Biomimetic alkane hydroxylation by cobalt(III) porphyrin complex and m-chloroperbenzoic acid

Article abstract of DOI:10.1039/b103986p

The catalytic hydroxylation of alkanes by an electron-deficient cobalt(III) porphyrin complex and m-chloroperbenzoic acid yielded alcohols as major products with a high k_H/k_D value, > 99% retention of stereochemistry, and a high regioselectivity; a high-valent cobalt - oxo porphyrin complex was suggested as a reactive hydroxylating intermediate.

Full text of DOI:10.1039/b103986p

Biomimetic alkane hydroxylation by cobalt(III) porphyrin complex and
m-chloroperbenzoic acid†
Wonwoo Nam,*a Inwoo Kim,a Youngmee Kima and Cheal Kim*b
a Department of Chemistry and Division of Molecular Life Sciences (BK 21), Ewha Womans University,
Seoul 120-750, Korea. E-mail: wwnam@mm.ewha.ac.kr
b Department of Fine Chemistry, Seoul National University of Technology, Seoul 139-743, Korea
Received (in Cambridge, UK) 3rd May 2001, Accepted 25th May 2001
First published as an Advance Article on the web 20th June 2001
The catalytic hydroxylation of alkanes by an electron-
deficient cobalt(III) porphyrin complex and m-chloroperben-
zoic acid yielded alcohols as major products with a high
kH/kD value, > 99% retention of stereochemistry, and a high
regioselectivity; a high-valent cobalt–oxo porphyrin complex
was suggested as a reactive hydroxylating intermediate.
The
catalytic
hydroxylation
of
alkanes
by
Co(TPFPP)(CF3SO3) [1, TPFPP = meso-tetrakis(pentafluoro-
phenyl)porphinato dianion] and m-CPBA was carried in a
solvent mixture of CH3CN and CH2Cl2 at rt.‡ The results in
Table 1 show that alcohols were yielded as major products with
high alcohol to ketone ratios under mild reaction conditions,
indicating that m-CPBA is a competent terminal oxidant for the
alkane hydroxylations by the cobalt porphyrin complex.§¶∑ The
kinetic isotope effect (KIE) for the cyclohexanol formation by 1
and m-CPBA was determined to be 8 ± 1 by carrying out
intermolecular competitive hydroxylation with cyclohexane
and cyclohexane-d12 (Table 1, entry 5).5,6
The stereochemistry of the alkane hydroxylations by 1 and m-
CPBA was investigated with cis- and trans-1,2-dimethylcyclo-
hexane. The alkane hydroxylations were highly stereospecific
with > 99% retention; no formation of isomerized alcohol
products (e.g. the formation of trans-1,2-dimethylcyclohexanol
in the hydroxylation of cis-1,2-dimethylcyclohexane was
observed (Table 1, entries 2 and 3). Interestingly, only small
amounts of secondary alcohol products such as 2,3- and
3,4-dimethylcyclohexanol were formed in these reactions, and
these results are different from those of the hydroxylations of
cis- and trans-1,2-dimethylcyclohexane by iron complexes of
porphyrin and non-porphyrin ligands.6 In the latter reactions,
moderate to high amounts of secondary alcohol products were
yielded. In a competitive hydroxylation of cis- and trans-
1,2-dimethylcyclohexane, the former was found to react 2.9
times faster than the latter (Table 1, entry 6). The alkane
hydroxylation by 1 and m-CPBA was also found to be highly
Cytochrome P-450 enzymes are capable of catalyzing a variety
of oxidation reactions, including the most energetically difficult
hydroxylation of unactivated C–H bonds of alkanes.1 Since
selective oxygenations of hydrocarbons under mild conditions
are of importance in both synthetic chemistry and industrial
processes, biomimetic hydroxylation reactions with synthetic
metalloporphyrins have been intensively studied over the past
two decades.2 It has been shown that metalloporphyrins
containing iron, manganese, and ruthenium ions, especially
with electron-deficient porphyrin ligands, are efficient catalysts
for the hydroxylation of alkanes by various oxidants.2,3
However, cobalt porphyrin complexes have been rarely used as
catalysts in alkane hydroxylation reactions, since the reactions
of cobalt complexes with hydroperoxides often proceed via
free-radical type of oxidation reactions.4 In the present study,
we report for the first time that an electron-deficient cobalt(III
)
porphyrin complex catalyzes the hydroxylation of alkanes by m-
chloroperbenzoic acid (m-CPBA) via a non-radical type of
oxidation reaction.
† Electronic supplementary information (ESI) available: Fig. S1. See http:
//www.rsc.org/suppdata/cc/b1/b103986p/
Table 1 Hydroxylation of alkanes by 1 and m-CPBAa
Entry Substrate
Products
Yields (%)b,c
A. Hydroxylation of alkanes
1
Cyclohexane
Cyclohexanol
Cyclohexanone
39 ± 4
8 ± 2
65 ± 5
< 1
5 ± 1
0
43 ± 4
8 ± 2
53 ± 3
9 ± 2
> 1
2
cis-1,2-Dimethylcyclohexane
cis-1,2-Dimethylcyclohexanol
trans-1,2-Dimethylcyclohexanol
2,3- and 3,4-Dimethylcyclohexanold
cis-1,2-Dimethylcyclohexanol
trans-1,2-Dimethylcyclohexanol
2,3- and 3,4-Dimethylcyclohexanold
Adamantan-1-ol
3
4
trans-1,2-Dimethylcyclohexane
Adamantanee
Adamantan-2-ol
Adamantan-2-one
B. Competitive hydroxylation of alkanesf
5
Cyclohexane
Cyclohexanol
32 ± 3
+
Cyclohexane-d12
Cyclohexanol-d12
4 ± 1
6
cis-1,2-Dimethylcyclohexane
+
cis-1,2-Dimethylcyclohexanol
41 ± 3
trans-1,2-Dimethylcyclohexane
trans-1,2-Dimethylcyclohexanol
14 ± 1
a See footnote ‡ for detailed reaction procedures. Since the hydroxylation reactions were not affected by molecular oxygen, all the reactions were performed
in air. b All reactions were run at least triplicate, and the yields reported represent the average of these reactions. c Based on the amount of m-CPBA added.
d The yield of 3,4-dimethylcyclohexanol was determined with commercially available 2,3-dimethylcyclohexanol, with an assumption that the response
factors for these alcohols are identical. e Reaction was run with 0.2 mmol of adamantane in CH2Cl2 (0.5 mL) due to the low solubility of adamantane. f Equal
amounts of competing substrates (1 mmol each) were used.
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Chem. Commun., 2001, 1262–1263
This journal is © The Royal Society of Chemistry 2001
DOI: 10.1039/b103986p

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regioselective, in which a high degree of selectivity for tertiary
C–H bond over secondary C–H bond was observed in the
hydroxylation of adamantane (Table 1, entry 4). The ratio of
3°/2° oxygenated products was ~ 18 after statistical correction;
such a high 3°/2° ratio was usually observed in iron and
manganese porphyrin-catalyzed hydroxylation of adaman-
tane.7
The results presented above demonstrate unambiguously that
the alkane hydroxylations by 1 and m-CPBA occur via radical-
free oxidation reactions:6 (1) the fact that alcohols were the
major products with high alcohol to ketone ratios and the ratios
of alcohol to ketone products were not affected by the presence
of O2, (2) a high KIE value for the formation of cyclohexanol,
and (3) a complete retention of stereochemistry in the
hydroxylations of cis- and trans-alkanes. Then, what is the
nature of a hydroxylating intermediate? Is a high-valent cobalt–
oxo porphyrin complex involved as a reactive species? Since
isotopically labeled water (H218O) experiments are a useful
mechanistic probe to test the involvement of high-valent metal
oxo intermediates in metal-mediated oxygen atom transfer
reactions,8 the hydroxylation of cyclohexane by 1 and m-CPBA
was conducted in the presence of a small amount of H218O [eqn.
(1)].** As the results show in Table 2 (entries 1 and 2), some of
m-CPBA. Future studies will focus on attempts to understand
the exact nature of the reactive intermediate.
This work was supported by the Korea Research Foundation
(KRF-99-042-D00068).
Notes and references
‡ Reaction conditions: m-CPBA (5 3 1023 mmol, diluted in 20 mL of
CH3CN) was added to a reaction solution containing 1 (1 3 1023 mmol) and
substrate (1 mmol) in a solvent mixture (0.5 mL) of CH3CN and CH2Cl2
(1+1) at rt. After the reaction mixture was stirred for 1 h, the reaction
solution was directly analyzed by a Hewlett-Packard 5890 II Plus gas
chromatograph with a FID detector and 30 m capillary column (Hewlett-
Packard HP-1 or HP-5). Product yields were determined by comparison of
peak area with that of decane or dodecane standard.
§ By following the time course of the hydroxylation of cyclohexane by 1
with 5 eq. of m-CPBA, we found that the alkane hydroxylation by 1 and m-
CPBA takes place slowly, and the formation of cyclohexanol lasted for 1 h
(data not shown).
¶ A control reaction carried out in the absence of the cobalt porphyrin
catalyst did not show the formation of cyclohexanol and cyclohexanone
products. Also, other cobalt porphyrin complexes such as
Co(TMP)(CF3SO3) [TMP = meso-tetramesitylporphinato dianion] yielded
only small amounts of cyclohexanol ( ~ 8%) and cyclohexanone ( ~ 2%). All
cobalt(III) porphyrin complexes were obtained from Mid-Century and used
without further purification.
∑ The catalytic activity of the cobalt porphyrin complex was examined by
adding 50 eq. of m-CPBA (10 aliquots of 5 eq. of m-CPBA each at 1 h time
intervals) into a reaction solution containing 1 (1 3 1023 mmol) and cis-
1,2-dimethylcyclohexane (1 mmol). Total reaction time was 10 h (see
footnote ‡ for detailed experimental procedures). The yield of cis-
1,2-dimethylcyclohexanol was 40% based on m-CPBA added, equivalent to
20 turnovers (see Fig. S1 for a plot of eq. of m-CPBA added vs. turnover
number). By comparing UV-vis spectra of 1 taken before and after the
reaction, we found that about 20% of the cobalt porphyrin catalyst was
degraded.
(1)
the oxygen in the cyclohexanol product came from H218O and
the percentage of 18O in the alcohol product was dependent on
the amount of H218O present in the reaction media. These
results imply that a reactive hydroxylating intermediate gen-
erated in the reaction of 1 and m-CPBA exchanges its oxygen
with labeled water prior to the oxygen atom transfer from the
intermediate to cyclohexane.8,9 For comparison, the 18O-
labeled water experiment was carried out with an iron porphyrin
complex, Fe(TPFPP)(CF3SO3), under the identical reaction
** 18O-labeled water experiments were performed under the identical
reaction conditions described in footnote ‡ except that H218O (5 mL,
95% 18O enriched), cyclohexane (0.5 mmol), and 15 eq. of m-CPBA (3
aliquots of 5 eq. of m-CPBA each at 1 h time intervals) were used. The 16
O
and 18O compositions in cyclohexanol were determined by the relative
abundances of mass peaks at m/z = 57 for 16O and 59 for 18O (HP 5989B
mass spectrometer). A control experiment showed that cyclohexanol does
not exchange its oxygen with water under the experimental conditions.
conditions, since we have shown previously that an oxoiron(IV
)
porphyrin cation radical complex was generated as a reactive
hydroxylating intermediate in the hydroxylation of alkanes by
Fe(TPFPP)(CF3SO3) and m-CPBA.10 The degree of 18O-
incorporation in the Fe(TPFPP)(CF3SO3) reaction was about
two times greater than that in the Co(TPFPP)(CF3SO3) reaction
(Table 2, entries 3 and 4). Since the observation of 18O-
incorporation from H218O into oxygenated products is indirect
evidence for the involvement of high-valent metal oxo inter-
mediates in metal-catalyzed oxygenation reactions,8–10 we
suggest that a high-valent cobalt–oxo porphyrin complex
participates as a reactive species in the cobalt porphyrin-
catalyzed hydroxylation of alkanes by m-CPBA.
In conclusion, we have shown for the first time that an
electron-deficient cobalt(III) porphyrin complex catalyzes the
hydroxylation of alkanes by m-CPBA via a non-radical type of
oxidation reactions. We suggest that a high-valent cobalt–oxo
porphyrin complex is generated as a reactive hydroxylating
intermediate in the reaction of the cobalt porphyrin complex and
1 M. Newcomb and P. H. Toy, Acc. Chem. Res., 2000, 33, 449; A. E.
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3 J. L. McLain, J. Lee and J. T. Groves, in Biomimetic Oxidations
Catalyzed by Transition Metal Complexes, ed. B. Meunier, Imperial
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Table 2 Percentages of 18O incorporated from H2 18O into cyclohexanol
producta
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1999, 38, 3238; C. Kim, K. Chen, J. Kim and L. Que, Jr., J. Am. Chem.
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122, 10805.
Amount (mL) of
H218O present
in reaction soln.
Cyclohexanol
Entry Catalyst
18O (%) Yield (%)b
1
2
3
4
Co(TPFPP)(CF3SO3)
Fe(TPFPP)(CF3SO3)
5
10
5
5 ± 1
10 ± 1
11 ± 2
18 ± 2
18 ± 2
17 ± 3
51 ± 4
53 ± 4
10
a See footnote ** for detailed reaction procedures. All reactions were run at
least triplicate, and the data reported represent the average of these
reactions. b Based on the amount of m-CPBA added.
Chem. Commun., 2001, 1262–1263
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