Reactivities of mononuclear non-heme iron intermediates including evidence that iron(III) hydroperoxo species is a sluggish oxidant

Article abstract of DOI:10.1021/ja055709q

There is an intriguing, current controversy on the involvement of iron(III)-hydroperoxo species as a second electrophilic oxidant in oxygenation reactions by heme and non-heme iron enzymes and their model compounds. In the present work, we have performed reactivity studies of the iron-hydroperoxo species in nucleophilic and electrophilic reactions, with in situ-generated mononuclear non-heme iron(III)-hydroperoxo complexes that have been well characterized with various spectroscopic techniques. The intermediates did not show any reactivities in the nucleophilic (e.g., aldehyde deformylation) and electrophilic (e.g., oxidation of sulfide and olefin) reactions. These results demonstrate that non-heme iron(III)-hydroperoxo species are sluggish oxidants and that the oxidizing power of the intermediates cannot compete with that of high-valent iron(IV)-oxo complexes. We have also reported reactivities of mononuclear non-heme iron(III)-peroxo and iron(IV)-oxo complexes in the aldehyde deformylation and the oxidation of sulfides, respectively.

Full text of DOI:10.1021/ja055709q

Published on Web 02/02/2006
Reactivities of Mononuclear Non-Heme Iron Intermediates
Including Evidence that Iron(III)-Hydroperoxo Species Is a
Sluggish Oxidant
Mi Joo Park, Jimin Lee, Yumi Suh, Jinheung Kim, and Wonwoo Nam*
Contribution from the Department of Chemistry and Center for Biomimetic Systems, Ewha
Womans UniVersity, Seoul 120-750, Korea
Received August 20, 2005; E-mail: wwnam@ewha.ac.kr
Abstract: There is an intriguing, current controversy on the involvement of iron(III)-hydroperoxo species
as a “second electrophilic oxidant” in oxygenation reactions by heme and non-heme iron enzymes and
their model compounds. In the present work, we have performed reactivity studies of the iron-hydroperoxo
species in nucleophilic and electrophilic reactions, with in situ-generated mononuclear non-heme iron(III)-
hydroperoxo complexes that have been well characterized with various spectroscopic techniques. The
intermediates did not show any reactivities in the nucleophilic (e.g., aldehyde deformylation) and electrophilic
(e.g., oxidation of sulfide and olefin) reactions. These results demonstrate that non-heme iron(III)-
hydroperoxo species are sluggish oxidants and that the oxidizing power of the intermediates cannot compete
with that of high-valent iron(IV)-oxo complexes. We have also reported reactivities of mononuclear non-
heme iron(III)-peroxo and iron(IV)-oxo complexes in the aldehyde deformylation and the oxidation of
sulfides, respectively.
Scheme 1. Iron(III)-Hydroperoxo Porphyrin Intermediate in
Introduction
Cytochrome P450-Catalyzed Reactions4b
Elucidation of the nature of reactive intermediates in the
catalytic oxygenation of hydrocarbons by heme and non-heme
iron enzymes has remained of continuing interest to the
bioinorganic chemistry community.1,2 In heme iron enzymes and
iron porphyrin models, high-valent iron(IV)-oxo porphyrin
π-cation radicals, the so-called Compound I, have been proposed
as active oxidants that effect the oxygenation reactions. How-
ever, recent studies have provided experimental evidence that
multiple oxidants are involved in the catalytic oxygenation
reactions and that the mechanism of oxygen atom transfer is
much more complex than initially believed.3 Especially, an iron-
(III)-hydroperoxo species, FeIII-OOH, has been proposed as
a “second electrophilic oxidant” in a variety of oxygenation
reactions including alkane hydroxylation and olefin epoxidation
(Scheme 1),3,4 but direct evidence for such reactions has yet to
be obtained.
by non-heme iron complexes and H2O2 has been interpreted
with the involvement of two distinct oxidants (i.e., a predomi-
nant epoxide formation by FeIII-OOH and a mixture of epoxide
and cis-diol formation by HO-FeVdO).6 In addition, a low-
spin FeIII-OOH species has been characterized for “activated
bleomycin”, which is the last detectable intermediate in the
reaction cycle of bleomycin and a plausible oxidant responsible
for DNA cleavage.7 The iron-hydroperoxo species have also
been often proposed as reactive intermediates in the oxygenation
of olefins and alkanes by non-heme iron catalysts and H2O2.8
The multiple oxidants hypothesis has also been invoked in
non-heme iron complex-catalyzed oxidation reactions.5 For
example, the formation of different products in olefin oxidation
(4) (a) Song, W. J.; Ryu, Y. O.; Song, R.; Nam, W. J. Biol. Inorg. Chem.
2005, 10, 294-304 and references therein. (b) Newcomb, M.; Shen, R.;
Choi, S.-Y.; Toy, P. H.; Hollenberg, P. F.; Vaz, A. D. N.; Coon, M. J. J.
Am. Chem. Soc. 2000, 122, 2677-2686. (c) Toy, P. H.; Newcomb, M.;
Coon, M. J.; Vaz, A. D. N. J. Am. Chem. Soc. 1998, 120, 9718-9719. (d)
Vaz, A. D. N.; McGinnity, D. F.; Coon, M. J. Proc. Natl. Acad. Sci. U.S.A.
1998, 95, 3555-3560.
(1) (a) Ortiz de Montellano, P. R. Cytochrome P450: Structure, Mechanism,
and Biochemistry, 3rd ed.; Kluwer Academic/Plenum Publishers: New
York, 2005. (b) Denisov, I. G.; Makris, T. M.; Sligar, S. G.; Schlichting,
I. Chem. ReV. 2005, 105, 2253-2277. (c) Meunier, B.; de Visser, S. P.;
Shaik, S. Chem. ReV. 2004, 104, 3947-3980.
(2) (a) Kryatov, S. V.; Rybak-Akimova, E. V.; Schindler, S. Chem. ReV. 2005,
105, 2175-2226. (b) Costas, M.; Mehn, M. P.; Jensen, M. P.; Que, L., Jr.
Chem. ReV. 2004, 104, 939-986. (c) Tshuva, E. Y.; Lippard, S. J. Chem.
ReV. 2004, 104, 987-1012.
(3) (a) Hlavica, P. Eur. J. Biochem. 2004, 271, 4335-4360. (b) Jin, S.; Bryson,
T. A.; Dawson, J. H. J. Biol. Inorg. Chem. 2004, 9, 644-653. (c) Nam,
W.; Ryu, Y. O.; Song, W. J. J. Biol. Inorg. Chem. 2004, 9, 654-660. (d)
Shaik, S.; de Visser, S. P.; Kumar, D. J. Biol. Inorg. Chem. 2004, 9, 661-
668. (e) Newcomb, M.; Hollenberg, P. F.; Coon, M. J. Arch. Biochem.
Biophys. 2003, 409, 72-79.
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(6) (a) Quin˜onero, D.; Morokuma, K.; Musaev, D. G.; Mas-Balleste´, R.; Que,
L., Jr. J. Am. Chem. Soc. 2005, 127, 6548-6549. (b) Bassan, A.; Blomberg,
M. R. A.; Siegbahn, P. E. M.; Que, L., Jr. Angew. Chem., Int. Ed. 2005,
44, 2939-2941. (c) Fujita, M.; Costas, M.; Que, L., Jr. J. Am. Chem. Soc.
2003, 125, 9912-9913.
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Am. Chem. Soc. 2002, 124, 10810-10822. (b) Sam, J. W.; Tang, X.-J.;
Peisach, J. J. Am. Chem. Soc. 1994, 116, 5250-5256. (c) Murugesan, N.;
Hecht, S. M. J. Am. Chem. Soc. 1985, 107, 493-500.
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L., Jr. Angew. Chem., Int. Ed. Engl. 1995, 34, 1512-1514.
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J. AM. CHEM. SOC. 2006, 128, 2630-2634
10.1021/ja055709q CCC: $33.50 © 2006 American Chemical Society

Iron(III)−Hydroperoxo Species: A Sluggish Oxidant
A R T I C L E S
Table 1. Mononuclear Non-Heme Iron Intermediates Used in
that acetophenone was produced as a major product (see
Experimental Section for detailed reaction procedures).
Reactivity Studiesa
+
+
L
[(L)FeIII
−
O2]+
[(L)FeIII
−
OOH]2
[(L)FeIVdO]2
N4Py
Bn-TPEN
TMC
O (1)
O (2)
O (3)
X
O (4)
O (5)
X
O (7)
O (8)
O (9)
O (10)
TPA
O (6)
a The circled (O) intermediates that have been spectroscopically char-
acterized previously were used in the present reactivity studies, whereas
the crossed (X) intermediates have not been identified yet.
We then investigated the reactivity of iron(III)-peroxo
complexes in electrophilic reactions such as the oxidation of
sulfide and olefin. When 1, 2, and 3 were reacted with
thioanisole and cyclohexene under the conditions of the aldehyde
deformylation, there were virtually no absorption spectral
changes of the reaction solutions. Also, product analysis of the
reaction solutions revealed that no oxygenated products were
formed in the oxidation of thioanisole and cyclohexene by the
iron(III)-peroxo complexes. These results demonstrate that non-
heme iron(III)-peroxo species do not react with nucleophiles
(eq 2). On the basis of the results presented above, we conclude
that as it has been well established in iron(III)-peroxo porphyrin
reactions,11 non-heme iron(III)-peroxo complexes are capable
of deformylating aldehydes via a nucleophilic reaction but not
capable of oxygenating substrates via an electrophilic reaction.
Iron(III)-Hydroperoxo Complexes. It has been proposed
that iron(III)-hydroperoxo porphyrins can behave as a nucleo-
phile and attack a carbonyl group of an aldehyde in cytochrome
P450-catalyzed deformylation of aldehydes (Scheme 1).12 We
therefore generated non-heme iron(III)-hydroperoxo complexes
such as [(N4Py)FeIII-OOH]2+ (4), [(Bn-TPEN)FeIII-OOH]2+
(5), and [(TPA)FeIII-OOH]2+ (6) and examined their reactivity
in the deformylation of aldehydes. Upon addition of 2-PPA to
the solutions of 4, 5, and 6 (eqs 3-5) (see Experimental Section
for reaction conditions), the reaction solutions did not show any
absorption spectral changes. Moreover, product analysis revealed
that the acetophenone product was not formed. These results
indicate that non-heme iron(III)-hydroperoxo species are not
capable of deformylating aldehydes via a nucleophilic reaction
(eqs 3-5).
Figure 1. Ligand structures of iron(II) complexes used in generating
mononuclear non-heme iron intermediates.
However, there is no direct evidence that such FeIII-OOH
species are indeed involved in the oxidative DNA cleavage
reaction and the oxygenation of hydrocarbons. Since the
participation of iron(III)-hydroperoxo intermediates in oxygen-
atom transfer reactions has been proposed mainly on the basis
of product analyses of catalytic reactions, we have investigated
reactivities of in situ-generated non-heme iron(III)-hydroperoxo
complexes in nucleophilic (e.g., deformylation of aldehydes)
and electrophilic (e.g., the oxidation of sulfides and olefins)
reactions under stoichiometric conditions. Other non-heme iron
intermediates such as iron(III)-peroxo and iron(IV)-oxo
species have also been studied in the aldehyde deformylation
and the oxidation of sulfides, respectively.
Results and Discussion
Mononuclear non-heme iron intermediates, such as iron(III)-
peroxo {[(L)FeIII-O2]+}, iron(III)-hydroperoxo {[(L)FeIII-
OOH]2+}, and iron(IV)-oxo {[(L)FeIVdO]2+} (Table 1), that
have been well characterized previously with various spectro-
scopic techniques were used in the present reactivity studies.
The ligand structures such as N4Py, Bn-TPEN, TMC, and TPA
are depicted in Figure 1,9 and the preparation of the intermedi-
ates has been described in detail in Experimental Section.
Iron(III)-Peroxo Complexes. We have shown very recently
that non-heme iron(III)-peroxo complexes such as [(N4Py)-
FeIII-O2]+ (1) and [(TMC)FeIII-O2]+ (3) are capable of
deformylating aldehydes via an oxidative nucleophilic reaction.10
For example, the reaction of 1 with 2-phenylpropionaldehyde
(2-PPA) afforded acetophenone as a major product within 1
min at -30 °C (eq 1).10 In the present study, we have tested
the reactivity of [(Bn-TPEN)FeIII-O2]+ (2) in the deformylation
of 2-PPA in CH3OH at -15 °C and obtained the same result
We then investigated the electrophilic character of the non-
heme iron-hydroperoxo complexes by carrying out the oxida-
tion of sulfide and olefin by 4, 5, and 6. Upon addition of
thioanisole and cyclohexene to the solutions of 4, 5, and 6 (eqs
6-8) (see Experimental Section for reaction conditions), the
intermediates remained intact without showing any absorption
spectral changes, and no oxygenated products were formed in
(11) (a) Wertz, D. L.; Valentine, J. S. Struct. Bonding 2000, 97, 37-60 and
references therein. (b) Wertz, D. L.; Sisemore, M. F.; Selke, M.; Driscoll,
J.; Valentine, J. S. J. Am. Chem. Soc. 1998, 120, 5331-5332. (c) Selke,
M.; Valentine, J. S. J. Am. Chem. Soc. 1998, 120, 2652-2653. (d) Goto,
Y.; Wada, S.; Morishima, I.; Watanabe, Y. J. Inorg. Biochem. 1998, 69,
241-247.
(12) (a) Meunier, B.; Bernadou, J. Struct. Bonding 2000, 97, 1-35. (b) Akhtar,
M.; Corina, D.; Miller, S.; Shyadehi, A. Z.; Wright, J. N. Biochemistry
1994, 33, 4410-4418.
(9) Abbreviation used: N4Py, N,N-bis(2-pyridylmethyl)-N-bis(2-pyridyl)-
methylamine; Bn-TPEN, N-benzyl-N,N′,N′-tris(2-pyridylmethyl)ethane-1,2-
diamine; TMC, 1,4,8,11-tetramethyl-1,4,8,11-tetraazacyclotetradecane; TPA,
tris(2-pyridylmethyl)amine.
(10) Annaraj, J.; Suh, Y.; Seo, M. S.; Kim, S. O.; Nam, W. Chem. Commun.
2005, 4529-4531.
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J. AM. CHEM. SOC. VOL. 128, NO. 8, 2006 2631

A R T I C L E S
Park et al.
the reactions. These results demonstrate that non-heme iron-
(III)-hydroperoxo complexes are not capable of oxidizing
sulfide and olefin, supporting the computational proposal that
iron(III)-hydroperoxo species cannot be an active oxidant for
the sulfoxidation and epoxidation reactions (eqs 6-8).13,14
However, upon warming the reaction solutions to room tem-
perature, we have observed the disappearance of the intermedi-
ates and the formation of oxygenated products (e.g., methyl
phenyl sulfoxide in the oxidation of thioanisole). We interpret
these results that the O-O bond cleavage of [(L)FeIII-OOH]2+
species at room temperature generates high-valent iron-oxo
intermediates that are responsible for the formation of oxygen-
ated products. Indeed, the product formation in the catalytic
oxygenation of organic substrates by non-heme iron complexes
and H2O2 at room temperature has been well demonstrated by
Que and co-workers.15,16
In the oxidation of PPh3, 4 and 5 disappeared immediately
upon addition of PPh3, whereas 6 disappeared slowly with a
rate comparable to the natural decay (Supporting Information,
Figure S1). The latter result is astonishing to us, since PPh3 is
an easily oxidized substrate and can be oxidized by H2O2 even
in the absence of metal catalysts. The hydroxylation of cyclo-
hexane by [(N4Py)FeIII-OOH]2+ (4) was also investigated, since
it has been reported previously that 4 is involved as an active
oxidant in the catalytic hydroxylation of cyclohexane by [Fe-
(N4Py)]2+ and H2O2.8b Upon addition of cyclohexane to the
solution of 4, neither the disappearance of 4 nor the formation
of oxygenated products were observed. These results clearly
indicate that 4 is not a hydroxylating intermediate and that an
intermediate different from 4 is generated as an active oxidant
in the reaction of [Fe(N4Py)]2+ and H2O2 that is responsible
for the cyclohexane hydroxylation (e.g., FeVdO species).16
In this section, we have demonstrated that iron(III)-hydro-
peroxo species are sluggish oxidants in both oxidative nucleo-
philic and electrophilic reactions and the oxidizing power of
the intermediates cannot compete with that of iron(IV)-oxo
complexes (vide infra).13,17 Further, the observation that non-
heme iron(III)-hydroperoxo species are not able to oxygenate
substrates leads us to suggest that porphyrin analogues, (Porp)-
FeIII-OOH, cannot be a “second electrophilic oxidant” in
Figure 2. Reactions of 7 with thioanisoles in CH3CN at 0 °C: (A) UV-
vis spectral changes of 7 (2 mM) upon addition of 20 equiv of thioanisole
(40 mM). (Inset) Time course of the reaction monitored at 695 nm. (B)
Determination of second-order rate constant by plotting kobs against thio-
anisole concentration. (C) Plot of log krel against σp of p-X-thioanisoles to
determine Hammett F value for the oxidation of para-substituted thioanisoles.
electrophilic reactions,4,13,14 since the latter species bearing a
negatively charged porphyrin ligand is presumed to be less
reactive than the former bearing a neutral non-heme ligand
toward nucleophiles {e.g., (Porp)FeIII-OOH vs [(L)FeIII-
OOH]2+}.18 Finally, it is worth noting that other metal-
hydroperoxo complexes (e.g., CuII-OOH) have shown low
reactivities with exogenous substrates19 and that, to the best of
our knowledge, there is no direct evidence for the involvement
of metal-hydroperoxo species in the oxygenation of hydrocar-
bons such as olefin epoxidation and alkane hydroxylation.
Iron(IV)-Oxo Complexes. It has been shown recently that
mononuclear non-heme iron(IV)-oxo species are capable of
oxygenating various organic substrates such as PPh3, sulfides,
olefins, alcohols, and alkanes.20 In the present study, we have
compared relative reactivities of non-heme iron(IV)-oxo
complexes such as [(N4Py)FeIVdO]2+ (7), [(Bn-TPEN)FeIVd
O]2+ (8), [(TMC)FeIVdO]2+ (9), and [(TPA)FeIVdO]2+ (10)
in the oxidation of thioanisoles (eq 9). Upon addition of
(13) (a) Kamachi, T.; Shiota, Y.; Ohta, T.; Yoshizawa, K. Bull. Chem. Soc.
Jpn. 2003, 76, 721-732. (b) Ogliaro, F.; de Visser, S. P.; Cohen, S.;
Sharma, P. K.; Shaik, S. J. Am. Chem. Soc. 2002, 124, 2806-2817.
(14) Sharma, P. K.; de Visser, S. P.; Shaik, S. J. Am. Chem. Soc. 2003, 125,
8698-8699.
thioanisole to the solutions of 7, 8, 9, and 10, the intermediates
(15) (a) Oldenburg, P. D.; Shteinman, A. A.; Que, L., Jr. J. Am. Chem. Soc.
2005, 127, 15672-15673. (b) Costas, M.; Que, L., Jr. Angew. Chem., Int.
Ed. 2002, 41, 2179-2181. (c) Mekmouche, Y.; Hummel, H.; Ho, R. Y.
N.; Que, L., Jr.; Schu¨nemann, V.; Thomas, F.; Trautwein, A. X.; Lebrun,
C.; Gorgy, K.; Lepreˆtre, J.-C.; Collomb, M.-N.; Deronzier, A.; Fontecave,
M.; Me´nage, S. Chem. Eur. J. 2002, 8, 1196-1204.
(16) (a) Chen, K.; Que, L., Jr. Chem. Commun. 1999, 1375-1376. (b) Chen,
K.; Que, L., Jr. J. Am. Chem. Soc. 2001, 123, 6327-6337. (c) Oh, N. Y.;
Seo, M. S.; Lim, M. H.; Consugar, M. B.; Park, M. J.; Rohde, J.-U.; Han,
J.; Kim, K. M.; Kim, J.; Que, L., Jr.; Nam, W. Chem. Commun. 2005,
5644-5646.
(17) Wada, A.; Ogo, S.; Nagatomo, S.; Kitagawa, T.; Watanabe, Y.; Jitsukawa,
K.; Masuda, H. Inorg. Chem. 2002, 41, 616-618.
(18) Kumar, D.; Hirao, H.; Que, L., Jr.; Shaik, S. J. Am. Chem. Soc. 2005, 127,
8026-8027.
(19) (a) Hatcher, L. Q.; Karlin, K. D. J. Biol. Inorg. Chem. 2004, 9, 669-683
and references therein. (b) Yamaguchi, S.; Nagatomo, S.; Kitagawa, T.;
Funahashi, Y.; Ozawa, T.; Jitsukawa, K.; Masuda, H. Inorg. Chem. 2003,
42, 6968-6970. (c) Li, L.; Sarjeant, A. A. N.; Vance, M. A.; Zakharov, L.
N.; Rheingold, A. L.; Solomon, E. I.; Karlin, K. D. J. Am. Chem. Soc.
2005, 127, 15360-15361.
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Iron(III)−Hydroperoxo Species: A Sluggish Oxidant
A R T I C L E S
Table 2. Comparative Reactivities of Non-Heme Iron(IV)-Oxo Complexes in Sulfide Oxidation
[(N4Py)FeIVdO]2+ (7)
[(Bn-TPEN)FeIVdO]2+ (8)
[(TMC)FeIVdO]2+ (9)
[(TPA)FeIVdO]2+ (10)
reaction temperature
k2 (M-1 s-1
Hammett F value
0 °C
-20 °C
35 °C
-45 °C
)
6.5(5) × 10-2
7.5(5) × 10-2
-1.5
2.9(3) × 10-2
4.4(3) × 10-1
-1.6
-1.4
-2.5
Scheme 2. Reactions of Mononuclear Non-Heme Iron
Intermediates
reverted back to the starting iron(II) complexes, yielding methyl
phenyl sulfoxide quantitatively (eq 9) (see Experimental Section
for detailed reaction procedures). Pseudo-first-order fitting of
the kinetic data allowed us to determine kobs values (Figure 2a
for the reaction of 7; Supporting Information, Figure S2 for the
reactions of 8, 9, and 10). The pseudo-first-order rate constants
increased proportionally with thioanisole concentration, allowing
us to determine the second-order rate constants for the reactions
of 7, 8, 9, and 10 (Table 2) (Figure 2b for the reaction of 7;
Supporting Information, Figure S3 for the reactions of 8, 9, and
10). Taking into consideration the second-order rate constants
and the different reaction temperatures, the relative reactivities
of the iron-oxo complexes are in the order of 10 > 8 > 7 >
9. The different reactivities have been rationalized previously
with the accessibility of substrates toward the iron-oxo group
of the intermediates.21 In addition to the steric effect, other
factors such as the electronic nature of iron(IV)-oxo complexes
may also influence the relative reactivities. Indeed, it has been
demonstrated that the reactivities of high-valent iron(IV)-oxo
porphyrin π-cation radicals are significantly affected by the
electronic nature of iron porphyrins.22 Further, when pseudo-
first-order rate constants were determined with various para-
substituted thioanisoles and plotted against σp, we were able to
determine Hammett F values for the reactions of 7, 8, 9, and
10 (Table 2) (Figure 2c for the reaction of 7; Supporting
Information, Figure S4 for the reactions of 8, 9, and 10). The
negative F values indicate the electrophilic character of the oxo
group of the non-heme iron(IV)-oxo complexes and a positive
charge buildup on sulfur in sulfoxidation reactions.20d,23 As a
conclusion, we have shown that non-heme iron(IV)-oxo species
oxidize sulfides to the corresponding sulfoxides via an electro-
philic reaction and that reactivities of the iron(IV)-oxo
complexes are markedly influenced by the ligand structures.
provided the first strong experimental evidence that non-heme
iron(III)-hydroperoxo complexes are sluggish oxidants in
nucleophilic and electrophilic reactions, indicating that the
oxidizing power of the intermediates cannot compete with that
of high-valent iron(IV)-oxo complexes in oxygen atom transfer
reactions. It should be noted here that the previous suggestions
for the involvement of iron(III)-hydroperoxo species in the
oxygenation of organic substrates such as olefins and alkanes
were mainly based on results obtained under catalytic conditions
in heme and non-heme iron enzymes and their model
compounds.4a Therefore, the evidence that has been used to
propose the iron(III)-hydroperoxo species as a second elec-
trophilic oxidant should be carefully reevaluated with isolated
intermediates. In the reactivity studies of non-heme iron(IV)-
oxo complexes, the electrophilic character and the relative
reactivities of the intermediates have been discussed with the
results of sulfide oxidation that has been performed with in situ-
generated iron(IV)-oxo complexes bearing different non-heme
ligands.
Experimental Section
Materials. All chemicals obtained from Aldrich Chemical Co. were
the best available purity and were used without further purification
unless otherwise indicated. Solvents were dried according to published
procedures and distilled under Ar prior to use.24 Iodosylbenzene was
prepared by a literature method.25 m-Chloroperbenzoic acid (m-CPBA)
purchased from Aldrich was purified by washing with phosphate buffer
(pH 7.4) followed by water and then dried under reduced pressure.
Peracetic acid (CH3CO3H, 32 wt % solution containing <6% H2O2)
and H2O2 (30 wt % solution in water) were obtained from Aldrich.
Iron(II) complexes such as Fe(N4Py)(ClO4)2,8b Fe(Bn-TPEN)(CF3-
SO3)2,20c,26 Fe(TMC)(CF3SO3)2,20a and Fe(TPA)(ClO4)220b were prepared
in a glovebox by literature methods.
Conclusions
The reactivities of mononuclear non-heme iron(III)-peroxo,
iron(III)-hydroperoxo, and iron(IV)-oxo complexes have been
investigated in nucleophilic and electrophilic reactions under
stoichiometric conditions. As the results are summarized in
Scheme 2, iron(III)-peroxo complexes are capable of deformy-
lating aldehydes via a nucleophilic reaction but not capable of
oxygenating substrates via an electrophilic reaction. We have
Caution: Perchlorate salts are potentially explosive and should be
handled with great care!
(20) (a) Rohde, J.-U.; In, J.-H.; Lim, M. H.; Brennessel, W. W.; Bukowski, M.
R.; Stubna, A.; Mu¨nck, E.; Nam, W.; Que, L., Jr. Science 2003, 299, 1037-
1039. (b) Lim, M. H.; Rohde, J.-U.; Stubna, A.; Bukowski, M. R.; Costas,
M.; Ho, R. Y. N.; Mu¨nck, E.; Nam, W.; Que, L., Jr. Proc. Natl. Acad. Sci.
U.S.A. 2003, 100, 3665-3670. (c) Kaizer, J.; Klinker, E. J.; Oh, N. Y.;
Rohde, J.-U.; Song, W. J.; Stubna, A.; Kim, J.; Mu¨nck, E.; Nam, W.; Que,
L., Jr. J. Am. Chem. Soc. 2004, 126, 472-473. (d) Sastri, C. V.; Seo, M.
S.; Park, M. J.; Kim, K. M.; Nam, W. Chem. Commun. 2005, 1405-1407.
(e) Kim, S. O.; Sastri, C. V.; Seo, M. S.; Kim, J.; Nam, W. J. Am. Chem.
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J.; Que, L., Jr. Angew. Chem., Int. Ed. 2005, 44, 3690-3694.
Instrumentation. UV-vis spectra were recorded on a Hewlett-
Packard 8453 spectrophotometer equipped with an OptostatDN variable-
temperature liquid-nitrogen cryostat (Oxford instruments) or a circu-
lating water bath. Product analyses for the deformylation of 2-phenyl-
propionaldehyde and the oxidation of thioanisole were performed with
(24) Armarego, W. L. F., Perrin, D. D., Eds. Purification of Laboratory
Chemicals; Pergamon Press: Oxford, 1997.
(25) Saltzman, H., Sharefkin, J. G., Eds. Organic Syntheses; Wiley: New York,
1973; Collect. Vol. V, p 658.
(26) Duelund, L.; Hazell, R.; McKenzie, C. J.; Nielsen, L. P.; Toftlund, H. J.
Chem. Soc., Dalton Trans. 2001, 152-156.
(22) Goh, Y. M.; Nam, W. Inorg. Chem. 1999, 38, 914-920.
(23) (a) Arias, J.; Newlands, C. R.; Abu-Omar, M. M. Inorg. Chem. 2001, 40,
2185-2192. (b) McPherson, L. D.; Drees, M.; Khan, S. I.; Strassner, T.;
Abu-Omar, M. M. Inorg. Chem. 2004, 43, 4036-4050.
9
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Park et al.
DIONEX Pump series P580 equipped with a variable wavelength UV-
200 detector (HPLC), Agilent Technologies 6890N gas chromatograph
(GC), and a Hewlett-Packard 5890 II Plus gas chromatograph interfaced
with Hewlett-Packard model 5989B mass spectrometer (GC-MS).
Product analysis for cyclohexene epoxidation was performed with
Agilent Technologies 6890N gas chromatograph (GC) and a Hewlett-
Packard 5890 II Plus gas chromatograph interfaced with Hewlett-
Packard model 5989B mass spectrometer (GC-MS).
to each reaction solution. All reactions were followed by monitoring
UV-vis spectral changes of the reaction solutions at 548, 537, and
538 nm for the reactions of 4, 5, and 6, respectively. The reaction
solutions did not show any absorption spectral changes at least for 1
h, and product analysis of the reaction solutions, performed with HPLC,
GC, and GC-MS and compared with authentic samples, did not show
the formation of oxygenated products. PPh3 (20 equiv, diluted in 50
µL of CH3CN) was added to the reaction solutions prior to the product
analysis.
Reactions of Iron(III)-Peroxo Complexes. Iron(III)-peroxo
complexes, [(N4Py)FeIII-O2]+ (1),27 [(Bn-TPEN)FeIII-O2]+ (2),28,29 and
[(TMC)FeIII-O2]+ (3),10 were prepared by adding 10 equiv of H2O2 to
the solutions of Fe(N4Py)(ClO4)2 (2 mM) in CF3CH2OH (2 mL) at
-30 °C, Fe(Bn-TPEN)(CF3SO3)2 (2 mM) in CH3OH (2 mL) at -15
°C, and Fe(TMC)(CF3SO3)2 (2 mM) in CF3CH2OH (2 mL) at 0 °C,
respectively, in the presence of triethylamine (10 mM). Then, 40 equiv
of substrates (2-phenylpropionaldehyde, thioanisole, and cyclohexene)
were added to the reaction solutions. All reactions were followed by
monitoring UV-vis spectral changes of the reaction solutions at 650,
745, and 750 nm for the reactions of 1, 2, and 3, respectively. In the
case of 2-phenylpropionaldehyde (2-PPA), the intermediates, 1, 2, and
3, disappeared within 1, 50, and 80 min, respectively. In contrast, the
intermediates remained intact for several hours in the cases of
thioanisole and cyclohexene under the identical conditions of aldehyde
deformylation reactions. Product analysis was performed by injecting
the resulting solutions directly into HPLC, GC, and GC-MS, and
products were identified by comparing retention times and mass patterns
of the products to those of known authentic samples. Product yields
were determined by comparison against standard curves prepared with
authentic samples. Decane was used as an internal standard for the
GC analysis. Product analysis of the 2-PPA reactions revealed that
acetophenone was produced as a major product,10 and the yields of
acetophenone were 15(3), 18(3), and 25(3)% (based on H2O2 used)
for the reactions of 1, 2, and 3, respectively.
In the oxidation of PPh3, the reaction conditions were the same as
described above except that 6 was prepared by reacting Fe(TPA)(ClO4)2
(1 mM) with 5 equiv of H2O2 at -35 °C in CH3CN (2 mL). Upon
addition of 20 equiv of PPh3 (diluted in a solvent mixture (100 µL) of
CH3CN and CH2Cl2 (1:1)), the intermediates, 4 and 5, disappeared
immediately, whereas the disappearance of 6 was slow. The rate of
the natural decay (kobs ) 3.8(6) × 10-3 s-1) and the reaction rate with
PPh3 (kobs ) 5.2(8) × 10-3 s-1) in the reactions of using 5 equiv of
H2O2 were determined by fitting the changes in absorbance at 538 nm
(Supporting Information, Figure S1).
Reactions of Iron(IV)-Oxo Complexes. Non-heme iron(IV)-oxo
complexes, [(N4Py)FeIVdO]2+ (7),20c [(Bn-TPEN)FeIVdO]2+ (8),20c
[(TMC)FeIVdO]2+ (9),20a and [(TPA)FeIVdO]2+ (10),20b were prepared
from the reactions of Fe(N4Py)(ClO4)2 (2 mM) and excess solid PhIO
or m-CPBA (2.4 mM) at 0 °C, Fe(Bn-TPEN)(CF3SO3)2 (2 mM) and
excess solid PhIO at -20 °C, Fe(TMC)(CF3SO3)2 (2 mM) and PhIO
(2 mM, diluted in 50 µL of CH3OH) at 35 °C, and Fe(TPA)(ClO4)2 (2
mM) and CH3CO3H (2.4 mM) at -45 °C, respectively, in CH3CN (2
mL). Then, appropriate amounts of thioanisole were added to the
reaction solution at the given temperature. All reactions were followed
by monitoring UV-vis spectral changes of the reaction solutions.
Pseudo-first-order rate constants were determined by fitting the changes
in absorbance at 695, 735, 820, and 720 nm for the reactions of 7, 8,
9, and 10, respectively (Figure 2 and Supporting Information Figures
S2-S4). Product analysis was performed by injecting the reaction
solution directly into GC and HPLC, and product yields were
determined by comparison with standard curves of known authentic
samples. In the oxidation of thioanisole by 7, 8, 9, and 10, methyl
phenyl sulfoxide was produced quantitatively.
Reactions of Iron(III)-Hydroperoxo Complexes. Iron(III)-hy-
droperoxo complexes, [(N4Py)FeIII-OOH]2+ (4),28 [(Bn-TPEN)FeIII-
OOH]2+ (5),28,29 and [(TPA)FeIII-OOH]2+ (6),30 were prepared by
adding 10 equiv of H2O2 to the solutions of Fe(N4Py)(ClO4)2 (1 mM)
in CF3CH2OH (2 mL) at -30 °C, Fe(Bn-TPEN)(CF3SO3)2 (1 mM) in
CH3OH (2 mL) at 0 °C, and Fe(TPA)(ClO4)2 (1 mM) in CH3CN (2
mL) at -45 °C, respectively. Then, 40 equiv of the respective substrate
(2-phenylpropionaldehyde, thioanisole, and cyclohexene) was added
Acknowledgment. This research was supported by the Korea
Science and Engineering Foundation through Creative Research
Initiative Program.
(27) Ho, R. Y. N.; Roelfes, G.; Hermant, R.; Hage, R.; Feringa, B. L.; Que, L.,
Jr. Chem. Commun. 1999, 2161-2162.
Supporting Information Available: Figures S1-S4. This
material is available free of charge via the Internet at
http://pubs.acs.org.
(28) Hazell, A.; McKenzie, C. J.; Nielsen, L. P.; Schindler, S.; Weitzer, M. J.
Chem. Soc., Dalton Trans. 2002, 310-317.
(29) Koehntop, K. D.; Rohde, J.-U.; Costas, M.; Que, L., Jr. Dalton Trans. 2004,
3191-3198.
(30) Mairata i Payeras, A.; Ho, R. Y. N.; Fujita, M.; Que, L., Jr. Chem. Eur. J.
2004, 10, 4944-4953.
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