Highly efficient and chemoselective reduction of sulfoxides using the system silane/oxo-rhenium complexes

Article abstract of DOI:10.1016/j.tetlet.2009.09.121

This work reports a novel method for the reduction of sulfoxides with silanes catalyzed by high valent oxo-rhenium(V) and (VII) complexes. The catalytic system PhSiH₃/ReIO₂(PPh₃)₂ (1 mol %) proved to be highly efficient for the reduction of a wide range of sulfoxides in excellent yields under mild conditions. This novel methodology is also highly chemoselective, tolerating several functional groups such as -CHO, -CO₂R, -Cl, -NO₂, and double or triple bonds.

Full text of DOI:10.1016/j.tetlet.2009.09.121

Tetrahedron Letters 50 (2009) 6872–6876
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Highly efficient and chemoselective reduction of sulfoxides using
the system silane/oxo-rhenium complexes
*
Sara C. A. Sousa, Ana C. Fernandes
Centro de Química Estrutural, Complexo I, Instituto Superior Técnico, Av. Rovisco Pais, 1049-001 Lisboa, Portugal
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 20 July 2009
Revised 18 September 2009
Accepted 22 September 2009
Available online 25 September 2009
This work reports a novel method for the reduction of sulfoxides with silanes catalyzed by high valent
oxo-rhenium(V) and (VII) complexes. The catalytic system PhSiH3/ReIO2(PPh3)2 (1 mol %) proved to be
highly efficient for the reduction of a wide range of sulfoxides in excellent yields under mild conditions.
This novel methodology is also highly chemoselective, tolerating several functional groups such as –CHO,
–CO2R, –Cl, –NO2, and double or triple bonds.
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
Sulfoxides
Reduction
Oxo-rhenium complexes
Silanes
The reduction of sulfoxides to the corresponding sulfides is an
important reaction that has found utility in organic synthesis and
in biochemical reactions. Over the years, several methods have
been developed to reduce sulfoxides,1–25 however, many of these
are limited by side reactions, low yields, lack of chemoselectivity,
or harsh conditions. For example, the use of hydrogen halides is
somewhat restricted with acid-sensitive substrates, the reductions
with the strong hydride systems LiAlH4–TiCl4 and NaBH4–CoCl2 are
incompatible with several functional groups, and the reactions
with phosphorous reagents, in most cases, require elevated tem-
perature and/or prolonged reaction times. Due to the high impor-
tance of selective reduction of sulfoxides, the search for
alternative efficient and highly chemoselective methods remains
an important target in organic synthesis.
Recently, we have demonstrated that high valent oxo-molybde-
num and -rhenium complexes were excellent catalysts for X–H
bond activation and for organic reactions.26–32 We also reported
the deoxygenation of sulfoxides with silanes33 and boranes34 cata-
lyzed by MoO2Cl2 in excellent yields.
In this work we have studied the reduction of sulfoxides with
silanes catalyzed by a series of high valent oxo-rhenium(V) and
(VII) complexes.
1–3). The progress of the reactions was monitored by thin layer
chromatography and by 1H NMR.
Among the oxo-rhenium complexes tested, ReIO2(PPh3)2 was
the most effective catalyst, reducing completely the 4-chloro-
phenyl sulfoxide in 5 min in THF at room temperature (Table 1, en-
try 1). The complex ReOCl3(PPh3)2 was also an excellent catalyst
for this reaction, giving the sulfide in 100% conversion after
15 min (Table 1, entry 2). The deoxygenations carried out with
Re2O7, MTO, and ReOCl3(dppm) also completely reduced the sulf-
oxide, but the reactions were much slower, taking 16–24 h (Table
1, entries 3–5). Finally, in the absence of catalyst no product was
detected after 1 day (Table 1, entry 6).
The reduction of 4-chlorophenyl sulfoxide performed with the
silanes PhSiH3, PMHS, PhMe2SiH, Et3SiH, and Ph3SiH (100 mol %),
catalyzed by 1 mol % of ReIO2(PPh3)2, showed that PhSiH3 was
the most efficient reagent, reducing completely the 4-chlorophenyl
sulfoxide in 5 min in THF at room temperature (Table 2, entry 1).
However, using only 33 mol % of PhSiH3, the reaction afforded
the sulfide in only 50% conversion after 24 h (Table 2, entry 2).
The deoxygenation carried out with polymethylhydrosiloxane
(PMHS) also gave the sulfide in 100% conversion, but the reaction
required 15 h (Table 2, entry 3). In contrast, the reactions per-
formed with PhMe2SiH, Et3SiH, and Ph3SiH at room temperature
afforded the sulfide in moderate conversions (Table 2, entries 4,
6, and 8). At reflux temperature, the reduction with PhMe2SiH is
completed after 24 h (Table 2, entry 5).
In order to optimize the reaction conditions, firstly we studied
the reduction of the test substrate 4-chlorophenyl sulfoxide cata-
lyzed by 1 mol % of high valent oxo-rhenium complexes Re-
IO2(PPh3)2, ReOCl3(PPh3)2, Re2O7, MTO, and ReOCl3(dppm), with
different silanes (100 mol %), and using several solvents (Tables
This method was also studied with different solvents. Tetrahy-
drofuran was the best solvent for the reduction of 4-chlorophenyl
sulfoxide with PhSiH3 catalyzed by ReIO2(PPh3)2, affording the
product in 100% conversion in only 5 min at room temperature
* Corresponding author. Tel.: +351 218419388; fax: +351 218464457.
E-mail address: anacristinafernandes@ist.utl.pt (A.C. Fernandes).
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.09.121

S. C. A. Sousa, A. C. Fernandes / Tetrahedron Letters 50 (2009) 6872–6876
6873
Table 1
Reduction of 4-chlorophenyl sulfoxide with phenylsilane catalyzed by high valent oxo-rhenium complexesa
Entry
Catalyst
Time
Conversionb (%)
1
2
3
4
5
6
ReIO2(PPh3)2
ReOCl3(PPh3)2
Re2O7
MTO
ReOCl3(dppm)
Without catalyst
5 min
15 min
16 h
22 h
24 h
100
100
100
100
100
No reaction
24 h
a
The reactions were carried out with 0.5 mmol of sulfoxide, 100 mol % of silane and 1 mol % of catalyst.
Conversion was determined by 1H NMR.
b
Table 2
a
Reduction of 4-chlorophenyl sulfoxide with different silanes catalyzed by ReIO2(PPh3)2
Entry
Silane
Silane (mol %)
Temperature
Time
Conversionb (%)
1
2
3
4
5
6
7
8
PhSiH3
PhSiH3
PMHS
PhMe2SiH
PhMe2SiH
Et3SiH
100
33
rt
rt
rt
rt
Reflux
rt
Reflux
rt
5 min
24 h
15 h
24 h
24 h
24 h
24 h
24 h
100
50
100
50
100
30
40
0.30
100
100
100
100
100
Et3SiH
Ph3SiH
47
a
All reactions were carried out with 0.5 mmol of sulfoxide and 1 mol % of ReIO2(PPh3)2.
Conversion was determined by 1H NMR.
b
Table 3
Reduction of 4-chlorophenyl sulfoxide in different solventsa
Entry
Solvent
Time
Conversionb (%)
1
2
3
4
5
6
THF
5 min
15 min
25 min
1 h 30 min
7 h 30 min
24 h
100
100
100
100
100
10
CH2Cl2
Toluene
CHCl3
Benzene
CH3CN
a
All reactions were carried out with 0.5 mmol of sulfoxide, 100 mol % of PhSiH3, 1 mol % of ReIO2(PPh3)2.
Conversion was determined by 1H NMR.
b
(Table 3, entry 1). Dichloromethane, chloroform, and toluene were
also good solvents, giving the sulfide within 15–90 min (Table 3,
entries 2–4). In contrast, the complete deoxygenation of 4-chloro-
phenyl sulfoxide performed in benzene required several hours (Ta-
ble 3, entry 5) and in acetonitrile only 10% conversion of product
was obtained after 1 day (Table 3, entry 6).
atmosphere. As shown in Table 4, this methodology is equally
applicable to diaryl, aryl alkyl, and dialkyl sulfoxides. The efficiency
of the catalytic system PhSiH3/ReIO2(PPh3)2 is also demonstrated
by the good yield obtained in the reduction of dibenzyl sulfoxide
(Table 4, entry 4), since several methods fail completely with this
substrate or only provide poor yields.
To assess the scope and limitations of this novel methodology,
we carried out the reduction of several sulfoxides bearing other
potentially labile functional groups with the catalytic system
PhSiH3/ReIO2(PPh3)2 (1 mol %).35 These reactions were performed
with 1.0 mmol of substrate in THF at room temperature under air
The high chemoselectivity of this method is evident from
entries 1, 6–11 of Table 4, which show that –Cl, –NO2, –CO2R,
–CHO, and double or triple bond functionalities are unaffected un-
der the reaction conditions. Remarkable is the chemoselective
reduction of the sulfinyl group observed in the substrate of entry

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S. C. A. Sousa, A. C. Fernandes / Tetrahedron Letters 50 (2009) 6872–6876
Table 4
a
Reduction of sulfoxides with the catalytic system PhSiH3/ReIO2(PPh3)2
Entry
1
Substrate
Product
Time
Yieldb (%)
30 min
96
2
20 min
97
3
4
25 min
30 min
95
83
5
6
10 min
15 min
91
90
7
8
9
25 min
94
92c
81
2 h 15 min
35 min
10
11
24 h
40 min
71
80d
12
15 min
100e
a
b
c
The reactions were carried out with 1.0 mmol of sulfoxide, 100 mol % of PhSiH3, 1 mol % of ReIO2(PPh3)2, and 3 mL of the solvent.
Isolated yields.
This reaction was carried out adding slowly 33 mol % of PhSiH3.
This reaction was carried out at reflux temperature.
d
e
Conversion was determined by 1H NMR.

S. C. A. Sousa, A. C. Fernandes / Tetrahedron Letters 50 (2009) 6872–6876
6875
Scheme 1. Reduction of omeprazole using the catalytic system PhSiH3/oxo-rhenium complexes.
8, adding slowly 33 mol % of PhSiH3, in which the carbonyl group
remained intact. Using 100 mol % of this silane, we observed the
reduction of both functional groups.
This novel methodology was also applied to the reduction of
anti-ulcer drug omeprazole (Scheme 1). The reduction was per-
formed with the catalytic systems PhSiH3 (200 mol %)/Re-
IO2(PPh3)2 (5 mol %) and PhSiH3 (100 mol %)/MTO (5 mol %) in
dichloromethane at room temperature under air atmosphere,
affording the corresponding sulfide in moderate yields.
Comparing this novel method with our previous catalytic sys-
tem PhSiH3/MoO2Cl2 (5 mol %),33 we conclude that the reactions
performed with the system PhSiH3/ReIO2(PPh3)2 (1 mol %) are
much faster and can be carried out at room temperature under
air atmosphere, using less amount of catalyst.
Mechanistically, we suggest the initial substitution of the phos-
phine by the sulfoxides, affording the complex ReIO2(R2SO)2 (see
Scheme 2). In the second step, the hydride species (R2SO)2(O)IRe
(H)OSiR3 is formed as a result of the addition of the Si–H bond of
the silane to one of the oxo-rhenium bonds. This reaction is similar
to the formation of the hydride (PPh3)2(O)IRe(H)OSiMe2Ph re-
ported by Toste and co-workers,36,37 reacting ReIO2(PPh3)2 with
PhMe2SiH.
In the next step, a molecule of HOSiR3 is eliminated, giving the
monoxo-rhenium(III) complex ReI(O)(R2SO)2. This complex can
easily rearrange to liberate the sulfide R2S and reform the species
ReIO2(R2SO). Finally, the latter will be stabilized by the entry of an-
other molecule of sulfoxide regenerating the dioxo-rhenium com-
plex ReIO2(R2SO)2.
In conclusion, we have demonstrated that oxo-rhenium(V) and
(VII) complexes are excellent catalysts for the reduction of several
sulfoxides with silanes. This novel methodology is highly chemose-
lective, tolerating a large range of functional groups such as –CHO,
–CO2R, –Cl, –NO2, and double or triple bonds. This method was ap-
plied in the deoxygenation of aromatic and aliphatic sulfoxides and
also in the reduction of the anti-ulcer drug omeprazole.
Other advantages of this procedure include high isolated yields,
low catalyst loading (1 mol %), fast and clean reactions, mild reac-
tion conditions, simple experimental operation, stability of the cat-
alysts toward air and moisture,38 allowing the reaction to be
carried out under air atmosphere.
We believe that this novel methodology will represent a useful
and efficient alternative to the traditional methods for the reduc-
tion of sulfoxides, especially, in natural products and pharmaceuti-
cal synthesis, which require mild conditions, selectivity, and
functional group tolerance.
Acknowledgments
This research was supported by FCT through project PTDC/QUI/
71741/2006. S.C. Sousa thanks FCT for grant. The Authors thank the
Portuguese NMR Network (IST-UTL Center) for providing access to
the NMR facilities and the Portuguese MS Network (IST Node) for
the ESI measurements.
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