Aryl- or alkylation of diaryl disulfides using organoboronic acids and a copper catalyst

Article abstract of DOI:10.1055/s-2006-939707

A variety of unsymmetrical monosulfides can be synthesized in good yields by copper-catalyzed coupling of disulfides with organoboronic acids in air. Furthermore, this method can result in the successful aryl- or alkylation of both organosulfide groups in a disulfide. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2006-939707

LETTER
1351
Aryl- or Alkylation of Diaryl Disulfides Using Organoboronic Acids and a
Copper Catalyst
A
ryl- or Alkylation
o
of
D
iaryl
D
b
isulfide
s
ukazu Taniguchi*
Department of Chemistry, Fukushima Medical University, Fukushima 960-1295, Japan
Fax +81(24)5471369; E-mail: taniguti@fmu.ac.jp
Received 1 February 2006
CuIX
Abstract: A variety of unsymmetrical monosulfides can be synthe-
sized in good yields by copper-catalyzed coupling of disulfides with
organoboronic acids in air. Furthermore, this method can result in
the successful aryl- or alkylation of both organosulfide groups in a
disulfide.
ArB(OH)2
CuI–SR
RS SR
+
+
Ar-SR
Oxidation
Oxidation
CuII
X
Ar
CuII
Key words: unsymmetrical monosulfide, diaryl disulfide, organo-
RS
RS
boronic acid, copper catalyst
ArB(OH)2
Scheme 1 A strategy for the copper-catalyzed coupling of (RS)2
with ArB(OH)2
Transition-metal-catalyzed aryl carbon–sulfur bond for-
mation is an important procedure for the preparation of
various sulfide derivatives, and many reactions have been
developed to date.1 The organosulfides synthesized herein
have found widespread application as convenient inter-
mediates or reagents in organic synthesis.2
by a copper catalyst in air. In this paper, we wish to de-
scribe the methodology.
Initially various solvents were investigated. When the
reaction was performed in DMF, we were surprised to ob-
tain 3 in 70% yield (Table 1, entry 1). Moreover, addition
of water to DMF increased the yield to 82% (Table 1,
entry 2). Other solvents such as DMI and dioxane also
showed similar results (Table 1, entries 3 and 4). How-
ever, the problem with the method described was that a
small amount of 1 was recovered in all cases and the
separation of 1 from 3 was very complicated.
To afford arylsulfides using a transition metal catalyst, a
combination of aryl halide and thiol is often employed un-
der basic conditions;3 however, a disulfide has been used
rarely.4 As a rule, transition-metal-catalyzed sulfidation of
an aryl halide using disulfide is performed under reductive
conditions in order to generate a thiolate anion or a metal-
monosulfide complex.4f,5
Fortunately, we found that DMSO and water afforded 3 in
97% yield with complete consumption of 1 (Table 1, entry
6). Other copper catalysts (CuCl, CuBr, CuOAc, CuCl2,
and CuBr2) also gave excellent yields (Table 1, entries 8–
12).10
To date, no metal-catalyzed preparation of monosulfides
using a disulfide under oxidative conditions has been
explored although the reaction of organoboronic acid with
thiol using a stoichiometric amount of a copper(II) salt has
been developed6,7 and a copper-catalyzed reaction with
other dichalcogenides (diselenides and ditellurides) hav-
ing higher reactivity was reported recently.8
We also looked at the ligand bpy; when bpy was not added
the yield of 3 decreased to 18% yield (Table 1, entry 7),
while other ligands such as TMEDA and PPh3 did not
work effectively.
The lack of such methodologies could be attributed to the
lower activity of the generated copper(I) sulfide interme-
diate. Therefore, a method using N-thioimides as a sulfur
source has been reported for the copper-catalyzed reac-
tion.9 Herein we describe the extension of this catalytic
method to disulfides.
Various organoboronic acids and diphenyl disulfides
were reacted under the optimized conditions in good
yields (Table 2, entries 1–11). ortho-Substituted (meth-
oxy and chloro) arylboronic acids gave slightly lower
yields (Table 2, entries 3 and 4). Furthermore, this proce-
dure could tolerate alkenyl- or alkylboronic acids, but the
employment of alkylboronic acids required longer reac-
tion times than the reaction of arylboronic acids (Table 2,
entries 12–16).
To accelerate the catalytic cycle the generation of
Cu(SR)Ar from Cu(I)SR and ArB(OH)2 is invoked in the
presence of an oxidant (Scheme 1).
Initially, we looked at the oxidant in a variety of condi-
tions and found that unsymmetrical monosulfides could
be synthesized from disulfides and organoboronic acids
Similarly, the combination of various diaryl disulfides
with phenylboronic acids also afforded good results
(Table 2, entries 17–22). Unfortunately, the reaction of
dibutyl disulfide proceeded in low yield (Table 2, entry
23).
SYNLETT 2006, No. 9, pp 1351–1354
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1.
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6.
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Advanced online publication: 26.04.2006
DOI: 10.1055/s-2006-939707; Art ID: U01506ST
© Georg Thieme Verlag Stuttgart · New York

1352
N. Taniguchi
LETTER
Table 1 Copper-Catalyzed Coupling of (4-MeC6H4S)2 with
PhB(OH)2
Table 2 CuI-Catalyzed Aryl- or Alkylation of Disulfide Using
a
Organoboronic Acida,11
CuI(bpy) (5 mol%)
[Cu]-bpy (5 mol%)
S
(4-MeC6H4S)2
PhB(OH)2
2 x 4-MeC6H4SPh
R2B(OH)2
R2
R1S SR1
R1
+
2
+
DMSO–H2O (2:1),
air, 100 °C
Solvent–H2O (2:1),
air, 100 °C, 12 h
1
2
3
4
5
6
(0.2 mmol)
(0.6 mmol)
Entry
1
R1
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
R2
Time (h) 6 (%)b
Entry
1d
2
[Cu]
CuI
Solvent
3 (%)b,c
70
1 (%)c
28
Ph
12
12
24
24
12
12
12
12
12
12
12
30
12
42
48
48
12
48
12
12
24
42
24
97
97
50
76
97
98
88
96
90
98
89
97
93
72
94
65
97
74
67
97
65
72
29
DMF
2
2-MeC6H4
2-MeOC6H4
2-ClC6H4
4-MeC6H4
4-MeOC6H4
4-BrC6H4
4-ClC6H4
4-HOC6H4
4-OHCC6H4
4-MeO2CC6H4
(E)-PhCH=CH
Me
CuI
DMF
82
13
3
3
CuI
DMI
86
10
4c
4
CuI
dioxane
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
75
21
5d
6
CuI
76
10
5
6
CuI
97
–
7e
8
CuI
18
79
7
8
CuCl
CuBr
CuOAc
CuCl2
CuBr2
90
trace
trace
–
9
9
93
10
11
12
13
14
15c
16c
17
18
19
20
21d
22
23c
10
11
12
95
97
–
92
trace
a Reagents: 1 (49.3 mg, 0.2mmol), 2 (73.1 mg, 0.6 mmol), Cu (cat.,
5 mol%).
b Isolated yields after silica gel chromatography.
c Yields of 3 are based on disulfide 1 (2 mol).
d H2O was not added.
n-Bu
c-C6H11
PhCH2CH2
Ph
e Without bpy.
4-MeC6H4
4-MeOC6H4
4-BrC6H4
Thus, the coupling of disulfides with organoboronic acids
by a copper catalyst afforded the desired sulfides in good
yields, and could afford the aryl- or alkylation of both sul-
fide groups in a disulfide.
Ph
Ph
4-O2NC6H4
4-H2NC6H4
Ph
Ph
bpy
PhSCu
4-MeC6H4B(OH)2
(0.2 mmol)
4-MeC6H4SPh
+
4-HO2CC6H4 Ph
n-Bu Ph
DMSO–H2O
(2:1), air,
100 °C, 18 h
3
(0.1 mmol)
3 (%)
53
a Reagents: organoboronic acid (0.6 mmol), diphenyl disulfide
(0.2 mmol), CuI(bpy) (5 mol%).
additive
none
b Isolated yields after silica gel chromatography.
c [CuI]-bpy (10 mol%).
n-Bu4NI
(0.1 mmol)
68
d This reaction was carried out at 90 ºC.
Scheme 2 Reaction of PhSCu with 4-MeC6H4B(OH)2
We then examined the reaction of PhSCu,12 considered as
an intermediate, with organoboronic acids in order to
investigate the reaction mechanism. When a mixture of
PhSCu and 4-MeC6H4B(OH)2 was treated in DMSO–wa-
ter, the corresponding diaryl sulfide 3 was obtained in
53% yield (Scheme 2). Moreover, when TBAI was added
as the iodide source, the yield increased to 68%.
CuI(bpy)
(5 mol%)
(PhS)2
4-MeC6H4B(OH)2
+
4-MeC6H4SPh
7%
DMSO–H2O
(2:1), 100 °C,
18 h, under N2
(1.0 mmol)
Scheme 3 Reaction of (PhS)2 with 4-MeC6H4B(OH)2 in the absence
of oxygen
Synlett 2006, No. 9, 1351–1354 © Thieme Stuttgart · New York

LETTER
Aryl- or Alkylation of Diaryl Disulfides
1353
On the other hand, in the absence of oxygen, the reaction
of (PhS)2 with 4-MeC6H4B(OH)2 afforded sulfide 3 in
only 7% yield (Scheme 3). Thus, we can conclude that
PhSCu(I) can react with an organoboronic acid through
formation of PhSCu(II)X by the oxidation of PhSCu(I) in
the presence of oxygen.
References and Notes
(1) (a) Ley, S. V.; Thomas, A. W. Angew. Chem. Int. Ed. 2003,
42, 5400. (b) Kondo, T.; Mitsudo, T. Chem. Rev. 2000, 100,
3205. (c) Comprehensive Organic Synthesis, Vol. 4; Trost,
B. M.; Fleming, I., Eds.; Pergamon Press: New York, 1991.
(2) (a) Metzner, P.; Thuillier, A. Sulfur Reagents in Organic
Synthesis; Katritzky, A. R.; Meth-Cohn, O.; Rees, C. W.,
Eds.; Academic Press: San Diego, 1994.
(b) Comprehensive Organic Synthesis, Vol. 6; Trost, B. M.;
Fleming, I., Eds.; Pergamon Press: New York, 1991.
(3) (a) Kosugi, M.; Shimizu, T.; Migita, T. Chem. Lett. 1978,
13. (b) Suzuki, H.; Abe, H.; Osuka, A. Chem. Lett. 1980,
1363. (c) Bowman, W. R.; Heaney, H.; Smith, P. H. G.
Tetrahedron Lett. 1984, 25, 5821. (d) Ciattini, P. G.;
Morera, E.; Ortar, G. Tetrahedron Lett. 1995, 36, 4133.
(e) Zheng, N.; McWilliams, J. C.; Fleitz, F. J.; Armstrong, J.
D. III; Volante, R. P. J. Org. Chem. 1998, 63, 9606.
(f) Bates, C. G.; Gujadhur, R. K.; Venkataraman, D. Org.
Lett. 2002, 4, 2803. (g) Kwong, F. Y.; Buchwald, S. L. Org.
Lett. 2002, 4, 3517. (h) Itoh, T.; Mase, T. Org. Lett. 2004, 6,
4587.
(4) Chalcogenations of alkyl halides using dichalcogenides are
known, see: (a) Chowdhury, S.; Roy, S. Tetrahedron Lett.
1997, 38, 2149. (b) Kundu, A.; Roy, S. Organometallics
2000, 19, 105. (c) Nishino, T.; Okada, M.; Kuroki, T.;
Watanabe, T.; Nishiyama, Y.; Sonoda, N. J. Org. Chem.
2002, 67, 8696. (d) Nishino, T.; Nishiyama, Y.; Sonoda, N.
Chem. Lett. 2003, 928. (e) Ranu, B. C.; Mandal, T. J. Org.
Chem. 2004, 69, 5793. (f) Ajiki, K.; Tanaka, K. Org. Lett.
2005, 7, 4193.
A plausible reaction mechanism is described in
Scheme 4.13 In cycle A, after R2Cu(I) 7 is formed from
R2B(OH)2 and CuX, both the expected sulfide 6 and
PhSCu(I)Ln 8 were produced by the reaction of 7 with
(R1S)2. In the following step, (R1S)(R2)Cu(II) 11 is
produced via the oxidation of R1SCu 8. Finally, R1SR2 6
is produced again through the oxidation of 11.
On the other hand, in cycle B, after the insertion of CuI to
(R1S)2, the sulfide 6 and R1SCu(I) 8 are produced from the
generated copper disulfide complex 9 with R2B(OH)2.14
R2B(OH)2
4
5
R2-CuILn
(R1S)2CuXLn
CuIXLn
7
9
6
(R1S)2
4
5
6
1/2O2, X–
CuIILn
R1S
R2
B
A
11
R1SR2
6
R1S-CuILn
R1S-CuILn
5
R1S
X
CuIILn
10
8
8
(5) (a) Millois, C.; Diaz, P. Org. Lett. 2000, 2, 1705.
(b) Taniguchi, N.; Onami, T. Synlett 2003, 829.
1/2O2, X–
1/2O2, X–
(c) Taniguchi, N.; Onami, T. J. Org. Chem. 2004, 69, 915.
(d) Taniguchi, N. J. Org. Chem. 2004, 69, 6904.
(e) Taniguchi, N. Synlett 2005, 1687.
Scheme 4 A plausible reaction mechanism
It seems that the mechanism is dependent on the sub-
strates (disulfide and organoboronic acid) or copper cata-
lyst. Further investigations on the exact details of the
copper-catalyzed coupling of disulfides with organo-
boronic acids are now in progress.
(6) Herradura, P. S.; Pendola, K. A.; Guy, R. K. Org. Lett. 2000,
2, 2019.
(7) For a review of carbon–heteroatom bond formations using
organoboronic acid, see: Miyaura, N. In Metal-Catalyzed
Cross-Coupling Reactions, Vol. 1; de Meijere, A.;
Diederich, F., Eds.; Wiley-VCH: Weinheim, 2004, 41–123.
(8) Wang, L.; Wang, M.; Huang, F. Synlett 2005, 2007.
(9) Savarin, C.; Srogl, J.; Liebeskind, L. S. Org. Lett. 2002, 4,
4309.
(10) Although Cu(II)X2 salts afforded 4-MeC6H4SPh in good
yield, the reaction with other substrates (alkylboronic acids
or other diaryl disulfides) showed lower reactivity.
(11) Typical Procedure.
CuI(bpy)
(5 mol%)
(PhY)2
+
4-OHCC6H4B(OH)2
2 x 4-OHCC6H4-YPh
DMSO–H2O
(2:1), air,
12
13
14
Y = Se: 96%
Y = Te: 88%
100 °C,12 h
Scheme 5 CuI-catalyzed arylation of diselenide or ditelluride with
organoboronic acid
To a mixture of CuI (1.9 mg, 0.01 mmol), bpy (1.6 mg, 0.01
mmol), DMSO (0.2 mL), and H2O (0.1 mL) were added
Ph2S2 (43.7 mg, 0.2 mmol) and PhB(OH)2 (73.1 mg, 0.60
mmol), and the mixture was stirred at 100 °C for 12 h in air.
After evaporation of the solvent, the residue was dissolved in
Et2O. The solution was washed with H2O, brine, and dried
over anhyd MgSO4. Chromatography (silica gel; hexane)
gave diphenyl sulfide (72.1 mg, 97%).
According to the procedure developed herein, the desired
selenide or telluride was prepared in 96% or 88% yield,
respectively, from diphenyl diselenide or ditelluride with
4-formylphenylboronic acid (Scheme 5).15
Diphenyl Sulfide: IR (neat): 3072, 1579, 1475, 1439 cm–1.
1H NMR (270 MHz, CDCl3): d = 7.36–7.22 (m, 10 H).
13C NMR (67.5 MHz, CDCl3): d = 135.7, 131.0, 129.1,
127.0. Anal. Calcd for C12H10S: C, 77.37; H, 5.41. Found:
C, 77.18; H, 5.49.
4-Formylphenyl Phenyl Sulfide: IR (neat): 3058, 1697,
1591, 1561, 1475 cm–1. 1H NMR (270 MHz, CDCl3):
d = 9.89 (s, 1 H), 7.70 (d, J = 8.6 Hz, 2 H), 7.49–7.53 (m, 2
H), 7.43–7.39 (m, 3 H), 7.23 (d, J = 8.6 Hz, 2 H). 13C NMR
(67.5 MHz, CDCl3): d = 191.0, 147.1, 134.2, 133.6, 131.2,
130.0, 129.7, 129.0, 127.1. Anal. Calcd for C13H10OS: C,
72.87; H, 4.70. Found: C, 72.69; H, 4.95.
In conclusion, various unsymmetrical monosulfides were
synthesized from disulfides using organoboronic acids by
a copper catalyst in air. Furthermore, the reaction condi-
tions tolerated aryl- or alkylation of both sulfide groups in
a disulfide.
Acknowledgment
This work was supported by Meiji Seika Co. Ltd.
Synlett 2006, No. 9, 1351–1354 © Thieme Stuttgart · New York

1354
N. Taniguchi
LETTER
Cyclohexyl Phenyl Sulfide: IR (neat): 2929, 2852, 1583,
1479, 1448 cm–1. 1H NMR (270 MHz, CDCl3): d = 7.40–
7.36 (m, 2 H), 3.30–3.17 (m, 3 H), 3.13–3.05 (m, 1 H), 2.01–
1.96 (m, 2 H), 1.78–1.74 (m, 2 H), 1.63–1.57 (m, 1 H), 1.42–
1.25 (m, 5 H). 13C NMR (67.5 MHz, CDCl3): d = 135.1,
131.8, 128.6, 126.5, 46.5, 33.3, 26.0, 25.7. Anal. Calcd for
C12H16S: C, 74.94; H, 8.39. Found: C, 74.96; H, 8.35.
(15) 4-Formylphenyl Phenyl Selenide: IR (neat): 3055, 2828,
2733, 1696, 1587 cm–1. 1H NMR (270 MHz, CDCl3):
d = 9.90 (s, 1 H), 7.67 (d, J = 8.6 Hz, 2 H), 7.62–7.59 (m,
2 H), 7.41–7.34 (m, 5 H). 13C NMR (67.5 MHz, CDCl3):
d = 191.2, 142.6, 135.4, 134.4, 130.1, 130.0, 129.7, 128.8,
127.8. Anal. Calcd for C13H10OSe: C, 59.78; H, 3.86. Found:
C, 59.55; H, 3.96.
(12) Org. Synth. Coll., Vol. V; John Wiley & Sons: New York,
1973, 107–110.
(13) (a) Evans, D. A.; Katz, J. L.; West, T. R. Tetrahedron Lett.
1998, 39, 2937. (b) Collman, J. P.; Zhong, M. Org. Lett.
2000, 2, 1233.
4-Formylphenyl Phenyl Telluride: IR (neat): 3052, 2827,
2734, 1694, 1582 cm–1. 1H NMR (270 MHz, CDCl3):
d = 9.89 (s, 1 H), 7.83 (d, J = 8.3 Hz, 2 H), 7.62–7.61 (m,
4 H), 7.59–7.25 (m, 3 H). 13C NMR (67.5 MHz, CDCl3):
d = 191.5, 139.8, 135.6, 135.1, 129.8, 128.9, 126.6, 112.9.
Anal. Calcd for C13H10OTe: C, 50.40; H, 3.25. Found: C,
50.12; H, 3.35.
(14) A disulfide bond can be cleaved by CuI; see ref. 5b and 5d.
Synlett 2006, No. 9, 1351–1354 © Thieme Stuttgart · New York