Stereoselective alkane hydroxylations by metal salts and m-chloroperbenzoic acid

Article abstract of DOI:10.1016/S0040-4039(02)01060-2

Simple metal (M=Mn, Fe, Co) perchlorates associated with m-chloroperbenzoic acid are able to conduct stereoselective alkane hydroxylations via a mechanism involving metal-based oxidants; the catalytic activity of the metal salts is in the order of Co(ClO₄)₂>Mn(ClO₄)₂>Fe (ClO₄)₂.

Full text of DOI:10.1016/S0040-4039(02)01060-2

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 5487–5490
Stereoselective alkane hydroxylations by metal salts and
m-chloroperbenzoic acid
a,
a
a
b
Wonwoo Nam, * Ju Yeon Ryu, Inwoo Kim and Cheal Kim
a
Department of Chemistry and Division of Molecular Life Sciences (BK21), Ewha Womans University, Seoul 120-750,
South Korea
b
Department of Fine Chemistry, Seoul National University of Technology, Seoul 139-743, South Korea
Received 4 March 2002; revised 27 May 2002; accepted 31 May 2002
Abstract—Simple metal (M=Mn, Fe, Co) perchlorates associated with m-chloroperbenzoic acid are able to conduct stereoselec-
tive alkane hydroxylations via a mechanism involving metal-based oxidants; the catalytic activity of the metal salts is in the order
of Co(ClO ) >Mn(ClO ) >Fe(ClO ) . © 2002 Elsevier Science Ltd. All rights reserved.
4
2
4 2
4 2
The selective hydroxylation of unactivated CꢀH bonds
of alkanes by metal complexes are of significant impor-
tance in both synthetic chemistry and industrial pro-
salts without porphyrin and non-porphyrin ligands are
able to conduct stereospecific alkane hydroxylations,
we have studied alkane hydroxylations with simple
metal salts and peracids. We now report that the first-
row transition metal perchlorates associated with m-
chloroperbenzoic acid (m-CPBA) are indeed able to
hydroxylate alkanes stereospecifically via a mechanism
involving metal-based oxidants and that, among the
tested metal salts, cobalt perchlorate shows the highest
reactivity.
cesses.
Since
heme-
and
nonheme-containing
monooxygenase enzymes catalyze the most energetically
difficult hydroxylation of alkanes under physiological
reaction conditions, biomimetic alkane hydroxylations
using the model compounds of monooxygenase
enzymes have received much attention in the communi-
1,2
ties of bioinorganic and oxidation chemistry. It has
been demonstrated that synthetic metal complexes with
porphyrin and non-porphyrin ligands mimic the chem-
istry of the monooxygenases and that alkane hydroxyl-
ations by the model compounds proceed via a
mechanism involving metal-based oxidants (e.g. high-
The catalytic hydroxylation of alkanes by metal
perchlorates and m-CPBA was carried out in a solvent
mixture of CH CN and CH Cl at room temperature.
3
2
2
Among the tested first-row metal salts, manganese(II),
iron(II), and cobalt(II) perchlorates yielded oxygenated
products in the hydroxylation of cyclohexane by m-
CPBA, whereas the formation of oxygenated products
was not detected in the reactions of other metal
perchlorates such as Cr(ClO ) , Ni(ClO ) , Cu(ClO ) ,
3
valent metal oxo intermediates). It has also been
shown that metal salts associated with peracids conduct
alkane hydroxylations via a non-radical type of oxida-
4
,5
tion reactions.
4
3
4 2
4 2
Very recently, Burgess and co-worker reported that
manganese(II) salts without organic ligands catalyze
epoxidation of olefins by aqueous 30% H O in bicar-
and Zn(ClO ) (data not shown). Therefore, we have
4
2
studied the alkane hydroxylation reactions with the
perchlorate salts of manganese(II), iron(II), and
cobalt(II) in detail. As the results show in Table 1 [see
2
2
6
bonate buffer, yielding epoxides exclusively. The
authors suggested that an active oxidant that reacts
−
the column of M(ClO ) ], the reaction of Co(ClO )
with manganese salts is percarbonate (HCO ), which is
4 2 4 2
4
with m-CPBA gave the highest yields of oxygenated
generated in situ by the reaction of H O and bicarbon-
2
2
7
products (e.g. ꢀ90% yield based on m-CPBA used in
the hydroxylation of cis-1,2-dimethylcyclohexane),
whereas only small amounts of oxygenated products
were yielded in the reaction of Fe(ClO ) with m-CPBA
ate. As an initial attempt to find out whether metal
4
2
Keywords: biomimetic; alkane hydroxylation; metal perchlorate;
monooxygenases; catalysis; m-chloroperbenzoic acid.
(
e.g. ꢀ15% yield based on m-CPBA in the hydroxyla-
8
*
Corresponding author. Tel.: +82 2 3277 2392; fax: +82 2 3277 2384;
tion of cis-1,2-dimethylcyclohexane). These results
e-mail: wwnam@ewha.ac.kr
indicate that cobalt salt is the most efficient catalyst in
0
040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)01060-2

5
488
W. Nam et al. / Tetrahedron Letters 43 (2002) 5487–5490
a,b
Table 1. Hydroxylation of alkanes by m-CPBA catalyzed by simple metal salts and their metalloporphyrin complexes
Substrate
Products
Yields of products (%)c
M(ClO4)2
Fe
M(TPFPP)(ClO4)d
Coe
Fe Mn
M= Co
Mn
cis-1,2-Dimethylcyclohexane
trans-1,2-Dimethylcyclohexane
cis-1,2-Dimethylcyclohexanol
trans-1,2-Dimethylcyclohexanol
8194 1092 2592 6093
B1 B1 B1 B1
1292 791
5593 4093
B1 B1
2092 1692
f
f
2,3- and 3,4-Dimethylcyclohexanol
891 491
cis-1,2-Dimethylcyclohexanol
trans-1,2-Dimethylcyclohexanol
0
0
0
0
0
0
6793 191
1692 491
2893 491
2993 391
892 4093
1492
991
2,3- and 3,4-Dimethylcyclohexanol
2293 1692
2193 2593
691 2193
4293 3693
6593 4493
Cyclohexane
Cyclohexanol
Cyclohexanone
591
791
a
Caution! Since perchlorate salts of metals and metal complexes with organic ligands are potentially explosive, only small amounts of perchlorate
−
3
salts should be handled with great care. Into a reaction solution of a metal catalyst (1×10 mmol) and substrate (1 mmol) in a solvent mixture
−
2
−2
(
0.5 mL) of CH CN and CH Cl (1:1), m-CPBA (2×10 mmol, diluted in 40 mL of CH CN) was added in two additions (1×10 mmol each)
3
2
2
3
at 30 min intervals at room temperature. After the reaction mixture was stirred for 1 h, the reaction solution was directly analyzed by GC and/or
GC/MS. Product yields were determined by comparison with standard curves of known authentic samples. Since the hydroxylation reactions
were not affected by molecular oxygen, all reactions were performed in air.
A control reaction showed that hydroxylation of cyclohexane by m-CPBA does not occur in the absence of metal catalysts.
Based on the amount of m-CPBA added. All reactions were run at least in triplicate, and the data reported represent the average of these
reactions.
b
c
d
e
f
All M(TPFPP)(ClO ) complexes were prepared by stirring equimolar amounts of M(TPFPP)Cl with Ag(ClO ) followed by filtering through a
4
4
0
.45 mM filter. The resulting solutions were used immediately for further studies.
m-CPBA was added in two additions at 2 h intervals due to the slow reaction of Co(TPFPP)(ClO ) with m-CPBA (see Fig. 2). Total reaction
4
2
time was 4 h.
The yields of alcohol products were calculated with commercially available 2,3-dimethylcyclohexanol, with an assumption that the response
factors for the alcohols are identical.
terms of yielding oxygenated products and that the
catalytic activity of the metal salts is in the order of
Co(ClO ) >Mn(ClO ) >Fe(ClO ) . We also found that
dimethylcyclohexane hydroxylations, we carried out the
following reactions and reached the conclusion that the
formation of cyclohexanone was not the result of the
generation of a long-lived alkyl radical but the result of
further oxidation of cyclohexanol product. First, when
the hydroxylation of cyclohexane by Co(ClO4)2 and
m-CPBA was carried out in the absence and presence
4
2
4 2
4 2
the alkane hydroxylations by Co(ClO ) and Mn(ClO )
4
2
4 2
were highly stereoselective, in which the hydroxylation
of cis-1,2-dimethylcyclohexane afforded cis-1,2-
dimethylcyclohexanol with >98% retention and the
hydroxylation of trans-1,2-dimethylcyclohexane yielded
trans-1,2-dimethylcyclohexanol as a major product with
no formation of its epimer. The high stereoselectivity
observed in the hydroxylation of cis- and trans-1,2-
dimethylcyclohexanes strongly indicate that the alkane
hydroxylations do not proceed via a typical free-radical
of O , the yields of cyclohexanol and cyclohexanone
2
products were the same in both reactions (data not
shown). This result indicates that the formation of the
products was not affected by the presence of O and
2
that O was not involved in the formation of cyclohex-
2
anone (see Eqs. (1) and (2)). Second, when the cyclo-
hexane hydroxylation was carried out by adding
m-CPBA incrementally, the formation of cyclohexanol
was dominant at the beginning of the reaction (Fig. 1).
As the amount of m-CPBA added to the reaction
solution gradually increased, the amount of cyclohex-
anol product did not change, but the yield of cyclohex-
anone increased linearly and it became the major
product. These results demonstrate that the formation
of cyclohexanone was the result of further oxidation of
cyclohexanol product (Eq. (3)).
3,9,10a
mechanism involving a long-lived alkyl radical.
However, the formation of equal amounts of cyclohex-
anol and cyclohexanone in the hydroxylation of cyclo-
hexane by Co(ClO ) and m-CPBA may suggest the
4
2
generation of a long-lived alkyl radical followed by the
formation of an alkylperoxyl radical by the reaction of
10,11
the alkyl radical with O2 (Eq. (1)).
Russell-type
termination of the alkylperoxyl radical results in the
formation of equimolar amounts of alcohol and ketone
1
1
(
Eq. (2)).
’
’
c-C H +O “c-C H OO
(1)
(2)
6
11
2
6
11
’
’
c-C H OO +c-C H OO “
6
11
6
11
c-C H OH+c-C H =O+O
2
6
11
6
11
(3)
Since the result of the cyclohexane hydroxylation was
inconsistent with that of the cis- and trans-1,2-
Other supporting evidence for the latter conclusion was
obtained by carrying out a competitive reaction with a

W. Nam et al. / Tetrahedron Letters 43 (2002) 5487–5490
5489
1
00:1 mixture of cyclohexane and cyclooctanol (Eq.
Then, the kinetic isotope effect (KIE) for the cyclohex-
†
(
4)).
anol formation by Co(ClO ) and m-CPBA was deter-
4
2
mined by carrying out an intermolecular competitive
hydroxylation with cyclohexane and cyclohexane-d12
under the reaction conditions where cyclohexanol was
‡
yielded as a major product (Eq. (5). The k /k ratio of
H
D
8
±1 obtained in the KIE study was the same as that
III +
obtained in the reaction of [Co (TPFPP)] [TPFPP=
meso-tetrakis(pentafluorophenyl)porphinato dianion]
and m-CPBA.
13
(
4)
In the competitive reaction, the oxidation of cyclooc-
tanol took place preferentially, and the ratio of alcohol
to alkane oxidation was determined to be ꢀ2700 after
‡
statistical correction (see footnote for the determina-
(
5)
tion of product percentages). We therefore conclude
that ketone is formed as the product of alcohol oxida-
tion and that the intermediate generated in the reaction
of Co(ClO ) and m-CPBA selectively oxidizes alcohols
1
8
We also performed an O-labeled water experiment in
the reaction of Co(ClO ) and m-CPBA in order to
understand whether the reactive species responsible for
hydroxylating alkanes exchanges its oxygen with
labeled water. The result in Eq. (6) shows that some
of the oxygen in the cyclohexanol product came from
4
2
4
2
1
2
to give the corresponding ketone products.
14
18
§
18
H2 O, and the observation of the O-incorporation
1
8
from H2 O into the alcohol product may suggest the
involvement of a high-valent cobalt-oxo species as a
reactive intermediate in the hydroxylation of alkanes by
1
5
Co(ClO ) and m-CPBA.
4
2
(6)
Lastly, the effect of porphyrin ligand on the reactivity
of metal ions has been investigated by performing the
alkane hydroxylations with metal salts and their metal-
loporphyrins under the identical reaction conditions.
The results in Table 1 show that the reactivity of the
iron ion markedly increased upon binding to an elec-
tron-deficient porphyrin ligand, resulting in high yields
of oxygenated products with a high alcohol to ketone
ratio and an almost complete retention of stereochem-
Figure 1. Yields (turnover number) of cyclohexanol (ꢀ) and
cyclohexanone (ꢁ) as a function of equivalents of m-CPBA
added. Inset: Magnification of the region of 0–20 equiv. of
m-CPBA. Turnover numbers were calculated as moles of
products per mole of Co(ClO ) . Reaction conditions: Into a
istry [Table 1, compare the results of Fe(ClO ) and
4
2
4 2
−
3
reaction solution of Co(ClO ) (1×10 mmol) and cyclohex-
Fe(TPFPP)(ClO )]. In the case of the manganese ion,
4
2
4
ane (1 mmol) in a solvent mixture (0.5 mL) of CH CN and
the yields of oxygenated products were almost doubled
3
CH Cl2 (1:1), m-CPBA (diluted in 20 mL of CH CN) was
in the reactions where Mn(TPFPP)(ClO ) was used as a
2
3
4
added at 30 min intervals at room temperature. The yields of
products were analyzed by sampling the reaction solution
before the new addition of m-CPBA.
catalyst [Table 1, compare the results of Mn(ClO ) and
4
2
Mn(TPFPP)(ClO )]. In contrast to the iron and man-
4
ganese cases, the yields of oxygenated products dimin-
ished slightly in the reactions where the cobalt ion was
bound to a porphyrin ligand [Table 1, compare the
†
m-CPBA (5×10−3 mmol, diluted in 20 mL of CH CN) was added to
3
−
3
a reaction solution containing Co(ClO4)2 (1×10 mmol) and sub-
strates (1 mmol of cyclohexane and 0.01 mmol of cyclooctanol) in
a solvent mixture (0.5 mL) of CH CN and CH Cl (1:1). After the
§
The 18O-labeled water experiment was run in the presence of H 18O
2
1
8
(10 mL, 95% O enriched) under the reaction conditions described
3
2
2
reaction mixture was stirred for 10 min, the reaction solution was
analyzed by GC. The yields of products were determined to be
in Table 1, footnote a. The yields of cyclohexanol and cyclohex-
1
6
18
anone were 27 and 26%, respectively. The O and O composi-
tions in cyclohexanol were analyzed by GC/MS (Hewlett–Packard
5890 II Plus gas chromatograph interfaced with Hewlett–Packard
Model 5989B mass spectrometer) and determined by the relative
−
3
cyclohexanol (1.1×10 mmol, 22% yield based on m-CPBA), cyclo-
−
3
−3
hexanone (0.4×10 mmol, 8%), and cyclooctanone (3.3×10 mmol,
6%).
6
‡
16
18
The reaction conditions were the same as described in footnote †
except that equal amounts (1 mmol each) of competing substrates
were used.
abundance of mass peaks at m/z=57 for O and 59 for O. A
control experiment showed that cyclohexanol does not exchange its
oxygen with water under the experimental conditions.

5
490
W. Nam et al. / Tetrahedron Letters 43 (2002) 5487–5490
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1
3
results of Co(ClO ) and Co(TPFPP)(ClO )]. More-
4
2
4
over, the formation of oxygenated products was found
to be much slower in the hydroxylation of cis-1,2-
dimethylcyclohexane by Co(TPFPP)(ClO ) than by
Co(ClO4)2 (Fig. 2). With the previous results that
4
cobalt porphyrins containing electron-rich porphyrin
+
ligand such as [Co(TMP)]
[TMP=meso-tetra-
6
. Lane, B. S.; Burgess, K. J. Am. Chem. Soc. 2001, 123,
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of simple cobalt salt compared to cobalt porphyrin
complexes suggests that as the electron-richness of
cobalt ion increases, the activity of cobalt ion toward
alkane hydroxylation becomes lower. In conclusion, the
results presented above indicate that, as we have
expected, there is a porphyrin ligand effect on the
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2
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1
1
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2
2
6,7
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Acknowledgements
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15. Although the structure of the high-valent cobalt-oxo
This research was supported by the Korea Research
Foundation (DP0270).
species is not clear at this moment, possible structures for
the suggested cobalt-oxo species are Co =OlCo –O .
V
IV
’