Phosphine-free Pd-salen complexes as efficient and inexpensive catalysts for Heck and Suzuki reactions under aerobic conditions

Article abstract of DOI:10.1016/j.tetlet.2008.03.109

Phosphine-free palladium-salen complexes, N,N′-bis(salicylidene)-ethylenediamino-palladium and N,N′-bis(salicylidene)-1,2-phenylenediamino palladium, are found to be highly active catalysts for the Heck olefination of aryl iodides and Suzuki reaction of aryl iodides and bromides giving excellent yields (70-90%) of products under aerobic conditions, in short reaction times (10-60 min).

Full text of DOI:10.1016/j.tetlet.2008.03.109

Available online at www.sciencedirect.com
Tetrahedron Letters 49 (2008) 3423–3429
Phosphine-free Pd–salen complexes as efficient and inexpensive
catalysts for Heck and Suzuki reactions under aerobic conditions
Sanjay R. Borhade, Suresh B. Waghmode *
Department of Chemistry, University of Pune, Ganeshkhind, Pune 411 007, India
Received 25 January 2008; revised 19 March 2008; accepted 24 March 2008
Available online 28 March 2008
Abstract
Phosphine-free palladium–salen complexes, N,N0-bis(salicylidene)-ethylenediamino-palladium and N,N0-bis(salicylidene)-1,2-phenyl-
enediamino palladium, are found to be highly active catalysts for the Heck olefination of aryl iodides and Suzuki reaction of aryl iodides
and bromides giving excellent yields (70–90%) of products under aerobic conditions, in short reaction times (10–60 min).
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords: Heck; Suzuki; Pd–Salen; Iodobenzene; Phenylboronic acid
1. Introduction
ureas,7a,8 tetrazoles,9 phenanthroline,10 bisimidazole,11 bis-
pyridines,12 amino acids,13 and hydroxyquinolines,14
hydrazones,15 N-phenylurea,16 and Schiff bases.17 Herein,
we report the synthesis of the symmetrical palladium(II)
complexes, N,N0-bis(salicylidene)-ethylenediamino-palla-
dium (A), and N,N0-bis(salicylidene)-1,2-phenylenediamino
palladium (B) and their catalytic activity in Heck and
Suzuki coupling reactions with various substrates.
The symmetrical palladium(II) complexes A and B were
synthesized by the reaction of the salen ligands, N,N0-
bis(salicylidene)-ethylenediamine and N,N0-bis(salicyl-
idene)-1,2-phenylenediamine, with palladium acetate for
18–20 h at room temperature (Scheme 1), in moderate
yields. The synthesis of complex A was previously reported
by Abu-Omar and co-workers in poor yield (17–30%).18
In our synthesis, complexes A and B were obtained as
yellow and brown crystalline solids in 76% and 55% yields,
respectively. The catalytic activities of complexes A and B
(0.5 mol %) were studied in the Heck reaction using iodo-
benzene and ethyl acrylate as substrates, in the presence
of triethylamine as base, at 130 °C under aerobic condi-
tions (Scheme 2). The catalytic activity showed that
complex A (100% in 10 min) was superior to B (69% in
10 min). Therefore, further reactions were optimized using
complex A.
The design of new ligands and transition metal catalysts
that are effective in C–C bond forming reactions with high
conversion and selectivity is an exciting and challenging
area of research.1 The palladium-catalyzed Heck and
Suzuki reactions have been used extensively for the syn-
thesis of natural products, pharmaceutical intermediates,
conducting polymers, pesticides, and liquid crystals.2–5 In
homogeneous reaction medium phosphine ligands play an
important role in C–C bond formation under an inert
atmosphere and moisture-free conditions.6 Since most of
the phosphine ligands are air- and moisture-sensitive,
P–C bond degradation sometimes occurs at elevated
temperatures, which poisons the metal, leading to decom-
position of the catalyst which strongly affects conversion
and selectivity.7a,b A number of methods on the use of
ligand-free palladium catalysts as well as phosphine-free
ligands have been reported for the Heck and Suzuki
reactions. Examples of phosphine-free ligands include the
N-heterocyclic carbene class of compounds,7c,d thio-
*
Corresponding author. Tel.: +91 20 2560 1394x545/585; fax: +91 20
2569 1728.
E-mail address: suresh@chem.unipune.ernet.in (S. B. Waghmode).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.03.109

3424
S. R. Borhade, S. B. Waghmode/ Tetrahedron Letters 49 (2008) 3423–3429
R
HN
HO
NH
OH
CHO
OH
R
MeOH, r.t.
+
NH2
NH2
Pd(OAc)2
DCM, r.t.
R
R= ethylenediamine A
1,2-phenylenediameine B
N
O
N
O
Pd
Scheme 1. General synthetic pathway for the preparation of Pd–salen complexes.
R
Catalyst, Base
+
X
R
Temp,Solvent
R= COOEt, Ph, COOH, CONH2, etc.
X= I, Br, Cl
Scheme 2.
The effect of temperature on the activity of complex A
was studied in the range 30 °C to 130 °C. The % conversion
increased with temperature and there was no conversion
observed below 80 °C. As the temperature increased from
100 to 130 °C, the conversion increased from 66% to
100% and the reaction time was also reduced considerably
from 60 to 10 min with excellent selectivity for the trans
product.
ing or donating substituents, and the results are shown in
Table 1. Iodobenzene reacts with various olefins such as
acrylates, acrylic acid, acryl amide, and styrene, delivering
the corresponding products in good to excellent yields
(entries 1–7). Ethyl acrylate was found to be the most reac-
tive amongst the olefins studied (entry 2). As expected, the
most electron rich olefin, acryl amide reacted more slowly
than the other acrylates, whereas methyl butyl acrylate
reacted very sluggishly under these reaction conditions
which may be due to steric hindrance (entry 7). Styrene
was less reactive than the acrylates. Among the various
substituted aryl iodides, both deactivated (electron rich)
and activated (electron poor) examples were converted effi-
ciently to the desired products in good to excellent yields
within 10–60 min (entries 8–16). In general, the ortho-
substituted aryl iodides required longer reaction times than
para-substituted aryl iodides. The biscoupled product was
obtained exclusively when 1,3-diiodobenzene was used
(entry 19). The comparatively less reactive bromobenzene
did not undergo any conversion even after 12 h, whereas
activated 4-bromoacetophenone gave only 20% conversion
(entry 22).
Further, under these optimized conditions we investi-
gated the usefulness of Pd–salen complex A in the Suzuki
reaction involving cross-coupling of an aryl halide with
phenyl boronic acid (Scheme 3). Table 2 illustrates that
the reaction was effective in the presence of a wide variety
of functional groups on the aryl iodides, bromides, and
chlorides, giving good to excellent conversions to the corres-
ponding products, within 15–180 min. Earlier, Phan and
co-workers reported on a polymer-supported salen type
Among the various solvents studied, polar aprotic sol-
vents DMF, NMP, DMAc, and DMSO gave excellent con-
versions (100%) at 130 °C in 10 min. Non-polar solvents
such as xylene showed 17% conversion for the desired
product even after 60 min. Water required the addition of
the phase transfer catalyst tetrabutylammoniumbromide
(TBAB) to deliver satisfactory conversion (59% in 60 min).
Among the various bases, triethylamine (TEA) and tri-
butylamine (TBA) were found to be the best (100% conver-
sion in 10 min). These organic bases were superior to
inorganic bases such as K2CO3, Na2CO3, NaOAc,
NaHCO3, Ca(OH)2, and Cs2CO3. This may be due to the
partial inhomogeneity of inorganic bases with the organic
substrate, reagent, and solvent, which lowered the conver-
sion and increased the reaction times compared to organic
bases (32–60% in 30 min). The effect of Pd concentration
on the Heck reaction was studied and the results show that
the reaction complete within 5 min, with excellent conver-
sion and selectivity for the b-arylated trans product using
0.5 mol % Pd.
Using the optimized reaction conditions, we explored
the general applicability of Pd–salen complex A with differ-
ent olefins and aryl halides containing electron withdraw-

S. R. Borhade, S. B. Waghmode / Tetrahedron Letters 49 (2008) 3423–3429
3425
Table 1
Heck reactions of aryl halides with olefins using Pd–salen complex Aa
Entry
Aryl halide
Olefin
Product
Time (min)
15
Conversionb (%)
95
CO2Me
CO2Et
1
I
I
CO2Me
CO2Et
2
3
4
10
12
10
96
91
93
CO2nBu
CO2H
I
CO2nBu
I
COOH
CONH2
5
6
30
60
74
79
I
I
CONH2
CO2nBu
7
8
60
10
60
15
10
30
15
12
93
92
88
97
81
84
I
CO2nBu
CO2Et
OH
OH
CO2Et
CO2Et
CO2Et
I
NO2
NH2
NO2
9
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
I
NH2
10
11
12
13
I
NHCOCH3
CO2Et
NHCOCH3
I
OCH3
OCH3
CO2Et
CO2Et
I
COOMe
COOMe
I
NHCOCH3
CO2Et
NHCOCH3
14c
15
30
10
89d
CO2Et
CO2Et
I
Br
Br
CO2Et
85
MeO
I
MeO
(continued on next page)

3426
S. R. Borhade, S. B. Waghmode/ Tetrahedron Letters 49 (2008) 3423–3429
Table 1 (continued)
Entry
Aryl halide
Olefin
Product
Time (min)
15
Conversionb (%)
91
CO2Et
16
MeOC
I
CO2Et
MeOC
CO2Et
17
18
10
15
94
91
Cl
Br
I
I
CO2Et
CO2Et
Cl
Br
CO2Et
CO2Et
I
19
10
86
CO2Et
I
EtO2C
CO2Et
I
20
21
22
10
15
97
94
CO2Et
CO2Et
CO2Et
CO2Et
MeOOC
MeOOC
MeOOC
MeOOC
CO2Et
I
CO2Et
Ac
6 h
20
Br
Ac
CO2Et
23
12 h
NR
Br
a
Conditions: aryl halide (1 mmol), olefin (3 mmol), triethylamine (3 mmol), DMF (4.0 mL), 0.5 mol % Pd catalyst A, 130 °C.
b
c
Conversions were determined by GC (Drel
=
5%).
Reaction was monitored by TLC.
Isolated yield after silica gel column chromatography (9:1 hexane/ethyl acetate).
d
R
R
Catalyst, Base
Temp,Solvent
B(OH)2
+
X
R= OMe, Cl, NO2, COCH3, etc.
X= I, Br, Cl
Scheme 3.
complex for the Suzuki reaction in 24 h at 90 °C under a
nitrogen atmosphere.17c In our studies, the ortho-substi-
tuted aryl iodides required longer reaction times to give sat-
isfactory conversions which might be due to steric
hindrance. Complete regioselectivity was observed for
4-bromo and 4-chloroiodobenzene on reaction with 1.0
equivalent of phenyl boronic acid (entries 5 and 6). 4-Bro-
moiodobenzene gave the diarylated product on reaction
with 2.2 equiv of phenyl boronic acid (entry 7). The less
reactive chlorobenzene showed low conversion. However,
the activated aryl chloride, 4-nitrochlorobenzene gave the
corresponding product in moderate yield, using 1.0 mol %
of palladium. The reaction of 2-bromopyridine with phenyl
boronic acid resulted in a low yield of the product, which
may be due to the coordination of the pyridine nitrogen
with palladium metal (entry 17).
In summary, we have shown that the palladium–salen
complex A efficiently catalyzes the Heck olefination of aryl

S. R. Borhade, S. B. Waghmode / Tetrahedron Letters 49 (2008) 3423–3429
3427
Table 2
Suzuki reaction of aryl halides with phenyl boronic acid using Pd–salen complex Aa
Entry
Aryl halide
Product
Temp (°C)
Time (min)
15
Conversionb
100
1
100
I
OH
OH
2
3
4
5
100
100
100
100
60
60
60
60
72
47
84
96
I
NH2
NH2
I
MeO
Cl
I
MeO
Cl
I
I
6c
7d
8
Br
100
100
100
110
15
120
120
90
78
83
87
88
Br
Br
I
Br
Br
9
10
11
12
13
14
110
110
110
110
110
90
30
30
60
90
94
100
100
81
MeO
Ac
Br
MeO
Ac
Br
OHC
O2N
Br
Br
OHC
O2N
CF3
Br
51
CF3
(continued on next page)

3428
S. R. Borhade, S. B. Waghmode/ Tetrahedron Letters 49 (2008) 3423–3429
Table 2 (continued)
Entry
Aryl halide
Product
Temp (°C)
Time (min)
120
Conversionb
22
15e
110
Cl
Br
16e
110
110
180
90
48
28
Cl
O2N
O2N
17
N
N
a
Conditions: substrate (1.0 mmol), phenyl boronic acid (1.25 mmol), base (2.0 mmol), DMF + H2O (1:1), Pd (0.5 mol %).
b
c
Conversions were determined by GC (Drel
=
5%).
1.0 equiv of phenyl boronic acid were used.
2.2 equiv of phenyl boronic acid were used.
1.0 mol % of Pd was used.
d
e
iodides with various alkenes and the Suzuki cross coupling
of aryl iodides, bromides, and activated chlorides with phe-
nyl boronic acid under aerobic conditions.
136.1, 142.9, 154.7, 165.8. FTIR (cmꢀ1): 1626, 1444,
1319, 1197, 1145, 746. Mass: m/z 420, 313, 257, 210, 167,
106, 91, 77, 65, 44. Anal. Calcd for C20H14N2O2Pd: C,
57.09; H, 3.35; N, 6.66. Found: C, 57.34; H, 3.42; N, 6.58.
2. Experimental
2.2. Typical experimental procedure for the Heck reaction
2.1. General procedure for the synthesis of Pd–salen
complexes A and B
To a 20 mL two neck round-bottom flask were added
aryl halide (1 mmol), olefin (3 mmol), triethylamine
(3 mmol), and Pd–salen complex (0.5 mol %) and 4.0 mL
of DMF. The reaction mixtures were heated at 130 °C
for the appropriate time.
To
a stirred solution of 2-hydroxybenzaldehyde
(1 mmol) in 5 mL of methanol, 1,2-diamine (0.5 mmol
ethylenediamine for complex A and phenylenediamine for
complex B) was added dropwise and the reaction stirred
for 20 min at room temperature. To the above solution,
dichloromethane (DCM) (5 mL) was added to dissolve
the formed precipitate. To this solution Pd(OAc)2
(0.5 mmol) in DCM (5 mL) was added dropwise. The
resulting reaction mixture was stirred for 18 to 20 h at
room temperature and then allowed to cool to 0 °C. The
product was filtered and washed with DCM and methanol
to remove the unreacted ligand.
2.3. Typical experimental procedure for the Suzuki reaction
To a 20 mL two neck round-bottom flask were added
aryl halide (1 mmol), phenyl boronic acid (1.25 mmol),
Na2CO3 (2 mmol), and Pd–salen complex A (0.5 mol %)
in DMFꢀH2O (1:1), and the reaction mixtures were heated
at the appropriate temperatures and durations.
Both reactions were monitored by gas chromatography.
After the completion of the reaction, the mixture was
extracted with ethyl acetate three times. The combined
organic extracts were dried over anhydrous sodium sulfate
solvent evaporated on reduced pressure. The crude prod-
ucts were purified by column chromatography [hexane or
hexane/ethyl acetate (9:1)]. The products were analyzed
by GC, GCMS, FTIR, and NMR.
2.1.1. Complex A
(N,N0-Bis(salicylidene)-ethylenediamino-palladium), yield
1
76%, yellow solid, H NMR (300 MHz, DMSO-d6): d 8.19
(s, 2H), 7.36 (d, J 7.7 Hz, 2H), 7.28 (t, 2H), 6.81 (d, J
8.5 Hz, 2H), 6.54 (t, 2H), 3.82 (s, 4H). 13C NMR
(75 MHz, DMSO-d6): d 59.5, 114.2, 120.2, 120.7, 134.3,
134.5, 160.2, 168.4. FTIR (cmꢀ1): 1629, 1600, 1446, 1192,
1136, 742. Mass: m/z 372, 325, 238, 132, 91, 77, 51. Anal.
Calcd for C16H14N2O2Pd: C, 51.56; H, 3.79; N, 7.52.
Found: C, 51.76; H, 3.75; N, 7.50.
Acknowledgment
The authors are thankful to the Department of Science
and Technology (DST), New Delhi for financial support.
2.1.2. Complex B
References and notes
(N,N0-Bis(salicylidene)-1,2-phenylenediaminopalladium),
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9.18 (s, 2H), 8.31–6.70 (m, 12H). 13C NMR (75 MHz,
DMSO-d6): d 115.1, 117.0, 120.5, 120.7, 128.0, 136.0,
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