Rhodium-catalyzed reductive coupling of disulfides and diselenides with alkyl halides, using hydrogen as a reducing agent

Article abstract of DOI:10.1021/ol051588n

(Chemical Equation Presented) We have established that RhCl(PPh ₃)₃ catalyzes a reductive coupling of disulfides and diselenides with alkyl halides in the presence of triethylamine using hydrogen as a reducing agent. This reaction serves as a convenient new method to produce unsymmetrical sulfides and selenides from disulfides and diselenides instead of unstable and odoriferous thiols and selenols.

Full text of DOI:10.1021/ol051588n

ORGANIC
LETTERS
2
005
Vol. 7, No. 19
193-4195
Rhodium-Catalyzed Reductive Coupling
of Disulfides and Diselenides with Alkyl
Halides, Using Hydrogen as a Reducing
Agent
4
Kaori Ajiki, Masao Hirano, and Ken Tanaka*
Department of Applied Chemistry, Graduate School of Engineering, Tokyo UniVersity
of Agriculture and Technology, Koganei, Tokyo 184-8588, Japan
tanaka-k@cc.tuat.ac.jp
Received July 7, 2005
ABSTRACT
3 3
We have established that RhCl(PPh ) catalyzes a reductive coupling of disulfides and diselenides with alkyl halides in the presence of
triethylamine using hydrogen as a reducing agent. This reaction serves as a convenient new method to produce unsymmetrical sulfides and
selenides from disulfides and diselenides instead of unstable and odoriferous thiols and selenols.
The reductive coupling of disulfides or diselenides with alkyl
or aryl halides is an important reaction in the synthesis of
various unsymmetrical sulfides and selenides, which can
eliminate the use of unstable and odoriferous thiols and
paper, we describe a rhodium-catalyzed reductive coupling
of disulfides and diselenides with alkyl halides using
hydrogen as a reducing agent.
Recently, we reported a rhodium-catalyzed dehydrogena-
1
6
selenols. Although some efficient reductive coupling reac-
tion of thiols to disulfides under an Ar atmosphere and a
tions using dicarcogenides have been reported, they require
a stoichiometric amount of metal reducing agents. In this
rhodium-catalyzed coupling reaction of thiols with alkyl
halides in the presence of triethylamine. The rhodium-
2
-5
7,8
catalyzed dehydrogenation reaction is highly dependent on
reaction temperature. Although a high yield of disulfides was
obtained at 4 °C, raising the reaction temperature to 25 °C
decreased the yield of disulfides and regenerated the thiols.6
Furthermore, when dioctyl disulfide was treated with an
atmospheric pressure of hydrogen in the presence of 5%
(
1) For reviews for transition-metal-catalyzed synthesis of carcogenides,
see: (a) Ogawa, A. In Main Group Metals in Organic Synthesis; Yamamoto,
H., Oshima, K., Eds.; Wiley-VCH: Weinheim, Germany, 2004; p 813. (b)
Ali, B. E.; Alper, H. In Handbook of Organopalladium Chemistry for
Organic Synthesis; Negishi, E., Ed.; Wiley-Interscience: New York, 2002;
Chapter VI, section 2.1.1.2. (c) Ogawa, A. In Handbook of Organopalladium
Chemistry for Organic Synthesis; Negishi, E., Ed.; Wiley-Interscience: New
York, 2002; Chapter VII. 6. (d) Kuniyasu, H. In Catalytic Heterofunction-
alization; Togni, A., Gr u¨ tzmacher, H., Eds.; Wiley-VCH: Weinheim,
Germany, 2001, p 217. (e) Kuniyasu, H.; Kurosawa, H. Chem. Eur. J. 2002,
,9
(4) Reductive coupling of diphenyl ditelluride with alkyl halides, see:
Nishiyama, Y.; Okada, M.; Nishino, T.; Sonoda, N. Bull. Chem. Soc. Jpn.
2005, 78, 341.
8
, 2660. (f) Ogawa, A. J. Organomet. Chem. 2000, 611, 463. (g) Kondo,
T.; Mitsudo, T. Chem. ReV. 2000, 100, 3205. (h) Han, L.-B.; Tanaka, M.
J. Chem. Soc., Chem. Commun. 1999, 395. (i) Beletskaya, I.; Moberg, C.
Chem. ReV. 1999, 99, 3435.
(5) Reductive coupling of disulfides and diselenides with aryl halides,
see: (a) Taniguchi, N.; Onami, T. Synlett 2003, 829. (b) Taniguchi, N.;
Onami, T. J. Org. Chem. 2004, 69, 915. (c) Taniguchi, N. J. Org. Chem.
2004, 69, 6904.
(
2) Reductive coupling of disulfides with alkyl halides, see: (a)
Chowdhury, S.; Roy, S. Tetrahedron Lett. 1997, 38, 2149. (b) Nishino, T.;
Okada, M.; Kuroki, T.; Watanabe, T.; Nishiyama, Y.; Sonoda, N. J. Org.
Chem. 2002, 67, 8696. (c) Nishino, T.; Nishiyama, Y.; Sonoda, N. Chem.
Lett. 2003, 918. (d) Ranu, B. C.; Mandal, T. J. Org. Chem. 2004, 69, 5793.
(6) Tanaka, K.; Ajiki, K. Tetrahedron Lett. 2004, 45, 25.
(7) Tanaka, K.; Ajiki, K. Org. Lett. 2005, 7, 1537.
(8) Platinum-catalyzed formaldehyde dithioacetal formation using thiols
and diiodomethane, see: (a) Page, P. C. B.; Klair, S. S.; Brown, M. P.;
Smith, C. S.; Maginn, S. J.; Mulley, S. Tetrahedron 1992, 48, 5933. (b)
Page, P. C. B.; Klair, S. S.; Brown, M. P.; Harding, M. M.; Smith, C. S.;
Maginn, S. J.; Mulley, S. Tetrahedron Lett. 1988, 29, 4477.
(
3) Reductive coupling of diphenyl diselenide with alkyl halides, see:
a) Kundu, A.; Roy, S. Organometallics 2000, 19, 105. (b) Ranu, B. C.;
Mandal, T.; Samanta, S. Org. Lett. 2003, 5, 1439. Also see refs 2b-d.
(
1
0.1021/ol051588n CCC: $30.25
© 2005 American Chemical Society
Published on Web 08/23/2005

[
2 4 3
Rh(cod) ]BF /8PPh at room temperature for 5 h, octanethiol
6
was generated in 7% yield. These phenomena prompted us
to investigate the rhodium-catalyzed reductive coupling of
disulfides with alkyl halides in the presence of triethylamine
under a hydrogen atmosphere.
Table 2. Rhodium-Catalyzed Reaction of Disulfides and
Diselenides with Alkyl Halides in the Presence of Triethylamine
a
and Hydrogen
Table 1. Rhodium-Catalyzed Reductive Coupling of Dibenzyl
Disulfide with 1-Bromododecane: Screening of Reaction
Conditionsa
temp time yield
entry
catalyst
solvent
(°C)
(h)
(%)
1
2
3
4
5
6
[Rh(cod)2]BF4/2PPH3
[Rh(cod)2]/4PPh3
RhCl(PPh3)3
RhCl(PPh3)3(0.3 equiv) toluene
RhCl(PPh3)3(0.3 equiv) THF
toluene
toluene
toluene
25
25
25
50
50
50
50
16
16
16
24
24
24
24
50
0
51
86
88
b
b
none
RhCl(PPh3)3
THF
THF
0
0
c
7
a
NMR yield based on disulfide. b Isolated yield based on disulfide.
c
Under Ar.
a
Isolated yield based on disulfide or diselenides. b The reactions were
conducted with catalyst (0.05 equiv) in toluene at 100 °C. c Reaction time:
30 h.
Table 1 shows screening of reaction conditions to promote
the rhodium-catalyzed reductive coupling of dibenzyl disul-
fide with 1-bromododecane in the presence of triethylamine
under a hydrogen atmosphere. Among the catalysts (5%
based on dibenzyl disulfide) examined, the commercially
available rhodium catalyst, RhCl(PPh ) , shows a high
3 3
catalytic activity (entries 1-3). Raising the reaction tem-
perature to 50 °C furnished benzyl dodecyl sulfide in 86%
high reaction temperature (100 °C), and prolonged reaction
time (30 h) were required, the reactions of ethyl bromoacetate
and benzoyl chloride proceeded in good to high yield (entries
9
and 10). Importantly, this reductive coupling protocol can
be applicable to the synthesis of various selenides. The
reactions of diphenyl diselenide with 1-bromododecane,
benzyl chloride, and benzoyl chloride proceeded in high yield
isolated yield by using 3% RhCl(PPh
reaction proceeded not only in toluene but also in THF (entry
). No reaction was observed in the absence of rhodium
3 3
) (entry 4). The
(entries 11-13).
The reaction of disulfides and diselenides with volatile
5
dichloromethane was also investigated. When the reactions
were carried out at 40 °C for 30 h, the corresponding
formaldehyde dithioacetals and diselenoacetal were obtained
in good to high yield (eq 1).
catalyst or hydrogen (entries 6 and 7).
A series of disulfides and alkyl halides were subjected to
1
0
the above optimal reaction conditions (Table 2). The
reactions of alkyl (entries 1 and 2), aryl (entries 4-6), and
heteroaryl (entry 7) disulfides with 1-bromododecane pro-
ceeded in high yield. Highly functionalized disulfides, a
protected cystine, reacted with 1-bromododecane at 100 °C
to furnish the corresponding sulfides in good yield (entry
3). Not only 1-bromododecane but also benzyl chloride could
be employed (entry 8). Although high catalyst loading (5%),
(9) Rhodium-catalyzed equilibrating disulfide exchange reaction, see: (a)
Arisawa, M.; Yamaguchi, M. J. Am. Chem. Soc. 2003, 125, 6624. (b)
Tanaka, K.; Ajiki, K. Tetrahedron Lett. 2004, 45, 5677.
3 3
Because RhCl(PPh ) is a highly active catalyst for the
hydrogenation of olefins, the tolerance of olefins in the
reductive coupling of disulfides with alkyl halides with
hydrogen as a reducing agent is of interest. The reaction of
(10) Representative procedure (Table 2, entry 4): Under an Ar
atmosphere, a THF (0.2 mL) solution of RhCl(PPh3)3 (5.6 mg, 0.0060 mmol)
was added to a THF (0.2 mL) solution of di-p-tolyl disulfide (49.3 mg,
0
.200 mmol), 1-bromododecane (109.7 mg, 0.440 mmol), and Et3N (0.2
(
2
p-TolS) with cinnamyl bromide under a hydrogen atmo-
mL) by using THF (0.6 mL). H2 was introduced to the resulting solution in
a Schlenk tube. The mixture was stirred at 50 °C for 24 h. The resulting
solution was concentrated and purified by preparative TLC (hexane), which
furnished dodecyl p-tolyl sulfide (117.0 mg, 0.400 mmol, 100%) as a
colorless oil.
sphere furnished the desired cinnamyl sulfide in 76% yield
and almost no hydrogenated phenylpropyl sulfide was
generated (eq 2).
4194
Org. Lett., Vol. 7, No. 19, 2005

Scheme 1
To confirm whether thiols were generated in this reductive
coupling reaction or not, the hydrogenation of disulfides was
1
1
investigated. When didodecyl disulfide was treated with
hydrogen in the presence of 3% RhCl(PPh at 100 °C,
3 3
)
dodecanethiol was generated in 94% yield (eq 3).
reported catalytic cycle via a rhodium(III) complex D may
7
also be included.
Scheme 1 depicts a plausible mechanism of this reaction.
3 3
In conclusion, we have established that RhCl(PPh )
The reaction of a rhodium(I) catalyst with H
2
affords a
catalyzes the reductive coupling of disulfides or diselenides
with alkyl halides in the presence of triethylamine using the
most atom economical reducing agent, hydrogen. This
reaction serves as a convenient new method to produce
unsymmetrical sulfides and selenides from disulfides and
diselenides instead of unstable and odoriferous thiols and
selenols.
rhodium(III) complex A. Elimination of HY with Et
3
N
furnishes a rhodium(I) hydride B, which reacts with disul-
fides followed by elimination of a thiol furnishing a rhodium-
(
S
I) thiolate C. The reaction of C with alkyl halides in an
2 fashion furnishes sulfides, regenerating the rhodium(I)
catalyst. In addition to this catalytic cycle, the previously
N
Supporting Information Available: Experimental pro-
cedures and compound characterization data. This material
is available free of charge via the Internet at http://pubs.acs.org.
OL051588N
(
11) Although metal complexe-catalyzed hydrogenation of disulfides to
thiols has not been reported, some heterogeneous catalyses were reported,
see: (a) Kessler, P.; Servent, D.; Hirth, C. Tetrahedron Lett. 1994, 35, 7237.
b) Calais, C.; Lacroix, M.; Geantet, C.; Breysse, M. J. Catal. 1993, 144,
60.
(
1
Org. Lett., Vol. 7, No. 19, 2005
4195