Phosphine-free cationic rhodium(I) complex-catalyzed disulfide exchange reaction: Convenient synthesis of unsymmetrical disulfides

Article abstract of DOI:10.1016/j.tetlet.2004.05.092

A phosphine-free cationic rhodium(I) complex, [Rh(cod)₂]BF ₄, is an effective catalyst for disulfide exchange reaction of symmetrical disulfides to unsymmetrical disulfides under inert atmosphere. This reaction could be carried out u

Full text of DOI:10.1016/j.tetlet.2004.05.092

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 5677–5679
Phosphine-free cationic rhodium(I) complex-catalyzed disulfide
exchange reaction: convenient synthesis of unsymmetrical disulfides
Ken Tanaka* and Kaori Ajiki
Department of Applied Chemistry, Tokyo University of Agriculture and Technology,
2-24-16, Nakacho, Koganei, Tokyo 184-8588, Japan
Received 17 April 2004; revised 15 May 2004; accepted 19 May 2004
Available online 10 June 2004
Abstract—A phosphine-free cationic rhodium(I) complex, [Rh(cod)2]BF4, is an effective catalyst for disulfide exchange reaction of
symmetrical disulfides to unsymmetrical disulfides under inert atmosphere. This reaction could be carried out using unpurified
commercial grade solvents under air without decrease of yields and reaction rates.
Ó 2004 Elsevier Ltd. All rights reserved.
Disulfides are important compounds for both chemical
and biological processes.1 The synthesis of symmetrical
disulfides can be carried out by selective oxidative cou-
pling of thiols to disulfides.2 On the other hand, for the
synthesis of unsymmetrical disulfides, disulfide exchange
reaction is one of the useful methods to eliminate the use
of thiols, which have unpleasant odour.3 The existing
methods of disulfide exchange reactions require severe
reaction conditions to generate sulfur radicals,4 cations,5
or anions,6 which react with disulfide to cleave the
disulfide bond. In order to overcome these problems,
Arisawa and Yamaguchi reported that RhH(PPh3)4/p-
tol3P/trifluoromethanesulfonic acid combination cata-
lyst is highly effective for disulfide exchange reaction and
two structurally different disulfides rapidly reach equi-
librium composition to give unsymmetrical disulfides.7;8
RSH,–H2
or
(RS)2, –RSH
RSH,–H2
or
(RS)2, –RSH
SR
+Rh SR
C
H
SR
+Rh
H
B
+Rh H
A
H2, –RSH
or
RSH, –(RS)2
H2, –RSH
or
RSH, –(RS)2
Scheme 1.
The mechanistic studies revealed that dehydrogenation
of thiols is reversible process.12 Plausible mechanism of
this reaction is illustrated in Scheme 1. Presumably, all
the steps shown in Scheme 1 are reversible and the
reaction proceeds via complexes A, B and C. Therefore,
if disulfides are used as substrates instead of thiols in
the presence of rhodium hydride complex, disulfide
exchange reaction may proceed via generation of cata-
lytic amount of thiol.13
During our program of the utilization of cationic rho-
dium(I) complexes for the variety of synthetic reactions,
we recently discovered that [Rh(cod)2]BF4/PPh3/H2
catalyst9 is the effective catalyst for the dehydrogenation
of thiols to symmetrical disulfides (Eq. 1).10;11
We first examined the disulfide exchange reaction of
dibenzyl disulfide and di-n-butyl disulfide in the presence
of [Rh(cod)2]BF4/PPh3/H2 catalyst9 in CH2Cl2 at 25 °C
for 1 h, and found that disulfide exchange smoothly
proceeded to give benzyl n-butyl disulfide in 48% yield
(Eq. 2).
5% [Rh(cod)2]BF4/
8 PPh3/H2
+ H2
(RS)2
ð1Þ
RSH
CH2Cl2, under Ar
4 ˚C, 1 h
5% [Rh(cod)2]BF4/
8 PPh3/H2
+ (n-BuS)2
(PhCH2S)2
PhCH2 S S n-Bu
CH2Cl2, under Ar
48%
Keywords: Disulfide; Disulfide exchange; Phosphine-free; Rhodium.
* Corresponding author. Tel./fax: +81-42-388-7037; e-mail: tanaka-k@
cc.tuat.ac.jp
25 ˚C, 1 h
ð2Þ
0040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.05.092

5678
K. Tanaka, K. Ajiki / Tetrahedron Letters 45 (2004) 5677–5679
Table 1. Screening of reaction conditions for rhodium(I)-catalyzed
disulfide exchange of symmetrical disulfidesa
The phosphine-free cationic rhodium(I) complex-cata-
lyzed disulfide exchange of structurally diverse disul-
fides, (R1S)2 (1 equiv) and (R2S)2 (4 equiv), was
investigated in detail as shown in Table 2. The disulfide
exchange of two different primary alkyl disulfides or
primary alkyl disulfide and aryl disulfide proceeded at
25 °C to give corresponding unsymmetrical disulfides
(entries 1 and 2). The reaction of secondary alkyl
disulfide and primary alkyl disulfide or aryl disulfide
proceeded at 80 °C (entries 3 and 4). The reaction of two
different aryl disulfides also proceeded at 80 °C (entry
5). The heteroaryl disulfide, which is used for rubber
industry could be employed (entry 6).
0.03 equiv
catalyst
+
(PhCH2S)2
(n-BuS)2
PhCH2
S S n-Bu
(1.0 equiv) (1.0 equiv)
25 ˚C, 1 h
Entry
Catalyst
Solvent
Yield (%)b;c
1d
2
[Rh(cod)2]BF4/4PPh3/H2
[Rh(cod)2]BF4/4PPh3
[Rh(cod)2]BF4
[Rh(cod)Cl]2/8PPh3
[Rh(cod)Cl]2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
Acetone
THF
48
49
48
47
1
3
4e
5e
6e
7
[Ir(cod)Cl]2/8PPh3
[Rh(cod)2]BF4
[Rh(cod)2]BF4
[Rh(cod)2]BF4
[Rh(cod)2]BF4
––
40
17
3
8
Exchange reaction of disulfide and diselenide or ditellu-
ride could be accomplished using phosphine-free cat-
ionic rhodium(I) complex to give corresponding
selenosulfide or tellurinosulfide (Eq. 3).14;15
9
CH3CN
Toluene
CH2Cl2
0
10
11
0
0
a The reaction was conducted using (PhCH2S)2 (0.25 mmol), (n-BuS)2
(0.25 mmol), catalysts (0.0075 mmol) and solvents (2 mL) under Ar.
b Yield based on the PhCH2S group.
c Determined by 1H NMR using hexamethylbenzene as an internal-
standard.
d The catalyst was prepared by mixing [Rh(cod)2]BF4 and PPh3 in
CH2Cl2 followed by hydrogenation (1 atm, rt, 0.5 h).
e [Rh(cod)Cl]2 (0.0038 mmol) or [Ir(cod)Cl]2 (0.0038 mmol) were used.
0.03 equiv
[Rh(cod)2]BF4
+
(PhX)2
(n-BuS)2
Ph
X S n-Bu
ð3Þ
(CH2Cl)2, 80 ˚C
(1.0 equiv)
(4.0 equiv)
0.5 h
X = Se, 41%
X = Te, 13%
Scheme 2 depicts a plausible mechanism of the phos-
phine-free cationic rhodium(I) complex-catalyzed
disulfide exchange reaction. Because the reaction pro-
ceeds in the absence of hydride complex, the reaction
presumably proceeds via complex D.
Various rhodium(I) catalysts were examined to facilitate
this transformation as shown in Table 1. In the case of
cationic rhodium(I) complex, treatment of catalyst with
hydrogen and addition of phosphine were not essential
(entries 1–3). On the other hand, addition of phosphine
was essential for neutral rhodium(I) complex (entries 4
and 5). Although the catalytic activity was lower than
rhodium(I) complex, iridium(I) complex also catalyzed
disulfide exchange (entry 6). Among the solvent exam-
ined, CH2Cl2 was the most effective (entries 3 and 7–10).
In the absence of rhodium catalyst no reaction was
observed (entry 11).
Importantly, this phosphine-free cationic rhodium(I)
complex-catalyzed disulfide exchange reaction could be
carried out using unpurified commercial grade solvents
under air without decrease of yields and reaction rates
(Eq. 4).16 We believe that this feature represents a
practical usefulness of this catalytic process.
0.03 equiv
[Rh(cod)2]BF4
R1
S S
R2
+
(RS)2
(n-BuS)2
under Air
(1.0 equiv) (4.0 equiv)
R = PhCH2
ð4Þ
Table 2. Phosphine-free cationic rhodium(I) complex-catalyzed disul-
fide exchange of symmetrical disulfidesa
CH2Cl2 (unpurified)
25 ˚C, 3 h
CH2Cl2 (unpurified)
79%
81%
R = p-MeOC6H4
0.03 equiv
[Rh(cod)2]BF4
25 ˚C, 1.5 h
(R1S)2
(R2S)2
R1
S S
R2
+
In conclusion, we have determined that a phosphine-free
cationic rhodium(I) complex is an effective catalyst for
disulfide exchange reaction of symmetrical disulfides to
unsymmetrical disulfides. This reaction takes place un-
der completely neutral conditions without any addi-
tional reagents except commercially available cationic
rhodium(I) complex, [Rh(cod)2]BF4. In addition, this
process is highly practical due to the usable of com-
mercial grade solvents without purification under air.
CH2Cl2, 25 ˚C
or
(CH2Cl)2, 80 ˚C
(1.0 equiv)
(4.0 equiv)
Entry
R1
R2
Condition
25 °C, 3 h
25 °C, 1 h
80 °C, 1 h
80 °C, 1 h
80 °C, 5 h
Yield (%)b;c
1
2
3
4
5
PhCH2
p-MeOC6H4
PhCH2
n-Bu
n-Bu
Cy
79
81
79
79
74
p-MeOC6H4
p-MeOC6H4
Cy
Ph
N
6
n-Bu
80 °C, 3 h
95
SR1
+Rh
SR2 SR2
(R2S)2
–R1SSR2
S
SR1
+Rh SR2
SR1
+Rh SR1
SR1
a The reaction was conducted using (R1S)2 (0.25 mmol), (R2S)2
(1.0 mmol), [Rh(cod)2]BF4 (0.0075 mmol) and solvent (2 mL) under
–(R2S)2
R1SSR2
Ar.
b Yield based on the R1S group.
c Isolated yield.
D
Scheme 2.

K. Tanaka, K. Ajiki / Tetrahedron Letters 45 (2004) 5677–5679
5679
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Future work will include elucidation of the role of
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(a) Kondo, T.; Mitsudo, T. Chem. Rev. 2000, 100, 3205;
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9. The active catalyst was prepared by mixing [Rh(cod)2]BF4
and PPh3 in CH2Cl2 followed by hydrogenation (1 atm, rt,
0.5 h).
10. Tanaka, K.; Ajiki, K. Tetrahedron Lett. 2004, 45, 25.
11. First report for the dehydrogenation of benzenethiol to
diphenyl disulfide under inert atmosphere, see: Ogawa, A.;
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12. The highest yield of disulfides was obtained at 4 °C for 1 h
(Eq. 1), but longer reaction time (16 h) at 4 °C decreased
the yield of disulfides and thiols were regenerated. This
result indicates that this cationic rhodium(I)-catalyzed
dehydrogenation reaction is reversible process. See Ref.
10.
13. Disulfide–thiol exchange reaction, see: Dalman, G.;
McDermed, J.; Gorin, G. J. Org. Chem. 1964, 29, 1480.
14. Arisawa and Yamaguchi reported the exchange reaction
of disulfide and diselenide or ditelluride using
RhH(PPh3)4/p-tol3P/trifluoromethanesulfonic acid combi-
nation catalyst, see: Ref. 7.
15. Exchange reaction of di-n-butyl disulfide (1 equiv) and
diphenyl diselenide (4 equiv) proceeded in the same
reaction conditions (CH2Cl2, 80 °C, 0.5 h) to give corre-
sponding selenosulfide in 43% yield.
16. Sample procedure (Eq. 4): Under air, to a CH2Cl2 (Wako
130-02457, 1.0 mL) solution of bis(p-methoxyphenyl)disul-
fide (278.4 mg, 1.00 mmol) and di-n-butyl disulfide
(713.4 mg, 4.00 mmol) was added a CH2Cl2 (7.0 mL)
solution of [Rh(cod)2]BF4 (12.2 mg, 0.030 mmol). The
resulting solution was kept at 25 °C for 1.5 h under air.
The solution was concentrated and purified by silica gel
chromatography (hexane/EtOAc ¼ 20:1), which furnished
n-butyl p-methoxyphenyl disulfide (370.8 mg, 1.62 mmol,
81%).
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