Water effects on SmI2 reductions: A novel method for the synthesis of alkyl thiols by SmI2-promoted reductions of sodium alkyl thiosulfates and alkyl thiocyanates

Article abstract of DOI:10.1081/SCC-200028622

Water as a cosolvent has significant improving effect on the reductivity of SmI₂ in the reduction of sodium alkyl thiosulfates and alkyl thiocyanates. A new method for synthesis of alkyl thiols by SmI ₂/THF/H₂O system has been developed.

Full text of DOI:10.1081/SCC-200028622

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Water Effects on SmI2
Reductions: A Novel Method
for the Synthesis of Alkyl
Thiols by SmI ‐Promoted
2
Reductions of Sodium Alkyl
Thiosulfates and Alkyl
Thiocyanates
a
a
a
Zhuang‐Ping Zhan , Kai Lang , Feng Liu
&
a
Li‐ming Hu
a
The Key Laboratory for Chemical Biology of
Fujian Province, Department of Chemistry ,
University of Xiamen , Xiamen, 361005, P.R. China
Published online: 12 Jan 2011.
To cite this article: Zhuang‐Ping Zhan , Kai Lang , Feng Liu & Li‐ming Hu (2004)
Water Effects on SmI Reductions: A Novel Method for the Synthesis of Alkyl Thiols
2
by SmI ‐Promoted Reductions of Sodium Alkyl Thiosulfates and Alkyl Thiocyanates,
2
Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 34:17, 3203-3208, DOI: 10.1081/SCC-200028622
To link to this article: http://dx.doi.org/10.1081/SCC-200028622
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w
SYNTHETIC COMMUNICATIONS
Vol. 34, No. 17, pp. 3203–3208, 2004
Water Effects on SmI Reductions: A Novel
2
Method for the Synthesis of Alkyl Thiols by
SmI -Promoted Reductions of Sodium Alkyl
Thiosulfates and Alkyl Thiocyanates
2
*
Zhuang-Ping Zhan, Kai Lang, Feng Liu, and Li-ming Hu
The Key Laboratory for Chemical Biology of Fujian Province,
Department of Chemistry, University of Xiamen, Xiamen, P.R. China
ABSTRACT
Water as a cosolvent has significant improving effect on the reductivity of
2
SmI in the reduction of sodium alkyl thiosulfates and alkyl thiocyanates.
A new method for synthesis of alkyl thiols by SmI
has been developed.
2 2
/THF/H O system
Key Words: Alky thiol; Cosolvent; Water; Reduction; Samarium
diiodide.
*
Correspondence: Zhuang-Ping Zhan, The Key Laboratory for Chemical Biology of
Fujian Province, Department of Chemistry, University of Xiamen, Xiamen 361005,
P.R. China; E-mail: zpzhan@xmu.edu.cn.
3
203
DOI: 10.1081/SCC-200028622
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com
Copyright # 2004 by Marcel Dekker, Inc.

3
204
Zhan et al.
Samarium diiodide as a single-electron transfer reagent has become one
of the most popular reducing agents in organic synthesis, because it is easy
to prepare and reasonably soluble in many organic solvents and it cleanly
[
reduces a wide range of functional groups. An important aspect concerning
1]
the reactivity of SmI is that the addition of cosolvents increases the reducing
2
power of SmI . Reactions utilizing SmI -cosolvent mixtures generally
2
2
[2]
proceed at accelerated rates compared to reductions without cosolvents.
The cosolvent HMPA is the most widely utilized; DMPU and 1,1,3,3-tetra-
[3]
methyl urea have also been employed in reactions of SmI2.
Recently, Hilmersson examined water/amine as cosolvents and found
that they accelerate the reduction of ketones, imines, and a, b-unsaturated
[
4]
esters mediated by SmI2. Water/DBU and water/1,1-3,3-tetramethylguani-
dine have been utilized in concert with SmI to accelerate the cyclization of
2
[5]
aryl radicals, but little work has been carried out on water alone as a cosol-
vent. Water has been thought to be served only to protonate basic organo-
[
6]
metallic intermediates. Although addition of water to the SmI /THF system
2
[
3a]
is reported to enhance the reductive potential, that is not supported by a
recent report. To pursue the further proof that water improves the reacting
[7]
ability of SmI , we investigated the reduction of alkyl thiocyanates and sodium
2
alkyl thiosulfates by SmI in aqueous and anhydrous media. The experiments
2
show that water has significant improving effect on the reactivity of SmI and
2
that as a cosolvent, water promoted the conversion from sodium alkyl thiosul-
fates and alkyl thiocyanates not to the reductive intermediate product alkyl
disulfides but all the way to the final reductive product alkyl thiols. Table 1
summarizes the results of all the experiments that we conducted.
In general, to the substrates with and without water, HMPA or absolute
methanol was added 0.1 M SmI in THF (2.2 equiv.), the reaction was
2
a
quenched after 1 min. The reactions were very clean and the product mixtures
a
General procedure: To the N -prepurged substrate (0.5 mmol) was added water
2
(
(
0.3 mL, 16.5 mmol) or HMPA (2.87 mL, 16.5 mmol) or absolute methanol
0.67 mL, 16.5 mmol) or no additive, and then 0.1 M SmI in THF (11 mL,
.1 mmol). The mixture was stirred for 1 min followed by bubbling of air and the sub-
2
1
4
sequent addition of saturated NH Cl. The mixture was extracted with ether and the
1
2 4
extract was washed with saturated brine and dried with Na SO . The H NMR analysis
of the crude products was performed. The crude product was purified by column
chromatography over silica gel (petroleum ether as eluent).

Water Effects on SmI Reductions
2
3205
Table 1. Reduction of RSSO
a
or MeOH.
3
Na and RSCN by SmI
2
with and without water, HMPA,
Reaction
medium
Ratio of
RSH : RSSR
Yield of
f
RSH
b
Entry
Substrate
17SSO
d
1
2
3
4
5
6
7
8
9
n-C
8
H
3
Na
THF
THF
,1 : .99
,1 : .99
,1 : .99
,1 : .99
92 : 8
—
—
d
n-C H SSO Na
1
0
21
3
3
3
d
n-C12
n-C16
H
H
25SSO
Na
Na
THF
THF
—
—
d
33SSO
e
n-C H SSO Na
8
THF/H O
2
78%
82%
86%
86%
—
17
3
e
n-C H SSO Na
THF/H O
2
96 : 4
96 : 4
1
0
21
3
3
3
e
n-C12
n-C16
H
H
25SSO
Na
Na
THF/H
THF/H
2
O
O
e
33SSO
2
95 : 5
d
d
e
n-C H SSO Na
THF/MeOH
THF/MeOH
,1 : .99
,1 : .99
98 : 2
1
2
25
3
3
3
10
11
12
13
14
15
16
17
18
19
20
21
22
n-C16
n-C12
H
H
33SSO
Na
Na
—
25SSO
THF/HMPA
THF/HMPA
c,d
THF
89%
92%
55%
53%
63%
60%
81%
84%
92%
90%
81%
85%
e
n-C H SSO Na
3
99 : 1
1
6
33
n-C
8
H17SCN
81 : 19
86 : 14
c,d
n-C10
n-C H SCN
H
21SCN
THF
THF
c,d
84 : 16
87 : 13
1
2
25
c,d
n-C16
n-C
n-C10
H
33SCN
THF
THF/H
THF/H
e
8
H17SCN
2
O
O
.99 : ,1
.99 : ,1
.99 : ,1
.99 : ,1
92 : 8
e
e
e
H
21SCN
2
n-C H SCN
25
THF/H O
2
1
2
n-C16
n-C12
H
H
33SCN
2
THF/H O
e
e
25SCN
THF/HMPA
THF/HMPA
n-C H SCN
16 33
94 : 6
a
Substrates/SmI /additive ¼ 1 : 2.2 : 33.
2
b
1
Determined by H NMR.
c
About 20%–30% unreacted substrates recovered.
The dark blue in the system still persisted after 1 min.
d
e
The color of blue faded after 1 min.
Isolated yield.
f
only consisted of alkyl disulfides and alkyl thiols. From Table 1, it can be seen
that reduction of sodium alkyl thiosulfates mediated by SmI /THF/H O led
2
2
predominantly to alkyl thiols (entries 5–8) compared to the complete conver-
sion to the coupling products alkyl disulfides in the absence of water (entries
1
–4). Methanol as a cosolvent proved ineffective in promoting the formation
of alkyl thiols from the reduction of sodium alkyl thiosulfates and only alkyl
disulfides were obtained (entries 9–10). Meanwhile, the addition of HMPA as
a cosolvent favored the formation of alkyl thiols (entries 11–12). Similar
results were obtained in the reduction of alkyl thiocyanates in aqueous

3
206
Zhan et al.
media (entries 17–20). However, although alkyl thiocyanate reductions
mediated by SmI in anhydrous conditions predominantly provided alkyl
2
thiols, 20%–30% of starting materials were recovered (entries 13–16).
Also, HMPA can promote the formation of alkyl thiols but it has a little
less promoting effect than water in the reduction of alkyl thiocyantates
(
entries 21–22).
Based on the nature of SmI as a single-electron transfer reagent and the
2
results in our experiment, Sch. 1 illustrates the proposed mechanism for the
reduction of substrates. Note that 1 reacts with SmI in a single-electron trans-
2
fer producing radical species 2. Subsequently, there are two possible scen-
arios: In path I, the formation of disulfides 4 by the coupling of radical 2,
by path II, the reduction of the radical 2 to samarium alkyl thiolate 3. Path I
is competitive with path II. Although 3 can be hydrolyzed into alkyl thiols
5
, this protonation cannot influence the overall rate of path II. Furthermore,
alkyl disulfide 4 cannot be reduced to 3, which is proved in our experiments.
For sodium alkyl thiosulfates, we speculate that path I should be almost exclu-
sive in dry conditions so almost only 4 was found and the amount of alkyl
thiols 5 is trace, and in the presence of water, path II predominates and pro-
vides a majority of 5 and very little of 4. Hence, we believe that water
increases the reducing power of SmI and strongly pushes the process of
2
path II. HMPA plays a role similar to that of water in the reduction of
sodium alkyl thiosulfates. Methanol, however, has no such promoting effect
on the reduction of sodium alkyl thiosulfates and only provided alkyl disul-
fides similar to the results observed in none-additive condition. Based on
the fact that water and HMPA promoted the reduction to final reductive
product alkyl thiols, but methanol didn’t, we proposed that just like HMPA,
Scheme 1.

Water Effects on SmI Reductions
2
3207
it is as an additive, which provides prominent enhancement of reactivity of
SmI , rather than as a proton source that water drives the reduction forward
to alkyl thiols.
2
As for alkyl thiocyanates, when the reactions were quenched within
min, 20%–30% of starting materials were recovered from the reduction
1
without any additives compared to the complete consumption of starting
materials with water or HMPA as additives. The results show that water
and HMPA accelerate these reductions and drive the reactions to completion
instantly. As cosolvents, water and HMPA helped to increase the proportion of
alkyl thiol (entries 17–22). This also indicates that these additives push the
rate of path II.
Our experiments indicated that alkyl disulfides cannot be reduced to
RSSmI by SmI . Deep blue color of the reaction systems in entries 1–4,
2
2
9
plenty of Sm cations. However, alkyl disulfide could not be converted to
–10, and 13–16 still persisted after 1 min, which shows that there are
2
þ
RSSmI , even if reaction time was prolonged. Hence, water and HMPA are
2
essential to the preparation of alkyl thiols using sodium alkyl thiosulfates
and alkyl thiocyanates as starting materials and SmI as reductive reagent.
2
Although HMPA can effectively promote the reactivity of SmI , it’s carcino-
2
genic. Hence, water is more advantageous with regard to environmental
concerns.
The experiments described in this paper show that water can promote
certain classes of SmI reductions and has underrecognized potential as a
2
free and healthy additive for improving SmI reductions. The reduction of
2
sodium alkyl thiosulfates and alkyl thiocyanates mediated by SmI using
2
water as a cosolvent provides a novel method for synthesis of alkyl thiols.
ACKNOWLEDGMENT
This project was sponsored by the Scientific Research Foundation for the
Returned Overseas Chinese Scholars, State Education Ministry.
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Received in Japan February 23, 2004