Copper- and phosphine-free Sonogashira coupling reactions of aryl iodides catalyzed by an N,N-bis(naphthylideneimino)diethylenetriamine-functionalized polystyrene resin supported Pd(II) complex under aerobic conditions

Article abstract of DOI:10.1016/j.tetlet.2010.07.011

A polymer-supported palladium(II) N,N-bis(naphthylideneimino) diethylenetriamine complex is found to be a highly active catalyst for Sonogashira coupling reactions. The reactions are performed under copper- and phosphine-free conditions in an air atmosphere. The palladium catalyst is easily separated, and can be reused several times without significant loss in catalytic activity.

Full text of DOI:10.1016/j.tetlet.2010.07.011

Tetrahedron Letters 51 (2010) 5653–5656
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Tetrahedron Letters
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Copper- and phosphine-free Sonogashira coupling reactions of aryl iodides
catalyzed by an N,N-bis(naphthylideneimino)diethylenetriamine-
functionalized polystyrene resin supported Pd(II) complex under
aerobic conditions
*
Mohammad Bakherad , Amir H. Amin, Ali Keivanloo, Bahram Bahramian, Mersad Raeissi
School of Chemistry, Shahrood University of Technology, Shahrood, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
A polymer-supported palladium(II) N,N-bis(naphthylideneimino)diethylenetriamine complex is found to
be a highly active catalyst for Sonogashira coupling reactions. The reactions are performed under copper-
and phosphine-free conditions in an air atmosphere. The palladium catalyst is easily separated, and can
be reused several times without significant loss in catalytic activity.
Received 12 April 2010
Revised 16 June 2010
Accepted 2 July 2010
Available online 7 July 2010
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
Copper- and phosphine-free
Sonogashira reaction
Supported catalyst
Aryl iodides
The Pd–Cu-catalyzed coupling reaction of terminal alkynes with
aryl and vinyl halides to give enynes (Sonogashira cross-coupling),
has become an extremely powerful tool for constructing conju-
gated acetylenes.1 Conventionally, the reaction is performed using
catalytic amounts of a palladium–phosphine complex and CuI in
the presence of a large excess of a secondary or tertiary amine or
various bases such as alkali-metal carbonates.2 However, many
Pd–phosphine complexes are sensitive to both air and moisture,
and their cost and toxicity limit large scale industrial applications.
Also, a major problem with Sonogashira reactions is the use of a
copper reagent (co-catalyst), which is frequently required to pro-
mote the reaction, and which results in contamination of the cou-
pling products with metal residues.
It has been well-documented that the Sonogashira coupling of-
ten suffers from Glaser-type oxidative dimerization of the alkyne
substrate,3 as a side-reaction in the presence of a Cu(I) co-catalyst.
In recent years, numerous modifications have been reported for the
Sonogashira coupling, these include reactions in ionic liquids,4
reaction as a microemulsion,5 a zeolite-supported reaction sys-
tem,6 a fluorous biphasic system (FBS) using fluorous palladium
catalysts,7 phase-transfer catalytic reaction conditions,8 various
copper-free conditions,9 non-phosphine Sonogashira coupling,10
the use of a variety of promoters11 such as Zn, Mg and Sn, and
microwave irradiation.12
Initially, a soluble palladium complex [(PdCl2(PPh3)2)] was used
as the catalyst for the Sonogashira coupling reaction. However, it
was later found that palladium metal can also catalyze the reac-
tion. The main advantage of using palladium in the form of a het-
erogeneous catalyst is the easy separation of the catalyst from the
reaction mixture. Moreover, from the standpoint of environmen-
tally benign organic synthesis, the development of highly active
and easily reusable immobilized catalysts is of significant interest
to chemists.13 To date, research on polymer-supported catalysts
suggests that these catalytic systems are promising alternatives.14
Despite numerous reports on the use of the Sonogashira reac-
tions in organic synthesis, polymer-supported palladium catalysts
have not been widely applied for this reaction.15 Polymer-sup-
ported palladium complex catalysts derived from chloromethyl
polystyrene resin have been employed in both the Heck16 and Su-
zuki17 reactions, and have shown lower levels of palladium leach-
ing during cross-coupling.
We previously reported on the Sonogashira coupling reactions
of aryl iodides with terminal alkynes using a water-soluble palla-
dium–N,O complex (Pd–salen complex) as
a homogenous
catalyst.18
Our continuing interest in the catalytic utility of polystyrene–
resin-supported palladium complexes19 led us to examine Sono-
gashira coupling reactions with the aforementioned palladium–
N,O complex as a heterogeneous catalyst. Herein, we report the
facile copper- and phosphine-free Sonogashira reactions of aryl
iodides with terminal alkynes catalyzed by an N,N-bis
* Corresponding author. Fax: +98 2733395441.
E-mail address: m.bakherad@yahoo.com (M. Bakherad).
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.07.011

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M. Bakherad et al. / Tetrahedron Letters 51 (2010) 5653–5656
(naphthylideneimino)diethylenetriamine-functionalized polysty-
rene resin-supported palladium(II) complex [PS–nap–Pd(II)] under
aerobic conditions.
To evaluate the catalytic activity of the polymer-supported pal-
ladium(II) catalyst, [PS–nap–Pd(II)], the Sonogashira coupling reac-
tions of terminal alkynes with aryl iodides were studied. Initially,
to determine the optimum conditions, the influence of base, sol-
vent, and amount of catalyst were investigated for the reaction of
iodobenzene with phenylacetylene (Table 1). Among the bases
tested (Et3N, DIEA, pyridine, and pyrrolidine), Et3N proved to be
the most efficient (entry 5). DMF was found to be the best choice
of solvent among those tested (entry 5). Increasing the amount
of palladium catalyst shortened the reaction time but did not in-
crease the yield of diphenylacetylene (entry 21). A low palladium
concentration prolonged the reaction time and gave a decreased
yield (entry 22). Thus the optimum conditions required 1.0 mol %
of the catalyst, Et3N as the base, and DMF as the solvent at room
temperature (entry 5).
To examine the scope of this coupling reaction, a variety of
terminal alkynes 3 were reacted with aryl iodides 4 containing
electron-withdrawing or donating groups under the optimized
conditions (Scheme 2). The results are summarized in
Table 2. The Sonogashira reactions of electron-rich aryl iodides
with terminal alkynes proceeded smoothly to give the corre-
sponding coupling products in good to high yields (entries 3,
11, and 14).
The ease of preparation of the complex, its long shelf-life, stabil-
ity toward air, and compatibility with a wide variety of aryl iodides
and alkynes make it ideal for the above mentioned reactions.
The immobilized Schiff base palladium [PS–nap–Pd(II)] can be
prepared easily from a commercially available polymer. We used
chloromethylated polystyrene (2% divinylbenzene) as the catalyst
support because it is a popular polymeric material due to its low
cost, ready availability, mechanical robustness, and ease of func-
tionalization. In this approach, the Schiff base palladium complex
is attached, via a covalent bond, to a pendant chloromethyl group
on the surface of the polymer resin particles.
Reaction of polystyrene–N,N-bis(naphthylideneimino)diethyl-
enetriamine (PS–nap) (1)20 with a solution of [PdCl2(PhCN)2] in
ethanol under reflux resulted in covalent attachment of the palla-
dium complex to give the polymer-supported palladium(II) com-
plex catalyst [PS–nap–Pd(II)] (2) (Scheme 1).
The extent of immobilization was confirmed by IR spectroscopy
(Pd–N ꢀ 550 cmÀ1). The metal loading of the polymer-supported
palladium complex, determined by neutron activation analysis
(NAA), was found to be 3.85% (0.36 mmol/g).
N
N
Pd
N
N
N
[PdCl2(PhCN)2]
N
OH
O
O
HO
EtOH, reflux, 10 h
1
2
Scheme 1.
Table 1
Optimization of the conditions for the copper- and phosphine-free Sonogashira reaction of iodobenzene with phenylacetylenea
PS-nap-Pd(II)
C
C
I
CH
+
base, solvent, r.t.
Entry
Solvent
Base
PS–nap–Pd(II) (mol %)
Time (h)
Yieldb (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
DMF
DMF
DMF
DMF
Et3N
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
2.0
0.5
4
5
4
6
3
3
4
4
3
5
4
4
5
7
5
6
6
8
7
7
2
6
80
78
82
81
95
91
90
92
92
88
90
93
90
86
91
87
82
80
84
81
95
85
DIEAc
Pyridine
Pyrrolidine
Et3N
DIEA
Pyridine
Pyrrolidine
Et3N
DMACd
DMAC
DMAC
DMAC
NMPe
NMP
NMP
NMP
THF
THF
THF
THF
DMF
DIEA
Pyridine
Pyrrolidine
Et3N
DIEA
Pyridine
Pyrrolidine
Et3N
DIEA
Pyridine
Pyrrolidine
Et3N
DMF
Et3N
a
b
c
Reaction conditions: iodobenzene (1.0 mmol), phenylacetylene (1.5 mmol), base (2.0 mmol), solvent (2 mL), room temperature, aerobic conditions.
GC yield.
Diisopropylethylamine.
Dimethylacetamide.
N-Methylpyrrolidone.
d
e

M. Bakherad et al. / Tetrahedron Letters 51 (2010) 5653–5656
5655
R2
R2
1 mol% PS-nap-Pd(II)
R1
R1
CH
C
C
C
I
+
Et3 N, DMF, r.t.
3
4
5
Scheme 2.
Table 2
1. N,N-Bis(naphthylideneimino)diethylenetriamine-function-
alized polystyrene resin-supported Pd(II) complex 2
Copper-free Sonogashira reactions of various terminal alkynes and aryl iodides (see
Scheme 2)a
Entry
R1
R2
Time (h)
Product
Yieldb (%)
A mixture of polystyrene–N,N-bis(naphthylideneimino)diethyl-
enetriamine (1) (3.0 g) and [PdCl2(PhCN)2] (0.25 g) in EtOH (50 mL)
was heated under reflux for 10 h. The resulting bright-yellow col-
ored polymer, impregnated with the metal complex, was filtered,
washed with EtOH, and dried at 50 °C to give [PS–nap–Pd(II)] (2)
(Scheme 1).
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
Ph
Ph
Ph
Ph
Ph
Ph
Ph
n-C4H9
n-C4H9
n-C4H9
n-C4H9
Me3Si
Me3Si
Me3Si
n-C6H13
n-C6H13
n-C6H13
H
3
3
4
3
3
3
3
4
3
3
4
4
3
4
5
3
3
5a
5b
5c
5d
5e
5f
5g
5h
5i
5j
5k
5l
5m
5n
5o
5p
5q
95 (90)
97 (93)
90
99 (95)
93
92
92
93
98 (93)
96 (90)
92
91
88
85
87
95 (91)
93 (88)
4-COCH3
4-OCH3
4-NO2
3-NO2
4-Cl
4-Br
H
4-NO2
4-COCH3
4-OCH3
H
4-Cl
4-OCH3
H
4-NO2
4-COCH3
2. General procedure for the Sonogashira coupling reaction
A round-bottomed flask was charged with aryl iodide (1.0 mmol),
terminal alkyne (1.5 mmol), [PS–nap–Pd(II)] (0.01 mmol), Et3N
(2 mmol), and DMF (2 mL). The mixture was stirred at room temper-
ature for 3–5 h under aerobic conditions. Upon completion of the
reaction, the solution was concentrated in vacuo, and the crude
product was subjected to silica gel column chromatography using
CHCl3–CH3OH (97:3) as eluent to afford the pure product.
a
Reaction conditions: 3 (1.5 mmol), 4 (1.0 mmol), PS–nap–Pd(II) (0.01 mmol),
Et3N (2 mmol), DMF (2 mL), room temperature, aerobic conditions.
b
GC yield. Numbers in parentheses are isolated yields.
Acknowledgment
Unsurprisingly, p-nitroiodobenzene was found to be the most
reactive among the aryl iodides studied (entries 4, 9, and 17). As
expected, aryl iodides with electron-withdrawing groups reacted
faster than aryl iodides possessing electron-donating groups to
give the desired products in high yields.
The authors are grateful to the Research Council of Shahrood
University of Technology for the financial support of this work.
References and notes
The recyclability of the PS–nap–Pd(II) catalyst 2 was examined
in the Sonogashira coupling of iodobenzene and phenylacetylene.
The catalyst was separated from the reaction mixture by filtration
after each experiment, washed with water and acetonitrile, and
dried carefully before use in subsequent runs. Thus after the first
reaction, which gave a quantitative yield of the coupling product
5a (Table 3, entry 1), the catalyst beads were recovered and succes-
sively subjected to nine further runs under the same conditions to
afford 5a in 93_85% yields (Table 3).
In conclusion, we have developed a protocol for the copper- and
phosphine-free Sonogashira coupling reactions of aryl iodides with
terminal acetylenes using a [PS–nap–Pd(II)] complex to give vari-
ous biaryl acetylene derivatives. The catalyst was recovered and re-
used 10 times with only marginal loss in catalytic activity.
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