Rhodium-catalyzed alkylthio exchange reaction of thioester and disulfide

Article abstract of DOI:10.1016/j.tetlet.2008.01.109

The Wilkinson complex RhCl(PPh₃)₃ catalyzes equilibrating alkylthio exchange reaction of thioesters with disulfides. The treatment of a thioester and a dialkyl disulfide in refluxing diethyl ketone in the presence of RhCl(PPh₃)₃ (2.5 mol %) for 1.5 h gave an alkylthio exchanged thioester. The reaction of S-methyl ester was conducted shifting the equilibrium by removing volatile dimethyl disulfide.

Full text of DOI:10.1016/j.tetlet.2008.01.109

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Tetrahedron Letters 49 (2008) 1975–1978
Rhodium-catalyzed alkylthio exchange reaction
of thioester and disulfide
Mieko Arisawa a, Tomohiro Kubota a, Masahiko Yamaguchi b,*
a Department of Organic Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba, Sendai 980-8578, Japan
b WPI Advanced Institute for Materials Research, Tohoku University, Aoba, Sendai, Japan
Received 5 December 2007; revised 17 January 2008; accepted 21 January 2008
Available online 31 January 2008
Abstract
The Wilkinson complex RhCl(PPh3)3 catalyzes equilibrating alkylthio exchange reaction of thioesters with disulfides. The treatment
of a thioester and a dialkyl disulfide in refluxing diethyl ketone in the presence of RhCl(PPh3)3 (2.5 mol %) for 1.5 h gave an alkylthio
exchanged thioester. The reaction of S-methyl ester was conducted shifting the equilibrium by removing volatile dimethyl disulfide.
Ó 2008 Elsevier Ltd. All rights reserved.
Rh cat
Alkoxy exchange is a fundamental reaction of esters
catalyzed by acid or base.1 The reaction being under equili-
brium proceeds via carbonyl addition of alcohol
generating tetrahedral carbon intermediate followed by
elimination. The reaction of the sulfur analog, alkylthio
exchange of thioesters, however, was not known. During
our investigations on the use of transition metal catalysis
for the synthesis of organosulfur compounds,2 rhodium
complexes were found to catalyze alkylthio exchange reac-
tion of organic disulfides,3 and sulfur atom exchange reac-
tion between sulfur and organic polysulfides.4 The
reactions were considered to proceed by the S–S bond
cleavage by the metal complex followed by ligand
exchange. It was also found that a rhodium complex cata-
lyzes alkylthio exchange reaction of 1-alkylthioacetylenes,
which contains S–C bond cleavage and metathesis with
S–S bond.5 It was therefore considered interesting to apply
the catalytic method to the activation of other S–C bonds,
since such methodology can be useful for the transfor-
mation of organosulfur compounds. Described here is the
rhodium-catalyzed alkylthio exchange reaction of thio-
esters with disulfide (Scheme 1).
+
+
R"SSR"
R"OH
R'SSR"
R'OH
RCOSR'
RCOOR'
RCOSR"
acid or base
+
+
RCOOR"
Scheme 1.
When a mixture of S-octyl benzenethioate 1 and bis(2-
methoxyethyl) disulfide 2 (4 equiv) in diethyl ketone was
heated at reflux for 1.5 h in the presence of RhCl(PPh3)3
(2.5 mmol %), S-(2-methoxyethyl) benzenethioate 3 was
obtained in 87% yield. The starting material 1 was reco-
vered in 11% yield, and a mixture of disulfides was
obtained containing 2 (72%), dioctyl disulfide 4 (11%),
and 2-methoxyethyl octyl disulfide (77%). The mass
balance regarding the octylthio group is quantitative.
RhH(PPh3)4
exhibited
similar
reactivity,
while
RhH(CO)(PPh3)3 and Pd(PPh3)4 were less effective. The
reaction could be conducted in various solvents such as
acetone, methanol, 1,4-dioxane, xylene, chlorobenzene,
1,2-dichloroethane, acetonitrile, and DMF (Scheme 2).
Equilibrium nature of the reaction is shown by the
experiments employing different amounts of 2 against 1.
The yields of 3 were 49%, 65%, and 87%, when the molar
ratio 2/1 was changed to 0.5, 1, and 4, respectively. The
yields coincided with the calculated values assuming the
*
Corresponding author. Tel.: +81 22 795 6812; fax: +81 22 795 6811.
E-mail address: yama@mail.pharm.tohoku.ac.jp (M. Yamaguchi).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.01.109

1976
M. Arisawa et al. / Tetrahedron Letters 49 (2008) 1975–1978
PhCOS
n
-C H
1
PhCOSCH CH OMe 3 87%
8
17
2
2
RhCl(PPh ) (2.5 mol%)
3 3
+
+ 1 11%
diethyl ketone, refl., 1.5 h
+ 2 72%
n-C H SSCH CH OMe 77%
(MeOCH CH S)
2
2 (4 eq)
2
2
+
8
17
2
2
+ (n-C H S) 4 11%
8 17 2
Scheme 2.
equal thermodynamical stability of 1 and 3. The reverse
reactions were conducted giving the same compositions
of the products (Scheme 3). Reaction of 1 (0.5 mmol) and
2 (0.25 mmol) gave 3 in 49% yield with recovered 1 in
50%, and the reaction of 3 (0.5 mmol) with 4 (0.25 mmol)
provided 1 in 48% yield with the recovered 3 in 48%.
Several thioesters were reacted with disulfides (4 equiv)
in the presence of RhCl(PPh3)3 (2.5 mol %) giving the
exchanged products generally in 85–90% yields (Table 1).
Thioesters derived from aromatic and aliphatic acids
equally reacted with dialkyl dilsulfides giving the products
in comparable yields. Unsaturation as shown by the reac-
tion of cinnamate did not interfere with the reaction (entry
8). Functional groups such as methoxycarbonyl, t-butoxy-
carbonylamino, and hydroxy did not affect the reaction
(entries 10–12). An aromatic thiol ester was formed from
an aliphatic thiol ester in a lower yield, which should be
due to the different thermodynamic stability of the com-
pounds (entry 4). In accordance, the reaction of S-phenyl
thiobenzoate and 4 in 1:0.5 molar ratio gave the corres-
ponding S-octyl ester and the starting material in 28 and
69% yields, respectively. The same mixture of the products
was obtained from S-octyl benzothioate and diphenyl
disulfide, which confirmed the lower thermodynamic stabil-
ity of S-phenyl thioester under equilibrium. The formation
of an apparently more reactive compound from the less
reactive compound is an interesting aspect of equilibrium
reaction.
Table 1
Rhodium-catalyzed alkylthio exchange reaction
RhCl(PPh ) (2.5 mol%)
3 3
+
R"SSR"
4 eq
+ R'SSR
"
RCOSR'
RCOSR"
diethyl ketone, refl., 1.5 h
Entry
R
R0
R00
Yield (%)
1
2
3
Ph
n-C8H17
(CH2)2OMe
CH2CO2Me
(CH2)2NHBoc
Ph
87
86
85
41
87
87
88
87
86
84
88
90
86
87
4
5
6
7
8
cyclo-C6H11
n-C8H17
n-C8H17
n-C8H17
n-C8H17
(CH2)2OMe
p-MeOC6H4
p-ClC6H4
PhCH@CH
n-C7H15
9
(CH2)2OMe
(CH2)2CO2Me
(CH2)2NHBoc
(CH2)6OH
(CH2)2OMe
(CH2)2OMe
10
11
12
13
14
PhCH2
cyclo-C6H11
n-C8H17
n-C8H17
tinuous bubbling of argon gave the exchanged product in
93% yield, while the use of S-octyl ester resulted in 63%
yield of the product. It was confirmed under these high
temperature conditions that the reaction did not proceed
without rhodium complex. Analogously, a glutathione thio-
ester was obtained in 85% yield from glutathione disulfide
and S-methyl butanethioate (4 equiv) (Scheme 5). This
yield is based on the two alkylthio moieties indicating both
alkylthio groups to be esterificated, which is another
advantage of equilibrium reaction.
The use of S-methyl thioester shifts the equilibrium to
the exchanged thioester using 1 equiv of disulfide, since
dimethyl disulfide formed can be removed by evaporation
(Scheme 4). Reaction of S-methyl decanethioate with 2
(1 equiv) at 150 °C for 1.5 h in o-dichlorobenzene with con-
The rhodium-catalyzed alkylthio exchange reaction
proceeded between two thioesters (Scheme 6).6 Reaction
0.5 mmol
1
17
PhCOS
n
-C H
8
+
from
from
(MeOCH CH S)
2
2
0.25 mmol
2
2
1 and 2 3 and 4
50%
49%
1
+
3
48%
48%
RhCl(PPh ) (2.5 mol%)
3 3
diethyl ketone, refl., 1.5 h
PhCOSCH CH OMe 3
0.5 mmol
2
2
+
(
n
-C H S)
4
0.25 mmol
8
17
2
Scheme 3.

M. Arisawa et al. / Tetrahedron Letters 49 (2008) 1975–1978
1977
RhCl(PPh ) (10 mol%)
3 3
n
-C H COSR
+
(RS)
1 eq
n
-C H COSMe
9 19
2
9
19
o-dichlorobenzene
150 °C, 90 min
R = CH CH OMe 93% (63%)*
R = CH CH NHBoc 92%
2
2
2
2
R = Bu 95%
*Reaction of S-octyl ester
Scheme 4.
O
O
O
CO Me
2
RhCl(PPh ) (20 mol%)
CO Me
3 3
2
HN
H
HN
H
N
NHBoc
N
NHBoc
CO Me
CO Me
o-dichlorobenzene
150 °C, 90 min
2
2
O
n
-C H COS
3 7
S
2
85% based on RS group
n
-C H COSMe
+
3
7
Scheme 5.
49%
PhCOSCH CH OMe
2
2
p
-MeOC H COS
n
-C H
+
RhCl(PPh ) (2.5 mol%)
6
4
8
17
3 3
51%
48%
p
-MeOC H COS
n
-C H
8 17
6
4
+
+
diethyl ketone, refl., 4.5 h
PhCOSCH CH OMe
PhCOS
n
-C H
2
2
8
17
+
49%
p
-MeOC H COSCH CH OMe
6 4 2 2
Scheme 6.
of S-octyl p-methoxybenzoate and S-(2-methoxyethyl)
benzoate in refluxing diethyl ketone for 4.5 h in the pres-
ence of RhCl(PPh3)3 (2.5 mol %) gave a mixture of four
possible exchanged thioesters in an equal amount.
yield with recovered 6 in 16%. The reaction of 6 most likely
involves the formation of BuSCO–Rh–SBu complex, and it
may be reasonable that the alkylthio exchange reaction of
thioesters proceeds by the similar mechanism.
The mechanism most likely involves the initial cleavage
of RCO–SC bond rather than RCOS–C bond forming an
acylrhodium(III) complex.7 The alkylthio ligand exchange
with disulfide on rhodium metal and reductive elimination
then give the exchanged thioesters. The interpretation is
supported by the experiments of dibutyl S,S0-dithiocarbon-
ate 6 (Scheme 7). The reaction of dibutyl disulfide 5 and
carbon monoxide (30 atm) in the presence of RhH(PPh3)4
(10 mol %) and dppe (20 mol %) in toluene at 180 °C for
24 h gave 6 in 15% yield with recovered 5 in 52%. The need
of rhodium complex was again confirmed, which excluded
the radical mechanism for the present reaction. This reac-
tion is under equilibrium, and the treatment of 6 with the
same catalyst under the same conditions gave 5 in 43%
Acknowledgments
This work was supported by JSPS (Nos. 16109001 and
17689001). M.A. expresses her thanks to the Grant-in-
Aid for Scientific Research on Priority Areas, ‘Advanced
Molecular Transformations of Carbon Resources’ from
MEXT (Nos. 18037005 and 19020008).
Supplementary data
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.tetlet.
2008.01.109.
RhH(PPh3)4 (10 mol%)
dppe (20 mol%)
References and notes
n-BuSCOSBu-n
+
(n-BuS)2
CO
1. Otera, J. Chem. Rev. 1993, 93, 1449.
toluene, 180 ºC, 24 h
30 atm
6 15%
5
2. Arisawa, M.; Yamaguchi, M. Pure Appl. Chem., in press; Arisawa, M.;
Yamaguchi, M. J. Synth. Org. Chem. Jpn. 2007, 65, 1213.
3. Arisawa, M.; Yamaguchi, M. J. Am. Chem. Soc. 2003, 125, 6624;
Arisawa, M.; Suwa, A.; Yamaguchi, M. J. Organomet. Chem. 2006,
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RhH(PPh3)4 (10 mol%)
dppe (20 mol%)
+
n-BuSCOSBu-n
CO
(n-BuS)2
toluene, 180 ºC, 24 h
30 atm
5 43%
6
Scheme 7.

1978
M. Arisawa et al. / Tetrahedron Letters 49 (2008) 1975–1978
6. Related reaction of 1-alkylthioalkynes: Arisawa, M.; Tagami, Y.;
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