Enantioselective manganese-porphyrin-catalyzed epoxidation and C-H hydroxylation with hydrogen peroxide in water/methanol solutions

Article abstract of DOI:10.1021/ic300457z

The asymmetric epoxidation of alkene and hydroxylation of arylalkane derivatives by H₂O₂ to give optically active epoxides (enantiomeric excess (ee) up to 68%) and alcohols (ee up to 57%), respectively, were carried out in water/methanol solutions using chiral water-soluble manganese porphyrins as catalysts.

Full text of DOI:10.1021/ic300457z

Article
pubs.acs.org/IC
Enantioselective Manganese-Porphyrin-Catalyzed Epoxidation and
C−H Hydroxylation with Hydrogen Peroxide in Water/Methanol
Solutions
Hassan Srour, Paul Le Maux, and Gerard Simonneaux*
Institute of Sciences Chimiques of Rennes, Ingen
35042 Rennes cedex, France
́ ́
ierie Chimique et Molecules pour le vivant UMR 6226 CNRS, Campus de Beaulieu
ABSTRACT: The asymmetric epoxidation of alkene and hydrox-
ylation of arylalkane derivatives by H2O2 to give optically active
epoxides (enantiomeric excess (ee) up to 68%) and alcohols (ee up
to 57%), respectively, were carried out in water/methanol solutions
using chiral water-soluble manganese porphyrins as catalysts.
was the introduction of four sulfonate groups into an optically
active porphyrin with the objective of preparing chiral water-
soluble porphyrins. We choose a C2-symmetric group that
contains two norbornane groups fused to the central benzene
ring, which was previously reported by Halterman and Jan.15
Initially, we planned to introduce first the sulfonic acid in the
porphyrin ring and then manganese insertion. The sulfonation
of the Halterman porphyrin was performed as we previously
reported.16 A 10-fold excess of MnBr2·4H2O was necessary to
get the expected metalloporphyrin (Figure 1) in a reasonable
yield (80%). The expected compound was characterized by
UV−visible spectrum, and mass spectrum (see the Exper-
imental Section). It is easily soluble in methanol and water.
Catalytic Asymmetric Epoxidation. Because of the high
solubility of the catalyst in methanol, the epoxidation of styrene
was first examined in this solvent at room temperature and with
imidazole as a co-catalyst. The rate of the epoxidation reaction
was very low to give 6% conversion after 1 h and 31% con-
version after 4 h (Table 1, entry 1). However, in the presence
of 25% phosphate buffer (pH 7), we noticed a large accelera-
tion, since the conversion increases to 68% after 1 h and a quasi-
completion after 4 h (93%) (Table 1, entry 2). In a typical oxida-
tion, 1 equiv of the Mn porphyrin catalyst 1, 24 equiv of imidazole,
120 equiv of H2O2, and 40 equiv of substrate were used under
anaerobic conditions. The reaction is quasi-complete after 4 h at
room temperature and the corresponding epoxide was obtained
with good yield (93%) and 47% ee (Table 1, entry 2). This situa-
tion was amplified with a 50/50 ratio of methanol/water, giving
100% conversion after 1 h but with a small decrease of the ee
(from 47% to 41%). Surprisingly, completion of the reaction in
pure water (without methanol) requires 4 h under similar
conditions (Table 1, entry 4). Probably, the weak solubility of
styrene in water may explain this result. It should be noted that an
increase of the epoxidation reaction was reported recently,17 because
of the presence of water in saturated CH2Cl2 solution for similar
INTRODUCTION
■
The use of water instead of organic solvents in transition-metal
homogeneous catalysis has received remarkable attention,1−3
because water is inexpensive, nontoxic, nonflammable, and environ-
mentally sustainable and, sometimes it allows simple separation and
reuse of the catalyst. Moreover, catalysis often permits the use of
less-toxic reagents, as in the case of oxidation by hydrogen peroxide.
Hydrogen peroxide (H2O2) is widely accepted as a green oxidant,
because it is relatively nontoxic and breaks down in the environment
into benign byproducts.4,5 Over the last three decades, there have
been large advances in the development of catalytic methodology
for epoxidation reactions.6 However, asymmetric epoxidations in
aqueous solution with H2O2 are still rare,7 although a nice pos-
sibility has been recently reported using iron and a chiral non-
porphyrin ligand.8 The main obstacle when using H2O2 is the high
activity of transition-metal complexes in the catalase reaction and
the homolytic cleavage of the peroxidic O−O bond with the
formation of the hydroxyl radical.9
A few examples of the use of H2O2 can be found in the literature
with manganese porphyrins as catalysts, giving low enantiomeric ex-
cess (ee) for epoxidation reaction in organic solvents or in a biphasic
medium.10−12 However, to our knowledge, there are no examples of
asymmetric hydroxylation by H2O2 in water catalyzed by Mn por-
phyrins. Our group11 reported the asymmetric oxidation of sulfides
into sulfoxides using macroporous resins containing chiral metal-
loporphyrins, and, more recently, catalytic sulfoxidation reactions
with H2O2 in water using a chiral iron porphyrin as a catalyst.12 We
now want to describe here chiral epoxidation of alkenes in water/
methanol solutions using H2O2 as an oxidant catalyzed by new
optically active water-soluble manganese porphyrins (Figure 1).
Because high-valency manganese(IV or V)-oxo porphyrins are capa-
ble of activating C−H bonds of alkanes,13,14 we also have consid-
ered the possibility of catalytic asymmetric hydroxylation with chiral
water-soluble manganese porphyrins, using H2O2 as an oxidant.
RESULTS
■
Preparation of Water-Soluble Chiral Manganese
Porphyrins. The starting point of the work described here
Received: February 29, 2012
Published: May 8, 2012
© 2012 American Chemical Society
5850
dx.doi.org/10.1021/ic300457z | Inorg. Chem. 2012, 51, 5850−5856

Inorganic Chemistry
Article
Figure 1. Structures of catalyst 1 and 2.
Table 1. Effects of the Amount of H2O, Relative to MeOH
on Mn HaltS−H2O2−Imidazole System
gave a low conversion (38%) with 43% ee. A similar value (52%)
was reported by Halterman and co-workers19 in organic solvent
(CH2Cl2) using NaOCl as an oxidant.
a
enantiomeric
pH-Dependent H2O2 Oxidation. To explore whether the pH
affects the yield and the ee at different pH values, we chose styrene
as a substrate because it is commonly applied for the catalytic activ-
ity of manganese porphyrins. The experiments for pH-dependent
styrene oxidation were carried out in the presence of H2O2 at 25 °C
with the ratio H2O2/styrene being 3 and the yields and ee values
were observed after 4 h. The results are summarized in Table 3. We
found that the reaction rate increases with increasing pH show-
ing 100% conversion at pH 10.5 after 1 h (Table 3, entry 4). In
contrast, at acidic pH (pH 4), we observed only 12% conversion
after 1 h. It is worth noting that the substitution of imidazole by
N-methyl imidazole as Mn ligand has a large negative effect, since
only 5% conversion is observed after 1 h (Table 3, entry 5).
Influence of an Excess of Oxidant. Since the oxide yields in
the oxidation were high (95% after 4 h) with 5 equiv of H2O2,
we have examined the effect of decreasing the ratio H2O2/styrene
on chemical yield. As expected, Table 4 shows that a decrease of
the oxidant/styrene ratio from 5 to 1.2 provides a decrease of the
epoxidation yield, varying from 83% to 50% after 1 h. However,
the yield (64%) is still acceptable after 4 h, according to the high
reactivity of the system, in the presence of water.
Influence of the Nature of Oxidant. The nature of the
active oxygen complex, which is able to transfer its O atom to
alkenes and hydrocarbons, although not completely established,
is generally considered to be a high-valency Mn-oxo complex, at
least formally, a MnV=O species, although a MnIII−OOH could
be invoked.20 In order to characterize the oxidizing species, in
the chiral Mn system, we have compared the yield and enantio-
meric excess using different oxidants (see Table 5). Using an
identical concentration of oxidant and styrene (Mn/imidazole/
oxidant/styrene =1/24/40/40), Table 5 shows that there is an
increase of the yield when the oxidant is iodobenzene diacetate
(from 49% to 75%). However, it is remarkable that, with three
different oxidantsmeta-chloroperoxybenzoic acid, H2O2, and
PhI(OAc)2the ee values are similar, according to a probable
common optically active intermediate. With t-buOOH, only
traces of styrene epoxide are observed, as previously reported
with oxidation of styrene catalyzed by Mn porphyrins.21
entry
1
MeOH/H2O
1/0
conversion (%)
excess, ee (%)
time (h)
6
47
47
47
47
41
37
35
36
36
1
4
1
4
1
1
4
1
4
31
2
3
3/1
68
93
1/1
0/1
100
7
b
4
100
46
b,c
5
0/1
100
a
The reaction was conducted with syringe-pump addition of 3 equiv
(relative to alkene) of H2O2 (30% in H2O, diluted 5 times in MeOH)
and imidazole (20 equiv relative to Mn) at 25 °C to a solution of
styrene/imidazole/Mn HaltS mixture (40:4:1) in 0.4 mL of MeOH/
b
buffer solution (pH 7). The reaction was conducted with syringe-
pump addition of 3 equiv (relative to alkene) of H2O2 (30% in H2O,
diluted 5 times in H2O and imidazole (20 equiv, relative to Mn) at
25 °C to a solution of styrene/imidazole/Mn HaltS mixture (40:4:1)
c
in 0.4 mL of MeOH/buffer solution (pH 7). The reaction was
conducted in buffer solution (pH 10.5).
systems with achiral metalloporphyrins. The key role of imidazole in
metalloporphyrin-catalyzed oxygenations with H2O2, evidenced by
Mansuy et al.18 in olefin epoxidation with iodosyl benzene, is con-
firmed herein, since only a weak conversion (4%) was detected in
the absence of this ligand (see Table 2, entry 3).
We also investigated the epoxidation of various substituted
styrenes with the same catalyst (1). Results for the catalytic
epoxidation of several alkenes are summarized in Table 2. As
shown in Table 2, epoxide yields in the range of 45%−100%
were obtained with enantiomeric excess (ee) as high as 68% for
1,2-dihydronaphthalene. Small amounts of aldehydes (<3%)
were also detected as byproduct, excepted for the reaction with
4-methylstyrene. As expected from the reactivity of electrophilic
oxo-manganese porphyrins, the best yields were obtained with
styrenes bearing electron-releasing substituents whereas no clear
trend was evident for optical yields upon changing the substituent.
Using the hydrophobic catalyst (2), without any sulfonate groups
(Figure 1), instead of 1 in dichloromethane/methanol solvent
5851
dx.doi.org/10.1021/ic300457z | Inorg. Chem. 2012, 51, 5850−5856

Inorganic Chemistry
Article
a
Table 2. Asymmetric Oxidation of Alkenes Catalyzed by Mn HaltS−H2O2−Imidazole System
b
b
c
d
entry
substrate
conversion (%)
epoxide/aldehyde ratio (%)
99/1
enantiomeric excess, ee (%)
47
config
time (h)
1
styrene
styrene
styrene
styrene
88
2
R
4
e
f
2
4
3
4
51
46
R
R
R
R
R
R
R
R
R
4
g
4
76
96
62
90
98
93
70
56
52
27
100
45
98/2
76/24
100/0
99/1
1
h
4
4-methylstyrene
20
1
5
4-(trifluoromethyl)styrene
4-chlorostyrene
38
48
46
46
52
46
68
65
5
6
5
7
3- methylstyrene
99/1
4
8
2- methylstyrene
99/1
4
9
3- (trifluoromethyl)styrene
2- (trifluoromethyl)styrene
100/0
100/0
100/0
100/0
100/0
100/0
4
10
11
12
13
14
1.5
2
g
1,2-dihydronaphthalene
1R, 2S
1R, 2S
1R, 2S
+
1,2-dihydronaphthalene
indene
2
h
40
0.5
4
2,2-dimethyl-2H-1-benzopyran-6-carbonitrile
57
a
The reaction was conducted with syringe-pump addition of 3 equiv (relative to alkene) of H2O2 (30% in H2O, diluted 5 times in MeOH) and
imidazole (20 equiv relative to Mn) over 1 h at 25 °C to a solution of alkene/imidazole/Mn HaltS mixture (40:4:1) in MeOH/PBS (pH 7) (3/1).
b
c
d
Determined by gas chromatography (GC) on the crude reaction mixture. Determined by GC on a chiral CP-Chirasil-Dex column. Absolute
configuration of the epoxide of styrene was determined by comparison with the authentic optically pure (R) (+) styrene oxide. Others were deduced
e
f
g
from analogy of the GC behavior and of the optical rotatory of (R) (+) styrene oxide. Without catalyst. Without imidazole. One equivalent
(1 equiv) of PhI(OAc)2 was used. Determined by chiral high-performance liquid chromatography (HPLC) on a chiral OB-H column.
h
Table 3. Asymmetric Oxidation of Styrene Catalyzed by Mn
HaltS−H2O2−Imidazole System at Different pH Values
Table 4. Effects of the Amount of H2O2 (x), Relative to
Styrene with the Mn HaltS−H2O2−Imidazole System
a
a
entry
1
pH
4
conversion (%) enantiomeric excess, ee (%) time (h)
entry amount of H2O2, x (equiv) conversion (%) ee (%) time (h)
12
81
68
93
79
94
100
5
43
41
48
47
44
44
40
49
49
1
4
1
4
1
4
1
1
4
1
2
3
4
5
6
5
83
95
75
93
68
90
50
64
12
92
52
64
46
45
48
47
44
44
43
43
37
36
42
43
1
4
1
4
1
4
1
4
1
4
1
4
2
3
4
7
9
3
2
10.5
10.5
1.2
1.2
1.2
b
5
b
c
32
a
The reaction was conducted with syringe-pump addition of 3 equiv
(relative to alkene) of H2O2 (30% in H2O, diluted 5 times in MeOH)
and imidazole (20 equiv relative to Mn) at 25 °C, to a solution of an
alkene/imidazole/Mn HaltS mixture (40:4:1) in 0.4 mL of MeOH/
a
The reaction was conducted with syringe-pump addition of x equiv
b
buffer solution (3/1). N-methylimidazole was used as an axial ligand.
(relative to alkene) of H2O2 (30% in H2O, diluted 5 times in MeOH)
and imidazole (20 equiv relative to Mn) at 25 °C to a solution of
styrene/imidazole/Mn HaltS mixture (40:4:1) in 0.4 mL of MeOH/
Catalytic Asymmetric Hydroxylation. Treatment of ethyl-
benzene (1 equiv) with hydrogen peroxide (5 equiv) and a
catalytic quantity of complex 1 in H2O/MeOH (1/1) at room
temperature for 7 h afforded (88% conversion) a mixture of
1-phenyl ethanol (57%) acetophenone (43%). The enantiopurity
of the phenyl ethanol was determined to be 38% by chiral
capillary GC analysis.
As shown in Table 6, 2-, 3-, and 4-ethyltoluenes, as well as
1-bromo-4-ethylbenzene, are also effective substrates for the
1-catalyzed asymmetric hydroxylation and the corresponding
1-arylethanols were produced in comparable yields and ee values
of 49%−57% (entries 4−7). Cyclic alkanes such as Indane and
tetrahydronaphtalene are more reactive substrates since a high
conversion was obtained after 1 h but enantioselectivities
decreased to 32% and 43%, respectively.
b
buffer solution pH 7 (3/1). The reaction was conducted in buffer
c
solution (pH 10.5) as solvent. The reaction was conducted in a
mixture of MeOH/buffer solution (pH 10.5) (3/1).
Table 5. Asymmetric Epoxidation of Styrene with the Mn
HaltS−Imidazole System in the Presence of Different
a
Oxidants
entry
oxidant
conversion (%)
ee (%)
1
2
3
4
m-CPBA
H2O2
47
49
46
47
46
PhI(OAc)2
t-BuOOH
75
traces
a
A solution of MnHaltS/imidazole/styrene/oxidant (1:24:40:40) in
0.4 mL of MeOH/buffer solution (pH 7) mixture was stirred for 1 h
at 25 °C.
DISCUSSION
■
Epoxidation. Catalytic asymmetric epoxidation (Figure 2)
in a safe and benign water solvent is still a challenge for chemists.22
Since the asymmetric epoxidation with an iron-porphyrin complex
bearing chiral groups at meso-carbon atoms was reported in
1983,23 a wide variety of chiral metalloporphyrins with iron,
5852
dx.doi.org/10.1021/ic300457z | Inorg. Chem. 2012, 51, 5850−5856

Inorganic Chemistry
Article
organic solvents. (See Figure 3.) In some cases, water was also
used as a solvent in the metalloporphyrin-catalyzed hydroxylation
of various substrates.27,28 There are three important reviews
dealing with these reactions.29−31 However, to our knowledge,
there is no asymmetric hydroxylation catalyzed by chiral manganese
porphyrins in water using hydrogen peroxide as an oxidant. This is
mainly due to three difficulties: (i) the preparation of optically active
water-soluble chiral metalloporphyrins showing catalytic activity; (ii)
the high activity of transition-metal complexes in the catalase
reaction and the homolytic cleavage of the peroxidic O−O bond
with formation of hydroxyl radical; and (iii) the functionalization
of C−H bonds, which is one of the most difficult transformations,
because of high thermal stability. To our benefit, we were able to
achieve asymmetric hydroxylation of benzylic C−H bonds in
aromatic hydrocarbons with our system. Although the enantio-
meric excess of the products was moderate, the Mn-based hy-
droxylation gave good yields of the corresponding secondary
alcohols, thanks to the manganese porphyrin catalytic efficiency.
Mechanism. Synthetic manganese(III) porphyrins have
been extensively studied as CYP450 models in oxygen-atom-
transfer reactions,20,32 and high-valency manganese-oxo por-
phyrins have been frequently proposed as reactive intermedi-
ates in the oxidation reactions.9,33,34 In particular, water-soluble
cationic manganese porphyrins, such as Mn(V) N-substituted
pyridylporphyrins, have been recognized for more than a
decade as very efficient catalysts for O-atom transfer reactions
in aqueous solution.35,36 From the mechanistic viewpoint, the
key oxomanganese(V) porphyrin intermediate has been iso-
lated and characterized spectroscopically. In 1999, Jin and Groves36
generated a Mn(V)O porphyrin complex in the reaction of
Mn(III) tetrakis(N-methyl-2-pyridyl)porphyrin with oxidants
such as m-chloroperoxybenzoic acid, HSO5− (oxone), and
OCl− in aqueous solution.32 A possible conclusion from this
work was that oxo-aqua- and oxo-hydroxo-manganese(V) are
reactive oxidants while the stable species observed at high pH
are trans-dioxo complexes. Definitive spectroscopic evidence
for trans-dioxo-manganese porphyrins [OMn(V)O] was
reported by the same group.37
Table 6. Asymmetric Hydroxylation Catalyzed by the Mn
HaltS−H2O2−Imidazole System
a
alcohol/
ketone
ee
time
(h)
b
entry
substrate
conversion
ratio (%)
(%) config
d
1
ethyl benzene
indane
88
88
57/43
77/23
62/38
93/7
38
32
43
57
50
52
49
S
S
S
S
S
S
S
7
1
1
7
7
7
7
c
2
c
3
tetralin
90
c
4
4-ethyltoluene
3-ethyltoluene
2-ethyltoluene
97
c
5
98
84/16
87/13
80/20
c
6
88
d
7
1-bromo-4-
ethylbenzene
100
a
The reaction was conducted with syringe-pump addition of 5 equiv
(relative to arylalkane) of H2O2 (30% in H2O, diluted 5 times in
MeOH) and imidazole (20 equiv relative to Mn) over 1 h at 25 °C to
a solution of arylalkane/imidazole/Mn HaltS mixture (40:4:1) in
b
0.4 mL of MeOH/PBS (pH 7) (1/1). Absolute configuration of
the alcohol of ethylbenzene was determined by comparison with the
authentic optically pure (S)-(−)-1-phenylethanol. Others were
deduced from analogy behavior and the sign of optical rotation.
c
Yield, ee, and alcohol/ketone ratio were determined by chiral HPLC.
Yield, ee, and alcohol/ketone ratio were determined by GC on a
d
chiral CP-Chirasil-Dex column.
manganese, and ruthenium at the central metal have been
introduced as epoxidation catalysts.24 Iodosylbenzene is
generally used as the stoichiometric oxidant for these en-
antioselective reactions. Prior to this work, aqueous hydrogen
peroxide has been used once as the oxidant for enantioselective
epoxidation using a manganese-glycoconjugated porphyrin as
the catalyst in a biphasic medium, but the enantioselectivity was
modest.25 Herein, we will first focus on our catalytic results
obtained with water-soluble manganese porphyrins for epoxi-
dation reaction. Thus, factors affecting the catalytic epoxidation
of olefins by chiral manganese porphyrins and hydrogen peroxide
have been extensively investigated. First, it was recognized that the
presence of water in methanol can be quite successful and that
working in basic buffered solutions deeply increases the efficiency
of the system. A deprotonation of imidazole may play a significant
role in the presence of water, in particular at pH 10.5. The
imidazolate form of the co-catalyst is a much stronger donor than
the imidazole itself, providing electron density to Mn(III) and
thus promoting oxygen transfer. This explanation was recently
suggested by Mohajer, Kopenol, and co-workers.17 The failure of
N-methylimidazole to increase the reaction rate supports this
hypothesis. To the best of our knowledge, efficient asymmetric
oxidation of alkenes with an equimolar amount of H2O2, with
respect of the substrate catalyzed by metalloporphyrins, has never
been achieved.
Using a tetrasulfonated porphyrin, it seems however that the
Mn(V)oxo complex is not stable in basic solution. Thus, the
water-soluble manganese(III) porphyrin complex 1 (λ = 470 nm,
ε = 35.50 cm−1 mM−1) after the addition of 2 equiv of H2O2
generates a new compound (λ = 425 nm, ε = 23.38 cm−1 mM−1)
in H2O at pH 14 (20 °C) (see Figure 4). The absorption band
corresponds to a Mn(IV) species. This compound reacts very
slowly with a large excess of styrene after 4 h, giving back the
starting compounds. The complex 2 in CH3CN (λ = 480 nm,
ε = 39.00 cm−1 mM−1) was treated with tetramethylammonium
hydroxide (TMAH) (λ = 444 nm, ε = 135.31 cm−1 mM−1) and
then with 2 equiv of H2O2 to generate a new compound (λ =
440 nm, ε = 140.50 cm−1 mM−1) and showed a spectrum
(Figure 5) that is very similar to the spectrum observed with the
tetramesitylporphyrin Mn(V) complex, previously reported by
Hydroxylation. Metalloporphyrin catalysts for selective
C−H bond hydroxylation have attracted considerable attention
since the discovery of the first examples reported by Groves
et al. in 1979.26 Most of the reactions have been realized in
Figure 2. Asymmetric epoxidation of alkenes catalyzed by MnHaltS(Cl).
5853
dx.doi.org/10.1021/ic300457z | Inorg. Chem. 2012, 51, 5850−5856

Inorganic Chemistry
Article
Figure 3. Asymmetric hydroxylation of arylalkanes catalyzed by MnHaltS(Cl).
important, the yield may be relatively high, but the enantio-
selectivity may be relatively low. Indeed, Tables 1 and 2 show
that the yield of oxidation and the enantioselectivity in its forma-
tion are not necessarily correlated. Generally, the ee values vary
over a small range (45%−65%), whereas the yield can increase to
completion under the best conditions, as in high pH situations.
Consequently, homolytic cleavage of H2O2, generating OH
radicals, is not probable under our conditions.
CONCLUSION
■
In conclusion, we have developed an efficient and enantiose-
lective epoxidation of terminal alkenes and hydroxylation of C−H
bonds using a safe and easily accessible oxidant catalyzed by
water-soluble chiral manganese porphyrins. Only a small excess
of alkene versus oxidant was necessary. Ongoing work includes
investigations of an extended range of substrates, particularly
those of pharmaceutical importance, further optimization of the
reaction medium, and more experiments to identify the precise
role of chirality in the mechanism.
Figure 4. UV/vis of MnHaltS. Reaction conditions: 2 equiv of H2O2
was injected into a 1-cm UV cuvette containing a solution of MnHaltS
(20 μM) in H2O (pH 14) at room temperature.
EXPERIMENTAL SECTION
■
General. All reactions were performed under argon. Solvents were
distilled from an appropriate drying agent prior to use: CH2Cl2 from
CaH2, CHCl3 from P2O5, 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 precoated aluminum foil sheets (Silica gel 60 with fluorescent
indicator UV254). Compounds were visualized with UV light at
254 nm. Column chromatographies were carried out using silica gel
1
from Merck (0.063−0.200 mm). H NMR and 13C NMR in MeOD
were recorded using Bruker (Advance 500dpx and 300dpx spectrom-
eters) at 500 MHz (or 400 MHz) and 175 MHz, respectively. High-
resolution mass spectra were recorded on a ZabSpec TOF Micromass
spectrometer in ESI positif 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.
All catalytic reactions were controlled on a Varian CP-3380 GC system
that was equipped with a CP-Chirasil-Dex Column. The enantiomeric
excess of epoxides and alcohols were determined on a HPLC Varian
Prostar 218 system equipped with Chiralcel OB-H, OD-H, and OJ-H
columns. The absolute configuration of epoxides and alcohols was
obtained from optical rotations.
Figure 5. UV/vis of MnHalt. Reaction conditions: 2 equiv of H2O2
was injected into a 1-cm UV cuvette containing a solution of MnHalt
(20 μM) in CH3CN, in the presence of TMAH, at room temperature.
Nam and co-workers38 and definitively characterized by Groves
and co-workers as the dioxo complex OMn(V)O.37 It is
worth noting that a Mn(V)dioxo complex bearing four negative
charges from the sulfonate groups will present a supplemental
negative charge, because of the Mn(V) oxidation state. This
could be an explanation for the difficulty in detecting the Mn(V)
dioxo band in water and also to explain the high reactivity of the
system under basic conditions. A more-thorough investigation
will be necessary to confirm this hypothesis.
Because the yield of epoxidation and hydroxylation depends
on the efficiency of the oxygen atom transfer, and the degree of
asymmetric induction depends on the chirality of the catalyst,
we can infer the state of the catalyst from its catalytic activity
under various conditions. The enantioselectivity of the reaction
is induced by the chiral environment around the active site in
the catalyst. If the contribution of H2O2 homolytic cleavage is
Tetrasodium-5,10,15,20-tetrakis[(1S,4R,5R,8S)-10-sulfonato-
1,2,3,4,5,6,7,8-octahydro-1,4:5,8-dimethano anthracene-9-yl]-
porphyrin (H2HaltSNa). Halterman porphyrin15 (100 mg,
0.087 mmol) and sulfuric acid 95% (10 mL) were stirred for 4−5 h
at room temperature. To the resulting solution was added slowly on
ice to give a green mixture. After addition of the ice, some water (30
mL) was added and the pH was regulated at 7 by adding sodium
carbonate. The solution was evaporated and the residue was treated by
a mixture of acetone/methanol to precipitate the salt. The filtrate with
Mn porphyrin was concentrated, solubilized in water, and purified by
passage through a Sephadex columm (G25). The solution was evaporated
by vacuum evaporation. Yield = 82%.
1H NMR (MeOD, 500 MHz): δ 8.78 (Br s, 8H, β pyrrole), 4.60 (s,
8H, CH), 2.72 (s, 8H, CH), 1.97 (m, 16H, CH2), 1.58−0.90 (m, 32H,
CH2).
5854
dx.doi.org/10.1021/ic300457z | Inorg. Chem. 2012, 51, 5850−5856

Inorganic Chemistry
Article
13C NMR (MeOD, 125 MHz): 170.42, 163.45−162.63 (br, weak
signal), 150.25, 142.61, 133.31, 131.18, 129.02−128.25 (br, weak signal),
121.67, 119.30, 117.43, 117.01, 114.68, 45.02, 43.83, 27.65, 27.56.
MALDI-TOF Linear: calcd m/z = 1483.849 [M−3Na+2H]− for
C84H74N4NaO12S4, found 1483.849 (425 ppm). UV−vis (MeOH) λmax
416 nm (ε = 210 cm−1 mM−1), 515 nm (ε = 6.56 cm−1 mM−1),
551 nm (ε = 1.28 cm−1 mM−1), 579 nm (ε = 1.48 cm−1 mM−1), 631 nm
(ε = 0.64 cm−1 mM−1).
complex 1 (9 mg, 5.4 μmol) and imidazole (1.5 mg, 22 μmol) were placed
in a Schlenk tube under argon. The solvent (2 mL MeOH + 2 mL
PBS, pH 7) was then added via syringe, followed by 1,2,3,4-
tetrahydronaphtalene (29.19 mg, 220 μmol). To this solution, a
mixture of hydrogen peroxide (110 μL, 1100 μmol) and imidazole
(8 mg, 117.5 μmol) dissolved in 1 mL of methanol, were slowly added
via a syringe pump over 1 h at 25 °C and the reaction mixture was
stirred for 1 h. The reaction was quenched with NaHCO3. The
solution was extracted with DCM three times and dried over MgSO4.
The product was purified with neutral silica gel (eluent: DCM) to give
1,2,3,4-tetrahydronaphthalen-1-ol (15 mg, 45% yield). 1H NMR
(CDCl3, 400 MHz): δ 7.42−7.43 (m, 1H), 7.19−7.21 (m, 2H), 7.09−
7.11 (m, 1H), 4.79 (t, 1H, J = 4.4 Hz), 2.69−2.87 (m, 2H), 1.88−2.02
(m, 3H), 1.74−1.84 (m, 1H), 1.69 (Br s, 1H). HPLC (chiralcel OB-H;
flow rate: 0.5 mL min−1; hexane/i-PrOH (95/5), 25 °C, detection at
220 nm): tR(+) = 16.4 min, tR(−) = 25 min, [α]22D + 11 (CHCl3), and
Chloro{tetrasodium-5,10,15,20-tetrakis[(1S,4R,5R,8S)-10-
sulfonato-1,2,3,4,5,6,7,8-octahydro-1,4:5,8-dimethano anthra-
cene-9-yl]-porphyrin} manganese(III). Under argon, the porphyrin
(H2)HaltSNa (120 mg, 0.077 mmol) and 2,6-lutidine (83 mg,
0.77 μmol) were dissolved in refluxing dimethylformamide (DMF)
(25 mL). After waiting for several minutes to allow the porphyrin to
dissolve, MnBr2·4H2O (222 mg, 0.77 mmol, 10 equiv) was added to
the solution. The reaction was followed by UV−vis treatment. After
refluxing for 1.5−2 h, the mixture was allowed to cool to room
temperature and evaporated by vacuum evaporation. The crude
product was dissolved in a mixture of hydrochloric acid (5%) and
methanol (15 + 3 mL), and stirred for 20 min. The solvent was then
evaporated and the product was treated with a cationic exchange resin
(Dowex 50) to give a green solid: Yield = 80%. MALDI-TOF Linear:
calcd m/z = 1514.364 [M−4Na+3H]− for C84H75MnN4O12S4, found
1514.363. UV−vis (MeOH) λmax 470 nm (ε = 35.50 cm−1 mM−1),
567 nm (ε = 3.47 cm−1 mM−1), 600 nm (ε = 2.43 cm−1 mM−1).
Gas Chromatography Conditions for the Oxidation of
Styrene Derivatives. CP-Chirasil-Dex column, temperature: 80 °C
(hold 1 min) to 120 at 2.5 °C min−1 over 18 min and then to 180 at
2.5 °C min−1, pressure = 15 psi, injector (pulsed split mode) at 200 °C,
detector (FID) at 220 °C.
1
1-tetralone (12.5 mg, 39% yield). H NMR (CDCl3, 400 MHz): δ 8.03
(dd, 1H, J = 0.8 Hz), 7.48 (m, 1H), 7.3 (t, 1H, J = 7.5 Hz), 7.25 (d, 1H, J =
7.5 Hz), 2.97 (t, 2H, J = 5.9 Hz), 2.66 (dt, 2H, J = 6.1 and 13.1 Hz)
1.74−1.84, 2.11−2.17 (m, 2H). HPLC: tR = 25.9 min.
(S)-(−)-1-Phenylethanol. HPLC tR(R) = 19.8 min, tR(S) = 30.2 min
(chiralcel OB-H; flow rate = 0.5 mL min−1; hexane/i-PrOH (95/5),
25 °C, detection at 220 nm. GC tR(R) = 17.1 min, tR(S) = 17.9 min.
(S)-(+)-1-Indanol. HPLC tR(+) =14.5 min, tR(−) = 42.49 min
(chiralcel OB-H; flow rate = 0.3 mL min−1; hexane/i-PrOH (97/3),
25 °C, detection at 220 nm).
(S)-(−)-1-(4-Methylphenyl)ethanol. HPLC tR(S) = 18.3 min, tR(R) =
24.2 min (chiralcel OB-H; flow rate = 0.5 mL min−1; hexane/i-PrOH
(95/5), 25 °C, detection at 220 nm).
(S)-(−)-1-(3-Methylphenyl)ethanol. HPLC tR(S) = 19.3 min, tR
(R) = 27.9 min (chiralcel OB-H; flow rate = 0.5 mL min−1; hexane/i-
PrOH (95/5), 25 °C, detection at 220 nm).
(S)-(−)-1-(2-Methylphenyl)ethanol. HPLC tR(R) = 16.1 min, tR(S) =
24.5 min (chiralcel OB-H; flow rate = 0.5 mL min−1; hexane/i-PrOH
(95/5), 25 °C, detection at 220 nm).
(S)-(−)-4-Bromo-α-methylbenzenemethanol. HPLC tR(R) = 31.2
min, tR(S) = 32 min (chiralcel OB-H; flow rate = 0.5 mL min−1;
hexane/i-PrOH (95/5), 25 °C, detection at 220 nm). GC: tR(R) =
31.2 min, tR(S) = 32 min.
Typical Procedure for Asymmetric Oxidation of Alkenes
with MnHaltS. (+)-6-Cyano-3,4-epoxy-3,4-dihydro-2,2-dimethyl-
2H-1-benzopyran. Manganese porphyrin complex 1 (6.6 mg, 4 μmol)
and imidazole (1 mg, 14.6 μmol) were placed in a Schlenk tube
under argon. The solvent (3 mL MeOH + 1 mL PBS, pH 7) was then
added via syringe, followed by the alkene 6-cyano-3,4-dihydro-2,2-
dimethyl-2H-1-benzopyran (30 mg, 162 μmol). To this solution, a
mixture of hydrogen peroxide (48.5 μL, 486 μmol) and imidazole
(5.34 mg, 78.4 μmol) dissolved in 1 mL of methanol, were slowly
added via a syringe pump over 4 h at 25 °C and the reaction mixture
was stirred for 1 h. The reaction was quenched with NaHCO3. The
solution was extracted with dichloromethane (DCM) three times and
then dried over MgSO4. The product was purified with neutral silica
gel (eluent: DCM) to give the corresponding epoxide (16 mg, 49%
AUTHOR INFORMATION
■
Corresponding Author
*Tel.: 33(0)223236285. Fax: 33(0)223235637. E-mail: gerard.
simonneaux@univ-rennes1.fr.
1
yield). H NMR (MeOD, 400 MHz): δ 7.82 (d, 1H, J = 2 Hz), 7.6
(dd, 1H, J = 2 Hz), 6.88 (d, 1H, J = 8.5 Hz), 4.02 (d, 1H, J = 4.4 Hz),
3.66 (d, 1H, J = 4.4 Hz), 1.55 (s, 3H), 1.28 (s, 3H). HPLC (chiralcel
OJ-H; flow rate = 0.5 mL min−1; hexane/i-PrOH (70/30), 25 °C,
detection at 220 nm): tR(+) = 24.7 min, tR(−) = 43 min. [α]22D + 62°,
(MeOH).
(R)-(+)-Styrene Oxide. GC tR(R) = 10.2 min, tR(S) = 10.9 min.
(R)-(+)-4-Methylstyrene Epoxide. HPLC tR(S) = 34.5 min, tR(R) =
37.3 min (chiralcel OD-H; flow rate = 0.3 mL min−1; hexane/i-PrOH
(98/2), 25 °C, detection at 220 nm.
(R)-(+)-3-Methylstyrene Oxide. GC tR(R) = 14.2 min, tR(S) = 14.7 min.
(R)-(+)-2-Methylstyrene Oxide. GC tR(R) = 14.3 min, tR(S) = 14.9 min.
(R)-(+)-4-Trifluoromethylstyrene Oxide. GC tR(R) = 11.9 min,
tR(S) = 12.8 min.
Notes
The authors declare no competing financial interest.
REFERENCES
■
(1) Lindstrom, U. M. Chem. Rev. 2002, 102, 2751−2772.
̈
(2) Li, C. J. Chem. Rev. 2005, 105, 3095−3165.
(3) Jung, Y.; Marcus, R. A. J. Am. Chem. Soc. 2007, 129, 5492−5502.
(4) Deng, Y.; Ma, Z.; Wang, K.; Chen, J. Green Chem. 1999, 1, 275−
276.
(5) Anastas, P. T.; Kirchhoff, M. M. Acc. Chem. Res. 2002, 35, 686−
694.
(6) De Faveri, G.; Ilyashenko, G.; Watkinson, M. Chem. Soc. Rev.
2011, 40, 1722−1760.
(R)-(+)-3-Trifluoromethylstyrene Oxide. GC tR(S) = 10.9 min, tR(S) =
11.1 min.
(R)-(+)-2-Trifluoromethylstyrene Oxide. GC tR(R) = 13.4 min,
tR(S) = 13.9 min.
(R)-(+)-4-Chlorostyrene Oxide. GC tR(R) = 8.1 min, tR(S) = 8.4 min.
(1R, 2S)-(−)-Epoxyindane. HPLC tR(1S,2R) = 30.1 min, tR(1R,2S) =
43 min (chiralcel OB-H; flow rate = 0.5 mL min−1; hexane/i-PrOH
(95/5), 25 °C, detection at 220 nm).
(1R,2S)-(+)-1,2-Dihydronaphthalene Oxide. GC tR(1S,2R) = 10.1 min,
tR(1R,2S) = 10.6 min.
(7) Arends, I. W. C. E. Angew. Chem., Int. Ed. 2006, 45, 6250−6252.
(8) Gelalcha, F. G.; Anilkumar, G.; Tse, M. K.; Bruckner, A.; Beller,
̈
M. Chem.Eur. J. 2008, 14, 7687−7698.
(9) Meunier, B. Chem. Rev. 1992, 92, 1411−1456.
(10) Collman, J. P.; Lee, V. J.; Kellen-Yuen, C. J.; Zang, X.; Ibers, J.
A.; Brauman, J. I. J. Am. Chem. Soc. 1995, 117, 692−703.
(11) Ferrand, Y.; Daviaud, R.; Le Maux, P.; Simonneaux, G.
Tetrahedron: Asymmetry 2006, 17, 952−960.
(12) Le Maux, P.; Simonneaux, G. Chem. Commun. 2011, 47, 6957−
6959.
Typical Procedure for Asymmetric Oxidation of Alkanes with
MnHaltS (1). 1,2,3,4-tetrahydronaphtalen-1-ol: Manganese porphyrin
5855
dx.doi.org/10.1021/ic300457z | Inorg. Chem. 2012, 51, 5850−5856

Inorganic Chemistry
Article
(13) Groves, J. T.; Kruper, W. J.; Haushalter, R. C. J. Am. Chem. Soc.
1980, 102, 6377−6380.
(14) Arunkumar, C.; Lee, Y. M.; Lee, J. Y.; Fukuzumi, S.; Nam, W.
Chem.Eur. J. 2009, 15, 11482−11489.
(15) Halterman, R. L.; Jan, S. T. J. Org. Chem. 1991, 56, 5253−5254.
(16) Nicolas, I.; Le Maux, P.; Simonneaux, G. Tetrahedron Lett. 2008,
49, 5793−5795.
(17) Mahmoudi, L.; Mohajer, D.; Kissner, R.; Koppenol, W. H.
Dalton Trans. 2011, 40, 8695−8700.
(18) Renaud, J. P.; Battioni, P.; Bartoli, J. F.; Mansuy, D. J. Chem. Soc,
Chem. Commun. 1985, 888−889.
(19) Halterman, R. L.; Jan, S. T.; Nimmons, H. L.; Standlee, D. J.;
Khan, M. A. Tetrahedron 1997, 53, 11257−11276.
(20) Jin, N.; Lahaye, D. E.; Groves, J. T. Inorg. Chem. 2010, 49,
11516−11524.
(21) Minisci, F.; Fontana, F.; Araneo, S.; F., R.; Banfi, S.; Quici, S.
J. Am. Chem. Soc. 1995, 117, 226−232.
(22) Zhuang, W.; Marigo, M.; Jorgensen, K. A. Org. Biomol. Chem.
2005, 3, 3883−3885.
(23) Groves, J. T.; Myers, R. S. J. Am. Chem. Soc. 1983, 105, 5791−
5796.
(24) Rose, E.; Andrioletti, B.; Zrig, S.; Quelquejeu-Etheve, M. Chem.
Soc. Rev. 2005, 34, 573−583.
(25) Vilain-Deshayes, S.; Robert, A.; Maillard, P.; Meunier, B.;
Momenteau, M. J. Mol. Catal. A: Chem. 1996, 113, 23−34.
(26) Groves, J. T.; Nemo, T. E.; Myers, R. S. J. Am. Chem. Soc. 1979,
101, 1032−1033.
(27) Yang, J.; Gabriele, B.; Belvedere, S.; Huang, Y.; Breslow, R.
J. Org. Chem. 2002, 67, 5057−5067.
(28) Spasojevic, I.; Colvin, O. M.; Warshany, K. R.; Batinic-Haberle,
I. J. Inorg. Biochem. 2006, 100, 1897−1902.
(29) Che, C. M.; Lo, V. K. Y.; Zhou, C. Y.; Huang, J. S. Chem. Soc.
Rev. 2011, 40, 1950−1975.
(30) Lu, H.; Zhang, X. P. Chem. Soc. Rev. 2011, 40, 1899−1909.
(31) Borovik, A. S. Chem. Soc. Rev. 2011, 40, 1870−1874.
(32) De Angelis, F.; Jin, N.; Car, R.; Groves, J. T. Inorg. Chem. 2006,
45, 4268−4276.
(33) Groves, J. T.; Shalyev, K.; Lee, J. The Porphyrin Handbook, Vol. 4;
Kadish, K. M., Smith, K. M., Guilard, R.; Academic Press, San Diego,
CA, 2000; pp 17−40.
(34) Meunier, B.; Robert, A.; Pratviel, G.; Bernadou, J. The Porphyrin
Handbook, Vol. 4; Kadish, K. M., Smith, K. M., Guilard, R.; Academic
Press, San Diego, CA, 2000; pp 119−187.
(35) Groves, J. T.; Lee, J.; Marla, S. S. J. Am. Chem. Soc. 1997, 119,
6269−6273.
(36) Jin, N.; Groves, J. T. J. Am. Chem. Soc. 1999, 121, 2923−2924.
(37) Jin, N.; Ibrahim, M.; Spiro, T. G.; Groves, J. T. J. Am. Chem. Soc.
2007, 129, 12416−12417.
(38) Song, W. J.; Seo, M. S.; George, S. B.; Ohta, T.; Song, R.; Kang,
M. J.; Tosha, T.; Kitagawa, T.; Solomon, E. I.; Nam, W. J. Am. Chem.
Soc. 2007, 129, 1268−1277.
5856
dx.doi.org/10.1021/ic300457z | Inorg. Chem. 2012, 51, 5850−5856