A general rhodium-catalyzed cross-coupling reaction of thiols with aryl iodides

Article abstract of DOI:10.1016/j.tetlet.2012.06.054

The general procedure for the rhodium-catalyzed cross-coupling of thiols with aryl iodides is described. The catalytic system consists of 5 mol % of [RhCl(cod)]₂ and 10 mol % of PPh₃ as a ligand. A variety of aryl iodides reacted with thiols, giving aryl thioethers in good to excellent yields. It is important to note that the deactivated aryl iodides such as 4-iodoanisole is worked smoothly to provide the corresponding aryl thioethers in excellent yields. Functional groups such as free-amines, chloro, are all tolerated under the employed reaction conditions.

Full text of DOI:10.1016/j.tetlet.2012.06.054

Tetrahedron Letters 53 (2012) 4365–4367
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A general rhodium-catalyzed cross-coupling reaction of thiols with aryl iodides
⇑
Chih-Shin Lai, Hsin-Lun Kao, Yan-Jhang Wang, Chin-Fa Lee
Department of Chemistry, National Chung Hsing University, Taichung 402, Taiwan, ROC
a r t i c l e i n f o
a b s t r a c t
Article history:
The general procedure for the rhodium-catalyzed cross-coupling of thiols with aryl iodides is described.
The catalytic system consists of 5 mol % of [RhCl(cod)]2 and 10 mol % of PPh3 as a ligand. A variety of aryl
iodides reacted with thiols, giving aryl thioethers in good to excellent yields. It is important to note that
the deactivated aryl iodides such as 4-iodoanisole is worked smoothly to provide the corresponding aryl
thioethers in excellent yields. Functional groups such as free-amines, chloro, are all tolerated under the
employed reaction conditions.
Received 26 April 2012
Revised 2 June 2012
Accepted 6 June 2012
Available online 16 June 2012
Keywords:
Rhodium
Ó 2012 Elsevier Ltd. All rights reserved.
Cross-coupling
Thiol
Aryl iodide
Phosphine
Aryl thioethers are present in many biologically active mole-
cules.1 As a consequence, many approaches have been described
for the synthesis of these compounds.2–11 Among these methods,
the transition-metal-catalyzed cross-coupling reaction of thiols
with aryl halides4–11 provides an attractive choice for this purpose
due to its more mild reaction conditions when compared to tradi-
tional methods.3 Palladium,5 nickel,6 cobalt,7 copper,8 indium,9
gold,10 and iron11 are known to catalyze C–S bond formation. A
wide array of ancillary ligands has also been used.4–11 While
PPh3 was shown to be successful in the first palladium-catalyzed
C–S coupling by Migita et al. in 1980,5a it has received minimal
attention since. When considering the mechanism of palladium-
catalyzed C–S coupling, the undesirable anionic and bridging
thiolate complexes can be formed when a monophosphine is used,
and this is thought to inhibit the efficiency of the catalysis by
decreasing the rate of reductive elimination. Recent studies
revealed that bisphosphines (Fig. 1), for example, Josiphos (1-dicy-
clohexylphosphino-2-di-tert-butylphosphinoethylferrocene, L1),5c–e
BINAP [2,20-bis(diphenylphosphino)-1,10-binaphthyl, L2],5f xant-
phos [9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene, L3],5g,5h
and DPEphos [bis(2-diphenylphosphinophenyl)ether, L4]5i are
more efficient than monophosphines in palladium-catalyzed
S-arylation of thiols with aryl halides. Bisphosphines have also re-
ceived significant attention with other metal-catalyzed reactions,
for example; nickel/dppf [1,10-bis(diphenylphosphanyl) ferrocene,
L5]-9 and cobalt/dppe [1,2-bis(diphenylphosphino)-ethane, L6]-
catalyzed10 C–S bond formation.
Rhodium has been shown to be an invaluable metal for bond-
forming transformations;12–16 rhodium-catalyzed C–C,13 C–N,14
and C–O15 cross-coupling reactions are well-known. Despite this
success, the rhodium-catalyzed C–S coupling is rare.16 Yamaguchi
and co-workers reported the rhodium-catalyzed coupling disul-
fides with aryl fluorides, however, the system is limited to strongly
electron-withdrawing aryl fluorides.16a In 2005, Tanaka reported
the rhodium-catalyzed reductive coupling of disulfides with alkyl
halides, but there remain some drawbacks in this system. First,
the substrates are limited to alkyl halides; on the other hand, the
diarylthioethers are not possible to be formed by this method.
Second, the preparation of disulfides in advance is required.16b
Thus, it is highly desirable to develop a general procedure of the
rhodium-catalyzed C–S bond formation from thiols. Here, we
PtBu2
PPh2
PPh2
Fe
PCy2
O
PPh2
PPh2
L1
L2
L3
PPh2
PPh2
Fe
Ph2P
O
PPh2 PPh3
PPh2
PPh2
L4
L5
L6
L7
⇑
Corresponding author. Tel.: +886 4 2284 0411x810; fax: +886 4 2286 2547.
E-mail address: cfalee@dragon.nchu.edu.tw (C.-F. Lee).
Figure 1. Structures of the ligands L1–L7.
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.06.054

4366
C.-S. Lai et al. / Tetrahedron Letters 53 (2012) 4365–4367
Table 1
Table 2
Optimized the reaction conditionsa
Rhodium-catalyzed coupling reaction of thiols with aryl iodidesa
SH
5 mol % [RhCl(cod)]2
5 mol % [RhCl (cod)]
S
2
I
10 mol % L7
S
10 mol % L
Ar-I
1
+
RSH
2
Ar
+
R
toluene, NaOtBu
100°C, 24 h
base, solvent
110°C, 24 h
3
1a
Entry
2a
Ligand
3a
Entry
1
Product
Yieldb (%)
Base
Solvent
Yield (%)
S
1
2
3
4
5
6
7
8
L1
L2
L3
L4
L5
L6
L7
L7
L7
L7
L7
L7
L7
L7
L7
L7
L7
L7
L7
L7
L7
L7
L7
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
KOtBu
KOH
NaOH
K3PO4
Cs2CO3
Et3N
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Toluene
DMF
89
28
Trace
98
93
73
99
39
20
3b
3c
86
98
Cl
S
2
3
OMe
9
S
S
10
11
12
13
14
15
16
17b
18b
19b
20b,c
21d
22e
23f
19
3d
85
Trace
Trace
88
99
99
60
85
98
88
67
78
45
28
4
5
6
7
3e
3f
90
99
94
82
DMSO
OMe
S
Dioxane
Toluene
DMF
Toluene
Toluene
Toluene
Toluene
MeO
MeO
MeO
tBu
S
3g
3h
a
Reaction conditions: [RhCl(cod)]2 (0.01 mmol, 5 mol %), ligand (0.02 mmol,
10 mol %), 4-iodotoluene (0.24 mmol), thiophenol (0.2 mmol), base (0.4 mmol) in
0.2 mL solvent.
Cl
S
S
OMe
b
100 °C.
c
[RhCl(cod)]2 (0.005 mmol, 2.5 mol %), ligand (0.01 mmol, 5 mol %).
OMe
Cod = cyclooctadiene.
d
OMe
RhCl(PPh3)3 as rhodium source.
Rh2(OAc)4 as rhodium source.
[RhCl(CO)2]2 as rhodium source.
e
f
8
3i
97
MeO
report the rhodium-catalyzed cross-coupling reaction of thiols
with aryl iodides in the presence of PPh3 as a ligand, L7.
S
9
3j
98
67
In order to determine the optimized reaction conditions, 4-
iodotoluene and thiophenol were selected as the model substrates
for this reaction. Several ligands were examined and the results are
summarized in Table 1. Interestingly, electron-rich and sterically
hindered ligand L1, showed good reactivity, giving the product in
89% yield (Table 1, entry 1). L2 and L3 were less effective (Table
1, entries 2 and 3). L4 possesses similar electronic effects when
compared with L3, however, it possesses a more flexible backbone
than L1 and L3. To our delight, a 98% of isolated yield was achieved
when L4 was employed (Table 1, entry 4). L5 and L6 also exhibited
good reactivity resulting in 93% and 73% yields, respectively (Table
1, entries 5 and 6). A 99% of isolated yield was obtained when PPh3,
and due to cost considerations, L7 was determined to be the ligand
of choice. After screening the effect of base, NaOtBu was found to
be superior when compared to the other bases (Table 1, entries
8–13). A variety of solvents were examined, and the use of toluene,
DMF, or dioxane, resulted in the product being formed in excellent
yields (Table 1, entries 7, 14, and 15), DMSO is not a good choice for
this reaction (Table 1, entry 16). At a lower temperature, interest-
ingly, the solvent effect (Table 1, entries 17–19) shows that toluene
is better than dioxane and DMF, providing the product in 98%
isolated yield at 100 °C (Table 1, entry 18). It was observed that
lower catalyst loadings diminished the yield of the target (Table
1, entry 20). We also examined the rhodium sources and found that
[RhCl(cod)]2 was superior to RhCl(PPh3)3, Rh2(OAc)4, [RhCl(CO)2]2
(Table 1, entries 21–23, respectively). Additionally, lower yields
MeO
Br
S
10
3k
S
11
12
13
14
3l
94
86
91
73
H2N
S
3m
3n
3o
S
F3C
S
S
15
3p
77

C.-S. Lai et al. / Tetrahedron Letters 53 (2012) 4365–4367
4367
catalyzed coupling of thiols with more challenging aryl bromides
and chlorides is currently under progress in our laboratory.
Table 2 (continued)
Entry
Product
Yieldb (%)
84
S
Acknowledgments
C6H13
16
3q
3r
The National Science Council, Taiwan (NSC 99-2113-M-005-
004-MY2) and the National Chung Hsing University are gratefully
acknowledged for financial support. We thank Prof. Fung-E Hong
for sharing his GC–MS instruments. C.F.L. is a Golden-Jade Fellow
of Kenda Foundation, Taiwan.
S
C12H25
S
17
18
84
83
C12H25
3s
3t
MeO
MeO
Supplementary data
S
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2012.06.
054.
19
20
21
98
92
85
S
S
3u
3v
References and notes
MeO
MeO
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C6H13
S
22
23
3w
3x
98
73
MeO
Br
S
C12H25
S
24
25
3y
3z
55
76
H N
2
S
a
Reaction conditions: [RhCl(cod)]2 (0.01 mmol, 5 mol %), L7 (0.02 mmol,
10 mol %), aryl iodide (0.24 mmol), thiol (0.2 mmol), NaOtBu (0.4 mmol) in 0.2 mL
toluene.
b
Isolated yield.
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were observed when 4-iodotoluene was replaced by 4-bromotolu-
ene (7% isolated yield) or 4-chlorotoluene (trace amount of product
was detected by GC–MS) under the same reaction conditions.
Based on the above results, we decided to use 5 mol % of
[RhCl(cod)]2 and 10 mol % of PPh3 as the catalyst; toluene as
solvent and NaOtBu as a base at 100 °C as the optimized reaction
conditions for further studying the scope of this novel catalytic
system. The results are summarized in Table 2. The aryl thiols
(Table 2, entries 1–13) and alkyl thiols (Table 2, entries 14–25)
reacted smoothly with a variety of aryl iodides, giving the products
in good to excellent yields. It is important to note that the func-
tional groups including chloro-(Table 2, entries 1 and 6), bromo-
(Table 2, entries 10 and 23), trifluoromethyl (Table 2, entry 13),
and free amine (Table 2, entries 11 and 24) are all tolerated during
this transformation. The aryl iodides bearing electron-rich groups
such as 4-iodoanisole can be coupled smoothly to provide the
products in excellent yields (Table 2, entries 5–9 and 18–22).
In conclusion, we have reported the coupling reaction of rho-
dium-catalyzed C–S bond formation between thiols and aryl
iodides by using [RhCl(cod)]2 and PPh3 as an auxiliary ligand. A
broad spectrum of thiols was reacted smoothly to provide the aryl
thioethers in good to excellent yields. Investigation of rhodium-
15. Kim, H. J.; Kim, M.; Chang, S. Org. Lett. 2011, 13, 2368.
16. (a) Arisawa, M.; Suzuki, T.; Ishikawa, T.; Yamaguchi, M. J. Am. Chem. Soc. 2008,
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