Equilibrating C-S bond formation by C-H and S-S bond metathesis. Rhodium-catalyzed alkylthiolation reaction of 1-alkynes with disulfides

Article abstract of DOI:10.1021/ja0527121

In the presence of a catalytic amount of RhH(PPh₃)₄ (2 mol %) and 1,1′-bis(diphenylphosphino)ferrocene (dppf) (3 mol %), silylacetylenes reacted with dialkyl disulfides giving 1-alkylthio-2-trialkylsilylethynes in high yields. Alkane

Full text of DOI:10.1021/ja0527121

Published on Web 08/13/2005
Equilibrating C-S Bond Formation by C-H and S-S Bond Metathesis.
Rhodium-Catalyzed Alkylthiolation Reaction of 1-Alkynes with Disulfides
Mieko Arisawa, Kenji Fujimoto, Satoshi Morinaka, and Masahiko Yamaguchi*
Department of Organic Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku UniVersity, Aoba,
Sendai, 980-8578, Japan
Received April 26, 2005; E-mail: yama@mail.pharm.tohoku.ac.jp
Table 1. Rh-Catalyzed Alkylthiolation of 1-Alkynes with Disulfidesa
Use of transition metal catalyst for the C-H functionalization
of organic molecules is a challenge in organic synthesis. For such
a reaction to proceed, the catalyst must effectively be able to activate
a C-H bond and form a new bond. Addition reaction to unsaturated
bonds has been employed for the latter process, particularly for
entry
R
R
′
yield/%
C-C bond formation.1-3 In contrast, in the synthesis of heteroatom
compounds such as organosulfur compounds, metathesis of C-H
and S-S bonds to form C-S bonds is more important,4,5 since a
variety of S-S compounds are readily available including organic
polysulfides and elemental sulfur.6 Such catalytic synthesis of
organosulfur compounds, however, is not known. Described herein
is the rhodium-catalyzed alkylthiolation reaction of 1-alkynes with
disulfides.7 This is an unprecedented equilibrating oxidation reaction
of hydrocarbons to organosulfur compounds involving reversible
C-H, C-S, S-S, and S-H bond cleavage and metathesis (Scheme
1). Conventional syntheses of alkylthioacetylenes from 1-alkynes
1
2
3
4
5
6
7
8
Et3Si
CH2CH2NHBoc
Me
77
74
80
81
86
76
83
86
82
79
62
75
54
64
81
66
81
96
86
n-C4H9
i-C5H11
n-C8H17
(CH2)2OMe
(CH2)2CO2Me
Ph
p-ClC6H4
p-MeC6H4
Me
n-C8H17
n-C8H17
Me
Ph
Me
9
10
11
12
13
14
15
16
17
18
19
i-Pr3Si
2,6-Me2C6H3
2,4,6-Me3C6H2
Scheme 1
1-adamantyl
n-C8H17
Ph
Ph
(CH2)5C(OMe)
(CH2)5C(OTBS)
require stoichiometric amounts of organometallic or organic bases
to promote the C-H activation or to trap the HX species generated.8
In contrast, the present reaction employs a catalytic amount of a
rhodium complex as the only activator without any added base.
To a mixture of triethylsilylacetylene 1, RhH(PPh3)4 (2 mol %),
and 1,1′-bis(diphenylphosphiono)ferrocene (dppf) (3 mol %) in
acetone was added bis{2-(t-butoxycarbonylamino)}ethyl disulfide
2 (3 equiv), and the mixture was heated at reflux for 1 h. 1-{2-(t-
Butoxycarbonylamino)ethyl}-2-triethylsilylacetylene 3 was obtained
in 77% yield, which was accompanied by 2-(t-butoxycarbonylami-
no)ethanethiol 4 (69%) and a small amount of 1-{2-(t-butoxycar-
bonylamino)ethyl}-1-triethylsilylethylene 5 (4%) (Scheme 2). Other
a Procedures for the reaction of dialkyl disulfide: RhH(PPh3)4 (2 mol
%) and dppf (3 mol %) were used, and the mixture was heated at reflux for
1 h. Procedures for the reaction of diaryl disulfide: RhH(PPh3)4 (2 mol %)
and dppf (4 mol %) were used, and the mixture was stirred at room
temperature for 12 h. See SI for details.
gave small amounts (<15%) of 3. Various dialkyl disulfides,
including dimethyl disulfide, underwent alkylthiolation with silyl-
acetylenes. In all cases, addition products of thiols to the acetylenes
were obtained in less than 5% yield (Table 1, entries 1-7, 11, and
12).
A notable aspect of this reaction is the formation of free thiols,
which does not interfere with the reaction. In addition, the thiols
do not add to the silylacetylenes, although several transition metal
complexes are known to catalyze such a reaction.9 The addition
products, however, were obtained by slightly modifying the
conditions: When 1 and 2 were reacted at room temperature in
the presence of Rh complex (2 mol %) and dppf (4 mol %), the
thiol adduct 5 was obtained in 31% and 3 was obtained in 64%
yield; under Rh complex (2 mol %) and dppf (2 mol %) conditions,
5 decreased to 6% and 3 to 47%. The dramatic effect of the catalyst
composition may be explained by the formation of 1:1 and 1:2
complexes, of which the latter is involved in the thiol addition
reaction. Under acetone refluxing conditions, 1:1 complex formation
should be favored.
Scheme 2
rhodium complexes such as RhCl(PPh3)3, [RhCl(cod)2]2, [RhCl2-
Cp*]2, Rh(acac)3, and RhCl3 in the presence of dppf showed very
low activities. A low yield (9%) of 3 was obtained in the absence
of dppf, and the use of several other bidentate ligands revealed a
high efficiency of dppf for this reaction: dppe (not detected), dppp
(not detected), dppb (34%), dpppentane (29%), and dpphexane
(4%). Monodentate ligands, PPh3, (p-ClC6H4)3P, and (p-MeOC6H4)3P,
Alkyacetylenes were also alkylthiolated, provided that they
possessed tertiary substituents (entries 16 and 17). Aromatic
acetylenes exhibited similar behaviors as shown by the reactions
of 2,6-dimethyl- and 2,4,6-trimethylphenylacetylene (entries 13 and
14). The need for the bulky group is partly due to competition with
9
12226
J. AM. CHEM. SOC. 2005, 127, 12226-12227
10.1021/ja0527121 CCC: $30.25 © 2005 American Chemical Society

C O M M U N I C A T I O N S
alkyne dimerization; such a byproduct was obtained in 50% yield
in the reaction of o-tolylacetylene and dioctyl disulfide with the
expected 1-octylthioacetylene in 28% yield.
disulfide, C-S bond cleavage of thioacetylene, S-H activation of
thiol, C-S bond formation between the alkylthio group and alkynyl
sp-carbon, C-H bond formation between hydride and alkynyl sp-
carbon. The catalyst can also participate in the addition reaction of
thiol to acetylene. We previously reported that a catalyst system
of RhH(PPh3)4, phosphine, and trifluoromethanesulfonic acid
catalyzes disulfide addition to alkynes,3 in which the presence of
the acid was critical for the addition to occur. Such multiple
functions and its selectivity control by judicious choice of the
conditions are other notable aspects of the rhodium catalysis in
organosulfur transformations.
It was shown that a rhodium catalyst can equilibrate a C-H bond
and a C-S bond by lowering the activation energies of multiple
organometallic processes. Such an equilibration methodology of
forming C-S bonds, which requires low energy and generates
minimum waste, would be a powerful tool for the synthesis of
organosulfur compounds from hydrocarbons.
Reactions of diaryl disulfides required a modification of the
conditions (entries 8-10, 15, 18, and 19), since the reaction under
the above conditions gave very small amounts of the arylthiolated
products because of serious deactivation of the catalyst. A mixture
of RhH(PPh3)4 (2 mol %) and dppf (4 mol %) was heated at reflux
for 10 min to form the active catalyst. Then, 1 and diphenyl disulfide
(3 equiv) were added, and the reaction was conducted at room
temperature for 12 h. 2-Phenylthio-1-triethylsilylacetylene was
obtained in 86% yield, although in this case, the thiol adduct was
formed in 40% yield, as expected from the catalyst composition
and reaction conditions.
Another interesting aspect of this reaction is its equilibrating
nature. Reaction of 1-octanethiol with 1-triisopropylsilyl-2-
{(t-butoxycarbonylamino)ethylthio}ethyne 6 in the presence of
RhH(PPh3)4 (4 mol %) and dppf (6 mol %) at acetone reflux for 1
h gave triisopropylsilylacetylene 7 (18%), 1-triisopropylsilyl-2-
octylthioethyne 8 (27%), and 4 (43%) with the recovered 6 (41%)
(Scheme 3). A mixture of disulfides possessing 1-octyl and 2-
(t-butoxycarbonylamino)ethyl groups was also formed.
Acknowledgment. This work was supported by JSPS (Nos.
16109001 and 17689001). M.A. expresses her thanks for financial
support from NEDO of Japan (No. 02A44003d) and the Asahi Glass
Foundation.
Supporting Information Available: Detailed experimental pro-
cedure and characterization data. This material is available free of charge
via the Internet at http://pubs.acs.org.
Scheme 3
References
(1) C-C bond formation by addition reactions. Ritleng, V.; Sirlin, C.; Pfeffer,
M. Chem. ReV. 2002, 102, 1731.
(2) C-S bond formation by addition reactions. (a) Kondo, T.; Mitsudo, T.
Chem. ReV. 2000, 100, 3205. Also see: (b) Ananikov, V. P.; Beletskaya,
I. P. Org. Biomol. Chem. 2004, 2, 284. (c) Ananikov, V. P.; Beletskaya,
I. P. Russ. Chem. Bull. 2004, 53, 561.
(3) (a) Arisawa, M.; Yamaguchi, M. Org. Lett. 2001, 3, 763. (b) Arisawa,
M.; Suwa, A.; Fujimoto, K.; Yamaguchi, M. AdV. Synth. Catal. 2003,
345, 560.
(4) Radical reactions. (a) Kharasch, M. S.; Read, A. T. J. Am. Chem. Soc.
1939, 61, 3089. (b) Kharasch, M. S.; Chao, T. H.; Brown, H. C. J. Am.
Chem. Soc. 1940, 62, 2393. (c) Dainton, F. S.; Ivin, K. J. Trans. Faraday
Soc. 1950, 46, 374, 382. (d) Balavoine, G.; Barton, D. H. R.; Boivin, J.;
Lecoupanec, P.; Lelandais, P. New J. Chem. 1989, 13, 691.
(5) Stoichiometric C-S bond formation. (a) Giolando, D. M.; Rauchfuss, T.
B. J. Am. Chem. Soc. 1984, 106, 6455. (b) Matsumoto, K.; Uemura, H.;
Kawano, M. Inorg. Chem. 1995, 34, 658. (c) Matsumoto, K.; Sugiyama,
H. Acc. Chem. Res. 2002, 35, 915. (d) Matsumoto, K.; Sugiyama, H. J.
Organomet. Chem. 2004, 689, 4564. Also see references cited.
(6) (a) Steudel, R. Chem. ReV. 2002, 102, 3905. (b) Meyer, B. Chem. ReV.
1976, 76, 367.
(7) Our recent works on the use of rhodium catalysts in the synthesis of
organosulfur compounds. (a) Arisawa, M.; Yamaguchi, M. J. Am. Chem.
Soc. 2003, 125, 6624. (b) Arisawa, M.; Ashikawa, M.; Suwa, A.;
Yamaguchi, M. Tetrahedron Lett. 2005, 46, 1727 and references therein.
(8) (a) Schmidt, M.; Potschka, V. Naturwissenschaften 1963, 50, 302. (b)
Yoshifuji, M.; Hanafusa, F.; Inamoto, N. Chem. Lett. 1979, 723. (c)
Miyachi, N.; Shibasaki, M. J. Org. Chem. 1990, 55, 1975. (d) Braga, A.
L.; Silveira, C. C.; Reckziegel, A.; Menezes, P. H. Tetrahedron Lett. 1993,
34, 8041. (e) Braga, A. L.; Reckziegel, A.; Menezes, P. H.; Stefani, H.
A. Tetrahedron Lett. 1993, 34, 393. (f) Taherirastgar, F.; Brandsma, L.
Chem. Ber./Recl. 1997, 130, 36. Also see the following for Cu-catalyzed
synthesis in the presence of a stoichiometric amount of a base. (g) Bieber,
L. W.; da Silva, M. F.; Menezes, P. H. Tetrahedron Lett. 2004, 45, 2735.
(9) Ogawa, A.; Ikeda, T.; Kimura, K.; Hirao, T. J. Am. Chem. Soc. 1999,
121, 5108.
In addition, alkylthio exchange reaction of disulfides and
thioacetylenes took place. The treatment of 1-butylthio-2-triethyl-
silylethyne 9 with bis(4-methoxybutyl) disulfide (3 equiv) in
refluxing acetone for 0.5 h in the presence of RhH(PPh3)4 (2 mol
%) and dppf (4 mol %) gave the exchanged product 10 in 80%
yield (Scheme 4). The experimental yield coincided with the yield
of 80% at the equilibrium, calculated assuming the same S-S bond
energies of two thioacetylenes. It is concluded that the present
oxidation reaction of C-H to C-S is under equilibrium, as shown
in Scheme 1.
Scheme 4
The catalyst may be involved in several reversible organometallic
processes: C-H activation of acetylene, S-S bond cleavage of
JA0527121
9
J. AM. CHEM. SOC. VOL. 127, NO. 35, 2005 12227