] These phosphine ligands give synthetically
useful yields indeed. However, most of P-containing
ligands have suffered from the following shortcomings:
highly toxic and air sensitive. So a number of
phosphine-free catalytic systems, such as wool-Pd,[14]
N,O-bidentate compounds,[15] 4-aminopyridine resin-
immobilized Pd,[16] pyridylbenzoimidazole,[17] palla-
dium immobilized on silica gel,[18] N,N-dimethyl-β-
alanine,[19] and so on,[20-22] have been used for palladium
We recently reported two diol-functionalized imida-
zolium ionic liquids (ILs), namely 2,2-bis(1-methyl-
methylimidazolium)propane-1,3-diol hexafluorophos-
phate and 1-(2,3-dihydroxypropyl)-3-methylimidazolium
hexafluorophosphate,[23-25] which were also proved to be
efficient phosphine-free ligands for palladium-catalyzed
Heck reaction of aryl halides with acrylates under aero-
bic condition in DMF. The predominant advantage of
diol-functionalized imidazolium ILs lies in the multiple
coordinating sites in the cation. Besides an excellent
O,O-ligand for the metal resulting from the ethylene
glycol group,[26] imidazolium skeleton can generate
N-heterocyclic carbene (NHC) in situ, which is benefi-
cial to the stabilization of Pd.[27,28] On the other hand,
Rach and Kühn[29] have pointed out that CN group
could ligate transition metal with weakly coordinating
counter anions and improve the catalysis reactivity sig-
nificantly. Their usefulness results from the labile coor-
dination mode of the CN group, which can be easily
replaced by more strongly coordinating ones, other
metal cores, or by substrates.
To date, functionalized imidazolium-based ILs have
been rapidly developed as the ligands for the palla-
dium-catalyzed Heck reaction. However, most of these
ligands are developed with advance in N-heterocyclic
carbenes (NHCs)[30,31] or with coordinating sites in the
cations.[23-25] The investigation on the effects of anions
*
E-mail: ghsong@ecust.edu.cn; Tel.: 0086-021-64253452; Fax: 0086-021-64253452
Received July 4, 2012; accepted July 20, 2012; published online October 30, 2012.
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/cjoc.20120675 or from the author.
Dedicated to the 60th Anniversary of East China University of Science and Technology.
†
Chin. J. Chem. 2012, 30, 2819—2822
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2819

Cai, Song & Zhou
FULL PAPER
General procedure for Heck reaction and recovery
of catalyst
of ILs in catalytic chemistry is only in its infancy. To
the best of our knowledge, there is no detailed report
about the co-actions of ILs-based ligands with com-
plexible counter anions, although they are highly worthy
to be investigated. Herein, we report a new phosphine-
free IL ligand 1 composed of a diol-functionalized imid-
azolium cation and a CN-containing anion. The IL
ligand was prepared from 2,2-bis(1-methyl-methyl-
imidazolium)propane-1,3-diol bromide, potassium hy-
droxide, and malononitrile (Scheme 1). The CN-con-
taining anion moiety was introduced into the ligand,
which could also weakly coordinate with the palladium
and lead to the superior retention of the palladium. The
application of it to the palladium-catalyzed Heck reac-
tion of aryl halides with acrylates was investigated in
detail. Compared to the ILs published before which
were applied as the ligands in the Heck reaction in
DMF,[23-25] using IL ligand 1 in water-DMF medium,
efficient conversion of aryl iodides/bromides with acry-
lates to the corresponding cross products was conducted
under mild reaction conditions. The recycling of the
catalytic species was also practicable. The high stability
and activity of catalyst was owing to the synergistic co-
ordinating action of diol-functionalized imidazolium
cation with CN-containing anion.
In a typical experiment, to a mixture of 1.02 g
phenyl iodide (5 mmol) with 0.86 g methyl acrylate (10
mmol) in 1.5 mL water and 0.5 mL DMF was added 1
(1.0 mol%), 0.69 g K2CO3 (5 mmol), and 0.009 g PdCl2
(1.0 mol%). The mixture was reacted at 80 ℃ for 1 h.
On completion monitored by TLC and GC, the reaction
mixture was extracted with ethyl ether (10 mL×3). The
combined organic extracts were dried with Na2SO4, fil-
tered and concentrated under vacuum to give the desired
product 0.79 g (97%). 1H NMR (DMSO-d6, 500 MHz) δ:
4.20 (s, 3H), 6.40 (d, J＝6 Hz, 1H), 7.40—7.50 (m, 5H),
7.70 (d, J＝6 Hz, 1H); MS (70 eV) m/z (%): 162 (M＋,
30), 147 (15), 131 (100), 103 (50), 77 (25), 51 (10).
The remaining liquid phase composed of PdCl2,
ligand and the formed salt of K2CO3 was used directly
without further treatment for the next run through
treated with phenyl iodide (1.02 g, 5 mmol), methyl
acrylate (0.86 g, 10 mmol), and K2CO3 (0.69 g, 5 mmol)
again.
Results and Discussion
The coupling of phenyl iodide and methyl acrylate
was chosen as the prototypical reaction for the optimi-
zation of reaction conditions.
Scheme 1
We began the investigation by conducting Heck re-
action in the presence of water. It is worth mentioning
that using water alone as a solvent would lead to re-
markable Pd precipitation with a very low yield of 20%
(Table 1, Entry 1). Therefore, DMF was selected as
co-solvent to increase both the stability of catalyst and
solubility of hydrophobic substrates in the solvent. The
results showed that the activity of catalyst increased
notably with the addition of DMF (Table 1, Entries 2—
5). Changing water/DMF volume ration from 9∶1 to
3∶1 caused a surprising increase in reaction yield from
51% to 97%. Hence, subsequent reactions were per-
formed in the mixed solution of water-DMF (V∶V＝
3∶1).
+
N
2Br-
+
N
KOH
N
N
+
NC
NC
CN
CN
Me
Me
OH OH
+
N
+
N
N
N
-
Me
Me
2
OH OH
1
Experimental
Further inspection revealed that the base, catalyst,
temperature, and the loading of catalyst also affected the
reaction quite notably. It was found that the best results
were obtained with the combination of K2CO3 as base
and PdCl2 as catalyst. The application of other bases, for
example, (n-Bu)3N, Et3N, pyridine, NaHCO3, Na2CO3,
or NMP (Table 1, Entries 6—11), or other catalysts
such as Pd(OAc)2 and Pd2(dba)3 (Table 1, Entries 12, 13)
would result in lower yields. Decreasing reaction tem-
perature or palladium loading showed a remarkably
slowing down of the reaction rate (Table 1, Entries 14,
15).
Synthesis of ionic liquid ligand 1
A mixture of 1.32 g malononitrile (20 mmol) and
1.12 g potassium hydroxide (20 mmol) in 10 mL
CH3CN was added 4.26 g of 2,2-bis(1-methyl-methyl-
imidazolium)propane-1,3-diol bromide (10 mmol) and
stirred at room temperature for 48 h. The solution was
concentrated under vacuum; ethanol was added to the
residue for extracting the product, which was dried in
vacuo to give 3.04 g of (77%) yellow oil. H NMR
(DMSO-d6, 500 MHz) δ: 3.09 (s, 4H), 3.48 (s, 2H), 3.84
(s, 6H), 4.20 (s, 4H), 5.15 (s, 2H), 7.65 (s, 2H), 7.75 (s,
1
2H), 8.61 (s, 2H); IR (KBr) ν: 3370, 3152, 3109, 2957,
2155, 1622, 1571, 1513, 1350, 1167, 1027 cm－
;
1
On the other hand, the nature of IL ligands also
played an important role in affecting the coupling reac-
tion. To demonstrate the effects of IL ligands, the
＋
ESI-MS m/z: 421.2 (M ＋ Na) , 265.1 (M －
[(CNCHCN)2]－H)＋, 133.1 ((CNCHCN)2＋3H)＋.
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Chin. J. Chem. 2012, 30, 2819—2822

Aqueous-Phase, Palladium-Catalyzed Heck Reaction
Table 1 Heck cross-coupling reaction of phenyl iodide with
methyl acrylatea
Scheme 2
COOMe
I
cat.-ligand
+
N
+
N
+
COOMe
Base/DMF/H2O
N
N
2Br-
Me
Me
Entry Cat. (Dosage/mol%) Base V(H2O)∶V(DMF) Yieldb/%
OH OH
1
2
PdCl2 (1.0)
PdCl2 (1.0)
PdCl2 (1.0)
PdCl2 (1.0)
PdCl2 (1.0)
PdCl2 (1.0)
PdCl2 (1.0)
PdCl2 (1.0)
PdCl2 (1.0)
PdCl2 (1.0)
PdCl2 (1.0)
Pd2(dba)3 (0.5)d
Pd(OAc)2 (1.0)
PdCl2 (1.0)
PdCl2 (0.5)
PdCl2 (1.0)
PdCl2 (1.0)
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
(n-Bu)3N
Et3N
Pure water
9∶1
17∶3
4∶1
3∶1
3∶1
3∶1
3∶1
3∶1
3∶1
3∶1
3∶1
3∶1
3∶1
3∶1
3∶1
3∶1
3∶1
20
51
63
83
97
44
61
65
54
58
38
35
56
63
60
58
63
70
2
3
+
N
4
5c
+
N
N
N
-
2PF6
Me
Me
6
OH OH
7
3
8
Pyridine
NaHCO3
Na2CO3
NMP
9
functionalized imidazolium cation and CN-containing
anion on stabilization and catalysis of palladium was the
key element to the success of Heck reaction in this case.
Recyclability of the catalyst PdCl2-1 was also inves-
tigated. After each cycle, the product was extracted with
ethyl ether, and the aqueous phase containing catalyst
PdCl2-1 was reused directly for the next catalytic run.
Recycling experimental results indicated that the cata-
lytic activity of the recycled catalyst was lower because
the time required to obtain the same conversion was
double. However, this catalytic system could be reused
at least 5 times without significant loss of activity (Ta-
ble 2). The good performance of the catalyst is ascribed
to the strong chelating coordination of both cation and
anion with the metal center, which makes catalyst ex-
hibit good thermal and oxidative stability in practice.
10
11
12
13
14e
15f
16g
17h
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
18 PdCl2(CH3CN)2 (1.0) K2CO3
a
The molar ratios of phenyl iodide/methyl acrylate/base/are 1∶
2∶1, the molar ratio of ligand 1 to PdCl2 is 1∶1, temperature 80
℃, reaction time 1 h. Isolated yields. Pd precipitations are not
found. dba, dibenzylidene acetone.
f Reaction time 15 h. g Ligand 2. h Ligand 3.
b
c
d
e
Temperature 60 ℃.
Table 2 Recycling of PdCl2-1 catalysta
analogous Br and PF6 anion-containing ILs, 2,2-bis(1-
methyl-methylimidazolium)propane-1,3-diol bromide (2)
and 2,2-bis(1-methyl-methylimidazolium)prpane-1,3-
diol hexafluorophosphate (3)[25] (Scheme 2) were syn-
thesized and applied to the model reaction. It was found
that the CN-containing anion IL 1 showed the highest
activity (Table 1, Entry 5), while ILs 2 and 3 gave lower
yields of products probably due to Pd precipitation (Ta-
ble 1, Entries 16 and 17). The higher capacity for im-
mobilization of the palladium complex and better cata-
lytic activity of IL 1 probably resulted from the
co-action of its cation ligand and counteranion. In addi-
tion to the coordination of diol-functionalized imida-
zolium cation, the CN-containing anion moiety could
also weakly coordinate with the palladium, which led to
the superior retention of the palladium and high activity
in catalyzing Heck reaction.
Run
1
Yieldb/%
Time/h
97
95
93
94
92
1
1
1
2
2
2
3
4
5
a
PdCl2 1.0 mol%, ligand 1 1.0 mol%, phenyl iodide 5 mmol,
methyl acrylate 10 mmol, H2O/DMF (1.5/0.5 mL), K2CO3
mmol (additionally added per pass). b Isolated yield.
5
To explore the scope of PdCl2-1 catalytic system in
catalyzing Heck coupling reactions in H2O/DMF,
methyl or ethyl acrylate was coupled with various sub-
stituted aryl halides. As can be seen from Table 3, in the
cases of bromides/iodides, all the reactions proceeded
with high selectivity and moderate to good yields. Ac-
cording with the earlier reports, aryl bromides/iodides
with an electron-withdrawing substituent (Table 3, En-
tries 5, 6, 11, 12) gave higher yields than those with an
electron-donating substituent (Table 3, Entries 3, 4, 7—
Furthermore, another catalyst with a CN-containing
anion, PdCl2(CH3CN)2 was adopted without ligand 1
(Table 1, Entry 18). Lower yield of 70% and Pd pre-
cipitation were obtained. Thus, the experimental results
clearly demonstrated that the synergistic effect of diol-
Chin. J. Chem. 2012, 30, 2819—2822
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2821

Cai, Song & Zhou
FULL PAPER
10, 13, 14). Unfortunately, however, as to the activation
of chlorides, relatively poor activity was observed (Ta-
ble 3, Entries 15, 16) probably due to poorer activity of
chlorides. To some degrees, some heterogeneous cata-
lysts like Pd/C[32] are even good for coupling aryl chlo-
rides compared with the catalyst PdCl2-1. But the recy-
clability of the heterogeneous catalysts is discounted
owing to the aggregation and agglomeration of Pd parti-
cles into less active large particles during the reac-
tion.[14]
recycling of PdCl2-1 was also achieved.
Acknowledgement
We acknowledge the National Natural Science
Foundation of China (No. 20676033), the China Post-
doctoral Science Foundation (No. 20070410169) and
the Shanghai Leading Academic Discipline Project (No.
B507) for financial support.
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COOR2
X
PdCl2-1
+
COOR2
K2CO3/DMF/H2O
R1
R1
Entry
R1
H
R2
Me
Et
X
I
Time/h
1
Yieldb/%
97
1
2
H
I
1
98
3
p-OCH3
p-OCH3
p-NO2
p-NO2
p-CH3
p-CH3
o-CH3
o-CH3
p-NO2
p-NO2
p-CH3
p-CH3
p-NO2
p-NO2
Me
Et
I
6
80
4
I
6
76
5
Me
Et
I
0.5
0.5
4
96
6
I
98
7
Me
Et
I
84
8
I
4
81
9
Me
Et
I
10
10
2
69
10
11
12
13
14
15
16
I
70
Me Br
Et Br
Me Br
Et Br
Me Cl
Et Cl
95
2
94
24
24
24
24
70
68
24
21
a PdCl2 1.0 mol%, ligand 1 1.0 mol%, haloarene 5 mmol, acrylate
b
10 mmol, K2CO3 5 mmol, H2O/DMF (1.5/0.5 mL). Isolated
yields.
Conclusions
In summary, an excellent catalytic system was
formed by the chelating coordination of a diol-func-
tionalized imidazolium ionic liquid involving a CN-
containing anion with the readily available PdCl2. With
this catalytic system, the arylation of aryl iodides/bro-
mides with acrylates could proceed smoothly in aqueous
media under air conditions. The good thermal, moist
and oxidative stability of catalyst was attributed to the
synergistic action of diol-functionalized imidazolium
cation and CN-containing anion. Moreover, effective
[32] Mukhopadhyay, S.; Rothenberg, G.; Joshi, A.; Baidossi, M.; Sasson,
Y. Adv. Synth. Catal. 2002, 344, 348.
(Zhao, C.)
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