Copper-Catalyzed Production of Diaryl Sulfides Using Aryl Iodides and a Disilathiane

Article abstract of DOI:10.1055/s-0036-1591723

A disilathiane was found to be a novel S1 source for the copper-catalyzed synthesis of diaryl sulfides using aryl iodides. The reaction of iodoarenes and hexamethyldisilathiane, (Me ₃ Si) ₂ S, in the presence of a catalytic amount of CuI/1,10-phenanthroline provided various types of diaryl sulfides in good yields.

Full text of DOI:10.1055/s-0036-1591723

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© Georg Thieme Verlag Stuttgart · New York
2017, 28, A–C
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A
en
Y. Ogiwara et al.
Letter
Synlett
Copper-Catalyzed Production of Diaryl Sulfides Using Aryl Iodides
and a Disilathiane
Yohei Ogiwara
CuI (cat)
I
S
1,10-phen (cat)
Hiromu Maeda
Norio Sakai*
+
(Me3Si)2S
R
R
R
K2CO3, NMP
120 °C
29–99%
17 examples
Department of Pure and Applied Chemistry, Faculty of Science
and Technology, Tokyo University of Science, 2641 Yamazaki,
Noda, Chiba 278-8510, Japan
R = H, OMe, SMe, Me, tBu, Ac, CF3, CN, NO2, F, Cl, Br, etc.
sakachem@rs.noda.tus.ac.jp
Received: 20.09.2017
Accepted after revision: 19.10.2017
Published online: 23.11.2017
tion of the corresponding diaryl alternatives in principle. To
produce diaryl sulfides, the transition-metal-catalyzed
double formation of a carbon–sulfur bond between two
molecules of an aryl halide and an appropriate S1 source
has been a reliable and efficient procedure. Various sulfur
sources have been utilized for this type of diaryl sulfide
synthesis: S8,3 thiourea,4 xanthogenate,5 thioester,6 KSCN,7
Na2S,8 CS2,9 Na2S2O3,10 and K2S.11 To the best of our knowl-
edge, the use of a disilathiane ([Si]2S) as a S1 source for the
catalytic construction of diaryl sulfides is unprecedented.
Herein, we describe the copper-catalyzed, one-pot synthe-
sis of symmetrical diaryl sulfides using a variety of aryl io-
dides and hexamethyldisilathiane (Scheme 1, b).
DOI: 10.1055/s-0036-1591723; Art ID: ss-2017-u0702-l
Abstract A disilathiane was found to be a novel S1 source for the cop-
per-catalyzed synthesis of diaryl sulfides using aryl iodides. The reaction
of iodoarenes and hexamethyldisilathiane, (Me3Si)2S, in the presence of
a catalytic amount of CuI/1,10-phenanthroline provided various types
of diaryl sulfides in good yields.
Key words copper catalyst, aryl iodides, disilathiane, carbon–sulfur
bond formation, diaryl sulfides
Sulfides (thioethers), R–S–R, are an important class of
structural units in organic chemistry, and a number of re-
search groups have devoted extensive effort to the develop-
ment of novel and efficient synthetic strategies for the con-
struction of these skeletons.1 Our group has reported the in-
dium-catalyzed reductive construction of thioethers from
benzoic acids,2a benzaldehydes,2a and benzyl alcohols2b us-
ing a combination of elemental sulfur (S8) and hydrosilanes.
In these reactions, the in situ generation of a disilathiane
([Si]2S) from unactivated S8 and a hydrosilane is considered
to be a key activation process for the formation of dibenzyl
sulfides (Scheme 1, a). Sulfides obtained by these proce-
dures, however, have primarily been limited to the dibenzyl
variety. Also, the protocol could not undertake the forma-
Table 1 Optimization of the Reaction Conditionsa
CuI (5 mol%)
S
I
ligand (5 mol%)
+
(Me3Si)2S
0.5 equiv
base (1 equiv)
solvent, 14 h
1a
2a
Entry
Ligand
Base
Solvent
Yield (%)b
1
2
3
4
5
6
7
8
9
none
phen
none
phen
phen
phen
phen
phen
phen
none
NMP, 120 °C
0
none
NMP, 120 °C
NMP, 120 °C
NMP, 120 °C
NMP, 100 °C
NMP, 80 °C
trace
66
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
90 (92)c
63
a) our previous results
R
InI3 (cat)
trace
64d
40e
0
S
+
+
[Si]H
S8
Ar
Ar
Ar
1,2-DCE
80 °C
DMF, 120 °C
DMSO, 120 °C
toluene, 120 °C
R = CO2H, CHO, CH2OH
via. [Si]2S
b) this work
CuI (cat)
phen (cat)
S
I
a Reaction conditions: 1a (0.5 mmol), (Me3Si)2S (0.25 mmol), CuI (0.025
mmol), 1,10-phenanthroline (0.025 mmol), and K2CO3 (0.5 mmol) in NMP
(0.5 mL) at 120 °C for 14 h.
+
(Me3Si)2S
Ar
Ar
Ar
K2CO3
NMP, 120 °C
b GC yield.
c Isolated yield, 1 mmol scale.
Scheme 1 Catalytic construction of a) dibenzyl sulfides, and b) diaryl
sulfides
d The corresponding disulfide was also generated in a 14% GC yield.
e The corresponding disulfide was also generated in a 13% GC yield.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–C

B
Y. Ogiwara et al.
Letter
Synlett
Optimization of the conditions for sulfidation using io-
dobenzene (1a) and (Me3Si)2S was initially investigated (Ta-
ble 1). When the reaction was performed with only a cata-
lytic amount of CuI in N-methyl-2-pyrrolidone (NMP) as a
solvent at 120 °C for 14 h, the formation of the desired sul-
fide 2a was not observed, as determined by GC analysis (Ta-
ble 1, entry 1). The addition of 1,10-phenanthroline (phen)
as a ligand produced a trace amount of 2a (Table 1, entry 2).
Instead, the addition of a stoichiometric amount of K2CO3
effectively increased the yield of 2a to 66% (Table 1, entry
3). The reaction with both the ligand and the base afforded
2a in a 90% GC yield.12 Under these conditions, 92% of di-
phenyl sulfide (2a) was isolated using 1 mmol of 1a (Table
1, entry 4). The reaction temperature was investigated to
achieve milder reaction conditions, but the higher reaction
temperature (120 °C) was essential to complete the conver-
sion (Table 1, entries 4–6). Next, the solvents were
screened. Reactions in either DMF or DMSO proceeded to
form sulfide 2a in moderate yields, but the undesired disul-
fide, diphenyl disulfide, was simultaneously detected as a
byproduct in 14% and 13% GC yields (Table 1, entries 7 and
8). The reaction did not proceed when using toluene as a
solvent (Table 1, entry 9).
Copper-catalyzed production of diaryl sulfides 2 using a
disilathiane was then conducted with several iodoarenes 1
(Scheme 2). When the reaction of iodobenzene bearing a 4-
methoxy group 1b was performed under the optimal condi-
tions, the corresponding product 2b was obtained in a 72%
isolated yield. Sulfur-containing iodoarene 1c was also con-
verted into product 2c, and the reactions with the alkyl-
substituted versions 1d–g proceeded to form the corre-
sponding diaryl sulfides 2d–g, regardless of the position of
the substituent on their benzene rings. Substrates bearing
electron-withdrawing acetyl 1h, trifluoromethyl 1i, cyano
1j, and nitro 1k groups were also suitable for the sulfida-
tion and provided products 2h–k in excellent isolated
yields. When using halogen-substituted iodobenzenes such
as 1-fluoro-4-iodobenzene (1l), 1-chloro-4-iodobenzene
(1m), and 1-bromo-4-iodobenzene (1n), each activation
occurred at the carbon–iodine bond selectively over C–F, C–
Cl, and C–Br bonds, giving 4-halo-diaryl sulfides 2l–n. The
reaction of an iodoarene bearing a 1-naphthyl moiety 1o
proceeded to give the corresponding sulfide 2o. Heteroaro-
matic substrates 3-iodopyridine (1p) and 2-iodothiophene
(1q) were also applicable to the conversion to afford prod-
ucts 2p and 2q, respectively.
CuI (5 mol%)
phen (5 mol%)
S
I
+
(Me3Si)2S
0.5 equiv
S
Ar
S
Ar
Ar
K2CO3 (1 equiv)
NMP, 120 °C
14 h
1
2
MeO
OMe MeS
SMe
2b, 72%
2c, 77%
S
S
2d, 84%
2e, 87%
S
S
A plausible catalytic cycle for the present reaction is il-
lustrated in Scheme 3. The starting copper(I) inserts to the
C–I bond of iodoarene 1 to afford the Ar–Cu–I species,
which undergoes a ligand exchange between a disilathiane
and a base. The first C–S bond formation occurs by reduc-
tive elimination and provides benzenethiol derivative 3
with a regeneration of copper(I). Again, the oxidative addi-
tion of 1 to copper(I) occurs to form an Ar–Cu–I species, fol-
lowed by transmetalation between 3 and the formed Ar–
2f, 78%
2g, 62%
S
S
F3C
CF3
NO2
Cl
2h, 79%
2i, 90%
O
O
S
S
NC
CN
F
O2N
2j, 91%
2k, 70%
Ar
S
Ar
Ar I
S
S
2
[Cu]X
1
F
Cl
Ar [Cu]
X
Ar [Cu]
I
X
2l, 65%
2m, 95%
S–Ar
S
[Si]2S
KX (base)
[Si]X
KI
S
Br
Br
2n, 60%a
Ar S[Si]
3
2o, 99%
[Si]X
KI
KX (base)
S
S
S
S
N
N
Ar [Cu]
I
X
Ar [Cu] X
S[Si]
2p, 98%
2q, 29%
[Cu]X
Scheme 2 Substrate scope for aryl iodides 1. Reagents and conditions: 1
(1 mmol), (Me3Si)2S (0.5 mmol), CuI (0.05 mmol), 1,10-phenanthroline
(0.05 mmol), and K2CO3 (1 mmol) in NMP (1 mL) at 120 °C for 14 h.
Isolated yields of diaryl sulfides 2 are shown. a NMR yield.
Ar
I
1
Scheme 3 Proposed mechanism for the preparation of diaryl sulfides
© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–C

C
Y. Ogiwara et al.
Letter
Synlett
Cu–I to generate an Ar–[Cu]–SAr species. Finally, the second
reductive elimination of the species occurs to provide diaryl
sulfide 2.13
(6) Park, N.; Park, K.; Jang, M.; Lee, S. J. Org. Chem. 2011, 76, 4371.
(7) (a) Ke, F.; Qu, Y.; Jiang, Z.; Li, Z.; Wu, D.; Zhou, X. Org. Lett. 2011,
13, 454. (b) Reddy, K. H. V.; Reddy, V. P.; Kumar, A. A.; Kranthi,
G.; Nageswar, Y. V. D. Beilstein J. Org. Chem. 2011, 7, 886. (c) Li,
X.; Yuan, T.; Chen, J. Chin. J. Chem. 2012, 30, 651. (d) Hajipour, A.
R.; Pourkaveh, R.; Karimi, H. Appl. Organometal. Chem. 2014, 28,
879.
(8) Li, Y.; Nie, C.; Wang, H.; Li, X.; Verpoort, F.; Duan, C. Eur. J. Org.
Chem. 2011, 7331.
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(b) Firouzabadi, H.; Iranpoor, N.; Samadi, A. Tetrahedron Lett.
2014, 55, 1212.
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3686.
In summary, we described an efficient copper catalytic
system for the production of diaryl sulfide using iodoarenes
and a disilathiane via a double carbon–sulfur bond forma-
tion.14 A variety of iodobenzene derivatives were applied to
this protocol with highly functional group tolerance, which
yielded the corresponding sulfides.15 The results of a pre-
liminary mechanistic study supported the plausibility of
using benzenethiol as an intermediate.16
Funding Information
This work was partially supported by JSPS KAKENHI Grant Number
(12) See the Supporting Information for more details on the screen-
ing of the ligands.
JP16K21400.
)(
(13) For a review of transition-metal-catalyzed C–S bond formation
via cross-coupling reactions, see: Beletskaya, I. P.; Ananikov, V.
P. Chem. Rev. 2011, 111, 1596.
Supporting Information
(14) General Procedure
Supporting information for this article is available online at
To a screw-capped test tube under a nitrogen atmosphere, 1,10-
phenanthroline (0.05 mmol, 9.0 mg), iodobenzene 1 (1 mmol),
K2CO3 (1 mmol, 138.2 mg), CuI (0.05 mmol, 9.5 mg), N-methyl-
2-pyrrolidone (1 mL), and 1,1,1,3,3,3-hexamethyldisilathiane
(0.5 mmol, 89.2 mg) were added. After the tube was sealed with
a cap, the mixture was heated at 120 °C for 14 h. After the reac-
tion, H2O was added to the mixture, which was then extracted
with EtOAc three times. The combined organic phases were
evaporated under reduced pressure. The crude material was
purified by silica gel column chromatography to give the corre-
sponding diaryl sulfide 2.
https://doi.org/10.1055/s-0036-1591723.
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References and Notes
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Diphenyl Sulfide (2a)
The general procedure was followed with iodobenzene (1a,
202.7 mg, 0.99 mmol) for 14 h. Column chromatography (hex-
ane) afforded 2a as a colorless oil (85.0 mg, 92%). 1H NMR (500.2
MHz, CDCl3): δ = 7.23 (t, J = 7.5 Hz, 2 H, ArH), 7.29 (t, J = 7.5 Hz,
4 H, ArH), 7.34 (d, J = 7.5 Hz, 4 H, ArH). 13C NMR (125.8 MHz,
CDCl3): δ = 127.0, 129.2, 131.0, 135.8. LRMS (EI): m/z (% relative
intensity) = 187 (17) [M + 1]+, 186 (100), 185 (69), 184 (27), 154
(14), 134 (14), 77 (15), 51 (20).
(15) An alkyl iodide was also applicable for this reaction (Scheme 4).
CuI (5 mol%)
phen (5 mol%)
+
Ph(CH2)3I
(Me3Si)2S
0.5 equiv
Ph(CH2)3S(CH2)3Ph
91%
K2CO3 (1 equiv)
NMP, 120 °C
14 h
Scheme 4
(16) See the Supporting Information for further results to support
the proposed mechanism.
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(b) Akkilagunta, V. K.; Kakulapati, R. R. J. Org. Chem. 2011, 76,
6819.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–C