Oxidation/reduction interconversion of thiols and disulfides using hydrogen and oxygen catalyzed by a rhodium complex

Article abstract of DOI:10.1016/j.tetlet.2005.06.169

RhH(PPh₃)₄ catalyzes reduction of disulfides to thiols by hydrogen and RhH(PPh₃)₄/1,4- bis(diphenylphosphino)butane (dppb) catalyzes oxidation of thiols to disulfides by oxygen.

Full text of DOI:10.1016/j.tetlet.2005.06.169

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 6097–6099
Oxidation/reduction interconversion of thiols and disulfides
using hydrogen and oxygen catalyzed by a rhodium complex
Mieko Arisawa, Chiyoshi Sugata and Masahiko Yamaguchi*,
Department of Organic Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba, Sendai 980-8578, Japan
Received 20 May 2005; accepted 30 June 2005
Available online 21 July 2005
Abstract—RhH(PPh3)4 catalyzes reduction of disulfides to thiols by hydrogen and RhH(PPh3)4/1,4-bis(diphenylphosphino)butane
(dppb) catalyzes oxidation of thiols to disulfides by oxygen.
Ó 2005 Elsevier Ltd. All rights reserved.
The interconversion of disulfides and thiols is a funda-
mental transformation in organosulfur chemistry and
such switching plays important roles in biological sys-
tem. Of various reductants and oxidants, hydrogen
and oxygen are apparently the most convenient. They
are inexpensive, easy to remove, and produce water as
the only byproduct. Since these reagents themselves
are inert to the sulfur compounds, metal catalysts are
employed.
These indicate that the development of a catalyst for the
interconversion of disulfides and thiols is still a subject
not fully solved. It would also be interesting if a single
catalyst can be used both for the oxidation and reduc-
tion by switching hydrogen and oxygen atmosphere. In
this regard, an oxidation reaction of thiols to disulfides
recently reported by Tanaka and Ajiki is interesting,
which proceeded rapidly at 0 °C using a rhodium cation
complex.5 It was considered to be a dehydration reac-
tion and reversible. Relatively high catalyst loading
(5 mol %), however, was employed for the oxidation
reaction and the reduction reaction was not examined.6
Hydrogen reduction of disulfide to thiol catalyzed by
metal complex was not known, which is contrasted to
many examples of hydrogenolysis of organosulfur com-
pounds. An exception is the reaction of a cyclic disulfide
reported by Kessler in the presence of 10 equiv of Pd
black.1 The lack of such study may be partly due to
the catalyst deactivation and the difficulty in the selec-
tive reduction of S–S bond without affecting C–S bond.
H2/Rh cat
RSSR
RSH
O2/Rh cat
Scheme 1.
What is called autoxidation of thiols to disulfides in the
presence of a metal complex, typically copper phthalo-
cyanine under alkaline conditions, is well known.2,3
Although the mechanism is not fully clear, the reaction
is considered to involve coupling reaction of sulfur rad-
icals, which are formed from thiolate anions by one-elec-
tron oxidation with the metal complex. Several thiol
oxidation reactions with oxygen under neutral condi-
tions were reported.4 However, they often required long
reaction time even at relatively high temperatures.
During our investigations on the development of
organosulfur transformations utilizing transition metal
catalysis, rhodium complexes were found effectively to
activate S–S bonds: disulfide exchange reaction,7 addi-
tion to unsaturated compounds,8 alkylthiolation of C–
H bond,9 and alkylthio exchange reaction with C–S
bond9 were reported. Mechanistically, the reactions
were considered to involve oxidative addition of S–S
bond with low valent rhodium complexes to form S–
Rh–S intermediates. It is a logical extension of this
methodology to examine hydrogenolysis of the Rh–S
bond to form S–H bond under hydrogen. We also found
that a rhodium complex activated a thiol and underwent
alkylthio exchange and reduction reaction with a
*
Corresponding author. Tel.: +81 22 795 6812; fax: +81 22 795
6811; e-mail: yama@mail.pharm.tohoku.ac.jp
Tohoku University 21st Century COE Program CRESCENDO.
0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.06.169

6098
M. Arisawa et al. / Tetrahedron Letters 46 (2005) 6097–6099
Table 1. RhH(PPh3)4 catalyzed disulfide reduction with hydrogen
Table 2. RhH(PPH3)4/dppb catalyzed thiol oxidation with oxygen
RhH(PPh3)4
RhH(PPh3)4-dppb
+
RSH
+
RSSR
H2
RSSR
Entry
O2
RSH
Entry
MeOH, 40 ˚C
toluene, refl. 0.5 h
R
Cat./mol % Time Yield
R
Cat./mol %
Yield (%)
(h)
(%)
1
2
3
4
5
6
7
8
n-C8H17
n-C12H25
p-(t-Bu)C6H4
p-(t-BuMe2SiO)C6H4
p-ClC6H4
MeO2CCH(NHBoc)CH2
t-BuCOO(CH2)2
t-BuOCONH(CH2)2
0.5
0.5
0.25
0.25
0.25
1.0
0.25
0.5
93
86
98
91
95
90
92
96
1
n-C8H17
n-C12H25
s-C4H9
0.1
0.5
0.1
0.1
2.5
5.0
0.1
0.1
0.1
1
2.5
1
1
2
93
99
95
100
91
89
2a
3
4
5
6
7
8
9
10
11
12
cyclo-C6H11
1-Adamantyl
Me2CH(CH2)3CMeEt
p-(t-Bu)C6H4
p-(MeO)C6H4
p-ClC6H4
MeO2CCH(NHBoc)CH2 0.5
HO(CH2)3
MeO2C(CH2)2
6
395
396
1.5
1.5
2
94
95
87
95
thioacetylene.9 Since, in this reaction, Rh–S compounds
should be formed from thiol S–H, it was conceivable
that the oxidation of the intermediate would generate
S–S bond. In accordance, we observed during our stud-
ies oxidation of thiols to disulfides by trace amounts of
oxygen. Described here is disulfide reduction reaction to
thiol under hydrogen and thiol oxidation reaction to
disulfide under oxygen, which are catalyzed generally
by 0.1–0.5 mol % of RhH(PPh3)4 (Scheme 1).
0.5
0.5
1
a Reaction in ethanol.
tane, and dppf gave considerable amounts of the disul-
fide, and the solution turned green.
Several thiols were oxidized to disulfides under the same
conditions. Primary and secondary thiols gave the prod-
ucts in quantitative yields using 0.1 mol % of catalyst in
methanol (entries 1–4). 1-Dodecanethiol was reacted in
ethanol because of low solubility of the substrate (entry
2). Reactions of tertiary thiols required higher catalysts
loading (entries 5 and 6). Aromatic substituents again
did not affect the reaction (entries 7, 8, and 9). Func-
tional groups such as carbamate, alcohol, and ester were
not affected.11
Treatment of dioctyl disulfide with atmospheric hydro-
gen at toluene reflux in the presence of RhH(PPh3)4
(0.5 mol %) gave 1-octanethiol in 93% yield (Table 1,
entry 1). Addition of phosphine invariably inhibited the
reaction, which is contrasted to the thiol oxidation reac-
tion (vide infra). The reduction proceeded in high yields
even at 80 °C in toluene or in THF, when 5 mol % of the
catalyst was employed. Several alkyl and aryl disulfides
were converted to thiols under the same conditions
employing 0.25–1 mol % of the catalyst. Aromatic disul-
fides possessing either electron-withdrawing or donating
groups effectively reacted (entries 3, 4, and 5). This is an
unprecedented metal-catalyzed reduction of disulfides to
thiols with hydrogen, and a rhodium catalyst turned out
to be effective for this transformation.10
In summary, a rhodium complex RhH(PPh3)4 catalyzes
disulfide reduction to thiol with hydrogen and thiol
oxidation to disulfide with oxygen. Search for the reac-
tion system, under which thiols and disulfides are effec-
tively interconverted by simply switching hydrogen
and oxygen atmosphere, is an interesting subject in
future.
The same rhodium complex is capable to catalyze the
oxidation reaction of thiols to disulfides in the presence
of oxygen. When 1-octanethiol was reacted in methanol
at 0 °C for 1 h under an oxygen atmosphere in the
presence of RhH(PPh3)4 (0.1 mol%) and 1,4-bis(di-
phenylphosphino)butane (dppb) (0.2 mol %), dioctyl
disulfide was obtained in 93% yield (Table 2, entry
1).11 Although the phosphine itself was not soluble in
methanol, the addition of the thiol formed a homo-
geneous orange solution under an argon atmosphere.
Then, the balloon was changed to oxygen, which rapidly
turned the solution green. At the end of the reaction, the
orange color was regenerated. Essentially no reaction
took place in the absence of RhH(PPh3)4 or under an
argon atmosphere with rigorous removal of oxygen.
Phosphine was important in the oxidation reaction,
and only 4% of the disulfide was formed in the absence
of dppb. Effect of other phosphines are as follows:
dppm, 8%; dppe, 6%; dppp, 62%; dpppentane, 32%;
dppf, 44%; PPh3, 4%; (p-ClC6H4)3P, 3%; (p-
MeOC6H4)3P, 4%. The reactions using dppp, dpppen-
Acknowledgements
This work was supported by Grants from the Japan
Society of Promotion of Science (Nos. 16109001 and
17689001). M.A. thanks for the support from NEDO
of Japan (No. 02A44003d) and the Takeda Science
Foundation.
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M. Arisawa et al. / Tetrahedron Letters 46 (2005) 6097–6099
6099
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