Mono- or dichalcogenation of aryl iodide with sulfur or selenium by copper catalyst and aluminum

Article abstract of DOI:10.1055/s-2005-871545

The copper-catalyzed mono- or dichalcogenation of aryl halide with sulfur or selenium can be carried out with the addition of aluminum. This method takes advantage of two properties of both the insertion of copper into the chalcogen-chalcogen bond and the reductive ability of aluminum. Furthermore, the addition of MgCl₂ or Na₂CO₃ enables the selective synthesis of diaryl monochalcogenides or disulfides. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2005-871545

LETTER
1687
Mono- or Dichalcogenation of Aryl Iodide with Sulfur or Selenium by Copper
Catalyst and Aluminum
Mono- or
D
ichalco
o
genation of
b
A
ryl Iodide ukazu Taniguchi*
Department of Chemistry, Fukushima Medical University, Fukushima 960-1295, Japan
Fax +81(24)5471369; E-mail: taniguti@fmu.ac.jp
Received 6 April 2005
Oxidation
Reduction
Yn + Cu(0)
Abstract: The copper-catalyzed mono- or dichalcogenation of aryl
halide with sulfur or selenium can be carried out with the addition
of aluminum. This method takes advantage of two properties of
both the insertion of copper into the chalcogen–chalcogen bond and
the reductive ability of aluminum. Furthermore, the addition of
MgCl2 or Na2CO3 enables the selective synthesis of diaryl mono-
chalcogenides or disulfides.
YCu(II)
Inactive
[M]-Y-Cu(I)
Active
[M] = metal ion
(Y = S or Se)
Ar-X
Y
Y
Ar
or
Ar
Ar
Ar
Y
Scheme 1 Strategy for copper-catalyzed chalcogenation of aryl
halide using chalcogen.
Key words: diaryl chalcogenide, aryl iodide, chalcogen, copper
catalyst, aluminum
Transition metal-catalyzed aromatic carbon–chalcogen
bond formation is an important reaction in chemical syn-
thesis.1 The aryl chalcogenides produced by this method
are widely used as convenient synthetic intermediates or
reagents.2
As an initial attempt to execute a copper-catalyzed synthe-
sis of diaryl chalcogenide from aryl iodide with chalco-
gen, we investigated the selenation of 2-iodotoluene (1a)
using CuI and reductive metals (Table 1). It was obvious
that the CuI catalyst or aluminum itself could not promote
the reaction (Table 1, entries 1 and 2). Fortunately, we
found that when both aluminum and CuI–bpy (10 mol%)
were added, di-2-tolyl selenide (2a) and di-2-tolyl dise-
lenide (3a) were obtained in 75% and 6% yield, respec-
tively (Table 1, entry 3). Although other metals (Sm, Mg,
and Zn) were examined, no satisfactory results were ob-
served (Table 1, entries 4, 5, and 6). Notably, under the
conditions in Table 1 entry 3, the addition of MgCl2 could
selectively synthesize 2a in 80% yield without the forma-
tion of 3a (Table 1, entry 7). The reaction with sulfur also
afforded the mono-sulfide 2 in 71% yield (Table 1, entry
9).
In general, to achieve chalcogenation of aryl halides by a
transition metal catalyst,3 a combination of a copper cata-
lyst with thiol under basic conditions4 or sodium sulfide5
is often employed. But the reaction using copper with
chalcogen itself in one step has not been completely
explored to date.
On the other hand, the chalcogen (S or Se) usually has the
structure of a polymer possessing the chalcogen–chalco-
gen bond by catenation. The chalcogen–chalcogen can be
easily cleaved by the transition metal,6,7 whereas the gen-
erated metal–chalcogen complex cannot be used for a re-
action such as the chalcogenation of aryl halides, owing to
the stability of the metal–chalcogen bond. Similarly, cop-
per(II) chalcogenide or copper(II) diorganochalcogenide
is very unreactive.
In contrast, the addition of Na2CO3 could give the disul-
fide 3 in 92% yield, however, using Se it was impossible
to produce any selenide derivatives (Table 1, entries 8 and
10).
To exploit these copper(II) chalcogenides for the chalco-
genation of aryl halides, it is necessary to convert them
into copper(I) chalcogenides by reduction (Scheme 1).8
For instance, we have recently reported that Cu(II)(YR)2
can be reduced by magnesium.9 This study indicates that
the copper(II) chalcogenide is available for the introduc-
tion of chalcogenide groups to aryl halides in the presence
of a reducing reagent. Therefore, we anticipated that a
copper-catalyzed chalcogenation of aryl halide with chal-
cogen is a feasible strategy. In this paper, we describe a
copper-catalyzed mono- or dichalcogenation of aryl io-
dide with S or Se using aluminum.
Although other Cu catalysts (Cu2O, CuCl, CuBr, CuOAc,
CuCl2, and CuBr2), ligands (phen, TMEDA, and PPh3),
and solvents (PhCH3, NMP, and DMI) were investigated,
the results were poor.
On the basis of the optimized conditions, the copper-cata-
lyzed mono-chalcogenation of aryl iodide using Se or S
was carried out (Table 2). Diaryl mono-chalcogenides 2
were available in 40–84% yields when a mixture of aryl
iodide (0.3 mmol), Se or S (0.3 mmol), CuI–bpy (1:1, 10
mol%), Al (0.6 mmol), and MgCl2 (0.15 mmol) in DMF
(0.5 mL) was treated at 110 °C.10
For the selenation, substituents had no effect, however,
for sulfidation a long reaction time was often necessary.
SYNLETT 2005, No. 11, pp 1687–1690
Advanced online publication: 14.06.2005
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7
.0
7
.2
0
0
5
DOI: 10.1055/s-2005-871545; Art ID: U10105ST
© Georg Thieme Verlag Stuttgart · New York

1688
N. Taniguchi
LETTER
Table 1 Copper-Catalyzed Chalcogenation of 2-Iodotoluene (1a)
Table 2 Copper-Catalyzed Mono-Chalcogenation of ArI with
Selenium or Sulfur
Using Chalcogena
Y (Se or S),
CuI-bpy (10 mol%),
Additive
CuI-bpy (10 mol%),
Al, MgCl2
Me
Me
Ar
Y
I
Y
Y
+
+
Y
Ar I
1
Ar
Ar
Y
Ar
DMF, 110 °C
2
3
DMF, 110 °C, 24 h
(Y = Se or S)
Me
1a
2a
Me
Entry ArI
Y
Time (h) 2 (%)a
3 (%)a
Y
Y
+
1
2
C6H5I
Se
S
24
22
24
24
24
43
24
45
24
45
40
40
24
18
18
78
75
80
71
79
62
77
73
84
76
70
43
74
40
82
0
Me
3a
0
Entry
1
Y
Additiveb
None
2a (%)c
3a (%)c
1a (%)c
94
3
2-MeC6H4I
4-MeC6H4I
4-MeOC6H4I
4-ClC6H4I
4-BrC6H4I
Se
S
0
Se
Se
Se
Se
Se
Se
Se
Se
S
0
0
0
0
4
0
0
2d
3
Al
93
5
Se
S
Al
75
64
32
0
6
5
6
5
4
Sm
0
32
7
Se
S
0
5
Mg
15
0
0
8
trace
trace
0
6
Zn
95
9
Se
S
7e
8e
9e
10e,f
Al, MgCl2
Al, Na2CO3
Al, MgCl2
Al, Na2CO3
80
0
0
0
10
11
12
13
14
15
0
92
Se
S
0
71
0
0
trace
trace
11
0
S
92
4-F3CC6H4I
4-AcHNC6H4I
1-naphthyl-I
Se
Se
Se
a The reactions were carried out using 1a (0.3 mmol), Se or S
(0.3 mmol), CuI–bpy (10 mol%), reductive metal (0.6 mmol) in DMF
(0.5 mL).
0
trace
b Al (53–150 mm), Sm (20 mesh), Mg (212–600 mm) or Zn (75–150
mm) was used.
a Isolated yields after silica-gel chromatography.
c Isolated yields after silica-gel chromatography.
d CuI–bpy was not added.
e MgCl2 or Na2CO3 (0.15 mmol) was added.
f CuI–bpy (15 mol%) was used.
Table 3 Copper-Catalyzed Disulfidation of ArI with Sulfur
CuI-bpy (15 mol%),
Al, Na2CO3
Ar
S
S
+
S
+
Ar I
Ar
Ar
Ar
S
DMF, 110 °C
1
2
Thus application of the present method produces symmet-
rical diarylselenides or sulfides in good yields and by the
addition of MgCl2, it is possible to suppress the formation
of other chalcogenide isomers.
3
Entry
ArI
Time (h)
3 (%)a
85
2 (%)a
0
1
2
3
4
5
6
C6H5I
45
24
45
65
24
24
As shown in Table 3, we then performed the disulfidation
of aryl iodide with S using Na2CO3 (Table 3). Aryl iodides
1 were transformed into the corresponding diaryl disul-
fides 3 in 72–92% yields by employing CuI–bpy (15
mol%), Al (0.6 mmol), and Na2CO3 (0.15 mmol) in DMF
(Table 3, entries 1–5).11 For the disulfidation, the reaction
time differed depending on the substituent. Regrettably,
for 4-bromo-1-iodobenzene, the yield of the expected di-
sulfide decreased to 16% on account of the formation of
mono-sulfide 2 (Table 3, entry 6).12
2-MeC6H4I
4-MeC6H4I
4-MeOC6H4I
4-H2NC6H4I
4-BrC6H4I
92
0
82
trace
trace
0
72
75
16
71
a Isolated yields after silica-gel chromatography.
To understand the mechanism, we initially researched the
role of Cu and aluminum (Table 4). In the selenation of 2-
iodotoluene (1a), the independent utilization of CuI or
aluminum could not promote the reaction and 1a was re-
covered (Table 4, entries 1 and 2).13,14 Interestingly, the
use of Cu(0) (200 mol%) in the absence of aluminum gave
2a in only 22% yield, the mixture of Cu(0) (10 mol%) and
aluminum afforded 2a in 91% yield (Table 4, entry 4).
Synlett 2005, No. 11, 1687–1690 © Thieme Stuttgart · New York

LETTER
Mono- or Dichalcogenation of Aryl Iodide
1689
Thus, it seems that aluminum does not have the ability to Actually, after the sulfidation of CuI using Na2S, the ad-
reduce selenium under the conditions employed, but the dition of S and 1a gave disulfide 3 in 75% yield, neverthe-
Cu(0) and Cu(I)-selenide species generated by aluminum less the reaction of Na2S with ArI produced only mono-
serve as the reducing reagent.9 In addition, the copper– sulfide 2 (Scheme 4). These suggest that Cu(I)SSNa is
selenide complex is produced by the reaction of Cu(0) or formed in the presence of Na2CO3.16 On the contrary, the
CuI with Se.15
addition of MgCl2 suppresses the generation of CuSS[M].
Consequently, it is considered that in the sulfidation of
aryl iodide, the addition of Na2CO3 promotes the forma-
tion of Cu(I)SSNa, but MgCl2 or the selenation cannot
generate Cu(I)YY[M].
Table 4 Research of the Reaction Mechanism
Se (0.3 mmol), [Cu]-bpy,
Al (0.6 mmol), MgCl2 (0.15 mmol)
1a
2a
DMF, 110 °C
(0.3 mmol)
1a (0.3 mmol),
Additive
(0.3 mmol)
Me
Me
Me
Entry
Cu (mol%)
None
Time (h)
2a (%)a
1a (%)a
)
S
S
2
+
1
18
18
45
30
0
0
96
96
61
0
Na2S·9H2O+ CuI-bpy
DMF, 110 °C,
20 h
(0.3 mmol) (15 mol%)
2b
3b
4
CuI (100)
Cu (200)
Cu (10)
3
2
2 (%)
3 (%)
Additive
22
91
S
none
trace 75
91
0
a Isolated yields after silica-gel chromatography.
b Aluminum was not added.
Scheme 4
From these results, the proposed mechanism is outlined in
Scheme 5. The reaction of Cu(0) or CuI with chalcogen
gave copper(II) chalcogenide or copper(I) chalcogenide
[Cu(II) chalcogenide shows no activity, it is reduced to
copper(I) chalcogenide 7 by aluminum].9 Sequentially, in
the presence of MgCl2, the intermediate 8 is produced
from 7 with ArI.5 Finally, diaryl chalcogenide 2 is ob-
tained (Cycle A).8
Next, we examined the role of MgCl2 and Na2CO3, we
researched the influence of additives on the reactivity of
PhYCu considered as an intermediate. However, the reac-
tion of PhYCu with aryl iodide was not affected by addi-
tives, and afforded the corresponding chalcogenides in
good yields (Scheme 2).
bpy,
YPh
I
On the other hand, by the addition of Na2CO3, the copper–
disulfide complex 10 is generated, and diaryl disulfide 3
is produced (Cycle B).
MgCl2 or Na2CO3
PhYCu
+
DMF, 110 °C,
18 h
Me
Me
2
1a
Investigation of the detailed process for the formation of
diaryl mono-chalcogenides or disulfides is now in
progress.
2 (%)
Y = S
Y = Se
MgCl2
72
80
79
75
Na2CO3
ArYAr
2
ArSSAr
Scheme 2
3
Ar
Ar
Cu(I)ILn
[Cu]ILn
9
LnI[Cu]
Y
4
On the other hand, the reaction of aryl iodide with dichal-
cogenide did not give the mono-chalcogenide in the pres-
ence of additives (Scheme 3). Moreover it was observed
that the addition of these salts tends to inhibit the cleavage
of the dichalcogenide bond. Thus, diaryl dichalcogenide
cannot be used for the mono-chalcogenation.
SSAr
Al
ArY
12
Cu(0)
5
CuIYn
6
Al
A
B
1
1
Y
LnCu(I)Y[M]
ArYCu(I)Ln
7
LnCu(I)SSAr
S, [M] = Na+
[M] = Mg2+
8
11
LnCu(I)SSNa
CuI-bpy (15 mol%),
Al (200 mol%),
MgCl2 or Na2CO3
10
1
[M]-I
Ar I
1
1a
+
No Reaction
(PhY)2
DMF, 110 °C,
18 h
Scheme 5 A plausible reaction mechanism.
1a and (PhY)2 were recovered.
Y = Se or S
Scheme 3
In conclusion, we have achieved a copper-catalyzed
synthesis of symmetrical diaryl chalcogenide from aryl
iodide with chalcogen by the addition of aluminum. Fur-
thermore, the use of MgCl2 or Na2CO3 could selectively
synthesize diaryl mono-chalcogenide or disulfide.
Therefore, it is estimated that the formation of mono-chal-
cogenide or disulfide is an independent process, and these
additives are involved in the generation of copper-sulfide
in the first step.
Synlett 2005, No. 11, 1687–1690 © Thieme Stuttgart · New York

1690
N. Taniguchi
LETTER
(8) Org. Synth., Coll. Vol. 5; John Wiley & Sons: New York,
1973, 107.
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H), 7.49–7.52 (m, 2 H); 13C NMR (67 MHz, CDCl3): d =
20.0, 126.7, 127.3, 128.7, 130.3, 135.4, 137.4; Anal. Calcd
for C14H14S2: C, 68.24; H, 5.73. Found: C, 68.19; H, 5.70.
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(13) Selenium was recovered in 90–92% yields.
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Synlett 2005, No. 11, 1687–1690 © Thieme Stuttgart · New York