Rhodium-catalyzed sulfur atom exchange reaction between organic polysulfides and sulfur

Article abstract of DOI:10.1016/j.tetlet.2005.05.024

RhH(PPh₃)₄ and cis-1,2-bis(diphenylphosphino)ethylene (dppv) catalyze the exchange of sulfur atoms between sulfur and organic polysulfides. The exchange of dialkyl trisulfides with sulfur proceeds at a high efficiency within 5 min at room temperature yielding a mixture of organic polysulfides.

Full text of DOI:10.1016/j.tetlet.2005.05.024

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 4797–4800
Rhodium-catalyzed sulfur atom exchange reaction between
organic polysulfides and sulfur
Mieko Arisawa, Ken Tanaka and Masahiko Yamaguchi*
Department of Organic Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba, Sendai 980-8578, Japan
Received 4 April 2005; revised 2 May2005; accepted 6 May2005
Available online 24 May2005
Abstract—RhH(PPh3)4 and cis-1,2-bis(diphenylphosphino)ethylene (dppv) catalyze the exchange of sulfur atoms between sulfur and
organic polysulfides. The exchange of dialkyl trisulfides with sulfur proceeds at a high efficiency within 5 min at room temperature
yielding a mixture of organic polysulfides.
Ó 2005 Elsevier Ltd. All rights reserved.
Sulfur, one of the few elements produced in nature, is an
important starting material for the synthesis of organo-
sulfur compounds used in pharmaceutics. The direct use
of sulfur in organic synthesis, however, is rare, which is
due to the lack of an efficient activation method for sul-
fur. Thermal/photochemical1 or acid/base2 activations
require harsh reaction conditions, and are not easyto
control. Often, these methods employstoichiometric
amounts of activating reagents. The catalytic activation
of sulfur bytransition metal complexes can provide a
new approach in this field, which has an advantage of
It is therefore an interesting subject whether this method
can be used to control middle sulfur. In this study, the
exchange reaction of sulfur atoms between organic poly-
sulfides and sulfur is examined (Scheme 1). Such a reac-
tion of acyclic polysulfides is generally slow even at high
temperatures.7–9 For example, an equilibrium was
reached in a neat mixture of dimethyl disulfide and ele-
mental sulfur after 40 days at 120 °C.8 The exchange
reaction between neat diethyl disulfide and sulfur was
conducted at 120–128 °C for 5 h in the presence of a
catalytic amount of dibutylamine.9 Although some
exchange reactions of sulfur and cyclic polysulfides
proceed under milder conditions, theyat least in some
part relyon ring strain, and therefore have limitation
in the substrate.10 It was found here that the rhodium
complex with a suitable ligand can catalyze the very
rapid exchange reaction of acyclic polysulfides without
deactivation.
3
being controllable bychanging metal and ligand. The
method, however, has not been well developed because
of the serious deactivation of metal catalysts by sulfur.4
Recent examples of the catalytic activation of organic
disulfides are notable,5,6 although their application to
sulfur activation is not straightforward. Sulfur atoms
in disulfides with C–S and S–S bonds are called the Ôter-
minal sulfurÕ, while atoms in sulfur with two S–S bonds
are called the Ômiddle sulfurÕ. The reactivities of these
sulfurs are considerablydifferent, and in particular the
interaction of the latter with transition metal complexes
readilyleads to the formation of unreactive metal sul-
fides. The manipulation of middle sulfur atoms is essen-
tial for the development of effective transition metal
catalysts for sulfur.
As a preliminarystudy, the reaction of a trisulfide and a
disulfide was examined. Bis{p-(tert-butyl-dimethylsilyl-
oxy)phenyl} disulfide 1f (0.25 mmol) and dibutyl trisul-
fide 2a (0.25 mmol) were reacted in the presence
of RhH(PPh3)4 (0.5 mol %) and dppv (1.0 mol %) in
acetone with stirring for 5 min at room temperature,
and butyl p-(tert-butyldimethylsilyloxy)phenyl disulfide 3
We previouslyreported that a rhodium complex cata-
lyzes disulfide exchange reactions,6 which proceed very
rapidlyat room temperature even with alkyl disulfides.
Rh cat.
.....
+
RSS SR
+
+
+
R S SR
RS S SR
S
8
RSS SR
x
2
"terminal
sulfur"
"middle
sulfur"
*
Corresponding author. Tel.: +22 795 6812; fax: +22 795 6811; e-mail:
yama@mail.pharm.tohoku.ac.jp
Scheme 1.
0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.05.024

4798
M. Arisawa et al. / Tetrahedron Letters 46 (2005) 4797–4800
+
middle S = 0.25 mmol atom
Ar = p-(t-BuMe SiO)C H
Ar S S Ar
1f (0.25 mmol)
n-C H S S S n-C H
4
9
4
9
2a (0.25 mmol)
2
6 4
RhH(PPh ) (0.5 mol%)
3 4
dppv (1.0 mol%)
Acetone, r.t., 5 min
+
+
+
Ar S S n-C H
4
Ar S S S n-C H
4
n-C H S S S S n-C H
9
9
4
9
4
9
3 (0.21 mmol)
4 (0.09 mmol)
5a (0.02 mmol)
+
+
+
1f (0.06 mmol)
2a (0.08 mmol)
n-C H S S n-C H
Ar S S S Ar
4
9
4
9
1a (trace)
2f (0.03 mmol)
middle S = 0.24 mmol atom (96%)
Scheme 2.
(0.21 mmol), butyl p-(tert-butyldimethylsilyloxy)phenyl
trisulfide (0.09 mmol), dibutyl tetrasulfide 5a
NMR) (Table 1, entry1). The polysulfides were isolated
bypreparative reverse-phase HPLC, and higher organic
polysulfides were observed by HPLC (Fig. 1). The struc-
4
(0.02 mmol), dibutyl disulfide 1a (trace), and diaryl tri-
sulfide 2f (0.03 mmol) were obtained with the recovery
of 1f (0.06 mmol) and 2a (0.08 mmol) (Scheme 2). The
mass balance for terminal sulfur atoms was 98%, and
that for middle sulfur atoms was 96%. This indicates
that middle sulfur atoms exchange rapidlyin the pres-
ence of a rhodium catalyst without loss.
1
tures of 5a, 6a, 7a, and 8a were determined by H/13C
1
NMR spectroscopy, and MS. The H NMR chemical
shifts of the methylene protons adjacent to the sulfur
atom in the organic polysulfides showed a tendency to
appear at a lower field as the sulfur atom increased in
number from disulfide to heptasulfide.7
Then, the method was applied to the exchange reaction
of sulfur. When 2a (0.25 mmol) was treated with sulfur
(0.25 mmol atom) in the presence of RhH(PPh3)4
(2.5 mol %) and dppv (5.0 mol %) in acetone with stir-
ring, sulfur rapidlydisappeared within 5 min at room
temperature yielding the disulfide 1a (0.005 mmol), tet-
rasulfide 5a (0.096 mmol), pentasulfide 6a (0.034 mmol),
hexasulfide 7a (0.021 mmol), and heptasulfide 8a (trace)
with the recoveryof 2a (0.096 mmol) (determined by 1H
Exchange efficiency DS = {[5a] + 2[6a] + 3[7a] ꢀ [1a]}/
[sulfur]0 is defined here, where [5a], [6a], [7a], and [1a]
are the yields (mmol) of all products, and [sulfur]0 is
the initial amount (mmol atom) of sulfur. DS shows
the amount of middle sulfur atoms transferred to the
organic polysulfides, and DS = 100% indicates that all
the sulfur atoms of sulfur are introduced into the poly-
sulfides. The above exchange reaction occurred at a high
exchange efficiency DS = 89% (entry1). Catalyst loading
Table 1. Rhodium-catalyzed sulfur atom exchange between trisulfides and sulfura
RhH(PPh ) (2.5 mol%)
3 4
+
R S
R
R S
R
4
5
dppv (5 mol%)
+
R
S
8
5
6
R S
3
Acetone, r.t., 5 min
+
+
R S
R
R S
R
2
6
2
7
1
Run
R
Phosphineb
dppv
Yield/mmol
DS/%
5
6
7
1
2
1
2c
n-C4H9
a
0.096
0.174
0.053
0.064
0.030
0.030
0.092
0.091
0.098
0.097
0.027
0.034
0.065
0.021
0.028
0.012
0.020
0.028
0.035
0.033
0.058
0.010
0.021
0.045
0.011
0.010
0.004
0.005
0.022
0.022
0.017
—
0.005
0.015
0.026
0.024
0.012
0.011
0.004
0.007
—
0.096
0.191
0.126
0.124
0.188
0.178
0.100
0.093
0.101
0.097
0.030
89
85
50
50
26
30
84
88
86
85
25
3
dppm
dppe
dppBz
dppf
4
5
6
7
n-C5H11
b
dppv
8
i-C4H9
s-C4H9
cyclo-C6H11
c
9
d
10
11d
e
—
0.031
p-(t-BuMe2SiO)C6H4
f
0.003
a See text for reaction conditions and yield determination.
b dppv: cis-1,2-bis(diphenylphosphino)ethylene; dppm: 1,2-bis(diphenylphosphino)methane; dppe: 1,2-bis(diphenylphosphino)ethane; dppBz: 1,2-
bis(diphenylphosphino)benzene; dppf: 1,10-bis(diphenylphosphino)ferrocene.
c The reaction was conducted using 2a (0.5 mmol) and sulfur (0.5 mmol atom) in the presence of RhH(PPh3)4 (0.5 mol %) and dppv (1.0 mol %) for
5 min.
d The reaction was conducted using 2f (0.1 mmol) and sulfur (0.1 mmol atom) in the presence of RhH(PPh3)4 (2.5 mol %) and dppv (5.0 mol %) for
15 min.

M. Arisawa et al. / Tetrahedron Letters 46 (2005) 4797–4800
4799
The same rhodium system catalyzes the sulfur atom
exchange between organic disulfides and sulfur with
slightlydifferent reaction profiles ( Table 2). When 1f
(0.5 mmol) was treated with sulfur (0.5 mmol atom) in
the presence of RhH(PPh3)4 (0.5 mol %) and dppv
(1.0 mol %) in acetone with stirring for 5 min at room
temperature, the trisulfide 2f (0.189 mmol), tetrasul-
fide 5f (0.075 mmol), pentasulfide 6f (0.032 mmol), and
hexasulfide 7f (0.011 mmol) were obtained with the
recoveryof
1f (0.170 mmol) (by 1H NMR) at
DS = {[2f]+2[5f]+3[6f]+4[7f]}/[sulfur]0 = 96% (entry1).
The diaryl disulfides 1g and 1h with electron-donating
substituent showed higher DS values than 1i and 1j
(entries 2, 3, 4, and 5). The exchange reaction took place
with the dialkyl disulfides 1k and 1l with attached meth-
oxycarbonyl groups (entries 6 and 7); dibutyl disulfide
1a did not undergo an exchange reaction under these
conditions. The substituent effect of disulfides suggests
that the balance between the stabilityand reactivityof
the polysulfides to be important. Polysulfides with
appropriate substituents maybe used as mediators for
the transfer of sulfur atoms from sulfur to organic
molecules.
Figure 1. Reverse-phase HPLC/UV (MeOH, 5 mL/min) chart of a
mixture of 1a, 2a, 5a, 6a, 7a, 8a, and higher polysulfides obtained after
silica gel treatment of reaction mixture formed from 2a and sulfur
(Table 1, entry1). The formation of RS xR (x = 8, 9, 10, and 11) was
assumed on the basis of retention time.
could be reduced to 0.5 mol % RhH(PPh3)4 and
1.0 mol % dppv at approximatelythe same efficiency
DS = 85% (entry2). The rhodium complex and dppv
are essential in this reaction; no reaction takes place in
the absence of either reagent under the same conditions.
DS decreased when other bidentate ligands such as
dppm (entry3), dppe (entry4), dppBz (entry5), and
dppf (entry6) were used, and dppb was not effective
at all. Monodentate phosphines such as triphenylphos-
phine, tris(p-tolyl)phosphine, and tributylphosphine
did not exhibit catalytic activity. It turned out that the
bidentate ligand with a C2 chain was effective for the
manipulation of the middle sulfur atom, while the elec-
tron-rich monodentate ligand was effective for the
manipulation of the terminal sulfur atom, as previously
reported.6 The secondarydialkyl trisulfides 2d and 2e as
well as the primaryderivatives 2b and 2c undergo rapid
exchange reactions with sulfur (entries 7, 8, 9, and 10).
Di(tert-butyl) trisulfide, however, did not react under
the same conditions. The aromatic trisulfide 2f exhibited
a lower DS (entry11).
The equilibrium nature of the present reaction is shown
bythe following experimental results. The reaction of
1f (0.5 mmol) and sulfur (0.25 mmol atom) in the
presence of RhH(PPh3)4 (1.0 mmol %) and dppv
(2.0 mol %) at room temperature for 1 h yielded 2f,
5f, and 6f at DS = 99% (Scheme 3). The addition of
sulfur (0.25 mmol atom) to this mixture increased the
amounts of 2f, 5f, 6f, and 7f, and decreased that of
1f at DS = 97%. The second sulfur was almost
completelyincorporated in the organic disulfide, during
which this catalyst maintained its activity. An analo-
gous behavior was observed in the reaction of 2a and
sulfur.
To summarize, the exchange of sulfur atoms between an
organic disulfide or trisulfide and sulfur rapidlyoccurs
in the presence of RhH(PPh3)4 and dppv catalyst.
Table 2. Rhodium-catalyzed sulfur atom exchange between disulfides and sulfura
RhH(PPh ) (0.5 mol%)
3 4
dppv (1.0 mol%)
S
8
+
+
R R S
+
R S
R
R S
R
R S
R
2
3
4
5
Acetone, r.t., 5 min
2
5
6
1
Run
Ar
Yield/mmol
DS/%
2
5
6
1
1
p-(t-BuMe2SiO)C6H4
f
0.189
0.185
0.171
0.132
0.171
0.159
0.123
0.075
0.083
0.069
0.041
0.005
0.045
0.065
0.033b
0.040
0.033
0.011
—
0.170
0.184
0.227
0.302
0.320
0.293
0.231
96
94
82
49
36
50
85
2
p-MeOC6H4
p-MeC6H4
C6H5
p-ClC6H4
MeO2CCH2
g
3
h
4
i
5
j
6c
7c
k
—
0.034d
MeO2C(CH2)2
l
a See text for reaction conditions and yield determination.
b Hexasulfide 7f was also formed in 0.011 mmol amount.
c The reaction was conducted using 1 (0.5 mmol) and sulfur (0.5 mmol atom) in the presence of RhH(PPh3)4 (2.0 mol %) and dppv (4.0 mol %) for
5 min.
d Hexasulfide 7 l was also formed in 0.017 mmol amount.

4800
M. Arisawa et al. / Tetrahedron Letters 46 (2005) 4797–4800
sulfur
(0.25 mmol atom)
RhH(PPh ) (1.0 mol%)
3 4
dppv (2.0 mol%)
+
Ar S Ar
2
1f (0.5 mmol)
S
8
sulfur
Acetone
r.t., 1 h
r.t., 15 min
n
(0.25 mmol atom)
Ar = p-(t-BuMe SiO)C H
6 4
2
+
+
+
+
Ar S Ar
1f
6
Ar S Ar
4
Ar S Ar
Ar S Ar
5
3
5f
7f
2f
6f
n = 0
n = 1
0.052
0.080
0.144 mmol
0.182 mmol
trace
0.033
-
∆S = 99%
∆S = 97%
0.274
0.172
0.011
Scheme 3.
4. Exceptional examples of catalytic reactions: Adam, W.;
Bargon, R. M.; Schenk, W. A. J. Am. Chem. Soc. 2003,
125, 3871; Rys, A. Z.; Harpp, D. N. Tetrahedron Lett.
1998, 39, 9139; Tsuda, T.; Takeda, A. Chem. Commun.
1996, 1317; Kajitani, M.; Suetsugu, T.; Wakabayashi, R.;
Igarashi, A.; Akiyama, T.; Sugimori, A. J. Organomet.
Chem. 1985, 293, C15. Our recent results. Arisawa, M.;
Ashikawa, M.; Suwa, A.; Yamaguchi, M. Tetrahedron
Lett. 2005, 46, 1727.
Acknowledgements
This work was supported byJSPS (Nos. 14207094 and
16109001). M.A. expresses her thanks for financial sup-
port from the New Energyand Industrial Technology
Development Organization (NEDO) of Japan (No.
02A44003d).
5. Also see the following for our Rh-catalyzed activation of
disulfides: Arisawa, M.; Kozuki, Y.; Yamaguchi, M. J.
Org. Chem. 2003, 68, 8964; Arisawa, M.; Suwa, A.;
Fujimoto, K.; Yamaguchi, M. Adv. Synth. Catal. 2003,
345, 560; Arisawa, M.; Yamaguchi, M. Org. Lett. 2001, 3,
763.
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