A palladium salen complex: An efficient catalyst for the Sonogashira reaction at room temperature

Article abstract of DOI:10.1039/c4nj01822b

A tetradentate Schiff base derived palladium complex has been developed as a catalyst for the room temperature Sonogashira reaction under copper free conditions. The main catalytic species, a Pd-complex was derived from Schiff base ligand N,N′-bis(salicylidene)-arylmethanediamine and Pd(OAc)₂. Electron rich, electron deficient and sterically hindered aryl iodides underwent smooth coupling to afford good to excellent yield of diaryl alkynes in isopropanol at room temperature. The protocol is also suitable for aliphatic alkynes.

Full text of DOI:10.1039/c4nj01822b

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A palladium salen complex: an efficient catalyst
for the Sonogashira reaction at room
temperature†
Cite this:DOI: 10.1039/c4nj01822b
Received (in Montpellier, France)
17th October 2014,
Ankur Gogoi,a Anindita Dewan,*ab Geetika Boraha and Utpal Bora*ab
Accepted 24th February 2015
DOI: 10.1039/c4nj01822b
www.rsc.org/njc
A tetradentate Schiff base derived palladium complex has been devel- N-based ligands such as N-heterocyclic carbenes,9 hydrazones,10
oped as a catalyst for the room temperature Sonogashira reaction pyrimidines11 etc. and complexes such as palladacycles12 are
under copper free conditions. The main catalytic species, a Pd-complex unanimously tested in the Sonogashira reaction. Among the
was derived from Schiff base ligand N,N0-bis(salicylidene)-aryl- several N-based ligands, Schiff bases draw considerable attention
methanediamine and Pd(OAc)2. Electron rich, electron deficient owing to their easy methods of preparation and high coordinating
and sterically hindered aryl iodides underwent smooth coupling to capacity for different transition metals.
afford good to excellent yield of diaryl alkynes in isopropanol at
Moreover, electronic and steric properties of Schiff-bases
room temperature. The protocol is also suitable for aliphatic alkynes. could be easily tuned by properly selecting the condensing
partners. Thus a countless number of Schiff base complexes
In recent decades the Pd-catalyzed Sonogashira reaction has with different metal ions such as Cu, Pd, Fe, Ni, Co etc. are
contributed immensely towards the incorporation of an alkyne reported in the literature.13 Many of these complexes demon-
moiety in the organic molecule which serves as a key inter- strate their capacity as catalysts in different organic reactions.13
mediate for pharmaceutical and natural products.1 In addition, Although Pd-Schiff base complexes are very common and
alkyne derivatives find wide applications in material chemistry extensively studied in the Suzuki–Miyaura14 cross coupling
due to their unique electrical and optical properties.2 The reaction but their application in the Sonogashira reaction is
Sonogashira reaction is a cross coupling reaction between an limited.15 Recently we have demonstrated the efficiency of
alkyne and an electrophile such as aryl halides, vinyl halides or tetradentate Pd-Schiff base complexes in Suzuki–Miyaura16
triflates in the presence of a suitable Pd-source.1 Convention- and Cu-Schiff base complexes in Chan–Lam17 coupling reac-
ally these reactions are accelerated by the addition of Cu-salt tions respectively. So in order to extend the scope of Pd-Schiff
and suitable phosphine based ligands.3 However formation of base complexes under green conditions, we herein report a
an undesired Glaser type coupling product from Cu-mediated simple and efficient protocol for the Sonogashira reaction of
reactions enforce the researchers to develop a Cu free protocol aryl iodides in isopropanol at room temperature.
for the Sonogashira reaction.4 As a result several alternate proto-
The three Pd–salen complexes C1–C3 were prepared by
cols have been designed where the use of other additives such as refluxing Pd(OAc)2 with their respective N,N0-bis(salicylidene)-
Ag,5 Zn,6 Sn,7 tetra-n-butyl ammonium salt8a and sodium sulfate8b arylmethanediamine (L1–L3) ligand following a literature
as an activator was utilized. Furthermore phosphine based report (Fig. 1).16
ligands are usually toxic and unstable in air which restricts their
Our next goal was to evaluate the catalytic activity of the
wide spread application. In that regard nitrogen based ligands synthesized Pd-salen complex in the Sonogashira reaction of
and their complexes with palladium can be a good alternative as aryl iodides. For that purpose iodobenzene (0.5 mmol) and
these are quite stable in comparison to phosphines. Thus several phenyl acetylene (1 mmol) were considered as model substrates
for reaction optimization. Initial reactions were performed with
2 mol% of Pd-source and three equivalents of K2CO3 (1.5 mmol)
in isopropanol (2 mL) at room temperature under aerobic
conditions. The optimization results are highlighted in Table 1.
Among the three Pd-complexes (C1–C3) maximum reactivity
was observed in the case of complex C2 which has a nitro group
at the para-position of the phenylmethanediamine moiety
a Department of Chemistry, Dibrugarh University, Dibrugarh-786004, Assam, India.
E-mail: utbora@yahoo.co.in, ubora@tezu.ernet.in, adewan@tezu.ernet.in;
Fax: +91-373-2370323
b Department of Chemical Sciences, Tezpur University, Tezpur 784028, Assam, India
† Electronic supplementary information (ESI) available. See DOI: 10.1039/
c4nj01822b
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Table 2 Effect of base in the Sonogashira reactiona
Entry
Base
Time (h)
Yieldb (%)
1
2
—
Et3N
Pyridine
KOH
NaOH
NaHCO3
Na3PO4ꢀ12H2O
Na2CO3
K2CO3
24
24
24
24
24
24
12
10
07
09
Trace
67
61
41
40
68
89
92
98
3
4c
5c
6c
7
Fig. 1 Screened ligands and complex.
8
9
10
Cs2CO3
97
a
(Table 1, entry 2 vs. entries 1 and 3). However two other
complexes C2 and C3 also produce good yield of the isolated
cross coupling product.
Reaction conditions: iodobenzene (0.5 mmol), phenylacetylene (1 mmol),
b
Pd complex C2 (2 mol%), base (1.5 mmol), isopropanol (2 mL). Iso-
lated yields. Reaction did not complete.
c
It is worth mentioning that in many reported procedures of
the Sonogashira reaction, usually electron rich substrates result
in a comparatively low yield of the cross coupling product.18
However our catalyst system is compatible with this type of
substrate (Table 1). It is interesting to observe that the reaction
fails to complete when 2 mol% L2 was used with Pd(OAc)2
under the same reaction conditions (Table 1, entry 7). The
application of only Pd(OAc)2 afforded a low yield of the corres-
ponding cross coupling product (Table 1, entry 8). Next we
found that the amount of C2 also affects the yield up to some
extent. The optimum result was achieved with 2 mol% of C2
(Table 1, entry 2 vs. 9). It is a well known fact that base plays a
crucial role in the overall performance of a catalytic system in a
Sonogashira reaction (Table 2, entry 1). Thus to investigate its
effect several inorganic and organic bases were tested in the
Sonogashira reaction of iodobenzene (0.5 mmol) and phenyl-
acetylene (1 mmol) with catalyst C2 (2 mol%) in isopropanol
(2 mL). The common organic bases such as Et3N and pyridine
generally used in the Sonogashira reaction were found to be
less reactive in our catalytic system (Table 1, entries 2 and 3).
The same behaviour was also observed with hydroxide (Table 2,
entries 4 and 5) and bicarbonate base (Table 2, entry 6) as in
both the cases the reaction did not complete even after 24 h.
In contrast carbonate bases viz. Na2CO3, K2CO3 and Cs2CO3
provide excellent yield of the cross coupling product (Table 2,
entries 8–10). So we have considered K2CO3 for further
optimization.
Next we investigated the effect of solvent in the Sonogashira
reaction. As shown in Table 3 better performance of the
catalytic system was observed when alcoholic solvents viz.
MeOH, EtOH and isopropanol were used (Table 3, entries 1–3).
Similar results were also noticed with DMF and DMSO (Table 3,
entries 4 and 5). However the yield was significantly decreased
when H2O was used as the solvent (Table 3, entry 6); this may be
due to the insolubility of the substrate and catalyst in water.
Application of 1 : 1 aqueous isopropanol did not improve the
yield to a significant extent (Table 3, entry 7). On the other hand
inferior results were obtained with solvents like THF, CH3CN
and DCM (Table 3, entries 8–10). So based on the above we have
considered isopropanol for further optimization.
Finally we investigated the substrate ratio for efficient coupling.
The favourable conditions were observed with 1:1.5 equivalent of
iodobenzene to phenyl acetylene (Table 4, entry 2 vs. entries 1 and 3).
The scope and limitation of the current protocol has been
investigated with several electronically diverse aryl iodides and
aryl acetylenes in i-PrOH at room temperature. The results are
Table 3 Effect of solvents in the Sonogashira reactiona
Table 1 Optimization of catalysts for the Sonogashira reactiona
Entry
Solvent (2 mL)
Time (h)
Yieldb (%)
Entry
Pd source (2 mol%)
R
Time (h)
Yieldb (%)
1
2
3
4
5
6
7
8
9
10
MeOH
EtOH
Isopropanol
DMF
DMSO
10
11
07
14
10
24
18
24
24
24
96
94
98
91
89
72
83
64
58
69
1
2
3
4
5
6
7
8
9
C1
C2
C3
C1
C2
C3
H
H
H
OCH3
OCH3
OCH3
H
H
H
10
07
12
16
10
24
24
24
24
92
98
90
89
96
85
80
62
81
H2O
Isopropanol: H2O
DCM
THF
Pd(OAc)2 + L2
Pd(OAc)2
C2 (1 mol%)
CH3CN
a
a
Reaction conditions: aryl iodide (0.5 mmol), phenylacetylene (1 mmol),
Reaction conditions: iodo benzene (0.5 mmol), phenylacetylene
Pd-complex (2 mol%), K2CO3 (1.5 mmol), isopropanol (2 mL), 25 1C in (1 mmol), Pd-complex-C2 (2 mol%), K2CO3 (1.5 mmol), solvent (2 mL),
b
b
air. Isolated yields.
25 1C in air. Isolated yield.
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Table 4 Optimization of substrate ratio in the Sonogashira reaction
In conclusion we have developed a tetradentate Schiff base
derived Palladium complex for the Sonogashira reaction in
i-PrOH at room temperature under copper free conditions.
The catalyst is very simple and the starting materials used are
commercially available and cheap. Electronically diversified
aryl iodides underwent the coupling reaction with electronically
diversified aryl/alkyne acetylene in excellent yields. Absence of
additives, use of isopropanol as the solvent and the broad
substrate scope of this protocol make it an attractive alternative
for the existing protocols of the Sonogashira reaction of aryl
iodides.
Entry
A : B
Time (h)
Yielda (%)
1
1 : 2
1 : 1.5
1 : 1
7
7
8
98
98
74
2
3b
a
b
Isolated yields. Reaction did not complete.
Table 5 C2 complex promoted synthesis of internal acetylenea
Experimental
R1
R2
X
Time (h)
Yieldb (%)
A 50 mL oven dried round bottomed flask was charged with
aryl iodide (0.5 mmol), alkyne (0.75 mmol), K2CO3 (1.5 mmol,
207 mg), C2 complex (2 mol%, 4.79 mg) in 2 mL of isopropanol
at room temperature (25 1C) under aerobic conditions. The
reaction mixture was stirred on a magnetic stirrer for appro-
priate time. The progress of the reaction was monitored by TLC.
After the completion of the reaction, the mixture was diluted
with 20 mL of water and extracted with diethyl ether (3 ꢁ 20 mL).
The combined organic layer were washed with brine and dried
over anhydrous Na2SO4 and evaporated in a rotary evaporator
under reduced pressure. The crude compound was purified by
column chromatography on silica gel (hexane) to afford the
desired product. The purity of the compound was confirmed
by 1H NMR, 13CNMR and MS data.
1
2
3
4
5
6
7
8
H
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
4-MeC6H4
4-MeC6H4
4-MeC6H4
4-MeC6H4
4-MeC6H4
C6H5
C10H21CRCH
C10H21CRCH
C6H5
I
I
I
I
I
I
I
I
I
I
I
I
I
I
Br
Br
I
7
10
12
15
3
98
97
94
88
99
98
90
93
94
96
99
92
90
91
54c
62c
90
4-Me
4-OMe
4-NH2
4-NO2
4-COCH3
H
4-OMe
4-Me
4-COCH3
4-NO2
2-NO2
H
6
18
15
15
10
6
10
14
8
9
10
11
12
13
14
15
16
17
4-NO2
4-Me
4-OMe
H
24
24
12
C6H5
4-NO2C6H4
The authors acknowledge the Department of Science and
Technology, New Delhi, for financial support of this work under
DST Woman Scientist Scheme (No. SR/WOS-A/CS-78/2011(G)).
A.G. thanks the Department of Science and Technology,
New Delhi, for an INSPIRE research fellowship.
a
Reaction conditions: aryl iodide (0.5 mmol), alkyne (0.75 mmol),
Pd-complex-C2 (2 mol%), K2CO3 (1.5 mmol), isopropanol (2 mL),
b
25 1C in air unless otherwise noted. Yields are given for isolated
products. Reaction did not complete.
c
summarised in Table 5. The electron donating groups such as
–OMe, –Me, –NH2 at the para position of aryl iodide couple
smoothly with phenyl acetylene to give good to excellent yield of
isolated cross coupling products (Table 5, entries 2–4).
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