One-pot synthetic method of allyl sulfides: Samarium-induced allyl bromide mediated reduction of alkyl thiocyanates and diaryl disulfides in methanolic medium

Article abstract of DOI:10.1246/cl.2004.1370

A convenient synthetic method of allyl sulfides by the treatment of alkyl thiocyanates or diaryl disulfides with Sm and allyl bromide in methanol has been developed.

Full text of DOI:10.1246/cl.2004.1370

1370
Chemistry Letters Vol.33, No.10 (2004)
One-pot Synthetic Method of Allyl Sulfides: Samarium-induced Allyl Bromide Mediated
Reduction of Alkyl Thiocyanates and Diaryl Disulfides in Methanolic Medium
Zhuang-Ping Zhanà and Kai Lang
The Key Laboratory for Chemical Biology of Fujian Province, Department of Chemistry, University of Xiamen,
Xiamen 361005, P. R. China
(Received August 10, 2004; CL-040941)
A convenient synthetic method of allyl sulfides by the
treatment of alkyl thiocyanates or diaryl disulfides with Sm
and allyl bromide in methanol has been developed.
Sm/Allyl bromide/ MeOH
rt, 30min
RSCN
RSCH2CH=CH2
ArSCH2CH=CH2
Sm/Allyl bromide/ MeOH
rt, 30min
ArSSAr
The use of samarium diiodide as a single electron transfer
reagent in organic synthesis has drawn chemist’s attention. Nu-
merous examples, such as coupling reduction, cyclization, and
the Barbier reaction, have been widely reported.1 Though SmI2
is a useful reductive reagent, it is expensive. Furthermore, sama-
rium diiodide is very sensitive to oxidation by air, so storage is
difficult. Whereas metallic samarium is stable in air and has
strong reducing power. Recently, it has been noted that cheaper
and more convenient metallic samarium can be used directly as
an alternative reductant of SmI2 in organic synthesis.2
Scheme 1.
Table 1. Synthesis of allyl sulfides
Molar Ratio
(Substrate:Sm:Allyl
Bromide)
Yielda
of Allyl
Product/%
Entry
Substrate
1
2
3
4
5
6
7
8
9
HO(CH2)6SCN
TsO(CH2)6SCN
PhCH2SCN
n-C12H25SCN
n-C16H33SCN
(PhS)2
(p-MeC6H4S)2
(p-ClC6H4S)2
(p-BrC6H4S)2
(n-C16H33S)2
n-C16H33SCN
1:3:3
1:3:3
1:3:3
1:3:3
1:3:3
1:5:6
1:5:6
1:5:6
1:5:6
1:5:6
1:3:0.6
91%
93%
80%
84%
86%b
76%
80%
83%
81%
Because metallic samarium which is commercially availa-
ble is not sufficiently reactive,3 a lot of activating agents, such
as I2, HCl, HgCl2, and TMSCl have been used to activate
metallic samarium to mediate the reactions.4 Recently, Banik
B. K. reported that reductive coupling of aromatic ketones was
achieved by samarium metal in the presence of allyl bromide.5
Interestingly, no allylated product was obtained. Yet, when we
used alkyl thiocyanates and diaryl disulfides as substrates in this
system, allylated product was obtained. Herein we report that, by
modifying the ratio of starting materials, allyl sulfides can be
prepared efficiently in Sm/Allyl bromide/MeOH system.
We found that treatment with 3 equiv. of samarium metal
and 3 equiv. of allyl bromide, alkyl thiocyanates were converted
to allyl sulfides quickly and in good yields (Table 1, Entries1–5).
When diaryl disulfides were treated with 5 equiv. of samarium
metal and 6 equiv. of allyl bromide, we also got corresponding
allyl sulfides in good yields (Entries 6–9). However, when we
treated alkyl disulfides in this method, no allylated product or
other reduced products were detected and only starting material
recovered (Entry 10). Our experiment also showed that alkyl di-
sulfides cannot be reduced to alkyl thiolates by SmI2 at room
temperature. In Entry 2, though TsO is a good leaving group,
substrate was smoothly converted into corresponding allylated
product with TsO group intact. Benzyl thiocyanate was allylated
in 80% yield (Entry 3), yet, in SmI2/THF/H2O system, benzyl
thiocyanate was rapidly reduced to toluene owing to the strong
reducing power of SmI2. On the basis of the above results, we
consider the Sm/Allyl bromide/MeOH system has a moderate
reducing power.
c
10
11
—
30%d
aIsolated yield. b1H NMR analysis of the crude product was
performed, the ratio of n-C16H33SCH2CH=CH2:n-C16H33SH:
(n-C16H33S)2 was 92:7:1. cNo reaction, only starting material re-
covered. d1H NMR analysis of the crude product was performed,
the ratio of n-C16H33SCH2CH=CH2:n-C16H33SH:(n-C16H33S)2
was 37:58:5.
(n-C16H33S)2 was 37:58:5 (Entry 11), yet, when 3 equiv. of
allyl bromide was used in this reaction, the ratio of n-C16H33-
SCH2CH=CH2:n-C16H33SH:(n-C16H33S)2 was 92:7:1 (Entry
5), where allylated product was increased greatly. On the basis
of the results in Table 1, we consider that allyl bromide might
act as an activator of metalic samarium to mediate the reduction
from alkyl thiocyanates to alkyl thiolates and alkyl disulfides.6 In
this process, allyl bromide was partially consumed to activate
Sm, alkyl thiolate captured the remained allyl bromide and
hence gave allylated product. Similarly, diaryl disulfides can
also be reduced by activated Sm to aryl thiolates and allylated
by allyl bromide.
The possible mechanism for the reaction is proposed in
Scheme 2. Taking n-C16H33SCN as an example, it may involve
the single-electron transfer (SET) process.
A single-electron transfer to alkyl thiocyanate firstly gives
radical A. Subsequently, either self-coupling of radical A or fur-
ther a single-electron transfer to radical A is feasible. As a result,
In the process of exploring the role of allyl bromide, we
found that in the absence of allyl bromide, no reaction was going
on. When 0.6 equiv. of allyl bromide was used to mediate the
reaction of n-C16H33SCN, 1H NMR analysis of the crude product
showed the ratio of n-C16H33SCH2CH=CH2:n-C16H33SH:
Copyright Ó 2004 The Chemical Society of Japan

Chemistry Letters Vol.33, No.10 (2004)
1371
starting material was verified to have been consumed complete-
ly. The reaction mixture was diluted with 10 mL ethyl acetate,
and was filtered through a small quantitative of silica gel. The
filtrated solution was dried (Na2SO4) and then concentrated.
For some cases, the 1H NMR analysis of the crude products
was performed. All crude products were purified by flash
chromatography to yield the desired products.
In summary, a one-pot synthetic method of allyl sulfides by
the treatment of alkyl thiocyanates or diaryl disulfides with Sm
and allyl bromide in methanol has been developed. The notable
advantages of this method are good yields, simple operation and
neutral reaction conditions.
Allyl bromide
Br
SET
SET
CN
•
RSCH CH=CH
RS
B
RSCN
RS
A
2
2
E
coupling
protonation
RSSR
RSH
D
C
Scheme 2.
trace of disulfides C and a large amount of alkyl thiolate B are
formed. Meanwhile, alkyl thiolate B can be protonated to gener-
ate the alkyl thiol D or more smoothly allylated by alkyl bromide
to provide product E.
We thank FuJian Provincial Department of Science and
Technology for financial support (2003J019).
Table 2. Reactions of n-C16H33SCN with samarium metal and
allyl bromide in various protic solvent
References
Reaction
Medium
Reaction Yield of
Time n-C16H33SCH2CH=CH2
1
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Entry
1
2
3
4
5
6
MeOH
EtOH
i-PrOH
30 min
45 min
24 h
24 h
24 h
86%a
31%a
b
—
—
2
b
t-BuOH
THF/H2O(10/1)
MeOH/H2O(10/1)
b
—
—
b
24 h
aisolated yield. bno reaction, only starting material recovered.
We also attempted several other protic solvent as reaction
medium in addition to MeOH. We found that using EtOH as
reaction medium, the highest yield of allyl product we got was
31% (Table 2, Entry 2), and a prolonged reaction time did no
service to yield. When secondary or tertiary alcohol was used
in place of MeOH, even the mixture was stirred overnight, still
no reduced product was detected, and there was only starting
material recovered (Entries 3, 4). Although water as a protic sol-
vent, efficaciously promotes the reductivity of SmI2,7 the action
of Sm/Allyl bromide in the medium containing water was inert
(Entries 5, 6).
The general procedure is as follows: At room temperature,
to a mixture of samarium metal (1.5 mmol for alkyl thiocyanates
or 2.5 mmol for diaryl disulfide) and substrate (0.5 mmol), allyl
bromide (1.5 mmol for alkyl thiocyanate or 3 mmol for diaryl
disulfide) was added under nitrogen. Subsequently, MeOH
(8 mL) was added by a quick syringe. An exothermic reaction
occurred, when MeOH was added. After 30 min, by TLC, the
3
4
5
A. Ghatak, F. F. Becker, and B. K. Banik, Tetrahedron Lett.,
41, 3793 (2000).
6
7
S. Matsukawa and Y. Hinakubo, Org. Lett., 5, 1221 (2003).
E. Hasegawa and D. P. Curran, J. Org. Chem., 58, 5008
(1993).
Published on the web (Advance View) September 18, 2004; DOI 10.1246/cl.2004.1370