Catalytic asymmetric oxidation of sulfide and styrene derivatives using macroporous resins containing chiral metalloporphyrins (Fe, Ru)

Article abstract of DOI:10.1016/j.tetasy.2006.03.003

Chiral metalloporphyrin (Fe, Ru) complexes, functionalized with four vinyl groups, have been polymerized with styrene and divinylbenzene (or ethylene glycol) to obtain supported iron and ruthenium complexes. The heterogeneous asymmetric oxidation of sulfides and styrene derivatives was carried out by using these polymers as catalysts. The reaction proceeded under mild conditions and gave sulfoxides and epoxides with good enantiomeric excesses (up to 75-76%). The catalysts keep constant ee values for the recycle tests of up to six times for asymmetric oxidation of styrene derivatives and of up to 14 times for asymmetric oxidation of sulfides with only traces of sulfones.

Full text of DOI:10.1016/j.tetasy.2006.03.003

Tetrahedron: Asymmetry 17 (2006) 952–960
Catalytic asymmetric oxidation of sulfide and styrene derivatives
using macroporous resins containing chiral metalloporphyrins (Fe,Ru)
Yann Ferrand, Romain Daviaud, Paul Le Maux and G e´ rard Simonneaux*
Ing e´ nierie Chimique et Mol e´ cules pour le Vivant, UMR 6226, Universit e´ de Rennes 1, Campus de Beaulieu, 35042 Rennes Cedex, France
Received 28 January 2006; accepted 7 March 2006
Available online 4 April 2006
Abstract—Chiral metalloporphyrin (Fe,Ru) complexes, functionalized with four vinyl groups, have been polymerized with styrene and
divinylbenzene (or ethylene glycol) to obtain supported iron and ruthenium complexes. The heterogeneous asymmetric oxidation of sul-
fides and styrene derivatives was carried out by using these polymers as catalysts. The reaction proceeded under mild conditions and gave
sulfoxides and epoxides with good enantiomeric excesses (up to 75–76%). The catalysts keep constant ee values for the recycle tests of up
to six times for asymmetric oxidation of styrene derivatives and of up to 14 times for asymmetric oxidation of sulfides with only traces of
sulfones.
Ó 2006 Elsevier Ltd. All rights reserved.
1
. Introduction
Another alternative approach is to use functionalized com-
plexes, which can be co-polymerized or self-polymerized to
form cross-linked insoluble polymers. It was expected that
these polymers contain large pores, which are well-suited
for use in asymmetric reactions catalyzed by rigid and large
chiral metalloporphyrin species.
1
Catalytic asymmetric oxidation of sulfides and olefins is an
important and rapidly growing area in organic synthesis.
Recently, attention has been focused on the immobilization
1
–3
of homogeneous chiral catalysts.
This is particularly
important for oxidation reactions both from a practical
and mechanistic point of view, since chiral sulfoxides and
epoxides are versatile building block for the synthesis of
numerous natural products and biological active sub-
stances. Immobilization can avoid the necessity of chiral
ligand recovery and hence improve asymmetric catalyst
application. One of the simplest ways to prepare a poly-
mer-immobilized catalyst is a direct reaction of a simple
functionalized polymer, such as Merrifield’s resin with a
derivative of the desired ligand and then insertion of the
metal. This route has been used many times and is still
We have previously shown that chiral ruthenium porphy-
5
rins immobilized in spirobifluorene polymers or in macro-
6
porous polymers are effective catalysts in the asymmetric
carbene transfer to olefins. We herein report the prepara-
tion of optically active Frechet type polymers bearing chiral
metalloporphyrins and asymmetric heterogeneous oxida-
tion catalyzed by these polymers. It is expected that these
polymers containing large pores are well-suited for use in
asymmetric oxidation reactions, catalyzed by rigid and
large chiral metalloporphyrin species. To the best our
knowledge, this system is the first example showing such
asymmetric oxidation with chiral metalloporphyrins
co-polymerized to form cross-linked insoluble polymers as
catalysts and also the first asymmetric sulfoxidation under
heterogeneous conditions with chiral metalloporphyrins.
4
the preparative method of choice. There are however, dis-
advantages to grafting metal complexes onto previously
prepared polymers. Treatment of cross-linked polymers
can lead to unwanted side reactions, such as an attack on
the carbon–carbon double bonds of the divinyl cross-link-
ing. Also metal insertion in the active site may be far from
complete.
2. Results
2.1. Preparation of metallopolymers
*
0
Corresponding author. Tel.: +33 22 323 6285; fax: +33 22 323 5637;
e-mail: gerard.simonneaux@univ-rennes1.fr
The starting point of the work described herein was the
introduction of a vinyl group into an optically active
957-4166/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2006.03.003

Y. Ferrand et al. / Tetrahedron: Asymmetry 17 (2006) 952–960
953
porphyrin, with the aim of preparing polymers using the
chiral porphyrin as a co-monomer. We have previously
reported such a synthesis with ruthenium leading to car-
bonyl-[5,10,15,20-tetrakis-[(1S,4R,5R,8S)-10-vinyl-1,2,3,4,
Next, chiral iron vinylporphyrin 2 was used in different
random co-polymerizations with divinyl benzene (DVB)
7
using a protocol previously described for the preparation
of monolithic resins (Scheme 1). Three different chiral iron
polymers P1-FeCl, P2-FeCl, and P3-FeCl were prepared
from 2 by changing the degree of cross-linking and the
porogen (toluene or chloroform/dodecane), using AIBN
as a radical initiator. The different ratios are summarized
in Table 1. The brown polymers were ground and the near
5
,6,7,8-octahydro-1,4:5,8-dimethanoanthracene-9-yl]-por-
6
phyrinato]ruthenium(II) as monomer 3 (Scheme 1). The
corresponding iron complex was prepared by the addition
of iron dichloride to the free-base porphyrin 1 in dimethyl
formamide to give 2 with a 47% yield (Scheme 1).
NH
N
N
HN
1
FeCl2 DMF,140°C
1,2-dichlorobenzene,180°C Ru
CO12
3
Cl
CO
N
N
N
N
N
N
N
N
Fe
Ru
3
2
DVB, styrene
porogen, AIBN
DVB, styrene
porogen, AIBN
DVB =
R
R =
p
n
R
Cl
CO
N
N
N
N
N
N
R
Fe
R
R
Ru
R
N
N
R
R
4
5
R =
p
n
O
O
O
O
O
O
O
O
EGDMA =
Scheme 1.

954
Y. Ferrand et al. / Tetrahedron: Asymmetry 17 (2006) 952–960
Table 1. Polymerization conditions used for the preparation of Fe and Ru
catalysts
was only 43% (Table 2, entry 1). Moreover, we noted a sig-
nificant amount of sulfone through over oxidation (ꢀ5%).
Polymer
Monomer DVB/styrene Porogen
w/w)
AIBN
(%)
a
(
Table 2. Asymmetric oxidation of sulfides by [Fe]
b
c
P1-FeCl 4a
2 (10%)
1.2
5.0
1.2
1.2
Toluene
3
3
3
3
Run Substrates
Catalysts Yield (%) ee (% )
sulfoxide (configuration)
P1-RuCO 5a 3 (10%)
P2-FeCl 4b 2 (10%)
P2-RuCO 5b 3 (10%)
P3-FeCl 4c 2 (10%)
P3-RuCO 5c 3 (10%)
P4-FeCl 4d 2 (10%)
P4-RuCO 5d 3 (10%)
(
sulfone)
Toluene
1
2
6a
43 (5)
75 (1)
73 (1)
89 (1)
85 (1)
68 (S)
66 (S)
68 (S)
65 (S)
60 (S)
P1-FeCl
P2-FeCl
P3-FeCl
P4-FeCl
3
CHCl /
dodecane (1/1)
3
4
5
Ph–S–Me
a
Toluene
a
6
7
6a
P1-FeCl
31 (2)
82 (1)
68 (S)
65 (S)
Ethylene glycol dimethacrylate (EGDMA)/styrene.
p-MePh–S–Me
8
9
6a
P1-FeCl
75 (6)
84 (1)
54 (S)
56 (S)
p-OMePh–S–Me
quantitative incorporation of the iron porphyrin in the
polymer was evidenced by the fact that the chloroform
washing solutions were colorless. These polymers were
characterized by UV–vis (large absorption band at
10
11
12
6a
P1-FeCl
6a
15 (15)
45 (3)
58 (11)
83 (3)
52 (S)
49 (S)
75 (S)
75 (S)
2
PhCH –S–Ph
4
24 nm corresponding to the Soret band of the porphyrin)
2
p-NO Ph–S–Me
1
3
P1-FeCl
and scanning electronic microscopy (Fig. 1). All of the
porous polymers showed small holes of about 0.5 lm dia-
meter. The iron contents were determined by electronic
microanalysis. The more polar monomer ethyleneglycol
dimethacrylate (EGDMA) was also chosen because it
forms highly cross-linked polymers, which can be used as
1
1
4
5
6a
P1-FeCl
67 (10)
83 (1)
49 (S)
69 (S)
p-BrPh–S–Me
a
Reaction conditions: a mixture containing alkene (400 lmol), PhIO
200 lmol) and catalyst (1 lmol) in degassed CH Cl (1 ml) was stirred
at room temperature for 5 h.
Yields are based on the limiting reactant: PhIO.
The ee values were determined by HPLC on a chiral phase.
The absolute configuration was obtained from optical rotations.
(
2
2
8
,9
supports for metal catalysts.
Thus, co-polymerization
b
c
of iron monomer 2 with ethylene glycol dimethacrylate in
the presence of toluene as the porogen, which is necessary
for creating the pore structure, resulted in the orange,
insoluble polymer P4-FeCl. All the ruthenium polymers
d
showed in the IR spectrum, a C@O absorption at
In contrast, the observed sulfoxide yields increased to 75–
84% with ees of about 65% with the chiral iron polymers
P1-FeCl for all the substrates, if we exclude the more-chal-
lenging substrate phenyl benzyl sulfide, which gave the cor-
responding sulfide with 49% ee. However, even in this case,
the yield was much better than under homogeneous condi-
tions: 45% versus 15%. The improved ee, 75%, was
obtained with p-nitrophenyl methyl sulfoxide. The ees of
sulfoxides with a substituent electroacceptor on the phenyl
À1
ꢀ
1945 cm which is similar to the value observed for
the monomer 2. Their characterization has previously been
6
reported.
2
.2. Catalytic asymmetric sulfoxidation
Following, the successful synthesis of the iron porphyrin
polymers, their catalytic activity was tested in the oxidation
of sulfides. Sulfoxidation was initially catalyzed by the chi-
(p-NO , p-Br), 75% and 69%, respectively, were better than
2
1
0
ral iron porphyrin 6a to obtain a reference. Although the
asymmetric induction in the iron-catalyzed sulfoxidation
with 6a is reasonable (68% ee), the viability of the process
is limited, owing to low conversion of the sulfide. Thus,
under homogeneous conditions, large amounts of uncon-
verted sulfides remained and the best yield of sulfoxide
the sulfoxides with a substituent electron donor (p-Me,
p-OMe), 65% and 56%, respectively.
We also investigated the efficiency of three other chiral iron
polymers P2-FeCl, P3-FeCl, and P4-FeCl, which were pre-
pared from 2 by changing the degree of cross-linking and
x 5000
x 20000
Figure 1. Scanning electronic microscopy of P1-FeCl.

Y. Ferrand et al. / Tetrahedron: Asymmetry 17 (2006) 952–960
955
the porogen (toluene or chloroform/dodecane), using
AIBN as a radical initiator (see Table 1). Thus it can be
the complex stability in the reaction media and the possibil-
ity of reusing the catalyst after reaction by simple filtration.
We have selected the catalyst P1-FeCl using thioanisole as
a model substrate for the recycling study. The results are
summarized in Figure 2. If we except the decrease of ee
in the second run, from 68% to 58%, the enantioselectivity
together with the reactivity is maintained after 14 runs,
confirming the high stability of the system. For comparison
to the previous system, the recovery–reuse outcome from
the oxidation of the same substrate with 2,6-dichloropyri-
seen from Table 2 that the use of CHCl /dodecane as a
3
porogenic mixture: P3-FeCl does not seem to be detrimen-
tal to the enantiomeric excess and yield (entry 4). To shed
some light on this area, we also carried out a comparative
study with a different polymer P4-FeCl, using a different
cross-linker, ethylene glycol. As can be seen in Table 2
(
entries 3, 4, and 5), the ees are only slightly lower than
those obtained with P1-FeCl.
dine N-oxide catalyzed with P1-Ru(O) is reported in Fig-
2
Sulfoxidation with chiral ruthenium monomer 6b,11,12
ure 3. In contrast, we should note a progressive decrease of
the reactivity with the Ru/thioanisole system, whereas the
enantioselectivity was maintained at a moderate level
(ꢀ48%).
polymers P1-RuCO and P1-Ru(O) was also examined.
2
First, the homogeneous oxidation of thioanisole was inves-
tigated using 6b (Scheme 2) as catalyst (Table 3, entries 1
and 2). At both 22 and 60 °C, the oxidation yields were
very low (<5%). Since it was previously reported that di-
oxoruthenium analogues are more efficient, the dioxo com-
plex 6c was used as a catalyst under similar reaction
conditions. Accordingly, the yield increased from 13%
2.3. Catalytic asymmetric epoxidation
We first employed the system previously reported by
1
3
Hirobe et al., which is 2,6-dichloro-pyridine N-oxide
as the oxygen donor in toluene at room temperature, with
chiral ruthenium porphyrin polymers. This system was
preferred to the iodosylbenzene with iron catalyst, since it
has previously been found to give lower yields and lower
enantiomeric excesses than the ruthenium system under
(
22 °C) to 97% (60 °C) with 55% ee for the sulfoxide in
the latter case. Thus, high temperature and preoxidation
of the catalyst seem necessary. For polymeric catalysts,
the latter conditions were also examined. The best results
were obtained with P1-Ru(O) , leading to an oxidation of
2
1
0
the substrate with 92% yield after 24 h, but with a quite
moderate enantiomeric excess (48%).
similar conditions. It must be emphasized that a different
system, supporting nonchiral ruthenium porphyrins, has
recently been reported by Nestler and Severin for the ep-
8
oxidation of olefins. Our results obtained in epoxidation
catalysis with ruthenium polymers are summarized in
Table 4.
L
N
N
N
N
The epoxide was formed in 70% yield and 71% enantio-
selectivity from unsubstituted styrene with P1-RuCO (entry
M
2). We also investigated the oxidation of ortho-, meta-,
and para-trifluoromethyl substituted styrenes with the
same polymer (Table 4). As shown in Table 4, para- or
meta-substitution does not have a significant effect upon
the enantioselectivity of styrene epoxidation; the ee (73%
and 74%) for the epoxide were maintained with the para-
and meta-CF derivatives. In contrast, with the ortho-CF
ML= 6a FeCl, 6b RuCO, 6c Ru(O)2
Scheme 2.
3
3
styrene, we noted a decrease of the yield (ꢀ39%) probably
due to steric reasons, and a decrease in the enantioselectiv-
ity (ꢀ44%). It can also be seen from Table 4 that the use
of P2-RuCO, a polymer prepared with a high DVD/styrene
ratio (entry 3) seems to be detrimental to the yield (entry 3).
This may be due to the high cross-linking and consequently,
reduced accessibility of the sites. In contrast, changing
P1-RuCO to P3-RuCO (entry 4) has only a weak influence,
a
Table 3. Asymmetric oxidation of thioanisole by [Ru]
b
c
Run
Catalysts
Time
h)
Temperature
(°C)
Yield (%)
sulfoxide
ee
(
(%)
1
2
3
4
5
6
7
6b
6b
24
24
24
24
24
5
22
60
22
60
60
60
60
2
4
14
24
13
55
50
—
48
d
6c
6c
13
97
27
48
92
as evidenced by the results obtained with CHCl /dodecane
3
as a porogenic mixture, since the amount of cross-linking is
maintained in this case.
P1-RuCO
P1-Ru(O)
P1-Ru(O)
d
2
2
24
a
The recovery and recyclability of the P1-RuCO polymer
have been also examined for the epoxidation reaction. The
polymer was tested for enantioselectivity and reactivity in
the epoxidation of styrene with 2,6-dichloropyridine N-
oxide leading to three recycling steps with a weak progressive
decrease of enantioselectivity (from 71% to 64%) and a de-
crease of yield (from 70% to 19%) (Fig. 4). Thus, the yield
markly decreased to 13% after the third run whereas the
enantioselectivity was maintained at ꢀ64%. A progressive
Reaction conditions: a mixture containing thioanisole (400 lmol), 2,6-
dichloropyridine N-oxide (200 lmol) and catalyst (1 lmol) in degassed
toluene (1 ml) was stirred at 60 °C.
Yields are based on the limiting reactant: 2,6-dichloropyridine N-oxide.
The ee values were determined by HPLC on a chiral phase.
Prepared by addition of m-CPBA.
b
c
d
The most important advantages of heterogeneous catalysis
over its homogeneous counterpart are a high increase of

956
Y. Ferrand et al. / Tetrahedron: Asymmetry 17 (2006) 952–960
90
80
70
60
50
40
30
20
10
0
Yield
Ee
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
Cycle
Figure 2. Recovery–reuse from the oxidation of thioanisole with PhIO using P1-FeCl as catalyst. Reaction time: 24 h.
1
00
9
8
7
6
5
4
3
2
1
0
0
0
0
0
0
0
0
0
0
Yield
Ee
1
2
3
4
5
6
Cycle
Figure 3. Recovery–reuse from the oxidation of thioanisole with 2,6-dichloropyridine N-oxide using P1-Ru(O)
2
as catalyst for 24 h.
decrease of the number of active sites may explain
this result, since the enantioselectivity was only slightly
decreased.
3. Discussion
Although some progress has been made in heterogeneous
organic oxidations catalyzed by soluble and insoluble poly-
mer-supported metalloporphyrins, a similar strategy was
not suitable for the development of polymer-supported chi-
ral metalloporphyrins because of the difficulty involved in
attaching a chiral porphyrin ligand, particularly D -sym-
metric porphyrin, onto a polymer chain. An alternative
method has previously been reported by Che et al., which
attaches a ruthenium chiral porphyrin to meso-porous sil-
ica material by coordinative grafting. We herein report a
different system that circumvents the problem encountered
The heterogeneous asymmetric epoxidation of styrene
catalyzed by Fe polymers P1-FeCl together with its homo-
geneous counterpart, 6a, is summarized in Table 5. In both
cases, the enantiomeric excess was quite moderate. Fur-
thermore, we observed a large decrease of the chemical
yield under heterogeneous conditions, especially in a tolu-
ene solvent (from 60% to 14%). Accordingly, the recovery
and recyclability of polymer P1-FeCl have not been exam-
ined for epoxidation reaction.
4
1
4
1
5

Y. Ferrand et al. / Tetrahedron: Asymmetry 17 (2006) 952–960
957
a
a
Table 4. Asymmetric oxidation of alkenes by [Ru]
Table 5. Asymmetric oxidation of styrene by [Fe]
b
c
Run Substrates
Catalysts Yield (%) ee (%) Turn over
Run
Catalysts
Time
Solvent
CH Cl
Toluene
CH Cl
Toluene
Yield (%)
ee (%)
1
2
3
4
6b
78
76
71
74
72
257
231
43
1
2
3
4
6a
6a
5
5
24
24
2
2
45
60
30
14
50
59
41
47
P1-RuCO 70
P2-RuCO 13
P3-RuCO 72
P1-FeCl
P1-FeCl
2
2
238
a
Reaction conditions: a mixture containing styrene (1000 lmol), PhIO
200 lmol) and catalyst (1 lmol) in degassed toluene or CH Cl (1 ml)
5
6
7
8
CF3
6b
P1-RuCO 39
P2-RuCO
P3-RuCO 35
57
44
44
43
43
188
129
16
(
2
2
was stirred at room temperature.
Yields are based on the limiting reactant: PhIO.
The ee values were determined by GC on a chiral phase.
5
b
c
115
9
0
1
2
6b
P1-RuCO 59
P2-RuCO
P3-RuCO 52
77
76
74
42
71
254
195
20
F3C
1
1
1
parison to titanium, manganese, and vanadium counter-
6
1
8,19
parts.
This work presents a possible example of the
171
use of heterogeneous catalysis to solve this problem. For
all the sulfide substrates assessed, the heterogeneous system
greatly improved results with enantioselectivities of up to
75% and yields up to 82%. Whereas 43% was the best yield
under homogeneous conditions with thioanisole, almost all
sulfoxides were now obtained in more than 70%, using the
different polymers, and only traces of sulfones were
observed. In contrast, a significant amount of sulfone
was detected under the homogeneous conditions. Thus,
the results herein suggest that the oxidation promoted by
the catalyst in our case is a fully enantioselective process,
without a significant contribution from kinetic resolution
since there were only traces of sulfones.
13
14
15
16
6b
P1-RuCO 89
P2-RuCO
P3-RuCO 40
71
76
73
72
73
234
293
30
9
F3C
132
17
18
19
20
6b
P1-RuCO 30
P2-RuCO
P3-RuCO 33
41
71
70
62
68
135
99
23
7
109
a
Reaction conditions: a mixture containing alkene (330 lmol), Cl
330 lmol) and catalyst (1 lmol) in degassed toluene (1 ml) was stirred at
room temperature for 24 h.
2
pyNO
(
There are previously reported homogeneous metallopor-
1
0,20–23
phyrin-catalyzed sulfide oxidations in the literature.
Complexation of sulfoxides to iron(III) porphyrins, which
8
7
6
5
4
3
2
1
0
0
0
0
0
0
0
0
0
Yield
Ee
2
4
have previously been reported in solution, is weak and
needs a high concentration of the ligand. However, this sit-
uation can be detrimental to the turn-over of the catalytic
reaction and may explain why the yield herein of the sul-
foxidation is low under homogeneous conditions and much
higher in heterogeneous conditions. The small cavity inside
the polymer will decrease the local amount of the newly
prepared sulfoxide near the metal and will facilitate a sec-
ond catalytic cycle. This also may explain why the ruthe-
nium polymers are very poor catalysts, since it is well
known that the strength of the ruthenium–sulfoxide bond
is much higher than that of the corresponding iron–sulf-
1
2
3
Cycle
Figure 4. Recovery–reuse from the oxidation of styrene with 2,6-dichlo-
ropyridine N-oxide using P1-RuCO as catalyst for 24 h.
2
5
oxide bond.
Recently, there has also been a renewed interest in reac-
tions catalyzed by porphyrin ruthenium(II) complexes,
simultaneously with the development of new chiral ruthe-
in the structural modification of the chiral porphyrin
ligand, which involved the introduction of a vinyl group
into an optically active porphyrin with the aim of preparing
polymers using the chiral metalloporphyrin as a co-mono-
mer.
2
6
nium porphyrins. These reactions focus mainly on asym-
metric epoxidation of olefins, although in some cases, a
gradual inactivation of the catalytic system is observed
due to the possible formation of inactive carbonyl com-
plexes when trans-dioxo(tetramesitylporphyrinato)ruthe-
Catalytic asymmetric sulfide oxidations for the synthesis of
biologically active sulfoxides are currently applied on an
2
7
nium(VI) is used as the catalyst. However, very few
metalloporphyrin polymers bearing chiral groups have
1
6
industrial scale. However, new technological advances
are still necessary to overcome the limitations of the cur-
been tested in the heterogeneous catalytic epoxidation reac-
1
7
15,28
rent systems. Despite careful control of the reaction tem-
perature, reaction time and the relative amounts of
oxidants, it is difficult to completely avoid over-oxidation.
Moreover, catalysts based on nontoxic and inexpensive
metal, such as iron, are relatively rare, if we make the com-
tions.
Our polymers are monolithic resins bearing
ruthenium porphyrins, previously used by us in asymmetric
6
cyclopropanation. This system was quite efficient for the
first run (253 turnovers), since there is a stoichiometric
ratio of alkene/oxidant, and the enantiomeric excess was

958
Y. Ferrand et al. / Tetrahedron: Asymmetry 17 (2006) 952–960
close to that obtained in solution (70–74%). Unfortunately,
we observed a gradual decrease of activity over three suc-
cessive reactions. The diminishing activity of this hetero-
geneous catalyst was ascribed to catalyst deactivation
through a blocking of the reactant (possibly 2,6-dichloro-
pyridine N-oxide or 2,6-dichloro-pyridine) to the active
sites of the resins. These results are in contrast to those
observed with the sulfoxidation reaction, since both the
enantiomeric excess and the yield are maintained in this
case, due to high accessibility of the reactant to active sites
through large pores in such resins.
HPLC Varian Prostar 218 system equipped with Chiralcel
OD-H and OJ-H columns. For the p-bromophenyl methyl
sulfoxide and the p-methoxyphenyl methyl sulfoxide, the
enantiomeric excesses were determined on a Merck Hitachi
D-7000 system equipped with a Chiralcel OB-H column at
the Laboratoire de St e´ r e´ ochimie Dynamique et Chiralit e´ of
r
P Roussel, Universit e´ Aix-Marseille III.
5.2. Preparation of iron porphyrin monomer 2
A mixture of the free base porphyrin, 50 mg (40 lmol) and
FeCl Æ4H O, 80 mg (0.4 mmol), in refluxing dimethyl form-
2
2
amide under argon was left to react for 24 h. Then, the
solution was evaporated to dryness. The purple-brown res-
idue was dissolved in CHCl3 (20 ml) and washed with
water (20 ml) containing concentrated HCl (0.5 ml). The
organic portion was removed and dried. After evaporation,
the crude product was chromatographed on silica gel to
first yield any recovered free base porphyrin (24 mg) (elu-
ant: pentane/CH Cl , 1/1), then metalloporphyrin (25 mg,
4
. Conclusion
In conclusion, we have developed an asymmetric iron poly-
mer-catalyzed sulfide oxidation with iodosyl benzene as
oxidant, which provides sulfoxides with up to 89% yield
in good ee (up to 75%). The simplicity of the process (room
temperature, catalyst easily recovered), the high yields and
good enantioselectivity render this heterogeneous process
an attractive alternative to the few existing heterogeneous
methods available for metal-catalyzed asymmetric sulfide
oxidation. The analogous ruthenium polymers are much
less efficient for this reaction. In contrast, the reverse is true
for the epoxidation reaction; the better system is related to
the use of the ruthenium polymers, although the recycling
outcome needs to be increased. Ongoing work includes
investigations of an extended range of substrates, particu-
larly those of pharmaceutical importance and further opti-
mization of the reaction medium and oxidants.
2
2
1
yield: 47%) (eluant: CH Cl /CH OH, 4/1). H NMR
2
2
3
(
CDCl , ppm): d: 80 ppm (8H, br s); UV–vis (CH Cl ):
3
2
2
kmax/nm (loge): 381 (4.42), 426 (4.71), 511 (3.86), 577
(
3.25), 697 (3.23); MS (ESI, CH Cl /CH OH 9/1)
2 2 3
5
6
(m/z): calculated for C H N O F (MÀCl+CH OH)+:
9
3
88
4
3
1
332.6307, found: 1332.6321.
5.3. Preparation of polymers
In an oven dried test tube, iron porphyrin complex (9.6 mg,
7
1
.2 lmol) was dissolved in the porogen 160 ll (toluene
.5 mmol). Then, styrene (32 ll, 277 lmol) and divinyl-
benzene (49 ll, 340 lmol) were added to the solution.
The polymerization reaction was initiated by AIBN
5
. Experimental
(
1
10 mg, 60 lmol). The mixture was heated at 65 °C for
5
.1. General experimental
6 h without stirring. The resulting polymer was extracted
from the polymerization tube, crushed in a mortar, washed
with dichloromethane, and filtered on B u¨ chner funnel.
Recovered: 80 mg. UV–vis (powder): kmax/nm: 424 (Soret
band).
All reactions were performed under argon. Solvents were
distilled from an appropriate drying agent prior to use:
Et O and THF from sodium and benzophenone, toluene
2
from sodium, CH Cl from CaH , CHCl from P O ,
2
2
2
3
2
5
and all other solvents were HPLC grade. Commercially
available reagents were used without further purification
unless otherwise stated. All reactions were monitored by
TLC with Merck pre-coated aluminum foil sheets (Silica
gel 60 with fluorescent indicator UV254). Compounds were
visualized with UV light at 254 and 365 nm. Column chro-
matographies were carried out using silica gel from Merck
5.4. General procedure for homogeneous asymmetric oxida-
tion of sulfides with iron porphyrin complexes 6a
Iron porphyrin complex 6a (1.2 mg, 1 lmol) and PhIO
(44 mg, 200 lmol) were placed in a test tube under argon.
Then, 1 ml of degassed dichloromethane was added via syr-
inge, followed by sulfide (400 lmol). After 5 h, the mixture
was analyzed by GC for yield. The ee of the sulfoxide was
determined by chiral HPLC after purification by flash
chromatography on silica gel (pentane/dichloromethane
1
13
(
0.063–0.200 mm). H NMR and C NMR in CDCl were
3
recorded using Bruker (Advance 500dpx and 300dpx spec-
trometers) at 500 and 75 MHz, respectively. High-resolu-
tion mass spectra were recorded on a ZabSpec TOF
Micromass spectrometer in ESI positive mode at the
CRMPO. Liquid UV–visible spectra were recorded on a
UVIKON XL from Biotech. Solid UV–visible spectra were
recorded on a Cary 5000 NIR spectrophotometer. Scan-
ning electronic microscopy and microanalyses were
realized on a Jeol JSM 6301F and Jeol JSM 6400 spectro-
meters, respectively, at the CMEBA. All catalytic reactions
were controlled on a Varian CP-3380 Gas Chromatograph
equipped with a CP-Chirasil-Dex Column. The enantio-
meric excesses of the sulfoxides were determined on a
1:1, then ethyl acetate).
5.5. General procedure for heterogeneous asymmetric oxi-
dation of sulfides with iron polymers 4
Iron polymer P1-FeCl 4 (12 mg) and PhIO (44 mg,
200 lmol) were placed in a test tube under argon. Then,
1 ml of degassed dichloromethane was added via syringe,
followed by sulfide (400 lmol). After 5 h, the mixture was
filtered and analyzed by GC for yield. The ee of the sulf-

Y. Ferrand et al. / Tetrahedron: Asymmetry 17 (2006) 952–960
959
oxide was determined by chiral HPLC after purification by
flash chromatography on silica gel (pentane/dichlorometh-
ane 1:1, then ethyl acetate).
5.7.5. (S)-(À)-p-Nitrophenyl methyl sulfoxide. HPLC: tR
(R) = 62.6 min, (S) = 70.1 min (Chiralcel OJ-H;
flow rate: 0.5 ml min ; hexane/i-PrOH (8/2), 25 °C, detec-
tion at 225 nm.
t
R
À1
5
.6. General procedure for homogeneous and heterogeneous
asymmetric oxidation of thioanisole with ruthenium por-
phyrin 6b and polymer P1-RuCO
5.7.6. (S)-(À)-Phenyl benzyl sulfoxide. HPLC: tR (R) =
31.3 min, t (S) = 36.3 min (Chiralcel OD-H; flow rate:
R
À1
0
.5 ml min ; hexane/i-PrOH (9/1), 25 °C, detection at
Ruthenium porphyrin complex 6b (1.3 mg, 1 lmol) (or 12
mg of polymer P1-RuCO) and 2,6-dichloropyridine N-
oxide (33 mg, 200 lmol) were placed in a test tube under
argon. Then, 1 ml of degassed toluene was added via syr-
inge, followed by thioanisole (40 lmol). After 24 h at
225 nm.
5.8. General procedure for homogeneous asymmetric oxida-
tion of styrene derivatives with ruthenium porphyrin 6
6
0 °C the mixture was analyzed by chiral GC for yield.
Ruthenium porphyrin complex 6b (1.3 mg, 1 lmol) and
2,6-dichloropyridine N-oxide (54 mg, 330 lmol) were
placed in a test tube under argon. Then, 1 ml of degassed
toluene was added via syringe, followed by styrene derivat-
ive (330 lmol). After 24 h, the mixture was analyzed by
chiral GC for yield and ee.
The ee of the phenyl methyl sulfoxide was determined by
chiral HPLC after purification by flash chromatography
on silica gel (pentane/dichloromethane 1:1, then ethyl
acetate).
5
.7. General procedure for homogeneous and heterogeneous
asymmetric oxidation of thioanisole with ruthenium dioxo
porphyrin 6c and polymer P1-Ru(O)2
5.9. General procedure for heterogeneous asymmetric oxi-
dation of styrene derivatives with ruthenium polymers
The ruthenium dioxo porphyrin complex was prepared as
follows: to (1.5 mg, 1.2 lmol) ruthenium carbonyl porphy-
rin 6b in a test tube under argon were added 0.5 mg
Ruthenium polymer P1-RuCO (1 mg) and 2,6-dichloro-
pyridine N-oxide (54 mg, 330 lmol) were placed in a test
tube under argon. Then, 1 ml of degassed toluene was
added via syringe, followed by styrene derivative
(330 lmol). After 24 h, the mixture was filtered and ana-
lyzed by chiral GC for yield and ee.
(
2.5 lmol) of m-CPBA and 0.5 ml of degassed dichloro-
methane. After 5 min, the solution was purified by flash
chromatography on basic alumina eluted with dichloro-
methane and the solvent was removed. Then, the procedure
for catalysis was the same as described for ruthenium car-
bonyl porphyrin 6b.
5.10. General procedure for homogeneous and heterogeneous
asymmetric oxidation of styrene with iron porphyrin 6a and
polymer P1-FeCl
The polymer P1-Ru(O)2 was prepared as following: to
1
2 mg of polymer P1-RuCO 5 in a test tube under argon
Iron porphyrin complex 6a (1.3 mg, 1 lmol) (or 12 mg of
polymer P1-FeCl and PhIO (44 mg, 200 lmol) were placed
in a test tube under argon. Then, 1 ml of degassed toluene
(or CH Cl ) was added via syringe, followed by styrene
were added (0.5 mg, 2.5 lmol) of m-CPBA and 1 ml of
degassed dichloromethane. After 30 min, the solvent was
removed and the polymer was washed two times with
2
2
0
.5 ml dichloromethane. The IR spectrum show the disap-
derivative (1 mmol). After 24 h, the mixture was analyzed
by chiral GC for yield and ee.
À1
pearance of CO band at 1945 cm . Then, the procedure
for catalysis was the same as described for ruthenium car-
bonyl porphyrin 6b.
5.11. Gas chromatography conditions for oxidation of
sulfides and styrene derivatives
5
2
0
2
.7.1. (S)-(À)-Phenyl methyl sulfoxide. HPLC: tR (R) =
7.5 min, t (S) = 29.9 min (Chiralcel OD-H; flow rate:
CP-Chirasil-Dex column, temperature: 120 °C (hold 1 min)
R
À1
À1
.5 ml min ; hexane/i-PrOH (9/1), 25 °C, detection at
to 200 °C at 2.5 °C min , pressure 15 psi, injector (pulsed
25 nm.
split mode) at 200 °C, detector (FID) at 220 °C.
5
3
0
2
.7.2. (S)-(À)-Tolyl methyl sulfoxide. HPLC: tR (R) =
8.6 min, t (S) = 41.2 min (Chiralcel OD-H; flow rate:
Acknowledgements
R
À1
.5 ml min ; hexane/i-PrOH (9.5/0.5), 25 °C, detection at
25 nm.
We thank GIREX S.A., for financial support (Y.F.) and C.
Roussel (Universit e´ Aix-Marseille III), for his technical
assistance.
5
.7.3. (S)-(À)-p-Methoxyphenyl methyl sulfoxide. HPLC:
(S) = 6.1 min, t (R) = 10.3 min (Chiralcel OB-H; flow
t
R
R
À1
rate: 1 ml min ; hexane/i-PrOH (1/1), 25 °C, detection at
2
54 nm.
References
5
.7.4. (S)-(À)-p-Bromophenyl methyl sulfoxide. HPLC: tR
1. Fan, Q. H.; Li, Y. M.; Chan, A. S. C. Chem. Rev. 2002, 102,
(
S) = 5.4 min, t (R) = 6.6 min (Chiralcel OB-H; flow
3385–3466.
R
À1
rate: 1 ml min ; hexane/i-PrOH (1/1), 25 °C, detection at
2
2. Rechavi, D.; Lemaire, M. Chem. Rev. 2002, 102, 3467–
54 nm.
3494.

960
Y. Ferrand et al. / Tetrahedron: Asymmetry 17 (2006) 952–960
3
4
. Song, C. E.; Lee, S. G. Chem. Rev. 2002, 102, 3495–3524.
. Leadbeater, N. E.; Marco, M. Chem. Rev. 2002, 102, 3217–
274.
16. Legros, J.; Dehli, J. R.; Bolm, C. Adv. Synth. Catal. 2005,
347, 19–31.
3
17. Kowalski, P.; Mitka, K.; Ossowska, K.; Kolarska, Z.
Tetrahedron 2005, 61, 1933–1953.
18. Legros, J.; Bolm, C. Chem. Eur. J. 2005, 11, 1086–1092.
19. Kaczorowska, K.; Kolarska, Z.; Mitka, K.; Kowalski, P.
Tetrahedron 2005, 61, 8315–8327.
20. Groves, J. T.; Viski, P. J. Org. Chem. 1990, 55, 3628–3634.
21. Naruta, Y.; Tani, F.; Maruyama, K. J. Chem. Soc., Chem.
Commun. 1990, 1378–1380.
22. Naruta, Y.; Tani, F.; Maruyama, K. Tetrahedron: Asymmetry
1991, 2, 533–542.
5
6
. Ferrand, Y.; Poriel, C.; Le Maux, P.; Rault-Berthelot, J.;
Simonneaux, G. Tetrahedron: Asymmetry 2005, 16, 1463–
1
472.
. Ferrand, Y.; Le Maux, P.; Simonneaux, G. Tetrahedron:
Asymmetry 2005, 3829–3836.
7
8
9
. Fr e´ chet, J. M. Tetrahedron 1981, 37, 663–683.
. Nestler, O.; Severin, K. Org. Lett. 2001, 3, 3907–3909.
. Burri, E.; Ohm, M.; Daguenet, C.; Severin, K. Chem. Eur. J.
005, 11, 5055–5061.
¨
2
1
1
1
1
1
1
0. Halterman, R. L.; Jan, S. T.; Nimmons, H. L.; Standlee, D.
J.; Khan, M. A. Tetrahedron 1997, 53, 11257–11276.
1. Lo, W. C.; Che, C. M.; Cheng, K. F.; Mak, T. C. W. J. Chem.
Soc., Chem. Commun. 1997, 1205–1206.
23. Chiang, L. C.; Konishi, K.; Aida, T.; Inoue, S. J. Chem. Soc.,
Chem. Commun. 1992, 254–256.
24. Mashiko, T.; Kastner, M. E.; Spartalian, K.; Scheidt, R.;
Reed, C. A. J. Am. Chem. Soc. 1978, 100, 6354–6362.
25. Pacheco, A.; James, B. R.; Rettig, S. J. Inorg. Chem. 1999, 38,
5579–5587.
26. Berkessel, A.; Kaiser, P.; Lex, J. Chem. Eur. J. 2003, 9, 4746–
4756.
27. Scharbert, B.; Zeisberger, E.; Paulus, E. J. Organomet. Chem.
1995, 493, 143–147.
2. Berkessel, A.; Frauenkron, M. J. Chem. Soc., Perkin Trans.
1
997, 2265–2266.
3. Higushi, T.; Ohtake, H.; Hirobe, M. Tetrahedron Lett. 1989,
0, 6545–6548.
3
4. Xia, Q. H.; Ge, H. Q.; Ye, C. P.; Liu, Z. M.; Su, K. X. Chem.
Rev. 2005, 105, 1603–1662.
5. Zhang, J. L.; Liu, Y. L.; Che, C. M. Chem. Commun. 2002,
28. Zhang, R.; Yu, W. Y.; Wong, K. Y.; Che, C. M. J. Org.
Chem. 2001, 66, 8145–8153.
2
906–2907.