Hydrogen atom abstraction and hydride transfer reactions by iron(IV)-oxo porphyrins

Article abstract of DOI:10.1002/anie.200802346

(Chemical Equation Presented) True identity revealed: The C-H bond activation of alkyl aromatics by synthetic iron(IV)-oxo porphyrin species and the hydride transfer of NADH analogues to them occur through H-atom abstraction and proton-coupled electron-transfer mechanisms, respectively. Mechanistic studies revealed that iron(IV)-oxo porphyrin π, not iron(IV)-oxo porphyrin pradical cations, are the true oxidant.

Full text of DOI:10.1002/anie.200802346

Angewandte
Chemie
DOI: 10.1002/anie.200802346
Enzyme Models
Hydrogen Atom Abstraction and Hydride Transfer Reactions by
Iron(IV)–Oxo Porphyrins**
Yu Jin Jeong, Yaeun Kang, Ah-Rim Han, Yong-Min Lee, Hiroaki Kotani, Shunichi Fukuzumi,*
and Wonwoo Nam*
High-valent iron(IV)–oxo species are frequently invoked as
the key oxidizing intermediates in the catalytic cycles of heme
and nonheme iron enzymes.[1–3] In heme iron enzymes, high-
valent iron(IV)–oxo species are proposed as reactive inter-
mediates in dioxygen activation and oxygen-atom transfer
reactions, such as iron(IV)–oxo porphyrin p-radical cations,
referred to as compound I, and iron(IV)–oxo porphyrins,
referred to as compound II.[1] Whereas the reactivity of
compound I has been well investigated with synthetic iron
porphyrins in various oxidation reactions,[1,2c,4] compound II
has been rarely used as an oxidant because of its low oxidizing
power in nature.[5]
Very recently, we have observed significant progress in
understanding the reactivities of mononuclear nonheme
iron(IV)–oxo complexes, which are analogues to compoun-
d II in heme enzymes, in a variety of oxidation reactions,[2,6–8]
À
including the activation of C H bonds of alkanes and alkyl
aromatics.[7] As part of our efforts to elucidate the reactivities
Scheme 1. Iron(IV)–oxo porphyrins and substrates used in this study.
and mechanisms of iron(IV)–oxo complexes of heme and
nonheme ligands in oxidation reactions, we performed
hydrogen-atom abstraction (H-atom abstraction) and hy-
dride-transfer reactions with iron(IV)–oxo porphyrins gen-
erated in situ (Scheme 1). Herein, we report the first exam-
anion), [FeIV(O)(tdfpp)] (2; tdfpp
= meso-tetrakis(2,6-
difluorophenyl)porphinato dianion), and [FeIV(O)(tdcpp)]
(3; tdcpp = meso-tetrakis(2,6-dichlorophenyl)porphinato di-
anion) (Scheme 1a) were prepared by treating the iron(III)
porphyrin chlorides with meta-chloroperbenzoic acid (m-
CPBA) in the presence of a small amount of H2O in a solvent
mixture of CH3CN and CH2Cl2 (9:1) at 158C.[5] Subsequently,
the iron(IV)–oxo complexes were used in the oxidation of
À
ples of C H bond activation of alkyl aromatics and hydride
transfer of dihydronicotinamide adenine dinucleotide
(NADH) analogues by iron(IV)–oxo porphyrin complexes.
The nature of the active oxidant(s), such as an iron(IV)–oxo
porphyrin versus an iron(IV)–oxo porphyrin p-radical cation,
À
alkyl aromatics with weak C H bonds, such as xanthene
in the C H bond activation and hydride-transfer reactions is
(75.5 kcalmolÀ1), 9,10-dihydroanthracene (DHA) (77 kcal
molÀ1), 1,4-cyclohexadiene (CHD) (78 kcalmolÀ1), and fluo-
rene (80 kcalmolÀ1) (Scheme 1b).[9] Upon addition of sub-
strates to a reaction solution of 1, the iron(IV)–oxo porphyrin
complex reverted back to the starting iron(III) porphyrin
complex, showing isosbestic points at 472, 526, and 566 nm in
the UV/Vis spectrum (Figure 1a). Product analysis of the
reaction solutions revealed that xanthone (40 Æ 8% based on
the amount of 1 formed), anthracene (42 Æ 7%), benzene
(41 Æ 7%), and 9-fluorenone (26 Æ 5%) were yielded as
major products in the reactions of xanthene, DHA, CHD,
and fluorene, respectively [see Eq. (1) for the oxidation of
DHA by 1]. Fitting the kinetic data for the pseudo-first-order
decay of 1 allowed us to determine kobs values, and plotting
À
also discussed.
Iron(IV)–oxo porphyrin complexes [FeIV(O)(tpfpp)] (1;
tpfpp
= meso-tetrakis(pentafluorophenyl)porphinato di-
[*] Dr. H. Kotani, Prof. Dr. S. Fukuzumi
Department of Material and Life Science
Graduate School of Engineering, Osaka University
SORST (Japan) Science and Technology Agency (JST)
Suita, Osaka 565-0871 (Japan)
Fax: (+81)6-6879-7370
E-mail: fukuzumi@chem.eng.osaka-u.ac.jp
Y. J. Jeong,[+] Y. Kang,[+] A.-R. Han, Dr. Y.-M. Lee, Prof. Dr. W. Nam
Department of Chemistry and Nano Science
Ewha Womans University, Seoul 120-750 (Korea)
Fax: (+82)2-3277-4441
E-mail: wwnam@ewha.ac.kr
[+] These authors contributed equally to this work.
[**] The research at EWU was supported by KOSEF/MOST through the
CRI Program, Korea, and the research at OU was supported by a
Grant-in-Aid (No. 19205019) from the Ministry of Education,
Culture, Sports, Science and Technology (Japan).
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Communications
obtain the k2’ values).[10] These results indicate that an H-atom
À
abstraction is the rate-determining step for the C H bond
activation of alkyl aromatics. Further evidence supporting the
H-atom abstraction mechanism was obtained from measure-
ments of the kinetic isotope effect (KIE) of the oxidation of
DHA and xanthene, in which KIE values of approximately 20
were obtained in those reactions (Figure 1b). Large KIE
values (e.g., 10–20) were observed also in the oxidation of
DHA and xanthene by nonheme iron(IV)–oxo complexes,
[FeIV(O)(tmc)(X)]n+ (tmc = 1,4,8,11-tetramethyl-1,4,8,11-tet-
raazacyclotetradecane; X = NCCH3 or anion), for which an
À
H-atom abstraction mechanism was proposed for the C H
bond activation reactions.[7b] With the results of the good
correlation between reaction rates and BDE of substrates and
À
the large KIE values, we propose that the C H bond
oxidation of alkyl aromatics by iron(IV)–oxo porphyrins
occurs through an H-atom abstraction mechanism.
The hydride transfer from NADH analogues 10-methyl-
9,10-dihydroacridine (AcrH2), 1-benzyl-1,4-dihydronicotin-
amide (BNAH), and their derivatives (Scheme 1c),[11–13] to
iron(IV)–oxo porphyrins was also investigated under the
conditions of H-atom abstraction reactions. Addition of
substrates to a solution of 1 converted the intermediate into
the starting iron(III) porphyrin complex (see Figure S1a in
the Supporting Information). Pseudo-first-order rate con-
stants, determined by the fitting the kinetic data for the decay
of 1, increased linearly with the increase of the substrate
concentration, leading us to determine second-order rate
constants of 75 Æ 3mÀ1 sÀ1 for AcrH2 and 7.0 ” 102 Æ 30mÀ1 sÀ1
for BNAH (see Figure S1b in the Supporting Information).
Interestingly, the reaction rates of AcrH2 and BNAH were
well-fitted into the plot of logk2 and BDE of AcrH2
(73.7 kcalmolÀ1) and BNAH (67.9 kcalmolÀ1) (see Fig-
ure 1c).[12,14] Further, we have obtained large KIE values of
17 and 8.6 for the reactions of AcrH2 and BNAH, respectively
(see Figure S1b in the Supporting Information). These results
À
demonstrate that the C H bond activation of NADH
Figure 1. Reactions of 1 with substrates at 158C. a) UV/Vis spectral
analogues is involved as a rate-determining step in the
hydride transfer reactions by iron(IV)–oxo porphyrins. Fur-
thermore, when we compared the reactivities of 1 and p-
chloranil (Cl4Q) in hydride-transfer reactions of NADH
analogues (see Table S1 in the Supporting Information), we
observed a good linear correlation between the k2 values of 1
and the corresponding values of Cl4Q (Figure 2).[15] Such a
linear correlation between the logk2 values of [FeIV(O)-
(Porp)] and the corresponding values of Cl4Q suggests that
hydride transfer from NADH analogues to [FeIV(O)(Porp)]
proceeds through hydrogen-atom transfer, which is regarded
as proton-coupled electron transfer (PCET) from AcrH2 to
[FeIV(O)(Porp)],[11a,12,16] followed by rapid electron transfer
from the resulting AcrHC to an [FeIV(O)(Porp)] molecule to
afford the AcrH+ product, as in the proposed mechanism
depicted in Scheme 2.
changes of 1 (0.2 mm) upon addition of [D2]xanthene (20 mm). Inset
shows time course of the decay of 1 monitored at l=547 nm. b) Plot
of kobs against the concentration of DHA and [D4]DHA (leftpanel) and
xanthene and [D2]xanthene (right panel) to determine second-order
rate constants. Circles indicate the oxidation of xanthene and DHA;
triangles indicate the oxidation of [D2]xanthene and [D4]DHA. c) Plotof
À
logk2’ of 1 againstC H BDE of substrates. Second-order rate
constants k2 were determined at 158C and then adjusted for reaction
stoichiometry to yield k2’ based on the number of equivalent target
À
C H bonds of substrates (e.g., 4 for DHA and CHD and 2 for BNAH,
AcrH2, xanthene, and fluorene).
the pseudo-first-order rate constants against the concentra-
tion of substrates led us to determine second-order rate
constants for the reactions of xanthene (k2 = 14 Æ 2mÀ1 sÀ1),
DHA (k2 = 13 Æ 2mÀ1 sÀ1), CHD (k2 = 9.0 Æ 0.8mÀ1 sÀ1), and
fluorene (k2 = 2.3 Æ 0.2mÀ1 sÀ1) (Figure 1b for the reactions of
DHA and xanthene). As expected, the rate constants
We then investigated the porphyrin ligand effect on the
reactivities of [FeIV(O)(Porp)] in the H-atom abstraction and
hydride-transfer reactions (see Scheme 1a for porphyrin
ligands). In the oxidation of xanthene, second-order rate
constants of 14 Æ 2, 11 Æ 2, and 1.6 Æ 0.2mÀ1 sÀ1 were deter-
mined in the reactions of 1, 2, and 3, respectively, indicating
À
decrease with an increase in the C H bond dissociation
energy (BDE) of the substrates, and Figure 1c shows a linear
À
correlation between the logk2’ values and the C H BDE
values of the substrates (the k2 values are divided by the
À
number of equivalent target C H bonds of substrates to
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Scheme 3. Proposed mechanism for the oxidation of organic sub-
strates by iron(IV)–oxo porphyrins.
Figure 2. Plots of logk2 for hydride transfer from NADH analogues to
1 at15 8C vs. logk2 for hydride transfer from the same series of NADH
analogues to Cl4Q at 258C.
the substrate even at 258C (data not shown). If 1 is
disproportionated to [FeIV(O)(tpfpp)+C]+ and [FeIII(tpfpp)]+
through an equilibrium[18,20] and [FeIV(O)(tpfpp)+C]+ is the
true oxidant, then we should observe the decay of 1 because
[FeIV(O)(tpfpp)+C]+ reacts very rapidly with cyclooctane at
258C and 1 is used in generating the [FeIV(O)(tpfpp)+C]+
intermediate by the disproportionation process (Scheme 3).
Similarly, whereas 1 disappears in the reaction of CHD at
À208C, it remains intact upon the addition of ethylbenzene
(86 kcalmolÀ1) (see Figure S2 in the Supporting Information).
As we have discussed above, if the oxidation of CHD by 1
occurs by [FeIV(O)(tpfpp)+C]+ generated by the disproportio-
nation process (Scheme 3, pathway B), the disappearance of 1
should be observed in the ethylbenzene hydroxylation as well.
Thus, the results that 1 reacts with CHD but not with
ethylbenzene indicate that 1 is not a strong oxidant but is
capable of oxidizing CHD under the present reaction
conditions. Finally, since it has been shown that the oxidation
of substrates by iron(IV)–oxo species was suppressed by the
presence of iron(III) porphyrins because of the equilibrium
shift towards the inhibition of the generation of the true
Scheme 2. Proposed mechanism of hydride transfer reaction.
that an iron(IV)–oxo complex bearing a more electron-
deficient porphyrin ligand is a more powerful oxidant in the
[17]
À
activation of C H bonds.
Similarly, an iron(IV)–oxo
+
[18]
species bearing a more electron-deficient porphyrin ligand
showed a slightly greater reactivity in the hydride-transfer
reaction (i.e., k2 = 75 Æ 5, 43 Æ 3, and 25 Æ 3mÀ1 sÀ1 for the
reactions of 1, 2, and 3, respectively, with AcrH2). Interest-
ingly, the reactivity order 1 > 2 > 3 in the H-atom abstraction
and hydride-transfer reactions is different from that reported
in the oxidation of olefins and benzylic alcohols by the
iron(IV)–oxo porphyrins; in the latter reactions, an inverted
reactivity order 3 > 2 > 1 was reported.[18a] On the basis of the
inverted reactivity of iron(IV)–oxo porphyrins, Pan and
Newcomb proposed that the true active oxidant in the
oxidation of olefins and benzylic alcohols by iron(IV)–oxo
porphyrins is iron(IV)–oxo porphyrin p-radical cations
([FeIV(O)(Porp)+C]+), which were generated by the dispropor-
tionation of the iron(IV)–oxo species (Scheme 3).[18] Thus, we
carried out mechanistic studies to understand the nature of
oxidant (i.e., [(Porp)+CFeIV O] ),
we carried out the
=
oxidation of xanthene and the hydride transfer of AcrH2 by
adding two equivalents of [FeIII(tpfpp)]+ to the reaction
solution of 1 and found that reaction rates were not affected
by the presence of [FeIII(tpfpp)]+. These results indicate that
+
there is no disproportionation of 1 to [(Porp)+CFeIV O] and
=
[FeIII(tpfpp)]+ and that 1, not [(Porp)+CFeIV O] , is the true
active oxidant responsible for the weak C H bond activation
of alkyl aromatics and the hydride transfer of NADH
analogues under our reaction conditions.
+
=
À
In conclusion, we have reported two important findings in
the reactivity studies of iron(IV)–oxo porphyrin complexes.
First, we have shown that iron(IV)–oxo porphyrins are
competent oxidants in the oxidations of alkyl aromatics and
NADH analogues and that the oxidation reactions occur
through H-atom abstraction and PCET mechanisms, respec-
tively. Second, we have demonstrated that the active oxidant
À
active oxidant(s) in the C H bond oxidation and hydride-
À
transfer reactions by iron(IV)–oxo porphyrins (e.g.,
Scheme 3, pathway A vs. pathway B).
responsible for the activation of weak C H bonds and the
hydride transfer of NADH analogues is iron(IV)–oxo por-
First, the reactivity orders in the oxidation of alkyl
aromatics and NADH analogues follow the typical electro-
philic reaction; an electron-deficient iron(IV)–oxo species
shows a greater reactivity, although the reactivity difference
depending on the porphyrin ligands is not significant.[19]
Second, whereas [FeIV(O)(tpfpp)+C]+ hydroxylates cyclo-
octane (95.7 kcalmolÀ1) at À308C,[17] 1 does not react with
phyrins, but not iron(IV)–oxo porphyrin p-radical cations.
Received: May 20, 2008
Published online: August 7, 2008
À
Keywords: C H activation · enzyme models · hydride transfer ·
iron · oxo ligands
.
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