First enantioselective iron-porphyrin-catalyzed sulfide oxidation with aqueous hydrogen peroxide

Article abstract of DOI:10.1039/c1cc11675d

The asymmetric oxidation of sulfides by H₂O₂ to give optically active sulfoxides (ee up to 90%) was carried out in methanol and water using chiral water-soluble iron porphyrins as catalysts.

Full text of DOI:10.1039/c1cc11675d

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COMMUNICATION
First enantioselective iron-porphyrin-catalyzed sulfide oxidation with
aqueous hydrogen peroxidewz
Paul Le Maux and Gerard Simonneaux*
´
Received 23rd March 2011, Accepted 21st April 2011
DOI: 10.1039/c1cc11675d
The asymmetric oxidation of sulfides by H O to give optically
2
2
active sulfoxides (ee up to 90%) was carried out in methanol and
water using chiral water-soluble iron porphyrins as catalysts.
The selective oxidation of sulfides to sulfoxides has attracted
much attention over the years after the pioneering work
Scheme 1 Oxidation of sulfides by hydrogen peroxide.
1
of Kagan et al. and Modena et al. Sulfoxides constitute
2
the catalyst destruction by hydroxyl radicals readily released
by homolytic H O decomposition.
2
2
chiral synthons in organic synthesis for the preparation of
3
biologically active compounds. They also serve as chiral
A chiral water-soluble iron Halterman porphyrin, due to the
presence of four sulfonate groups at the para-position,
was previously reported by our group and used for chiral
4
auxiliaries. Among all methods described so far, the
5
asymmetric oxidation of sulfides by metal catalysts is one of
3
the most attractive routes to optically active sulfoxides,
2
7
,4,6
recognition of amino acids and catalytic carbene transfer in
2
8
water. Herein we report its use for catalytic asymmetric
sulfoxidation in polar solvents (water or methanol) by 35%
aqueous hydrogen peroxide (Scheme 1).
and quite recently, even nontoxic and inexpensive iron
complexes have been developed successfully, using hydrogen
7
–10
peroxide as an oxidant.
Metalloporphyrins, widely studied
The starting point of the work described here was the
introduction of four sulfonate groups into an optically active
porphyrin with the aim of preparing water soluble porphyrins.
as models of hemes or cytochrome P-450, have been known to
exhibit the catalytic activity for monooxygenation, proceeding
via the formation of a high valency metal–oxygen complex
intermediate. However the asymmetric oxidation of sulfides
catalysed by chiral iron porphyrin is still unprecedented when
the oxidant is hydrogen peroxide. This is quite surprising
since the first metalloporphyrin-catalyzed oxygenation with
hydrogen peroxide reported the formation of sulfoxide from
We choose a C -symmetric group which contains two
2
norbornane groups fused to the central benzene ring, previously
29
reported by Halterman and Jan. The resulting metallo-
2
porphyrin after iron insertion (Fig. 1) is an electron-rich
8
iron(III) porphyrin which may tend to favour O–O homolysis
2
of hydroperoxide. Since it has been reported many times
2
30,31
1
1
sulfide and the enzymatic oxidation of sulfides to optically
1
2–15
that solvent alcohols coordinate to the iron(III) porphyrin to
facilitate the heterolytic cleavage of the oxygen–oxygen bond,
we first use methanol as a solvent to favour the heterolytic
cleavage.
active sulfoxides catalysed by peroxidases
4
proteins have been reported.
and other heme
There are previously reported asymmetric homogeneous
iron-porphyrin-catalyzed sulfide oxidations in the literature
1
6–21
Oxidation of methyl phenyl sulfide was first examined with
this solvent at room temperature and lower temperatures.
The reaction is fast at room temperature though slight
over-oxidation to sulfones was observed (5%) and the
with iodosylbenzene as an oxidant.
systems have been studied to get information on the
Many iron porphyrin–
2 2
H O
2
2–25
mechanism and nature of the active intermediates.
The
two main obstacles when using hydrogen peroxide are the
high activity of many first-row transition metals in its
2
decomposition thereof, the so-called catalase reaction and
6
Inge´nierie Chimique et Mole´cules pour le Vivant, UMR CNRS 6226,
Campus de Beaulieu, Universite´ de Rennes 1, 35042 Rennes, France.
E-mail: gerard.simonneaux@univ-rennes1.fr;
Fax: +33 (0)223235637; Tel: +33 (0)223236285
w Electronic supplementary information (ESI) available: Experimental
details, chromatograms and visible spectra. See DOI: 10.1039/
c1cc11675d
zbi Dr t he dd iac ya .ted to Professor Didier Astruc on the occasion of his 65th
Fig. 1 Structure of the iron catalysts.
This journal is c The Royal Society of Chemistry 2011
Chem. Commun., 2011, 47, 6957–6959 6957

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corresponding sulfoxide was obtained with 71% ee. At ꢀ20 1C,
the ee increases to 84% whereas the yield is still maintained
after 1 hour. We next examined the oxidation of other alkyl
aryl sulfides with 1 as the catalyst under identical conditions.
Similar levels of yields and enantioselectivities were obtained.
The enantioselectivities were high (between 78 and 90%) at
Table 2 Asymmetric oxidation of thioanisole by the Fe HaltS–H
system in the presence of water
2
O
2
a
b
b
c
MeOH : H
Entry (%)
2
O
Conversion
(%)
SO : SO
(%)
2
ratio
Ee
(%)
1
2
3
4
5
100 : 0
70 : 30
50 : 50
30 : 70
0 : 100
100
100
79
55
18
98 : 2
97 : 3
97 : 3
98 : 2
99 : 1
71
63
56
50
15
ꢀ
20 1C, the best results being obtained with alkyl aryl sulfides
bearing electron-withdrawing groups onto the phenyl ring. It
is also interesting to note that ee is low when the phenyl group
is replaced by benzyl. The results are summarized in Table 1.
Our goal was not only to optimize this particular reaction,
but to use it as an indicator of the mechanism of oxygen atom
transfer. Because the sulfoxide yield depends on the efficiency
of the oxygen-atom transfer, and the degree of asymmetry
induction depends on the chirality of the catalyst, we can infer
the state of the catalyst from its catalytic activity in various
media. Furthermore, the enzymatic oxidation of sulfides to
sulfoxides in water by heme peroxidases is an important
a
Reaction conditions: a mixture containing catalyst 1 (1 mmol),
(120 mmol) in 1 ml distilled CH OH
thioanisole (100 mmol) and H
under argon was stirred at 20 1C for 1 h. Determined by GC on the
crude reaction mixture. Determined by HPLC on a chiral phase.
2
O
2
3
b
c
however, both chemical yields and ees are very poor, 18% and
1
5%, respectively. Low solubility of the aromatic sulfides in
pure water can decrease the rate of the catalysed oxidation.
Since the contribution of the non-catalyzed reaction is weak
(
o1%), the reason for low enantioselectivity may come
3
2–34
process from both the mechanistic
and synthetic point
from porphyrin degradation. Gas apparition and catalytic
destruction were also observed in the latter case. Hydroxyl
and hydroperoxyl radicals are shown to form in homolytic
cleavage, and thus these species may be involved in porphyrin
of view allowing to get optically active sulfoxides with high
1
2
enantiomeric excess. Consequently, a systematic investigation
of the effect of the water content on the oxidation of methyl
phenyl sulfide at room temperature was first undertaken. The
results are summarized in Table 2, showing an interesting
phenomenon for the different combination of methanol/water.
Indeed, the results show that the yield of sulfoxide and the
enantioselectivity in its formation are relatively correlated.
Even when a large amount of water is added, the yields and
ees are still maintained and correct. With pure water (pH 7)
3
5,36
degradation and the production of dioxygen.
We next explore the effect of alcohol solvents on the
catalytic sulfoxidation of sulfide by the chiral iron porphyrin
1
and H O . The results in Table 3 show that the yields and ees
2 2
of methyl phenyl sulfoxide were markedly influenced by
alcohol solvents; the yields and ees were high in methanol
and ethanol, whereas only small amount of sulfoxide (ee: 41%)
was yielded with isopropyl alcohol. In the latter case, however,
it was necessary to add 50% of water to solubilize the catalyst
and, accordingly we note both a decrease of the yield and
ee (vide supra). It should be also noted that it has been demon-
strated previously that alcohols bind to metalloporphyrins as
axial ligands, and one of the effects of the alcohol solvents on
the catalyst activity results from the coordination of alcohols
as axial ligands. Steric effects may also be observed for
branched alcohols, such as iso-propanol which may be too
large to fit inside the encumbered chiral metalloporphyrin but
the weak solubility of 1 in this alcohol prevents a definitive
interpretation.
Table 1 Asymmetric oxidation of sulfides catalyzed by the FeCl
a
2 2
HaltS–H O system
b
Conversion SO : SO
T/1C (%)
c
2
Ee (%)
d
ratio (%) (Config)
b
Entry
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
X = H
20 100
98 : 2
96 : 4
95 : 5
95 : 5
81 : 19
95 : 5
95 : 5
76 : 24
93 : 7
94 : 6
93 : 7
94 : 6
95 : 5
88 : 12
93 : 7
94 : 6
97 : 3
98 : 2
98 : 2
83 : 17
91 : 9
71 (S)-(ꢀ)
81 (S)-(ꢀ)
84 (S)-(ꢀ)
34 (S)-(ꢀ)
65 (S)-(ꢀ)
77 (S)-(ꢀ)
79 (S)-(ꢀ)
61 (S)-(ꢀ)
68 (S)-(ꢀ)
76 (S)-(ꢀ)
74 (S)-(ꢀ)
82 (S)-(ꢀ)
85 (S)-(ꢀ)
72 (S)-(ꢀ)
82 (S)-(ꢀ)
82 (S)-(ꢀ)
74 (S)-(ꢀ)
82 (S)-(ꢀ)
87 (S)-(ꢀ)
o1
H
H
0
100
ꢀ20 100
20 40
20 100
e
H
p-Me
p-Me
p-Me
p-OMe
p-OMe
p-OMe
0
100
87
ꢀ20
20 100
0
ꢀ20
20
100
95
99
94
90
99
99
82
0
1
2
3
4
5
6
7
8
9
0
1
The fact that in some cases there is a slight amount of
sulfone may suggest the existence of a kinetic resolution
process during the course of the reaction. In order to investigate
this aspect an experiment was performed under standard
p-NO
p-NO
p-NO
p-Br
p-Br
p-Br
o-Br
o-Br
o-Br
2
2
2
0
ꢀ20
20
0
ꢀ20
Table 3 Solvent effect on asymmetric oxidation of thioanisole by the
20 100
a
2 2
FeCl HaltS–H O system
0
98
98
ꢀ20
b
c
Conversion
(%)
SO : SO
2
Ee
(%)
MeSCH
MeSCH
2
C
C
6
H
H
4
4
20 100
0
b
ratio (%)
Entry
T/1C
Solvent
2
6
98
2 (S)-(ꢀ)
a
1
2
3
20
20
20
MeOH
EtOH
IprOH
100
100
30
98 : 2
97 : 3
100 : 0
71
70
43
Reaction conditions: a mixture containing catalyst 1 (1 mmol), sulfide
100 mmol) and H (120 mmol) in 1 ml distilled CH OH under argon
was stirred for 1 h. Determined by GC on the crude reaction
(
2
O
2
3
d
b
c
d
a
mixture. Determined by HPLC on a chiral phase. The configura-
e
tions were determined on the basis of the optical rotatory. Reaction
Reaction conditions: a mixture containing catalyst 1 (1 mmol),
(120 mmol) in a 1 ml solvent under
argon was stirred for 1 h at room temperature. Determined by GC
thioanisole (100 mmol) and H
2
O
2
b
conditions: a mixture containing catalyst 2 (1 mmol), thioanisole
c
(
100 mmol) and H
2
O
2
(120 mmol) in a 1 ml distilled CH
3
OH : CH
2
Cl
2
on the crude reaction mixture. Determined by HPLC on a chiral
d
phase. 50% of water was added.
mixture (1 : 1) under argon was stirred for 1 h.
6
958 Chem. Commun., 2011, 47, 6957–6959
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asymmetric sulfide oxidation conditions using racemic sulf-
oxide as a substrate. After 1 hour reaction time, the conversion
of sulfoxide to sulfone was 30%. The ee of 10% for recovered
sulfoxide (in favor for the S-configured sulfoxide) revealed that
the sulfoxidation was indeed enantioselective. However, the
importance of the kinetic resolution under the experimental
conditions applied for the sulfide oxidation (very low amount
of sulfone) is very weak and consequently, the observed
enantioselectivity originates from the sulfide oxidation itself.
Even though the degradation of the catalyst is weak after 1
hour (o10% decrease of the Soret band, see ESIw), we decided
to study the time dependence of the asymmetric process in
more detail. Actually, most of the sulfoxidations are ended up
after 15 min.
further optimization of the reaction medium and chiral
catalysts, and more experiments to precise the role of the
chirality in the mechanism.
Notes and references
1
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2
3
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4
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8
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Generally, in protic solvents which can act as a proton
donor, such as methanol and ethanol, the role of a cocatalyst
is not important, as shown by the unnecessary presence of a
10 H. Egami and T. Katsuki, Synlett, 2008, 1543.
1
3
7
1 S. Oae, Y. Watanabe and K. Fujimori, Tetrahedron Lett., 1982, 23,
189.
cocatalyst with the iron system as reported by Traylor et al.
1
Nevertheless, we noted a longer reaction time for complete
conversion of thioanisole after addition of 10 equivalents of
1
2 S. Colonna, N. Gaggero, G. Carrea and P. Pasta, J. Chem. Soc.,
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13 R. Z. Harris, S. L. Newmyer and P. R. Ortiz de Montellano,
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-methylimidazole at room temperature with a slight increase
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of the ee value: from 71% to 75%. All the results are
summarized in Table 4. As a possible explanation, imidazole
binds the iron center more strongly than methanol and may
decrease the rate of H O consumption.
1
2
2
1
1
1
2
7 Y. Naruta, F. Tani and K. Maruyama, J. Chem. Soc., Chem.
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In conclusion, this investigation of H O asymmetric oxidation
2
2
of sulfides in a protic solvent shows the practicability of the
process (absence of excess of oxidant and substrate, small
reaction time, room temperature reaction. . .) even though the
chiral catalyst does not bear a robust porphyrin ligand.
A protection of the oxoiron(IV) cation radical intermediate
from the two norbornane groups fused to the central benzene
ring is suggested since a similar reaction catalysed by
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2
2
3
5
FeClTPPS yields to the destruction of the porphyrin ring.
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2
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Table 4 Asymmetric oxidation of thioanisole by the FeCl HaltS–
H
a
2
O
2
system in the presence of 2-methylimidazole
2
8 I. Nicolas, P. Le Maux and G. Simonneaux, Tetrahedron Lett.,
2
b
-Methylimidazole/ Conversion SO : SO
c
2
2
Ee
ratio (%) (%)
008, 49, 5793.
b
Entry T/1C mmol
(%)
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1
2
3
4
5
6
7
20
20
0
—
10
—
10
—
10
10
100
100
100
99
100
99
98 : 2
91 : 9
96 : 4
91 : 9
95 : 5
92 : 8
92 : 8
71
75
78
84
3
3
3
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0
ꢀ20
ꢀ20
ꢀ20
82
85.5
90
d
61
a
Reaction conditions: a mixture containing catalyst 1 (1 mmol),
4
0, 554.
2
-methylimidazole (10 mmol) sulfide (100 mmol) and H (120 mmol)
2
O
2
35 G. Lente and I. Fabian, Dalton Trans., 2007, 4268.
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b
3
in 1 ml distilled CH OH under argon was stirred for 1 h. Determined
c
by GC on the crude reaction mixture. Determined by HPLC on a
d
chiral phase. With 2-bromothioanisole.
This journal is c The Royal Society of Chemistry 2011
Chem. Commun., 2011, 47, 6957–6959 6959