Reduction of sulfoxides with boranes catalyzed by MoO2Cl2

Article abstract of DOI:10.1016/j.tetlet.2007.10.106

The first example of an organic reduction with boranes catalyzed by a high valent oxo-complex is reported. The systems catecholborane/MoO₂Cl₂(H₂O)₂ (5 mol %) and BH₃·THF/MoO₂Cl₂ (5 mol %) proved to be very efficient for the reduction of sulfoxides to the corresponding sulfides in excellent yields.

Full text of DOI:10.1016/j.tetlet.2007.10.106

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Tetrahedron Letters 48 (2007) 9176–9179
Reduction of sulfoxides with boranes catalyzed by MoO2Cl2
Ana C. Fernandes* and Carlos C. Romao
˜
ˆ
Instituto de Tecnologia Quı´mica e Biolo´gica da Universidade Nova de Lisboa, Quinta do Marques, EAN,
Apt 127, 2781-901 Oeiras, Portugal
Received 6 September 2007; revised 17 October 2007; accepted 19 October 2007
Available online 25 October 2007
Abstract—The first example of an organic reduction with boranes catalyzed by a high valent oxo-complex is reported. The systems
catecholborane/MoO2Cl2(H2O)2 (5 mol %) and BH3ÆTHF/MoO2Cl2 (5 mol %) proved to be very efficient for the reduction of sulf-
oxides to the corresponding sulfides in excellent yields.
Ó 2007 Elsevier Ltd. All rights reserved.
High valent dioxomolybdenum(VI) complexes are
known for their abilities to catalyze oxygen-transfer
reactions to sulfides, phosphines and olefins.1–5
Recently, we have demonstrated the reversal of the role
of MoO2Cl2 (1) by showing its ability to catalyze organ-
ic reductions.6–10 In our previous works, we have shown
that MoO2Cl2 activates the Si–H bond of different
silanes such as PhSiH3, Ph(Me)2SiH, Et3SiH and PMHS
and that the system silane/MoO2Cl2 is very efficient for
the hydrosilylation of aldehydes and ketones, yielding
the corresponding silyl ethers6 and for the reduction of
imines,7 amides,8 esters,9 sulfoxides10 and pyridine
N-oxides10 to the corresponding amines, alcohols,
sulfides and pyridines (see Scheme 1).
lack of chemoselectivity or harsh conditions, a search
for new catalysts remains justifiable.
In the literature, there are only few examples of the
reduction of sulfoxides with boron reagents such as the-
xylchloroborane-methyl sulfide,19 dichloroborane20 and
tribromoborane,21 but the difficulty in handling these
highly reactive reagents makes their use somewhat
impracticable.
Catecholborane (HBcat) is one of the most versatile bor-
on hydride reagents available to the synthetic chemist.
This borane is stable in dry air and may be stored un-
changed for over a year at 0 °C, in contrast to certain
other substituted boranes.
Our interest in the study of the catalytic activity of this
high valent oxo-complex led us to explore the activation
of B–H bond of boranes and the use of the catalytic
system borane/MoO2Cl2 in organic reductions, parti-
cularly, in the reduction of sulfoxides.
Westcott16 described the reduction of sulfoxides with
3 equiv of HBcat at room temperature in quantitative
yields. However, with aromatic substrates these reduc-
tions required longer reaction times, for example, the
deoxygenation of phenyl sulfoxide or 4-chlorophenyl
sulfoxide required more than 500 h. These authors also
described the acceleration of this reduction upon the
addition of rhodium catalysts such as RhCl(PPh3)3
and Rh(acac)(dppe).
The deoxygenation of sulfoxides to the corresponding
sulfides is an important organic and biological reaction.
Over the years, several methods have been developed to
reduce sulfoxides.11–18 However, since many of these
transformations are limited by side reactions, low yields,
In this Letter, we investigated the activation of boranes
by dioxomolybdenum dichloride and the deoxygenation
of aromatic sulfoxides with the systems HBcat/
MoO2Cl2(H2O)2 and BH3ÆTHF/MoO2Cl2.
Keywords: Reduction; Sulfoxides; Dioxomolybdenum dichloride;
Boranes; B–H Activation.
*
The reduction of sulfoxides was initially studied with
2 equiv of HBcat in THF in the presence of 5 mol %
Corresponding author. Tel.: +351 214469758; fax: +351 214411277;
e-mail: anacris@itqb.unl.pt
0040-4039/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.10.106

A. C. Fernandes, C. C. Roma˜o / Tetrahedron Letters 48 (2007) 9176–9179
9177
Scheme 1. Organic reductions with the system silane/MoO2Cl2.
of a diethyl ether solution of MoO2Cl2(H2O)2, at reflux
temperature and under air atmosphere, as summarized
in Table 1.22 These reductions were very fast (15–
35 min), and the corresponding sulfides were obtained
in excellent yields (Table 1, entries 1, 3, 5, 7, 9 and 11).
To verify if the catalyst has an active role in the deoxy-
genation, all the reactions were carried out without cat-
alyst with the addition of 2 equiv of HBcat. Under these
conditions, the yields of sulfides were either very low or
the reactions did not occur.
When the reductions were carried out with 1.2 equiv of
HBcat, the sulfides were also obtained in low yields.
At room temperature, the reactions required signifi-
cantly longer reaction times (Table 1, entries 2, 4, 6, 8,
10 and 12).
Table 1. Reduction of sulfoxides with the system HBcat/MoO2Cl2-
(H2O)2
a
This novel method is compatible with halo and ester
groups (Table 1, entries 3–6, 9 and 10). However, the
analysis of the H NMR spectrum of the reaction mix-
Entry Sulfoxide
Temp Time
(°C)
Yieldb
(%)
1
ture obtained in the reduction of the phenyl vinyl sulf-
oxide with the system HBcat/MoO2Cl2(H2O)2 showed
that the double bond was affected.
1
2
67
rt
25 min 93
16 h
91
The reusability of MoO2Cl2(H2O)2 was evaluated using
4-chlorophenyl sulfoxide as test substrate. We carried
out five successive reactions by sequential addition of
fresh substrate and HBcat to the reaction mixture. The
catalytic activity of MoO2Cl2(H2O)2 was followed by
1H NMR, and after each 30 min at reflux temperature,
we observed the complete reduction of sulfoxide. This
result showed that the catalytic activity of MoO2Cl2(H2O)2
did not decrease with successive uses.
3
4
67
rt
30 min 95
16 h 91
5
6
67
rt
30 min 92
16 h 89
7
8
67
rt
30 min 93
16 h 89
We also investigated the reduction of sulfoxides with the
system BH3ÆTHF/MoO2Cl2 in refluxing THF under
nitrogen atmosphere.23 From the analysis of Table 2,
we concluded that the system BH3ÆTHF/MoO2Cl2 is
also very efficient for the reduction of sulfoxides and
these results are very similar to those obtained with
the system HBcat/MoO2Cl2(H2O)2. This catalytic sys-
tem is compatible with halo and ester substituents
(Table 2, entries 3–6, 9 and 10).
9
10
67
rt
35 min 89
16 h 85
11
12
67
rt
15 min 94
16 h 88
a All reactions were carried out with 1.0 mmol of sulfoxide, 2 mmol of
HBcat and 5 mol % of MoO2Cl2(H2O)2.
b Isolated yield.
The use of HBcat/MoO2Cl2(H2O)2 has some practical
advantages associated with the borane and the catalyst.

9178
A. C. Fernandes, C. C. Roma˜o / Tetrahedron Letters 48 (2007) 9176–9179
a
Table 2. Reduction of sulfoxides with the system BH3ÆTHF/MoO2Cl2
4-fluorphenyl methyl sulfone with BH3ÆTHF/MoO2Cl2
or HBcat/MoO2Cl2(H2O)2 resulted in the recovery of
the starting material.
The analysis of Tables 1 and 2 shows that the presence
of MoO2Cl2 is essential for the efficient reduction of
sulfoxides. We suggest that the mechanism for the deox-
ygenation of sulfoxide with the catalytic system HBcat/
MoO2Cl2(H2O)2 starts with the activation of the sulfox-
ide by the oxygen coordination to the molybdenum,
yielding the complex MoO2Cl2(sulfoxide)2. This com-
plex weakens the S–O bond and renders the sulfur atom
more susceptible to the reduction.
Entry Sulfoxide
Temp Time
(°C)
Yieldb
(%)
1
2
67
rt
25 min 91
16 h
88
3
4
67
rt
30 min 92
16 h 89
As mentioned above, Si–H bonds are activated by
Mo@O and other Re@O complexes leading to hydro-
silylation and other reduction reactions. In the case of
MoO2Cl2, computational DFT studies do not distin-
guish clearly between the so-called [2+2] and [3+2] addi-
tion modes, depicted in Scheme 2. No such studies have
yet been carried out for the interaction between boranes
and MoO2Cl2. However, the Lewis-acidic character of
the boranes will most likely assist B–H bond breaking
on this complex via the coordination of one oxo ligand
to the vacant orbital on the boron. Such process will be
even more favoured in a sulfoxide complex like (R2SO)2-
MoO2Cl2 (4), where the Mo@O bond is weakened by
the electronic competition from the trans sulfoxide
ligands. Of course, under catalytic reaction conditions
where a vast excess of the sulfoxide is present relative
to the MoO2Cl2, a sulfoxide like 4 is almost inevitably
present at the outset of the reaction.
5
6
67
rt
25 min 90
16 h 87
7
8
67
rt
30 min 91
16 h 88
9
10
67
rt
35 min 88
16 h 85
11
12
67
rt
10 min 93
16 h 87
a All reactions were carried out with 1.0 mmol of sulfoxide, 2.0 mmol
of BH3ÆTHF and 5 mol % of MoO2Cl2.
b Isolated yield.
With this in mind, Scheme 2 depicts our proposed reac-
tion mechanism for the catalytic deoxygenation of sulf-
oxides by HBcat.
Catecholborane is more stable and easily handled than
BH3ÆTHF, and the complex MoO2Cl2(H2O)2 is easily
and inexpensively prepared by extraction from a
hydrochloric acid solution of Na2MoO4 with diethyl
ether,24 in contrast to the difficult preparation of
MoO2Cl2. Other important advantage is related to the
air stability of the ether solution of MoO2Cl2(H2O)2,
which enables the reaction to be carried out under air
atmosphere.
Intermediates 3a and 3b result from the [2+2] addition
of the B–H bond to one Mo@O bond while 3c repre-
sents the result of the [3+2] addition. While they are
readily interconvertible for the MoO2Cl2/H–SiR3 addi-
tion,25 we cannot say the same for the present situation.
However, HOBcat elimination would, in both cases,
lead to the same species 4. This Mo(IV) complex is very
well known to cleave the S@O bond26 leading to the
final thioether R2S and reforming the initial species 2.
The HOBcat can react with another molecule of HBcat
giving catBOBcat and hydrogen. The formation of
As observed in our previous catalytic system, silane/
MoO2Cl2, attempted reduction of phenyl sulfone and
Scheme 2.

A. C. Fernandes, C. C. Roma˜o / Tetrahedron Letters 48 (2007) 9176–9179
9179
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Catalyzed reactions with boranes reported in the litera-
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´
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In summary, we have developed a novel method for the
reduction of sulfoxides using the systems HBcat/
MoO2Cl2(H2O)2 and BH3ÆTHF/MoO2Cl2 in excellent
yields. This work showed that MoO2Cl2 activates the
B–H bond and can be used as catalyst for reductions
with boranes. These results suggest several future appli-
cations of the system borane/MoO2Cl2, since reductions
with boranes are among the most important synthetic
methodologies in organic chemistry.
22. In a typical experiment, to the mixture of sulfoxide
(1.0 mmol) and the diethyl ether solution of
MoO2Cl2(H2O)2 (5 mol %) the solution of catecholborane
was added in THF (2.0 mmol). The reaction mixture was
stirred under air atmosphere (the temperature and the
reaction times are indicated in Table 1) and the progress of
The scope of these novel catalytic systems is now under
investigation in our group.
1
the reaction was monitored by TLC and H NMR. Upon
completion, the reaction mixture was evaporated and
purified by silica gel column chromatography with the
appropriate mixture of n-hexane and ethyl acetate to
afford the sulfides, which are all known compounds.
23. In a typical experiment, to a solution of MoO2Cl2
(5 mol %) in THF (3 ml) was added the sulfoxide
(1.0 mmol) and the solution of BH3ÆTHF in THF
(2.0 mmol). The reaction mixture was stirred under
nitrogen atmosphere (the temperature and the reaction
times are indicated in Table 2) and the progress of the
reaction was monitored by TLC and 1H NMR. Upon
completion, the reaction mixture was evaporated and
purified by silica gel column chromatography with the
appropriate mixture of n-hexane and ethyl acetate to
afford the sulfides, which are all known compounds.
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