Trimethylchlorosilane (TMCS) catalyzed efficient reduction of sulfoxides to thioethers using 3-mercaptopropionic acid under mild reaction conditions

Article abstract of DOI:10.1080/10426500490257050

A variety of alkyl and aryl sulfoxides were successfully deoxygenated using 3-mercaptopropionic acid as reducing agent and a catalytic amount of trimethylchlorosilane (10-20 mol%) in CH₃CN at ambient temperature.

Full text of DOI:10.1080/10426500490257050

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Phosphorus, Sulfur, and Silicon and the Related
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TRIMETHYLCHLOROSILANE (TMCS) CATALYZED
EFFICIENT REDUCTION OF SULFOXIDES TO THIOETHERS
USING 3-MERCAPTOPROPIONIC ACID UNDER MILD
REACTION CONDITIONS
Babak Karimi a & Daryoush Zareyee a
a Institute for Advanced Studies in Basic Sciences , Zanjan, Iran
Published online: 11 Aug 2010.
To cite this article: Babak Karimi & Daryoush Zareyee (2004) TRIMETHYLCHLOROSILANE (TMCS) CATALYZED EFFICIENT
REDUCTION OF SULFOXIDES TO THIOETHERS USING 3-MERCAPTOPROPIONIC ACID UNDER MILD REACTION CONDITIONS,
Phosphorus, Sulfur, and Silicon and the Related Elements, 179:1, 77-81, DOI: 10.1080/10426500490257050
To link to this article: http://dx.doi.org/10.1080/10426500490257050
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Phosphorus, Sulfur, and Silicon, 179:77–81, 2003
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Copyright Taylor & Francis Inc.
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500490257050
TRIMETHYLCHLOROSILANE (TMCS) CATALYZED
EFFICIENT REDUCTION OF SULFOXIDES TO
THIOETHERS USING 3-MERCAPTOPROPIONIC ACID
UNDER MILD REACTION CONDITIONS
Babak Karimi and Daryoush Zareyee
Institute for Advanced Studies in Basic Sciences, Zanjan, Iran
(Received April 11, 2003; accepted July 22, 2003)
A variety of alkyl and aryl sulfoxides were successfully deoxygenated
using 3-mercaptopropionic acid as reducing agent and a catalytic
amount of trimethylchlorosilane (10–20 mol%) in CH3CN at ambient
temperature.
Sulfoxides are important intermediates in a variety of synthetic trans-
formations, especially as chiral auxiliary during many asymmetric
syntheses.1 However, in the majority of their synthetic applications,
it is necessary to remove the residue of the sulfoxide moiety from the
target molecules. Such a transformation can be most easily achieved
by a two-step procedure that involves the deoxygenation of sulfoxides
to the corresponding sulfides followed by further reductive desulfur-
ization by treatment with either Raney nickel or dissolving metal sys-
tems such as lithium in liquid ammonia. A survey of the literature
reveals that though several methods have been reported for the re-
duction of sulfoxides,2,3 there still remain the important problems of
reaction, i.e., many of them need rather drastic conditions, long reac-
tion times,3i or stoichiometric amounts of expensive reagents.3j,k Among
the reported protocols, sulfur compounds such as thiols,4 sulfides,5
disulfides,6 thionyl chloride,7 elemental sulfur,8 and 1,3-dithianes,9
have been used for the conversion of sulfoxides to thioethers. However,
many of these methods suffer from drawbacks such as long reaction
The authors thank the Institute for Advanced Studies in Basic Sciences and the Re-
search Council for support of this work.
Address correspondence to Babak Karimi, Department of Chemistry, Institute for
Advanced Studies in Basic Science, PO Box 45195-159, GavaZang, Zanjan, Iran.
77

78
B. Karimi and D. Zareyee
time,4–6 harsh acidic conditions,4,7 high temperature,8 or difficult work-
up procedures.4,9 Therefore, there is still a demand for the development
of a new efficient method for this transformation using inexpensive and
common laboratory reagents.
RESULTS AND DISCUSSION
Very recently we discovered that TMCS effectively catalyzes oxidative
coupling of a variety of structurally diverse thiols to the corresponding
disulfides in the presence of DMSO as the final oxidant.10 Along this
line, we have found that this catalyst also efficiently accelerates the
reduction of sulfoxides using a thiol. Thiols that were utilized in this
study are thiophenol, butyl mercaptane, thiosalicylic acid (2-TSA), and
3-mecaptopropionic acid (3-MPA). We first examined the reduction of
phenylmethyl sulfoxide (PMS) using the thiols in the presence of TMCS
as catalyst at room temperature. Among all of the above-mentioned thi-
ols, we chose 3-mercaptopropionic acid in the subsequent studies owing
to its faster and cleaner reaction. Moreover, the presence of a CO2H
group in this molecule makes an easier separation of the by-product
disulfide during the work-up stage through a simple aqueous NaOH
washing of the reaction mixture. On the other hand, though 2-TSA has
also the same property as 3-MPA; however, the latter is the superior
reducing agent than the former from an atom economic point of view.
among different solvents such as CH3CN CH2CI2, CHCl3, and THF
that we used for the reduction of PMS as a model substrate, CH3CN
turned out to be the most suitable one. It is also worth mentioning that
in CH2Cl2 and CHCL3 the reactions are very sluggish. The optimum
ratios of the reacting species were also studied by using TMCS as cat-
alysts and PMS as substrate. The optimum molar ratio was found to
be 1: 2.1: 0.1, for PMS:3-MPA:TMCS, respectively, at room temperature
(Scheme 1, Table I, entries 1, 2).11
SCHEME 1
In a similar way, we have also discovered that the same ratios work
well for less hindered arylalkyl- and dialkyl sulfoxides. Inspection of
the data, which are summarized in Table I, clearly shows that various

Reduction of Sulfoxides
79
TABLE I TMCS Catalyzed Deoxygenation of Sulfoxides to Thioethers
Using 3-Mercaptopropionic Acid
Time
(h)
Subst./3-MPA/
Catalyst
Yield
(%)a
Entry
R1
R2
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
Ph
Ph
Ph
Ph
PhCH2
Ph
Ph
Bu
Ph
Ph
Me
Et
Bu
PhCH2CH2
PhCH2
PhCH2
Allyl
Bu
sec-Bu
i-Pr
1
3
3
0.5
1
0.5
3
0.5
10
16
18
40
42
48
48
48
1:2.1:0.1
1:2.1:0.1
1:2.1:0.1
1:2.1:0.1
1:2.1:0.1
1:2.1:0.1
1:2.1:0.1
1:2.1:0.1
1:2.2:0.2
1:2.2:0.2
1:2.2:0.2
1:2.2:0.2
1:2.2:0.2
1:2.2:0.1
1:2.2:0.1
1:2.2:0.1
93
97
97
94
95
93
93
96
90
90
70
95
90
58
60
40
3-MeC6H4
Ph
Ph
i-Pr
c-C5H9
c-C6H11
Ph
4-MeC6H4
Ph
Ph
4-MeC6H4
p-NO2C6H4
aIsolated yields.
types of both dialkyl- and arylalkyl including benzylic and allylic sul-
foxides, are efficiently deoxygenated to their sulfides in excellent yields
under similar reaction conditions (Table I, entries 3–16). Efficient de-
oxygenation of dibenzyl-, benzyl phenyl-, and allylphenyl sulfoxides to
the corresponding thioethers in excellent yields without the cleavage
of sensitive C S bond, shows the usefulenss of the presented method
(Table I entries 9–14). On the other hand, it was found that in the case of
substrates bearing at least one bulky group, larger amounts of 3-MPA
(2.2 equiv.) and the catalysts (0.2 equiv.) are required for completion
of the reactions (Table I, entries 17–32). However, substitution of one
nitro group in the case of p-nitrophenyl phenyl sulfoxide gave some-
what lower yields together with the formation of unidentified products
(Table I, entries 31, 32). This is presumably due to the reaction of the
3-MPA/TMCS system with the nitro group.
The exact mechanism of this reaction is not clear. However, a
pausible explanation for this is that at the first step of the reaction
TMSCl reacts with the sulfoxide to produce an activated species 1,
which in turn reacts with the thiol (3-mercaptopropionic acid) to give
the intermediate 2 with concomitant release of HCl and hexamethyl-
disiloxane, Then, a rapid reaction of 2 with a second molecule of the
thiol leads to disulfide and evolution of dimethyl sulfide. The HCl then
re-enters the reaction cycle and acts as TMCS (Scheme 2). In order to

80
B. Karimi and D. Zareyee
inspect the correctness of this opinion, we examined the oxidation of
thiophenol using DMSO (3 equiv.) in the presence of 10 mol% TMSCl
and pyridine (2 equiv.). Interestingly, the deoxygenation reaction was
completely retarded in this case.
SCHEME 2
In conclusion, we have demonstrated that TMCS is an excellent cat-
alysts for the convenient deoxygenation of various types of sulfoxides
using 3-mercaptopropionic acid (3-MPA). The present protocol is supe-
rior to most of the existing thiol-based sulfoxide reduction methods with
regard to its very simple work-up procedure. Moreover, in the present
procedure, the reaction conditions are quiet mild accompanied with rea-
sonable reaction times.
EXPERIMENTAL
General Procedure for Deoxygenation of Sulfoxides
To a solution of Sulfoxide (2 mmol) and 3-MPA (4.2–4.4 mmol) in dry
CH3CN (10 mL), TMCS (0.2–0.4 mmol) was added, and the resulting
solution was stirred at room temperature. After completion of the reac-
tion (TLC), an aqueous solution of NaOH (5%, 25 mL) was added and
the mixture was extracted with Et2O (3 × 20 mL). The organic extracts
were washed successively with NaOH (5%, 15 mL), water (2 × 15 mL)
and dried over anhydrous Na2SO4. Evaporation of the solvent under
reduced pressure gave almost pure products. Further purification was
performed by vacuum distillation or re-crystallization in an appropriate
solvent to afford pure thioethers (Table I).

Reduction of Sulfoxides
81
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