A. Rostami et al. / Tetrahedron Letters 57 (2016) 192–195
193
Table 1
Table 2
Optimization of the reaction conditions using 4-iodoanisole with triphenyltin
Synthesis of phenyl aryl/benzyl sulfides from the reaction of aryl/benzyl halides with
triphenyltin chloride
chloridea
I
Cu(OAc)
2
(10 mol%), S
8
(1.5 mmol), KF (3 mmol)
S
R
X
+
Ph
3
SnCl
R
Ph
S
Cu salt (cat), S-source, KF
K
2
CO
3
(2 mmol), PEG(200), 60-80 °C
+
Ph
3
SnCl
+
S S
base, solvent, 60 °C, 8 h MeO
R = Aryl, Benzyl
X = I, Br, Cl
OMe
Entry RX
Product
T (°C) Time (h) Yielda (%)
Entry
Base
Et
DABCO
NaOH
S-source
Solvent
Cu salts
GC yieldb,c (%)
1
2
3
I
I
S
60
70
70
3
7
5
95
89
87
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
3
N
S
8
S
8
S
8
S
8
S
8
S
8
S
8
S
8
S
8
S
8
S
8
S
8
S
8
S
8
S
8
S
8
S
8
DMF
DMF
DMF
DMF
DMF
PEG200
Dioxane
Cu(OAc)
Cu(OAc)
Cu(OAc)
Cu(OAc)
Cu(OAc)
Cu(OAc)
Cu(OAc)
Cu(OAc)
CuI
2
2
2
2
0/100
20/80
35/45
78/22
MeO
Me
I
MeO
S
2
Cs CO
3
I
Me
S
d
K
2
K
2
CO
CO
3
2
2
100/0
100/0d
65/0
76/0
76/0
81/0
3
S
4
70
5
86
2
K CO
2
K CO
2
K CO
2
K CO
2
K CO
2
K CO
2
K CO
2
K CO
2
K CO
2
K CO
3
3
3
3
3
3
3
3
3
3
2
Me
Me
3
CH CN
2
PEG200
PEG200
PEG200
PEG200
PEG200
PEG200
PEG200
PEG200
PEG200
PEG200
PEG200
PEG200
PEG200
5
6
7
8
O
2
N
I
O
2
N
S
60
60
80
80
1
95
95
83
80
0
1
2
3
4
5
6
7
8
9
0
1
CuCl
2
e
NC
I
NC
S
1.5
Cu(OAc)
Cu(OAc)
Cu(OAc)
Cu(OAc)
Cu(OAc)
Cu(OAc)
Cu(OAc)
Cu(OAc)
Cu(OAc)
Cu(OAc)
Cu(OAc)
2
2
2
2
2
2
2
2
2
2
2
35/0
78/0f
Br
Br
S
S
10
g
100/0
h
78/0
Me
Br
Me
S
17
17
i
75/0
j
NR/NR
9
80
80
NaOH
58/21j
Me
Me
j
2
K CO
2
K CO
2
K CO
2
K CO
3
3
3
3
Na
KSCN
Na
2
SÁ5H
2
O
48/52
91(89)b
92
0/100j
10
11
O
2
N
Br
Br
O
2
N
S
60
60
80
60
60
70
80
80
4
5
j
S
2 2
O
3
NR/NR
NC
NC
S
k
S
8
0/100
1
1
2
3
Cl
S
29
14
16
10
2
70
The bold letters represent the most effective reaction conditions.
a
Reactions conditions: 4-iodoanisole (1 mmol), triphenyltin chloride
0.35 mmol), S (1.5 mmol), Cu salts (10 mol %), KF (3 mmol), base (2 mmol), sol-
vent (2 mL).
O
2
N
Cl
O
2
N
S
83
(
8
14
15
16
NC
Cl
Cl
Br
NC
Cl
S
81
b
4
-Methoxy diphenyl sulfide.
c
d
e
f
S
79
Diphenyl sulfide.
Optimal reaction conditions.
KF (2 mmol).
CH
2
Br
CH
2
S
85
KF (1.5 mmol).
CH Cl
CH S
17
2
2
5
74
g
h
i
7
0 °C.
(1 mmol).
Cu(OAc) (5 mol %).
S
8
a
Isolated yield.
In parenthesis; yield performed using 1-bromo-4-nitrobenzene (10 mmol), Cu
(10 mol %), triphenyltin chloride (3.5 mmol), S (15 mmol), KF (30 mmol),
PEG200 (20 mL), K CO3 (20 mmol).
b
2
j
Without KF.
Without 4-iodoanisole.
(
OAc)
2
8
k
2
these solvents the most effective were DMF and PEG200 (Table 1,
entries 5–8). Among the copper salts tested, the most suitable
17). It was also shown that the method was suitable for large scale
reactions. For this purpose, the reaction of 1-bromo-4-nitroben-
zene with triphenyltin chloride was scaled-up 10 times and the
desired sulfide was isolated in 89% yield (Table 2, entry 10).
To ascertain the nature of the reaction mechanism and illustrate
the efficiency of this method, a control experiment was performed
using thiophenol (instead of Ph SnCl/S ) and 4-iodoanisole under
same reaction conditions. It was observed that both the desired
product and the diphenyl disulfide by-product were obtained after
24 h (Scheme 1). The results show that when thiophenol was used
was Cu(OAc)
product was observed (Table 1, entry 16). No improvement in yield
was observed when other S-sources; Na S, KSCN, and Na
were used (Table 1, entries 18–20). The optimized reaction condi-
tions were found to be S (1.5 mmol), KF (3 mmol), K CO (2 mmol)
in the presence of catalytic Cu(OAc) (10 mol %) in PEG200 or DMF.
2
(Table 1, entries 9 and 10). In the absence of KF, no
2
2 2 3
S O ,
8
2
3
3
8
2
In order to examine the reaction scope, a series of structurally
diverse aryl halides were reacted with triphenyltin chloride under
the optimized reaction conditions in PEG200. The reactions pro-
duced the corresponding phenyl aryl sulfides in moderate to excel-
lent yields ranging from 70% to 95% (Table 2). Interestingly, aryl
bromides and chlorides which are relatively unreactive substrates,
were also converted to the corresponding aryl phenyl sulfides in
good yields (Table 2, entries 7–15). It was observed that aryl
halides with electron-withdrawing groups showed greater activi-
ties than those with electron-donating groups (Table 2, entries
directly, both the deactivation of Cu(OAc) (an extended time was
2
required for complete conversion) and oxidation to diphenyl disul-
7
fide by air in the presence of Cu(OAc) occur, while the Ph SnCl/S
2
3
8
system generates thiophenol or thiolate in situ relieving these
difficulties.
Although the exact mechanism of this reaction is not clear, on
the basis of preliminary results (Table 1, entries 1, 6, 16, 17, and
1
4h,17
20), control experiment, and related studies,
we believe that
2
–6), and sterically demanding substrates gave the desired prod-
potassium disulfide is initially produced from the reaction of S8
ucts in good yields (Table 2, entries 4 and 9). The reaction of
dihalogenated 1-bromo-4-chlorobenzene was also studied to
investigate the selectivity of the reaction. The bromide functional
group showed higher reactivity (Table 2, entry 15) and this selec-
tivity allows the remaining active halide site to potentially undergo
further functionalization. Benzyl bromide and benzyl chloride sat-
isfactorily underwent C–S bond formation (Table 2, entries 16 and
Cu(OAc)
CO
2
3
(0.1 mmol),
(2 mmol)
I
SH
S
K
2
+
+
S
S
PEG (2 mL), 70 °C, 24 h
MeO
MeO
78%
22%
Scheme 1. Control experiment.