Catalytic oxidation of alkanes by iron bispidine complexes and dioxygen: Oxygen activation versus autoxidation

Article abstract of DOI:10.1039/c3cc47013j

Organic substrates (specifically cis-1,2-dimethylcyclohexane, DMCH) are oxidized by O₂ in the presence of iron(ii)-bispidine complexes. It is shown that this oxidation reaction is not based on O₂ activation by the nonheme iron catalysts as in Nature but due to a radical-based initiation, followed by a radical- and ferryl-based catalytic reaction.

Full text of DOI:10.1039/c3cc47013j

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Catalytic oxidation of alkanes by iron bispidine
complexes and dioxygen: oxygen activation
versus autoxidation†
Cite this: Chem. Commun., 2014,
0, 412
5
Received 13th September 2013,
Accepted 30th October 2013
a
b
b
a
Peter Comba,* Yong-Min Lee, Wonwoo Nam and Arkadius Waleska
DOI: 10.1039/c3cc47013j
www.rsc.org/chemcomm
Organic substrates (specifically cis-1,2-dimethylcyclohexane, DMCH)
are oxidized by O in the presence of iron(II)–bispidine complexes.
It is shown that this oxidation reaction is not based on O activation
2
2
by the nonheme iron catalysts as in Nature but due to a radical-based
initiation, followed by a radical- and ferryl-based catalytic reaction.
Scheme 1 Bispidine complexes 1 and 2; X = solvent molecule.
Nonheme iron oxidation and oxygenation enzymes, e.g. methane
1
2
3
monooxygenase, naphthalene dioxygenase, bleomycin, taurine
4
5
dioxygenase and cysteine dioxygenase, activate O , leading to a under ambient conditions in MeCN, conversion of cyclohexane
2
III
ꢀ1 12
14
putative superoxido Fe intermediate which, in subsequent steps, (BDE, ca. 105 kcal mol
)
to cyclohexanol was also observed.
III
is reduced (and protonated) to yield (hydro)peroxido Fe species, With iron bispidine complexes under ambient conditions in
which are generally converted to the high-valent iron-oxo active acetonitrile (MeCN) and with DMCH as the substrate, forma-
III
oxidant (an exception with known Fe reactivity is bleomycin). tion of a stable purple intermediate (characterized as the
III
III
However, the key superoxido Fe intermediate has so far not corresponding alkylperoxido-Fe species, vide infra) and oxida-
been trapped and characterized, and for nonheme iron model tion products was observed (alcohols as well as ketones with
III
systems, evidence for superoxido Fe complexes is extremely similar yields and in similar ratios as with H O as the oxidant,
2
2
6
–9
scarce, i.e. the reactive intermediate so far remains elusive.
see ESI,† Fig. S2). Here, we present an alternative reaction
It is expected that the ligand sphere has a significant effect on mechanism for the oxidation of organic substrates in the
III/II
the Fe
2
potential and hence on the O activation by the presence of iron–bispidine complexes and dioxygen.
ferrous center, with a predicted barrier for the activation of O
2
7,10
The assumed mechanism of alkane oxygenation by a super-
+
III
by nonheme iron centers of less than ꢀ0.10 V vs. Fc/Fc .
oxido Fe complex involves H atom abstraction by the super-
III
Interestingly, preliminary experiments indicated that iron bis- oxido complex, producing a hydroperoxido Fe intermediate
III/II
IV
6
pidine complexes with Fe
potentials much higher than the which then forms an Fe QO complex. This is known to be a
ꢀ
0.10 V limit [i.e. +0.84 V for complex 1 (Fig. S1, ESI†) and strong enough oxidant for the substrates studied here. More-
1
1
+
0.76 V for 2, see Scheme 1 for complex structures] catalyze over, preliminary DFT calculations indicated that the putative
III
0
the oxidation of cis-1,2-dimethylcyclohexane (DMCH) with O2. superoxido Fe complex 2 is able to abstract H atoms from
Importantly, DMCH has a significantly higher C–H bond dissocia- cyclohexadiene,
tion energy (BDE, ca. 96.5 kcal mol
similar experiments (e.g., cyclohexene, ca. 88.8 kcal mol
1
5–17
and electronic spectra of the supposedly
ꢀ
1 12
00
00
18,19
)
than the substrates used in emerging ferryl complexes 1 and 2 are well-known
and
ꢀ
1 6,12,13
II
)
and, are observed upon reaction of DMCH with the Fe complexes 1
and 2 in MeCN under ambient conditions (see ESI,† Fig. S3).
III
a
The fact that Fe hydroperoxido intermediates could also be
Universit a¨ t Heidelberg, Anorganisch-Chemisches Institut, D-69120 Heidelberg,
Germany. E-mail: peter.comba@aci.uni-heidelberg.de
2
0
trapped and characterized by EPR indicated that the assumed
b
III
Department of Bioinspired Science, Department of Chemistry and Nano Science,
Center for Biomimetic Systems, Ewha Womans University, Seoul 120-750, Korea
Electronic supplementary information (ESI) available: The synthesis of com-
superoxido-Fe -based mechanism might operate – although
III/II
10
the Fe
potentials of our ‘‘catalysts’’ are much too high. We
†
33–35
therefore studied the kinetics of the formation and decay of the
ferryl intermediate in detail.‡ Interestingly, with all substrates used,
the kinetic traces were sigmoidal with a substantial lag phase,
plexes 1 and 2 was reported previously.
Full description of the experiments
describing all relevant experimental and simulated spectra. See DOI: 10.1039/
c3cc47013j
4
12 | Chem. Commun., 2014, 50, 412--414
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Table 1 Comparison of the reactivities of 1.0 mM of 1 and various
substrates (18 h reaction time under ambient conditions in MeCN; 180 equiv.
of AIBN was used as a radical starter; (A), (O) and (C) [see text] were used as
radical scavengers, 9.0, 4.5 and 4.5 equiv., respectively; see ESI, Fig. S9 for
UV-vis-NIR spectra of entries a–d, f, and h)
III
Radical
starter
Radical
scavenger
Fe -OOR
a
Entry
Substrate
observed
a
b
c
d
e
f
g
h
i
DMCH (200 eq.)
DMCH (200 eq.)
DMCH (200 eq.)
DMCH (200 eq.)
MCH (200 eq.)
MCH (200 eq.)
1,4-DMCH (400 eq.)
1,4-DMCH (400 eq.)
—
—
—
—
—
—
|
—
|
|
—
|
—
(|)
—
—
|
—
|
—
| A
| C
| O
—
—
—
b
Fig. 1 (a) UV-vis-NIR spectral change observed in the reaction of 1.0 mM
aged
2
with 200 equiv. of DMCH
in O
2
-saturated DCM at ꢀ80 1C; the inset
shows the time profile of the absorbance at 604 nm. (b) The EPR spectrum
of the solution obtained in a reaction of 1.0 mM of 2 with 200 equiv. of
aged
ꢀ4
DMCH
modulation amplitude, 100 kHz modulation frequency, see ESI,† Fig. S8 for 1);
the inset shows a magnification of the signals at g = 2.04, 2.01 and 2.00.
in O
2
-saturated DCM at ꢀ80 1C (9.4369 GHz, 5 K, 3.0 ꢁ 10
T
—
—
c
a
III
Reactions are considered positive when a purple alkylperoxido Fe
species was observed; note that so far only complexes with tetradentate
III
22
bispidines have been shown to form stable alkylperoxido Fe species.
A strong increase of intensity in the UV region but no well-resolved
of the substrates by filtration over magnesium sulfate, alumina electronic transition at around 520 nm, see ESI, Fig. S9c.
which was irreproducible in length. After thorough purification
b
and silica, the duration of the lag phase increased (but not
aged
fully reproducible); with an older batch of DMCH (DMCH
),
the start of the formation of ferryl species was very fast (see
ESI,† Fig. S3). This indicates that DMCH might be oxidized
prior to the exposure to the iron bispidine compounds (from
diethylether it is well known that in an oxygen atmosphere
there is formation of peroxo compounds via hydrogen abstrac-
2
1
II
aged
tion by dioxygen ). Solutions of Fe complexes with DMCH
and O at ꢀ80 1C in dichloromethane (DCM) are bluish with
2
electronic transitions at 604 nm and EPR signals of at least
three different species (g
= 2.04, 2.01 and 2.00; see Fig. 1 for 2 and ESI,† Fig. S8 for 1).
The EPR spectrum with g = 2.19, 2.15 and 1.96 resembles that
of the previously published S = 1/2 hydroperoxido and alkyl-
a b
= 4.29; g = 2.19, 2.15 and 1.96;
g
c
b
III
20,22
peroxido Fe bispidine compounds.
It indicates that the
observed iron–bispidine-assisted oxidation might be initiated
by organic radicals.
To test this assumption we investigated the reactions of DMCH,
methylcyclohexane (MCH) and 1,4-dimethylcyclohexane (1,4-DMCH)
with added radical scavengers [2,6-bis(tert-butyl)-4-methylphenol
as an antioxidant (A), bromotrichloromethane as a carbon radical
scavenger (C) and diphenylamine as an oxygen radical scavenger the ferryl species at 735 nm; (c) EPR spectra, 9.4375 GHz, 110 K, 3.0 ꢁ 10
Fig. 2 (a) UV-vis-NIR spectra of 1.0 mM of 2 with 200 equiv. of DMCH and
75 equiv. of AIBN in MeCN at 25 1C; the inset shows the magnification of the
increasing ferryl band; (b) time-dependent generation and decomposition of
ꢀ4
T
modulation amplitude, 100 kHz modulation frequency; (d) simulation of the
(O)] as well as with the radical starter azobis-isobutyronitrile
25–27
EPR spectra after 985 s (black: experimental spectrum).
(AIBN; otherwise identical experimental conditions, see Table 1).
The BDEs of the three substrates used are very similar but they
have different hydrogen abstraction reactivities, as observed intermediate is generated (UV-vis-NIR, 735 nm) along with
2
3
III
before for cis- and trans-1,2-dimethylcyclohexane.
three different species with EPR signals for Fe S = 5/2,
For the reactions provided in Table 1, 1 was preferred over 2 S = 1/2 and a species of almost axial symmetry at g = 2.03,
because of the simple and fast visual detection of an activation 2.01 and 2.00 (see Fig. 2). In the reaction of 1 with tert-
0
0
and its beneficial reaction characteristics, i.e. 1 is a faster and butylhydroperoxide, we first observed the formation of an
0
0
stronger oxidant than 2 and is therefore expected to increase oxygen-based radical; after the decomposition, according to
1
1,18,19,24
III
the probability of a positive reaction.
From Table 1 it mass spectrometry a tert-butylalkoxido Fe compound emerged
can be observed that carbon-based radicals initiate the oxida- (see ESI,† Table S1).
tion sequence. Therefore, for 2 we studied the iron species that
Based on these observations, we propose a reaction mechanism
form during the sigmoidal activation and the exponential decay initiated by organic radicals and involving ferrous bispidine
phase in the presence of AIBN and DMCH (Fig. 2; note that complexes, O
2
and organic substrates (Scheme 2): (A) The EPR
aged
for 1 the corresponding EPR spectra did not reveal any low- and UV-vis-NIR spectra of 2 with DMCH
in DCM at ꢀ80 1C
spin ferric complexes). As the reaction proceeds, the Fe QO (Fig. 1) are due to the alkylperoxido Fe intermediate with an
IV
III
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Graeme Hanson (UQ Brisbane) for help with the EPR spectro-
scopy. The work at EWU was supported by NRF/MEST of Korea
through CRI (2-2012-1794-001-1 to W.N.).
Notes and references
‡
Product formation was monitored using the highly active 9,10-dihydro-
ꢀ1 36
anthracene (BDE: 75 kcal mol
)
as the substrate, see ESI.†
1
S.-K. Lee, J. C. Nesheim and J. D. Lipscomb, J. Biol. Chem., 1993,
68, 21569.
2
2
3
4
S. M. Resnick and D. T. Gibson, J. Ind. Microbiol. Biotechnol., 1996, 17, 438.
R. M. Burger, Chem. Rev., 1998, 98, 1153.
J. C. Price, E. W. Barr, B. Tirupati, J. M. Bollinger Jr. and C. Krebs,
Biochemistry, 2003, 42, 7497.
Scheme 2 Proposed autocatalytic radical chain mechanism.
5
S. Ye, X. Wu, L. Wei, D. Tang, P. Sun, M. Bartlam and Z. Rao, J. Biol.
Chem., 2007, 282, 3391.
electronic transition at 604 nm and g = 2.19, 2.15 and 1.96. The
assignment of these spectra to a metastable hydroperoxido Fe
III
6 S. Hong, Y.-M. Lee, W. Shin, S. Fukuzumi and W. Nam, J. Am.
Chem. Soc., 2009, 131, 13910.
derivative is ruled out because addition of a base to these
solutions did not lead to the corresponding peroxido complex
7
D. Mandon, H. Jaafar and A. Thibon, New J. Chem., 2011, 35, 1986.
8 A. Thibon, J. England, M. Martinho, V. G. Young Jr., J. R. Frisch,
R. Guillot, J.-J. Girerd, E. M u¨ nck, L. Que Jr. and F. Banse, Angew.
Chem., Int. Ed., 2008, 47, 7064.
2
0
(
whose spectroscopic signature is known ), and addition
2
0,22
V
22
of acid did not
yield the expected Fe complex, i.e. no
9
M. Martiho, G. Blain and F. Banse, Dalton Trans., 2010, 39, 1630.
conversion was observed under these conditions (see also ESI,† 10 Y. M. Badiei, M. A. Siegler and D. P. Goldberg, J. Am. Chem. Soc.,
2
011, 133, 1274.
1 P. Comba, H. Wadepohl and A. Waleska, Aust. J. Chem., DOI:
0.1071/CH13454.
Fig. S10 and S11). (B) The continuous formation and decom-
position of the alkylperoxido Fe species (see Fig. 2) with AIBN
1
III
1
at 25 1C yields the ferryl complex with a UV-vis-NIR feature at 12 S. J. Blanksby and G. B. Ellison, Acc. Chem. Res., 2003, 36, 255.
1
3 Y.-M. Lee, S. Hong, Y. Morimoto, W. Shin, S. Fukuzumi and W. Nam,
J. Am. Chem. Soc., 2010, 132, 10668.
7
35 nm, responsible for the oxygenation of the organic sub-
strate, and an oxygen-based radical with g = 2.03, 2.01 and 2.00.
14 P. Comba, M. Maurer and P. Vadivelu, J. Phys. Chem. A, 2008, 112, 13028.
This interpretation is supported by EPR spectra observed after 15 P. Comba, S. Pandian and A. Waleska, work in progress.
2
2
16 H. Chen, K.-B. Cho, W. Lai, W. Nam and S. Shaik, J. Chem. Theory
Comput., 2012, 8, 915.
the reaction of 1 with tert-butylhydroperoxide. The alkoxy
radical may react in different ways: (i) oxidative reaction with
Fe to yield a ferric alkoxido complex with S = 5/2 and g = 4.29
and also supported by mass spectrometry (see ESI,† Table S1),
followed by acid/base decomposition to yield the alcohol pro-
duct and a hydroxido Fe complex, which has an EPR transi- 19 P. Comba, S. Fukuzumi, H. Kotani and S. Wunderlich, Angew.
tion at approx. g = 4.3; (ii) the alkoxy radical may react as a
hydrogen atom abstracting species to pursue the radical chain
17 K. B. Cho, H. Chen, D. Janardanan, S. P. d. Visser, S. Shaik and
W. Nam, Chem. Commun., 2012, 48, 2189.
II
1
8 D. Wang, K. Ray, M. J. Collins, E. R. Farquhar, J. R. Frisch, L. Gomez,
T. A. Jackson, M. Kerscher, A. Waleska, P. Comba, M. Costas,
E. M u¨ nck and L. Que Jr., Chem. Sci., 2013, 4, 282.
III
1
8
Chem., Int. Ed., 2010, 49, 2622.
0 M. R. Bukowski, P. Comba, C. Limberg, M. Merz, L. Que Jr. and
2
T. Wistuba, Angew. Chem., Int. Ed., 2004, 43, 1283.
mechanism (this pathway is unlikely due to the relatively low 21 H. King, J. Chem. Soc., 1929, 738.
2
2 J. Bautz, P. Comba and L. Que Jr., Inorg. Chem., 2006, 45, 7077.
efficiency of the reaction; also, the observed product ratio,
which is similar to that with H as the oxidant, indicates
23 G. A. Hamilton, B. S. Ribner and T. M. Hellman, in The Mechanism of
Alkane Oxidation by Ozone, American Chemical Society, 1968, pp. 15–25.
2 2
O
IV
that an Fe QO based alkane oxidation mechanism is likely). 24 P. Comba, M. Maurer and P. Vadivelu, Inorg. Chem., 2009, 48,
10389–10396.
(C) The ferryl complex as well as the alkoxy and alkylperoxido
2
5 G. R. Hanson, C. J. Noble and S. Benson, in High Resolution EPR:
Applications to Metalloenzymes and Metals in Medicine, ed. G. R.
Hanson and L. J. Berliner, 2009, p. 105.
radicals may produce alkyl radicals needed for the formation of
2
8,29
the ferryl species.
2
2
6 T. L. Bohan, J. Magn. Reson., 1977, 26, 109.
In conclusion, we present evidence that the iron–bispidine-
assisted oxygenation of alkanes is initiated by organic radicals –
7 G. R. Hanson, C. J. Noble and S. Benson, in EPR of Free Radicals
in Solids: Trends in Methods and Applications, ed. A. Lund and
M. Shiotani, Springer, Heidelberg, 2013, p. 223.
8 K.-B. Cho, Y.-M. Lee, Y. H. Kwon, S. Shaik and W. Nam, J. Am. Chem.
Soc., 2012, 134, 20222.
9 X. Wu, M. S. Seo, K. M. Davis, Y.-M. Lee, J. Chen, K.-B. Cho,
Y. N. Pushkar and W. Nam, J. Am. Chem. Soc., 2011, 133, 20088.
0 Y. Morimoto, Y.-M. Lee, W. Nam and S. Fukuzumi, Chem. Commun.,
3
0
a similar autoxidation pathway has recently been proposed.
We cannot exclude that formation of these radicals may
2
2
3
3
II
2
involve Fe and O but with our ligand systems initiation by
III
10
superoxido Fe intermediates is very unlikely. We believe
that the pathway presented here is quite general, and one needs
to be very cautious when studying Fe-catalyzed oxidation
reactions of organic substrates in an ambient atmosphere –
and this includes reactions with various oxidants such as
peracids, peroxides and iodosylbenzene, and alkanes as well
2013, 49, 2500.
1 M. R. Bukowski, P. Comba, A. Lienke, C. Limberg, C. Lopez de Laorden,
R. Mas-Balleste, M. Merz and L. Que Jr., Angew. Chem., Int. Ed., 2006,
45, 3446.
3
3
2 P. Comba and G. Rajaraman, Inorg. Chem., 2008, 47, 78.
3 P. Comba, M. Kerscher and W. Schiek, Prog. Inorg. Chem., 2007, 55, 613.
2
4,31,32
as olefins.
34 H. B ¨o rzel, P. Comba, K. S. Hagen, M. Merz, Y. D. Lampeka, A. Lienke,
G. Linti, H. Pritzkow and L. V. Tsymbal, Inorg. Chim. Acta, 2002, 337, 407.
Generous financial support by the University of Heidelberg
and the German Science Foundation is gratefully acknowl-
35 P. Comba, B. Kanellakopulos, C. Katsichtis, A. Lienke, H. Pritzkow
and F. Rominger, J. Chem. Soc., Dalton Trans., 1998, 3997.
edged. We are thankful to Michael Westphal (Heidelberg) and 36 D. F. McMillen and D. M. Golden, Annu. Rev. Phys. Chem., 1982, 33, 493.
4
14 | Chem. Commun., 2014, 50, 412--414
This journal is ©The Royal Society of Chemistry 2014