Efficient ligand-free nickel-catalyzed C-S cross-coupling of thiols with aryl iodides

Article abstract of DOI:10.1016/j.tetlet.2007.12.118

NiCl₂·6H₂O efficiently catalyzes the C-S bond formation by the cross-coupling of aryl iodides with thiols in tetrabutylammonium bromide (TBAB) in excellent yield. The reaction functions in air and the NiLn-TBAB can be recovered and recycled without the loss of activity.

Full text of DOI:10.1016/j.tetlet.2007.12.118

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Tetrahedron Letters 49 (2008) 1484–1487
Efficient ligand-free nickel-catalyzed C–S cross-coupling of thiols
with aryl iodides
Suribabu Jammi, Priyanka Barua, Laxmidhar Rout, Prasenjit Saha,
Tharmalingam Punniyamurthy *
Department of Chemistry, Indian Institute of Technology Guwahati, Guwahati 781 039, India
Received 20 November 2007; accepted 24 December 2007
Available online 8 January 2008
Abstract
NiCl2Á6H2O efficiently catalyzes the C–S bond formation by the cross-coupling of aryl iodides with thiols in tetrabutylammonium
bromide (TBAB) in excellent yield. The reaction functions in air and the NiLn-TBAB can be recovered and recycled without the loss
of activity.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords: C–S bond formation; Cross-coupling; Thiols; Aryl iodides; Synthetic method
1. Introduction
product isolation, easy recovery and recyclability of the
catalysts, excellent thermal stability, and low vapor
pressure. Herein, we report that the readily available
NiCl2Á6H2O efficiently catalyzes the cross-coupling of
thiols with aryl iodides in tetrabutylammonium bromide
(TBAB) with excellent yield. It is ligand-free and the
Transition metal-catalyzed cross-coupling reactions of
aryl halides with various nucleophilic compounds are
now among the most prominent synthetic methods for
the formation of carbon-heteroatom bonds.1 Among these,
the formation of C–S bond has received much attention
due to the occurrence of this bond in many molecules that
are of biological, pharmaceutical, and material interest.2 In
1980, Migita and co-workers first reported the cross-
coupling of aryl halides with thiols in the presence of
[Pd(PPh3)4] as the catalyst and NaOtBu as a base in polar
solvents, such as ethanol at reflux or dimethyl sulfoxide
(DMSO) at 90 °C.3 Copper,4 palladium,5 nickel,6 and
cobalt-based7 catalytic systems have since been studied
for this purpose. Most of these studies have shown that
the catalysts with electron-rich ligands are effective and
usually function in anhydrous organic solvents under inert
atmosphere.
Table 1
The reaction of benzenethiol with aryl halides
5 mol % NiLn
1.5 equiv Base
SH
+
X
S
S
S
+
2 equiv TBAB
110 o
C
Catalyst
X
Base
Time (h) PhSPh (%) PhSSPha,b (%)
Ni(OAc)2Á4H2O
NiNO3Á6H2O
NiCl2Á6H2O
NiCl2Á6H2O
NiCl2Á6H2O
NiCl2Á6H2O
NiCl2Á6H2O
a
I
I
I
KOH
KOH
KOH
10
10
10
14
14
10
80
85
99
23
14
10
23
—
—
—
—
—
36
30
Br KOH
Cl KOH
I
I
K2CO3
Pyridine 10
The use of molten salt for organic reactions has been
intensive in recent years,8 because they provide simplified
Catalyst (5 mol %), benzenethiol (5 mmol), aryl halide (5.5 mmol),
base (7.5 mmol) and TBAB (10 mmol) were stirred at 110 °C for 10 h
under air.
*
Corresponding author. Tel.: +91 361 02582309; fax: +91 361 2690762.
b
Isolated yield.
E-mail address: tpunni@iitg.ernet.in (T. Punniyamurthy).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.12.118

S. Jammi et al. / Tetrahedron Letters 49 (2008) 1484–1487
1485
Table 2
alkyl chain, 1-butanethiol, was less reactive providing
butyl(phenyl)sulfide in 10% yield.
The reaction of various thiols with iodobenzene
Entry Thiol
1
Time (h) Product
Yielda,b (%)
89
The reaction of substituted aryl iodides with benzene-
thiol was further examined (Table 3).9 Aryl iodide having
electron withdrawing group was more reactive in compar-
ison to those with electron donating group. Thus, aryl
iodide with methyl and methoxy substituents underwent
reaction to give the corresponding C–S cross-coupled prod-
ucts in 70–99% yield, while the reaction of aryl iodides with
nitro substituent completed in 94–98% yield. Under these
conditions, 1-iodonaphthalene underwent reaction to give
the respective cross-coupled product in 91% yield.
Finally, we investigated the reaction of various thiols
with 1-iodo-4-nitrobenzene (Table 4). 2-Methyl-, 4-
methyl-, 4-methoxy-, 4-nitro-, 4-bromo-, and 4-chloro-
benzenethiol underwent reaction in 91–99% yield. Similar
results were observed with 2-naphthyl and benzyl thiol pro-
viding the cross-coupled products in 94% and 90% yield,
respectively.
The NiLn/TBAB is recyclable without the loss of activ-
ity (Table 5). After the completion of the reaction, the
product was isolated from the reaction mixture by extract-
ing with diethyl ether. The insoluble NiLn/TBAB was
reused for the fresh reaction of 4-methylbenzenethiol with
1-iodo-4-nitrobenzene. The reaction occurred to afford
the cross-coupled product in 99% yield. This process was
SH
S
10
Me
Me
SH
S
2
9
8
95
97
Me
Me
S
SH
3
MeO
MeO
SH
S
4
12
10
8
94
93
95
98
92
10
O2N
O2N
SH
S
5
Br
Br
S
SH
6
Cl
Cl
SH
S
7
8
8
S
Ph
SH
12
12
Table 3
Reaction of benzenethiol with aryl and naphthyl iodides
S
Entry Iodide
Product
Time (h) Yielda,b (%)
9
SH
I
S
1
10
12
99
a
NiCl2Á6H2O (5 mol %), thiol (1 mmol), iodobenzene (1.1 mmol), KOH
Me
Me
Me
(1.5 mmol) and TBAB (2 mmol) were stirred at 110 °C under air.
b
S
Isolated yield.
I
2
91
Me
Me
Me
S
NiLn/TBAB can be recovered and recycled without the
loss of activity.
I
We first studied the reaction of the model substrate ben-
zenethiol with iodobenzene (Table 1).9 The reaction
occurred to provide the desired C–S cross-coupled diphenyl-
sulfide in 99% yield when the substrate was stirred at
110 °C with 5 mol % of NiCl2Á6H2O, 1.1 equiv of iodo-
benzene, and 1.5 equiv of KOH in 2 equiv of TBAB under
air. Of the bases tested, KOH, K2CO3, and pyridine, the
former provided the best result. Among the nickel(II) salts
studied, NiCl2Á6H2O was superior to Ni(OAc)2Á4H2O and
Ni(NO3)2Á6H2O. Iodobenzene was a more reactive com-
pared to chlorobenzene and bromobenzene.
Next, we studied the scope of the procedure for the cross-
coupling of various thiols with iodobenzene (Table 2).9
2-Methyl-, 4-methyl-, 4-methoxy-, 4-nitro-, 4-bromo-, and
4-chlorobenzenethiol underwent reaction in 89–98% yield.
Similar results were observed with 2-naphthyl and benzyl
thiol affording the C–S cross-coupled products in 98%
and 92% yields, respectively, while the substrate having
3
4
94
98
70
91
O2N
NO2
I
S
4
3
O2N
O2N
I
S
5
10
10
MeO
MeO
I
S
6
a
NiCl2Á6H2O (5 mol %), benzenethiol (1 mmol), aryl/naphthyl iodide
(1.1 mmol), base (1.5 mmol) and TBAB (2 mmol) were stirred at 110 °C
under air.
b
Isolated yield.

1486
S. Jammi et al. / Tetrahedron Letters 49 (2008) 1484–1487
Table 4
R-I
Reaction of various thiols with 1-iodo-4-nitrobenzene
NiLn
Yielda,b
(%)
a
Entry Thiol Product
Time
(h)
ArSR
S
SH
Me
R = alkyl, aryl
1
6
92
R
Me
NO2
I
LnNi
LnNi
S
SH
R
b
c
2
3
97
SAr
NO2
Me
Me
I-
SH
S
ArS-
3
2
99
96
91
95
98
94
90
Scheme 1. Proposed reaction pathway.
NO2
MeO
MeO
NO2
SH
S
repeated up to five runs and no loss of activity was
observed.
4
5
NO2
O2N
The proposed reaction pathway for these reactions is
shown in Scheme 1. Oxidative addition of the aryl iodide
with the catalyst may provide intermediate b, which on
reaction with thiol can give intermediate c. Intermediate c
can provide the desired C–S cross-coupled product by
reductive elimination.
SH
Br
S
5
6
Br
NO2
NO2
S
SH
6
4.5
4
Br
Br
2. Conclusions
S
SH
A simple and efficient procedure is described for the C–S
cross-coupling of aromatic and benzyl thiols with aryl
iodides using NiCl2Á6H2O in TBAB under air. It is
ligand-free and the NiLn/TBAB can be recovered and recy-
cled without the loss of activity.
7
Cl
Cl
NO2
S
SH
8
4
NO2
Acknowledgments
S
Ph
SH
9
7
This work was supported by Department of Science and
Technology, New Delhi and Council of Scientific and
Industrial Research, New Delhi.
NO2
a
NiCl2Á6H2O (5 mol %), thiol (1 mmol), 1-iodo-4-nitrobenzene
(1.1 mmol), base (1.5 mmol) and TBAB (2 mmol) were stirred at 110 °C
under air.
References and notes
b
Isolated yield.
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Table 5
Recyclability of NiLn-TBAB
.
5 mol % NiCl2 6H2O
SH
I
S
2 equiv TBAB
+
1.5 equiv KOH
110 oC, 3 h
Me
O2N
Me
NO2
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>99
>99
>99
>99
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b
Isolated yield.
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1.5 mmol), aryl iodide (1.1 mmol) and thiol (1 mmol) were stirred at
110 °C under air for the appropriate time until complete consumption
of starting material. The progress of the reaction was monitored by
TLC using ethyl acetate and hexane as eluent. The reaction mixture
was then cooled to ambient temperature and extracted with diethyl
ether. The insoluble NiLn/TBAB was recovered and recycled without
the loss of activity. The combined diethyl ether solution was dried
(Na2SO4), concentrated and passed through a short pad of silica gel to
afford analytically pure C–S cross-coupled product.