Sodium 2-(2-pyridin-3-ylethylamino)sulfonate: an efficient ligand and base for palladium-catalyzed Heck reaction in aqueous media

Article abstract of DOI:10.1016/j.tetlet.2008.04.148

The first successful Pd(OAc)₂, N-donor ligand and base mediated Heck coupling reaction of aryl halides and alkenes in water is described. The corresponding Heck products were obtained in good to excellent yields.

Full text of DOI:10.1016/j.tetlet.2008.04.148

Tetrahedron Letters 49 (2008) 4252–4255
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Tetrahedron Letters
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Sodium 2-(2-pyridin-3-ylethylamino)sulfonate: an efficient ligand and base
for palladium-catalyzed Heck reaction in aqueous media
Shivaji S. Pawar a, Deepak V. Dekhane a, Murlidhar S. Shingare b, Shivaji N. Thore a,
*
a Department of Chemistry, Vinyakrao Patil Mahavidyala Vaijapur, Aurangabad 423701, MS, India
b Department of Chemistry, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad 431004, MS, India
a r t i c l e i n f o
a b s t r a c t
Article history:
The first successful Pd(OAc)2, N-donor ligand and base mediated Heck coupling reaction of aryl halides
Received 6 March 2008
Revised 19 April 2008
Accepted 26 April 2008
Available online 1 May 2008
and alkenes in water is described. The corresponding Heck products were obtained in good to excellent
yields.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords:
Heck coupling
N-Donor ligand
Palladium catalyzed
Aqueous media
Aryl halide
Alkene
The palladium-catalyzed Heck reaction1 between aryl halides
and alkenes is a versatile method for carbon–carbon bond forma-
tion in organic synthesis.2 To minimize the adverse impact of
organic solvents on the environment, recent efforts have been
directed towards using aqueous solvents for chemical reactions.3
Organic reactions in water or aqueous media have attracted
great interest.4 With tightened regulatory pressure focusing on
organic solvents, the search for alternatives is of increasing
importance. In this respect, the development of water-tolerant
catalysts has rapidly become an area of intense research. There
have been several reports concerning the Heck reaction in water;
however, in most cases, high temperatures were required.5,6
These findings prompted us to investigate the Heck reaction in
aqueous media, in continuation of our interest in developing novel
synthetic methodologies, particularly carbon–carbon bond forming
reactions.
in, for example, natural product synthesis. Recently, novel phos-
phine-free ligands8 and hydrazone9 were used as catalysts for
the Heck reaction. In addition, Li and Wang reported triethanol-
amine as a ligand as well as base for Heck reactions.10 As part of
an ongoing project,11 we herein disclose a novel protocol for the
Heck reaction using N-donor ligand (1a) as a ligand and base,
which makes use of milder conditions compared to those reported,
Scheme 1. The method is simple and affords good to excellent
yields. N-donor ligand 1a was synthesized by reaction of the corre-
sponding primary amine (2-(pyridine-3-yl)ethyl amine) with
sodium vinylsulfonate in water using a literature procedure.12
We initially studied the effect of 1a as a base along with other
bases in different solvents for Heck reactions, and our results are
summarized in Table 1.
We employed the coupling reaction of iodobenzene with
methyl acrylate as a model reaction to study the effect of base on
the reaction. The reactions were carried out using K2CO3 (1 equiv)
as base and ligand 1a (0.25 equiv, which is highly water soluble) in
the presence of 0.3 mol % Pd(OAc)2 at room temperature. The reac-
tion in pure DMF afforded 3-phenyl acrylic acid methyl ester in
very low yield after 4 h (Table 1, entry 1). If we kept the catalyst,
base and ligand 1a constant and used different solvents such as
DME, NMP, NMP–water and DMF–water, the desired product was
obtained in 40–61% yields (Table 1, entries 2–5). However, in neat
water we obtained the desired product in 67% yield (Table 1, entry
6) indicating water to be the solvent of choice for this Heck
reaction. Next, we kept the catalyst and ligand 1a constant and
Palladium-catalyzed Heck reactions between aryl halides and
alkenes continue to attract attention within the chemistry commu-
nity because of the versatility of the reaction and the potential of
the products formed.7 The area that has perhaps received most
research effort is the development of new catalysts and ligands
for Heck coupling reactions and the use of these catalyst systems
* Corresponding author. Tel.: +91 2436 222086; fax: +91 2436 224581.
E-mail address: snthore@rediffmail.com (S. N. Thore).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.04.148

S. S. Pawar et al. / Tetrahedron Letters 49 (2008) 4252–4255
4253
X
Y
Pd(OAc)2, ligand (1a)
Y
Water, 3–4 h, rt
X = I, Br
X = I, Br (90-94%)
Y = COOMe, COOEt
H
N
–
+
SO3 Na
N - donor Ligand =
1a
N
Scheme 1.
Table 1
Effect of N-donor ligand 1a as a base and other bases on the Heck coupling reaction
I
COOMe
Pd(OAc)2, ligand (1a)
base, solvent, rt, 4 h
COOMe
Entry
Catalyst
Base
Solvent (ml)
Ligand
Yielda
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
K2CO3 (1 equiv)
K2CO3 (2 equiv)
K2CO3 (2 equiv)
K2CO3 (2 equiv)
K2CO3 (2 equiv)
K2CO3 (2 equiv)
NaOAc (2 equiv)
Cs2CO3 (2 equiv)
Na2CO3 (2 equiv)
NaOH (2 equiv)
KOH (2 equiv)
1a (0.25 equiv)
1a (0.50 equiv)
1a (0.75 equiv)
1a (1 equiv)
DMF
DME
NMP
NMP–water (1:1)
DMF–water (1:1)
Water
Water
Water
Water
Water
Water
Water
Water
Water
Water
DMF–water (1:1)
DMF
NMP
DME
1a (0.25 equiv)
1a (0.25 equiv)
1a (0.25 equiv)
1a (0.25 equiv)
1a (0.25 equiv)
1a (0.25 equiv)
1a (0.25 equiv)
1a (0.25 equiv)
Trace
40
51
54
61
67
55
62
66
59
57
—
94
94
94
77
75
65
62
1a (0.25 equiv)
1a (0.25 equiv)
1a (0.25 equiv)
—
—
—
—
—
—
—
—
1a (0.50 equiv)
1a (0.50 equiv)
1a (0.50 equiv)
1a (0.50 equiv)
a
Isolated yields after column chromatography based upon starting iodobenzene.
investigated bases such as NaOAc, Cs2CO3, Na2CO3, NaOH and KOH
in water. The desired products were obtained in average yields (Ta-
ble 1, entries 7–11). Due to the basic nature of ligand 1a, we
decided to use it as both ligand and base. Reaction of 0.25 equiv
of ligand 1a and 0.3 mol % of Pd(OAc)2 in water at room tempera-
ture for 4 h did not lead to formation of the desired product (Table
1, entry 12). However, on using 0.5 equiv of ligand 1a, we obtained
the desired product in 94% yield (Table 1, entry 13). Further
increasing the equivalents of ligand 1a did not improve the yield
(Table 1, entries 14 and 15). The use of solvents including DMF,
DME, NMP and the co-solvent DMF–water (1:1) led to decreased
yields compared to those in neat water (Table 1, entries 16–19).
These results indicate that 0.5 equiv of N-donor ligand 1a,
0.3 mol % of Pd(OAc)2 in water at room temperature for 4 h is the
best protocol for the present Heck coupling reactions. This may
be due to N-donor ligand 1a having better solubility and showing
stronger basicity in water. The catalytic system was applicable to
a wide range of aryl halides and two different types of alkenes
(Table 2).
We also investigated the scope of this method on aryl chlorides,
but found that the coupling of an aryl chloride with acrylate did
not work; even on heating the reaction mixture up to 100 °C and
extending the reaction time. This proved to be the only limitation
of the method. We observed that when 3-chloroiodobenzene was
used as the alkyl halide, coupling only with the iodo function
occurred and not with the chloro function (Table 2, entries 2
and 11).
In conclusion, N-donor ligand 1a is an efficient catalyst for the
synthesis of a,b-unsaturated carbonyl compounds via Heck reac-
tion in water. The advantages offered by this method are simple
procedure, mild conditions, fast reactions and excellent yields of
products.
Typical
experimental
procedure:
Iodobenzene
(0.30 g,
1.47 mmol), methyl acrylate (0.14 g, 1.67 mmol), N-donor ligand
1a (0.19 g, 0.73 mmol) and Pd(OAc)2 (3 mol %) were taken in a
25 ml single neck round-bottomed flask to which 10 ml of water
was added. The reaction mixture was stirred for 4 h at room tem-
perature. The progress of the reaction was monitored by TLC. After
completion of the reaction, the reaction mixture was filtered and
the filtrate extracted with ethyl acetate (10 ml  2). The combined
organic layer was dried over anhydrous Na2SO4 and evaporated
under reduced pressure. The crude material was purified by
The coupling of aryl iodides and bromides was superior and
afforded the desired products in excellent yields (Table 2 entries
1–18).13 1H NMR, 13C NMR, mass spectroscopy, elemental analysis
and IR were used to characterize the products.

4254
S. S. Pawar et al. / Tetrahedron Letters 49 (2008) 4252–4255
Table 2
Heck coupling reaction of aryl halides with alkenes in aqueous mediaa
Entry
1
Aryl halide
Alkene
Product
Time (h)
4
Yieldb (%)
94
I
COOMe
COOMe
Cl
I
Cl
COOMe
2
3.5
91
COOMe
F
I
F
COOMe
3
4
5
6
4
93
90
94
93
COOMe
COOMe
COOMe
COOMe
O
I
COOMe
O
4
Br
COOMe
3
O
O
I
COOMe
3.5
O
O
O
O
O
I
COOMe
7
8
3
3
90
91
COOMe
COOMe
O
F3C
Br
F3C
COOMe
Br
COOMe
9
10
11
12
13
14
15
3
92
92
93
90
92
90
94
COOMe
COOEt
COOEt
COOEt
COOEt
COOEt
COOEt
I
COOEt
4
COOEt
Cl
F
I
Cl
F
3
COOEt
I
3.5
3
O
I
COOEt
O
Br
COOEt
3
O
O
I
COOEt
3
O
O

S. S. Pawar et al. / Tetrahedron Letters 49 (2008) 4252–4255
4255
Table 2 (continued)
Entry
Aryl halide
Alkene
Product
Time (h)
Yieldb (%)
O
O
I
COOEt
16
17
3
90
COOEt
O
O
F3C
Br
F3C
COOEt
3
4
92
91
COOEt
COOEt
Br
COOEt
18
a
Standard conditions: aryl iodide or aryl bromide (1.0 mmol), alkene (1.1 mmol), base and ligand (1a, 0.5 mmol), Pa(OAc)2 (3 mol %), water (10 ml), rt.
Isolated yields after column chromatography based upon starting aryl halide.
b
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Catal. 2002, 344, 348; (g) Ansos, M. S.; Mirza, A. R.; Tonks, L.; William, J. M. J.
Tetrahedron Lett. 1999, 40, 7147; (h) Uozumi, Y.; Kimura, T. Synlett 2002, 2045;
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column chromatography over silica gel to afford the corresponding
product in high purity. Same procedure was used with aryl
bromides.
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