Hydroxylation of Aromatics by H2O2 Catalyzed by Mononuclear Non-heme Iron Complexes: Role of Triazole Hemilability in Substrate-Induced Bifurcation of the H2O2 Activation Mechanism

Article abstract of DOI:10.1002/chem.201903239

Rieske dioxygenases are metalloenzymes capable of achieving cis-dihydroxylation of aromatics under mild conditions using O₂ and a source of electrons. The intermediate responsible for this reactivity is proposed to be a cis-Fe^V(O)(OH) moiety. Molecular models allow the generation of a Fe^III(OOH) species with H₂O₂, to yield a Fe^V(O)(OH) species with tetradentate ligands, or {Fe^IV(O); OH^.} pairs with pentadentate ones. We have designed a new pentadentate ligand, mtL₄², bearing a labile triazole, to generate an “in-between” situation. Two iron complexes, [(mtL₄²)FeCl](PF₆) and [(mtL₄²)Fe(OTf)₂]), were obtained and their reactivity towards aromatic substrates was studied in the presence of H₂O₂. Spectroscopic and kinetic studies reflect that triazole is bound at the Fe^II state, but decoordinates in the Fe^III(OOH). The resulting [(mtL₄²)Fe^III(OOH)(MeCN)]²⁺ then lies on a bifurcated decay pathway (end-on homolytic vs. side-on heterolytic) depending on the addition of aromatic substrate: in the absence of substrate, it is proposed to follow a side-on pathway leading to a putative (N₄)Fe^V(O)(OH), while in the presence of aromatics it switches to an end-on homolytic pathway yielding a {(N₅)Fe^IV(O); OH^.} reactive species, through recoordination of triazole. This switch significantly impacts the reaction regioselectivity.

Full text of DOI:10.1002/chem.201903239

A Journal of
Accepted Article
Title: Hydroxylation of aromatics by H2O2 catalyzed by mononuclear
non-heme iron complexes. Role of triazole hemilability in
substrate-induced bifurcation of the H2O2 activation mechanism
Authors: Jean-Noel Rebilly, Wenli Zhang, Christian Herrero, Hachem
Dridi, Katell Sénéchal-David, Régis Guillot, and Frederic
Banse
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To be cited as: Chem. Eur. J. 10.1002/chem.201903239
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Hydroxylation of aromatics by H2O2 catalyzed by mononuclear
non-heme iron complexes. Role of triazole hemilability in
substrate-induced bifurcation of the H2O2 activation mechanism
Jean-Noël Rebilly*, Wenli Zhang, Christian Herrero, Hachem Dridi, Katell Sénéchal-David, Régis
Guillot, and Frédéric Banse*
Dedication ((optional))
Abstract: Rieske dioxygenases are metalloenzymes capable of
achieving cis-dihydroxylation of aromatics under mild conditions
using O2 and a source of electrons. The intermediate responsible for
this reactivity is proposed to be a cis-FeV(O)(OH) moiety. Molecular
models allow generating FeIII(OOH) species with H2O2, to yield a
FeV(O)(OH) species with tetradentate ligands, or {FeIV(O)/OH•} pairs
with pentadentate ones. We have designed a new pentadentate
FeV(O)(OH) reactive species.[6]
Molecular models have been developed to mimic such enzymes
by replacing the cofacial triad[2,
(two imidazoles and a
7]
carboxylate from His and Asp residues) by polydentate chelating
ligands, mostly based on aza coordination spheres, which allows
to ensure stability and mononuclearity for the resulting iron
8]
complexes.[2,
These systems proved capable of achieving
2
ligand mtL4 bearing a labile triazole, to generate an “in-between”
biomimetic catalytic activity in the oxidation of alkanes, alkenes
and aromatics using the peroxide shunt pathway (H2O2 instead
of O2, protons and electrons).[9-16] For this purpose, at least one
exchangeable position must remain in the coordination sphere to
generate reactive intermediates. Hence, tetradentate or
pentadentate ligands are traditionally used, leaving respectively
either two or one labile site(s) at the iron. Hexadentate ligands
bearing a labile arm can also give access to pentadentate-like
reactivities. Depending on the ligand, different types of activation
mechanisms were proposed for the generated FeIII(OOH)
2
situation.
Two
iron
complexes
[(mtL4 )FeCl](PF6)
and
2
[(mtL4 )Fe(OTf)2]) were obtained and their reactivity studied towards
aromatic substrates in the presence of H2O2. Spectroscopic and
kinetic studies reflect that triazole is bound at the FeII state, but
decoordinates
in
the
FeIII(OOH).
The
resulting
[(mtL4 )FeIII(OOH)(MeCN)]2+ then lies on a bifurcated decay pathway
(end-on homolytic vs side-on heterolytic) depending on the addition
of aromatic substrate: in the absence of substrate, it is proposed to
follow a side-on pathway leading to a putative (N4)FeV(O)(OH), while
in the presence of aromatics it switches to an end-on homolytic
2
intermediate, either by homolytic cleavage of the O-O bond,
17-20]
pathway yielding
a
{(N5)FeIV(O);OH•} reactive species, through
yielding {FeIV(O)/OH•}[13,
or heterolytic cleavage, to yield
21-24]
recoordination of triazole This switch significantly impacts the
reaction regioselectivity.
FeV(O)(OH)[9,
or FeV(O)(OAc) when assisted by acetic
acid.[25-27] The formation of these species is dictated by the
ligand backbone, and in turn the reactivity pattern is intimately
related to the nature of the reactive species. Formation of the
FeV(O)(OH) or FeV(O)(OAc) motif requires two cis labile sites
Introduction
which are found in complexes derived from tetradentate
25-26]
ligands,[21,
while the {FeIV(O)/OH•} pair is often proposed
with pentadentate ones.[13, 16, 28-29]
Finding ways to achieve selective oxidation of organic molecules
is of high interest in organic synthesis. Metalloenzymes are
capable of doing such conversions under mild conditions using
readily available metals as catalysts, O2 as the oxidant and
generating H2O as a by-product, and are thus a source of
inspiration to develop green processes.[1] In particular, non-
heme iron enzymes such as Rieske dioxygenases can achieve
cis-dihydroxylation of aromatics at a mononuclear iron site by
activating O2 using two electrons and two protons.[2-3] In the
course of dioxygen activation, an FeIII(OOH) intermediate has
been identified[4-5] which is proposed to evolve towards a
For this reason, we have developed a new pentadentate ligand
where one pyridyl group was replaced by a triazole, known to be
less donating and more labile than pyridine,[14, 30] with the aim of
generating a system that could possibly gather the stability and
robustness of pentadentate systems while being able to access
a tetradentate coordination sphere in situ through triazole
labilization.
Herein, we report new FeII complexes based on the
2
pentadentate ligand mtL4 (Scheme 1), their characterization in
solution and in the solid state, and the evaluation of their
catalytic properties towards oxidation of aromatics by H2O2 in
MeCN. These studies evidence the hemilability of triazole, which
allowed to accumulate an FeIII(OOH) intermediate under
catalytic conditions and get direct insight into the reactive
species, which was not possible with parent pentadentate
ligand-based complexes.[13] The experimental observations
suggest that in the absence of aromatic substrate the
[a]
Dr J-N Rebilly*, W Zhang, Dr C Herrero, Dr H Dridi, Dr K Sénéchal-
David, Dr R Guillot, Pr F Banse*
Institut de Chimie Moléculaire et des Matériaux d’Orsay
Université Paris-Sud, Université Paris-Saclay
91405 Orsay cedex, France
E-mail: jean-noël.rebilly@u-psud.fr; frederic.banse@u-psud.fr
2
(mtL4 )FeIII(OOH) intermediate decays along a side on pathway
to generate a formally cis (N4)FeV(O)(OH) species, similarly to its
Supporting information for this article is given via a link at the end of
the document.((Please delete this text if not appropriate))
2
2
(L4 )FeIII(OOH) analogue, derived from the tetradentate L4
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10.1002/chem.201903239
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ligand. However, addition of aromatic substrates in the medium
induces a switch in the FeIII(OOH) decay pathway involving
recoordination of triazole and the generation of a different
reactive intermediate, a {(N5)FeIV(O)/HO•} caged pair, which
significantly impacts the regioselectivity of the reaction.
dissolved in MeOH. The crystal structure of the molecular cation
2
[(mtL4 )FeCl]+ is displayed in Figure 1. The metal center sits in a
2
distorted octahedral environment with mtL4 acting as
a
pentadentate ligand and
a chloride anion completing the
coordination sphere. The ligand adopts a configuration with the
two pyridyl groups lying in trans positions oriented perpendicular
to each other. Fe-N bond distances sit in the range 2.21-2.29 Å
while the Fe-Cl is 2.32 Å, which is consistent with a high spin
FeII center.[14]
Results
2
The ligand mtL4 (Scheme 1) was synthesized in 77% yield
Solution studies
following the CuAAC (Cu-catalyzed alkyne-azide cycloaddition)
methodology from ligand mpL42 and the copper sulphate/sodium
ascorbate catalytic system in a tBuOH/water mixture at 60°C
(Supporting Information, Scheme S1).
i (A)
1
N5Fe(MeCN)
A
B
2.5 10-5
Synthesis of the complexes
MeCN 0.1 mM
MeOH 0.2 mM
0.5
2
2
N5Fe(OTf)
Complex [(mtL4 )Fe(OTf)2] was synthesized from mtL4 and
Fe(OTf)2 in methanol and isolated by precipitation with diethyl
ether. Complex [(mtL4 )FeCl](PF6) was synthesized from mtL4
0
2
2
and FeCl2.2H2O in methanol followed by the addition of AgPF6 to
precipitate AgCl. The complex was isolated by precipitation of
the filtrate with diethyl ether.
0
300
400
500
600
700
800
0
0.5
1
wavelength (nm)
E (V vs SCE)
Figure 2. (A) UV-vis spectra of [(mtL42)Fe(OTf)2] at 298 K in MeCN and
MeOH. (B) CV at a GC electrode of [(mtL42)Fe(OTf)2], at 298 K in MeCN ([Fe]
= 2 mM, [NBu4PF6] = 0.1 M, CE = Pt, RE = SCE, scan rate = 0.2 V.s-1).
O
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
2
2
2
L5
mpL4
mtL4
2
2
The two complexes [(mtL4 )Fe(OTf)2] and [(mtL4 )FeCl](PF6)
were studied by UV-vis absorption spectroscopy and cyclic
N
N
N
N
N
N
2
voltammetry. The characerizations of [(mtL4 )Fe(OTf)2] are
N
N
N
N
2
2
displayed in Figure 2, whereas those of [(mtL4 )FeCl](PF6) are
L4
TPEN
shown in Supporting Information, Figure S5.
2
[(mtL4 )Fe(OTf)2] in MeCN displays an absorption band (MLCT)
Scheme 1. Structure of the ligands mentioned in this article
at λ = 373 nm (ε = 7110 M-1.cm-1) while in MeOH it is at λ = 356
nm (ε = 2090 M-1.cm-1) (Figure 2A). The difference in the
extinction coefficient suggests a solvent-dependent coordination
sphere. The low value in MeOH is consistent with a high spin
FeII complex encountered when anion binding occurs and
suggests a N5FeII(OTf)-type coordination sphere.
In MeCN, the much higher ε value suggests an FeII complex in a
predominantly low spin form in agreement with acetonitrile
binding (N5FeII(MeCN) coordination sphere). These results are
consistent with MeCN acting as a stronger and more competitive
ligand than MeOH.
2
The CV of [(mtL4 )Fe(OTf)2] in MeCN (Figure 2B) displays a
a
c
major reversible wave at Ep = 1.00 V/ Ep = 0.91 V assigned to
a
the [N5FeII(MeCN)]2+ species and a minor one at Ep = 0.66 V/
Figure 1. An ORTEP drawing of compound [(mtL42)FeCl]+. Thermal ellipsoids
are shown at the 30% level. Fe is in orange-red, C in grey, N in blue, O in dark
red, Cl in green, F in yellow, P in light orange. Hydrogen atoms are omitted for
clarity.
c
Ep = 0.60 V assigned to the [N5FeII(OTf)]+ species. The
c
reduction wave at Ep = 0.82 V is tentatively assigned to an
isomer of the [N5FeIII(MeCN)]3+ species where the triazole and
pyridine are exchanged, or to the binding of water instead of
MeCN. These assignments are consistent with the CV of
Solid state studies
2
[(mtL4 )FeCl](PF6) in MeCN which reveals an equilibrium
between a [N5FeIICl]+ and [N5FeII(MeCN)]2+ species (Supporting
2
Single crystals of [(mtL4 )FeCl](PF6) were obtained by diffusion
Information, Figure S5).
of tert-butylmethyl ether into a solution of the precipitate
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2
Furthermore, the potentials observed for [(mtL4 )Fe(OTf)2] are
With PhIO (entries 6-10), complexes derived from tetra- (N4),
penta- (N5) and hexadentate (N6) ligands are inactive in the
oxidation of aromatics (Table 1), in agreement with the formation
of a common reactive species (Nx)FeIV(O) (vide infra). It has
indeed been frequently reported that non heme FeIV(O)
very close to those found with complexes derived from ligand
pL5 ([N5FeII/III(MeCN)]2+/3+ at Ep = 1.06V/ Ep = 0.97 V,
2
a
c
[N5FeII/IIICl]+/2+ at Ep = 0.69 V/ Ep = 0.62 V).[14] Thus, the
a
c
replacement of pyridine by triazole does not affect
a
a
significantly the donating strength of the overall coordination
sphere.
These assignments were confirmed by HR-ESI-MS (Figures S4
and S6).
intermediates
substrates.[14, 17, 31]
In contrast, formation of phenol products were observed with
H2O2. Comparison of [(mtL4 )FeCl](PF6) and [(mtL4 )Fe(OTf)2]
shows that the presence of the chloride induces a significant
drop in the conversions of anisole (entries 1 and 2). This is in
line with the involvement of a FeIII(OOH) species (vide infra) and
the competitive character of chloride (vs HOO-) for FeIII binding,
which lowers the amount of intermediate in solution.
cannot
hydroxylate
external
aromatic
2
2
Reactivity studies
The catalytic properties of the complexes in the oxidation of
aromatics were tested on the substrates anisole, benzene and
chlorobenzene (Table 1) with PhIO and H2O2 as oxidants.
Table 1. Oxidation of aromatic substrates by hydrogen peroxide and iodosylbenzene catalyzed by [(mtL42)FeCl](PF6) and [(mtL42)Fe(OTf)2] at room
temperature.[a] % Yields are given with respect to the oxidant.
Substrate
Products
Anisole
Benzene
PhOH
Cl-benzene
m
o
p
m
PhOH
o
p
PhOH
entry
1
Oxidant
Nx[b]
N5
N5
N5
N6
N4
N5
N5
N5
N6
N4
Catalyst
[(mtL42)FeCl](PF6)
[(mtL42)Fe(OTf)2]
[(L52)Fe(OTf)2]
[(TPEN)Fe](PF6)2
[(L42)Fe(OTf)2]
[(mtL42)FeCl](PF6)
[(mtL42)Fe(OTf)2]
[(L52)Fe(OTf)2]
TPENFe(PF6)2
[(L42)Fe(OTf)2]
34
63
66
36
62
/
6
13
7
4
/
1
1
6
1
/
5
11
10
6
8
/
H2O2
H2O2
H2O2
H2O2
H2O2
PhIO
PhIO
PhIO
PhIO
PhIO
2
50
7
/
6
/
3
4
5
6
/
/
7
/
/
/
/
8
/
/
/
/
9
/
/
/
/
10
/
/
/
/
[a] Fe / H2O2 / anisole : 1 / 20 / 3000, Fe / PhIO / anisole : 1 / 2 / 3000. PhOH is phenol, o, refer to o-methoxyphenol or o-chlorophenol, p to to p-methoxyphenol
or p-chlorophenol, and m to m-methoxyphenol or m-chlorophenol. Phenol is formed via oxidative demethylation of anisole whereas all other products derive from
aromatic hydroxylation. All assays were performed under aerobic conditions. [b] Ligand denticity: Nx.
(N5) and (N4) triflate complexes display very good and similar
yields in anisole oxidation products with H2O2 conversions in the
range 70-89% (entries 2, 3, 5). The TPEN complex (N6 ligand,
entry 4) shows a strong drop in yield with respect to (N5) and
(N4) complexes, despite the formation of a similar (N5)FeIII(OOH)
intermediate.[32] Again, this can be ascribed to the better
coordinating ability of the pyridyl group with respect to the triflate
or the solvent ligand. The efficiency of a hexacoordinated iron
catalyst in aromatic hydroxylation has recently been proposed to
In anisole oxidation, in all cases the reaction is chemoselective
(aromatic hydroxylation is preferred over oxidative
demethylation) and displays significant regioselectivivity
a
(o/(o+m+p), see Table 1) with a preference for o-hydroxylation,
2
far above the statistical ratio of 40%. [(L4 )Fe(OTf)2] gives the
best selectivity for o-hydroxylation. (100% vs 80-85% for the (N5)
2
systems). [(mtL4 )Fe(OTf)2] also gave satisfactory results when
less reactive aromatic substrates (Table 1) were used such as
benzene (50% conversion of H2O2) and chlorobenzene (13%).
In order to get insight into the reactivity mechanism of
partly depend on the lability of a pyridine moiety.[33]
.
2
It has previously been shown that the complex evolves via
oxidative cleavage of the dangling pyridine towards a species
which displays an altered reactivity vs H2O2 (Figure S20).[31]
[(mtL4 )Fe(OTf)2], we carried out spectroscopic and kinetic
studies in the presence of H2O2 and PhIO.
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Spectroscopic studies. Characterisation of intermediates
To confirm the nature of the transient species, an EPR sample
was drawn from the solution at the maximum of accumulation of
the 520 nm chromophore and frozen in an EPR tube. The EPR
spectrum shows three sets of signals. The signal in the g = 4
region (Figure S16) can be ascribed to a non-specific ubiquitous
high spin FeIII species, whereas the other two correspond to low
spin FeIII species (Figure 3B). Double integration of the EPR
signal allows estimating the high spin FeIII / low spin FeIII ratio to
be 30 / 70 and spectral simulation the relative weight of LS
species.
1.5
A
B
exp.
sim.
0.75
The minor low spin FeIII species (2% of total FeIII) at g = (2.345,
2.140, 1.915) corresponds to the N5FeIII(OH) species resulting
from the oxidation of FeII to FeIII, and the major one (68% of total
0
300
2800
3150
Field [G]
3500
3850
400
500
600
700
800
wavelength (nm)
FeIII) at g = (2.210, 2.155, 1.965), is assigned to an FeIII(OOH)
34, 41-42]
Figure 3. UV-vis spectra at 293 K (A) of [(mtL42)Fe(OTf)2] 1 mM in MeCN
before (black) and immediately after addition of 20 equiv. of hydrogen
peroxide (red). EPR spectrum at 20 K (B) of [(mtL42)Fe(OTf)2] 1 mM in MeCN
after addition of 20 equiv. of hydrogen peroxide (red). The solution was drawn
at the maximum of FeIII(OOH) accumulation. Simulated spectrum (grey) as the
sum of FeIII(OOH) (97% of LS signal, gx = 2.210; gy = 2.155, gz = 1.965) and
FeIII(OH) (3% of LS signal, gx = 2.345; gy = 2.140, gz = 1.915).
species.[13-14,
Typical N5FeIII(OOH) species with
2
2
aminopyridyl ligands (TPEN or L5 , or tL5 ) display two sets of
signals for the hydroperoxo species, assigned to two rotamers
(Scheme 2),[34] as initially proposed for [(N4Py)FeIII(OOH)]2+ by
Feringa, Münck and Que.[39] By contrast, complexes with L4 or
2
related ligands only show a single signal.[17, 37]
The EPR signature of [(mtL4 )FeIII(OOH)]2+ is very close to that
2
of [(L4 )FeIII(OOH)]2+.[17] This likely results from the
2
2
Upon addition of 1.2 equiv. of iodosylbenzene to a solution of
decoordination of the labile triazole, leading to a L4 -type
2
[(mtL4 )Fe(OTf)2] at 253 K in acetonitrile, the solution turned
coordination sphere (Scheme 2). Hence, the different behaviour
2
2
from brown to green. The UV-vis spectrum shows the
disappearance of the MLCT band at 373 nm and the growth of a
band at 735 nm typical of other (N5)FeIV(O) species (Figure S14).
This latter intermediate exhibits a half-life of 135 min under
these conditions.
of (mtL4 ) and (L5 ) could be assigned to the weaker donating
ability and increased lability of triazole (vs pyridine).
Kinetic studies in the absence or presence of substrate.
In the absence of substrate, the kinetics for the development
and decay of the FeIII(OOH) reaction intermediate (formed from
Upon addition of 20 equiv. H2O2 to
a
solution of
2
2
[(mtL4 )Fe(OTf)2] in acetonitrile at 293 K (Figure 3), the solution
turns from brown to purple. The UV-vis spectrum shows the
disappearance of the MLCT band at 373 nm, ascribed to the
oxidation of FeII, together with the growth of a new band at 520
nm, which decays in 140 s (Figure S15). Such a chromophore
(520 nm) is typical of NxFeIII(OOH) species within this family of
ligands.[11-14, 34-36]
[(mtL4 )Fe(OTf)2] and 20 equiv. of H2O2 in MeCN) can be
described by global fit to a A → B → C model, where A is the
FeII precursor, B is FeIII(OOH) and C is the decay product, and
the rate constants k1obs and k2obs extracted (Figure S22).
We investigated the dependence of the rate constants on [H2O2]
(Figures 4 and S23) and temperature (Figure S26-S27). The
rate of formation of FeIII(OOH) (k1obs
) displays a linear
dependence on [H2O2], in line with a bimolecular process
involving H2O2, though it is in fact a fast two-step process:
[(L52)FeIII(OOH)]2+
[(L42)FeIII(OOH)]2+
[(mtL42)FeIII(OOH)]2+
R
N
N
N
FeII + H2O2 à FeIII(OH) + HO•
(0)
(1)
πA
N
N
N
N
N
N
O
N
N
N
FeIII(OH) + H2O2 D FeIII(OOH) + H2O
N
N
S
S
FeIII
N
N
N
FeIII
N
O
H
FeIII
N
FeIII
N
O
H
O
H
N
O
O
O
OH
πB
0.65
0.6
0.7
0.6
0.5
0.4
0.3
0.2
10 H2O2
20 H2O2
30 H2O2
40 H2O2
50 H2O2
100 H2O2
rotamer A
rotamer B
0.55
0.5
Scheme 2. Proposed structures of different FeIII(OOH) intermediates
10 H2O2
20 H2O2
30 H2O2
40 H2O2
50 H2O2
100 H2O2
0.45
0.4
Remarkably, such a chromophore can be generated in MeCN
0.35
0.3
2
similarly to [(L4 )Fe(OTf)2] (with a maximum at 560 nm, Figure
S21) or other FeII complexes with tetradentate ligands,[37-38] but
0.25
0
2
4
6
8
10
12
0
100
200
300
400
500
cannot be accumulated in MeCN with [TPENFe](PF6)2,
[(L5 )Fe(OTf)2] (Figures S19-S20) and most FeII precursors with
2
t (s)
t (s)
pentadentate ligands for which MeOH has to be used instead.[32,
39-41]
Figure 4. Time traces for the formation (left) and decay (right) absorption band
at 520 nm from the UV-vis spectra (293 K) of [(mtL42)Fe(OTf)2] 1 mM in MeCN
upon addition of x equiv. of H2O2.
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The decay rate of FeIII(OOH) (k2obs) shows a slight dependence
on [H2O2] reminiscent of a saturation kinetics (Figures 4 and
S24). As water does not affect the decay rate (Figure S24-S25),
the saturation curve we observed is thus due to excess H2O2. A
classical deactivation pathway of the FeIII(OOH) intermediate is
hydrogen peroxide disproportionation (catalase effect), as
reported recently for (N4Py)FeIII(OOH).[41]
substrate. For simplification, we used benzene as its
hydroxylation leads to a single phenol product.
We followed, by stopped-flow methods, the addition of 20 equiv.
2
of H2O2 to a solution of [(mtL4 )Fe(OTf)2] in MeCN in the
presence of benzene (Figure 5).
The first observed step (Figure 5A) occurs in the first 5 s and
corresponds to the formation of the FeIII(OOH) species (λmax
=
FeIII(OH) + H2O2 D FeIII(OOH) + H2O
(1)
(2)
520 nm). In a second step from 5 to 150 s (Figure 5B), two new
broad bands grow up around 650 nm and below 490 nm, which
decays in a final step (Figure 5C). With a maximum at 650 nm,
this spectrum can be ascribed to the LMCT of a FeIII(OPh)
adduct (Figure 5E). The kinetics were adjusted to a A → B → C
→ D model by global fit (A=FeII, B=FeIII(OOH), C=FeIII(OPh),
D=decay product), allowing to access simulated spectra of
FeIII(OOH) and of the transient species formed in the second
step.
FeIII(OOH) + H2O2 D FeIII(OH) + O2 + H2O
This is in line with the turnover experiments which show a drop
in the yields of anisole products at higher H2O2 concentrations
where H2O2 disproportionation becomes competitive with
substrate hydroxylation (Figure S37).
1
1
A
B
Phase 1 : 0 - 5 s
Phase 2 : 5 - 150 s
The rate of formation of FeIII(OPh) (k2obs’) is independent of
benzene concentration (Figure S30) and lies in the same order
of magnitude as the natural decay rate of FeIII(OOH) in the
absence of substrate (k2obs). This suggests that FeIII(OOH) does
not directly react with the substrate but decays in the rate
limiting step to generate a species that reacts with benzene.
To get further insight into the FeIII(OOH) formation and decay
into the reactive species, temperature studies were carried out in
the absence of substrate allowing us to access activation
parameters via Eyring plots (Figure S26-S27).
0.5
0.5
0
1
0
500
600
700
800
900
500
600
700
800
900
wavelength (nm)
wavelength (nm)
510 nm
650 nm
C
D
Phase 3 : 150 - 500 s
≠
0.6
For the formation step, a relatively high activation enthalpy (ΔH1
= 49 ± 2 kJ.mol-1) and negative entropy (ΔS1≠ = -74 ± 5 J.K-1.mol-
1) were found, in line with an associative process, as described
0.5
2
≠
in equation (1). With complex [(L4 )FeII(MeCN)2](ClO4)2 (ΔH1
=
0.3
≠
55
kJ.mol-1
and
ΔS1
=
-29
J.K-1.mol-1)[17]
and
[(bzTPENFeIIICl](ClO4)2 (ΔH1 = 53 kJ.mol-1 and ΔS1 = -72 J.K-
≠
≠
1.mol-1)[43], the same trend is observed. For the decay step
0
500
600
700
800
900
0
100
200
300
time (s)
400
500
≠
wavelength (nm)
(equation 2), the activation enthalpy is low (ΔH2 = 28 ± 3
kJ.mol-1), but a strongly negative entropy is obtained (ΔS2 = -
≠
1500
0.0008
0.0004
0
193 ± 9 J.K-1.mol-1), which indicates a strongly organized or
FeII
FeIII(OOH)
FeIII(OPh)
FeII
FeIII(OOH)
FeIII(OPh)
Decay products
F
E
associative transition state. [(L4 )FeIII(OOH)]2+ decays with very
2
close parameters in MeCN (ΔH2≠ = 32 ± 2kJ.mol-1 ; ΔS2≠ = -158 ±
7 J.K-1.mol-1 , Figure S32-S34). Thus, it can be concluded that
Decay products
750
the triazole is likely dangling in [(mtL4 )Fe(OOH)]2+ and that it is
2
not involved in the rate determining step of the decay process.
Interestingly, these parameters are far different from those
previously reported for [(L)FeIII(OOH)]2+ species (Table 2) and
particularly from those determined for the decay of
0
500
600
700
800
900
0
100
200
300
time (s)
400
500
wavelength (nm)
2
≠
≠
[(L5 )FeIII(OOH)]2+ (ΔH2 = 81 kJ.mol-1, ΔS2 = -1J.K-1.mol-1).[13]
2
Figure 5. UV-vis spectra (stopped flow, 293 K) of [(mtL42)Fe(OTf)2] / benzene
1 / 300 (1mM Fe in MeCN) + 20 equiv. H2O2 monitored in time (A, B, C), and
time traces of the characteristic bands observed (D). (A) growth of FeIII(OOH),
(B) growth of FeIII(OPh), (C) decay of FeIII(OPh). Simulated spectra (E) and
kinetics (F) extracted from the fit to in a ABCD model. A=FeII, B=FeIII(OOH), C
= FeIII(OPh), D = decay product. The raw simulated extinction coefficients and
concentrations were corrected to take into account the fact that only 70% of
FeII is converted to FeIIIOOH (from EPR integration). The corrected values are
displayed in panels E and F (see text).
With a stronger donor arm, ligand (L5 ) remains pentadentate in
2
2
2
[(L5 )FeIII(OOH)]2+. With penta- (L5 ) or tetradentate ligands (L4
or mtL4 ), FeIIIOOH thus decays through very different pathways.
2
Kinetic and reactivity studies on [(L5 )FeIII(OOH)]2+ showed the
2
intermediate evolved following a homolytic path to yield a
{FeIV(O), OH•} caged pair as the reactive species: the strong
activation enthalpy reflects the cost of O-O bond breaking in the
TS and the near-zero entropy was ascribed to a radical process
involving the reaction of the OH• moiety with CH3CN or another
FeIII(OOH) species during the decay of the intermediate
(Scheme 3).[44]
As the system proved to be efficient in aromatic oxidation, we
also carried out kinetic studies in the presence of an aromatic
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2
In the case of [(mtL4 )FeIII(OOH)]2+, the strongly negative
Hypothesis (iii), O-O bond breaking via a side-on transition
state,[36, 46] appears to be a likely pathway, as tetradentate based
systems are often proposed to form cis Fe(O)(OH) species. With
the solvent playing no important role, it is likely to remain bound,
otherwise it would be reflected in a higher activation enthalpy.
Additionally, hypothesis (iv) can be considered plausible since it
rationalizes the [H2O2] dependence on the decay rate.
entropy suggests an associative transition state. In the absence
of substrate, H2O2 is likely involved in this associative process
(leading to catalase effect, vide supra). The particularly low
activation enthalpy suggests that any O-O bond breaking might
be partly compensated by another bond formation. Four scenarii
could rationalize these observations (Scheme 3) : i) O-O bond
cleavage is concerted with H atom abstraction (HAA) from the
cis bound MeCN ligand; ii) the activation is assisted by water as
proposed by Que and coworkers;[45-47] iii) the hydroperoxide
binds in a side-on fashion to the iron in the transition state, as
proposed for many systems based on tetradentate ligands;[36, 46]
or iv) a second H2O2 molecule is involved in the process.
As already mentioned above, since there is no water
dependence on the observed decay rate (Figure S24-S25),
hypothesis (ii) can be discarded.
When carried out in CD3CN (Figure S29), the decay (step 2) is
not significantly slowed down, which is not compatible with HAA
from the solvent. Accordingly, the activation parameters
obtained in MeOH (Figure S28 and Table 2) are very close to
those found in MeCN, suggesting a similar pathway that is
compatible with a subordinate role of the solvent and therefore
hypothesis (i) can be discarded.
Table 2. Activation parameters for the decay of various FeIII(OOH) species
O-O bond
cleavage
ΔH≠
ΔS≠
System
kJ.mol-1
J.mol-1.K-1
This work
[(mtL42)FeIII(OOH)]2+ in MeCN
[(mtL42)FeIII(OOH)]2+ in MeOH
[(L42)FeIII(OOH)]2+ in MeCN
28 ± 3
33 ± 4
32 ± 2
-193 ± 9
- 176 ± 13
-158 ± 7
[(L42)FeIII(OOH)]2+ in MeCN +
benzene
26.3 ± 2
-178 ± 5
[(mtL42)FeIII(OOH)]2+ in MeCN
+ benzene
[(L52)FeIII(OOH)]2+ : large ΔH‡, near zero ΔS‡
43.5 ± 4
44
-133 ± 1.5
-89
[(TMC)FeIII(OOH)]2+
in MeCN[48]
+
HClO4
octene
in
Heterolytic
FeIII
FeIII
FeIV
O
O
O H
O
O
H
H
O
[(TPA)FeIII(OOH)]2+
in MeCN[47]
+
TS
45
-95
[(L42)FeIII(OOH)]2+ and [(mtL42)FeIII(OOH)]2+
:
[(PyNMe3)FeIII(OOH)]2+
MeCN + H+[26]
small ΔH‡, strongly negative ΔS‡
46
-79
H
H
H
(BnTPEN)FeIII(OOH)2+
+
N
HOAc + HOTf in MeCN[49]
30
-118
FeIII
H
O
O
H
O
H
[(PyNMe3)FeIII(OOH)]2+
MeCN[26]
+ in
FeIII
Homolytic
O
(ii)
TS (i)
O
H
O
43
81
-137
-1
H
(i)
H
O
FeIII
[(L52)FeIII(OOH)]2+ in MeCN[13]
TS (ii)
+H2O
-MeCN
(iii)
O
H
H
H
H
[(TMC)FeIII(OOH)]2+
N
in acetone/CF3CH2OH[16]
FeIII
56
-75
O
H
H
H
O
H
[(N4Py)FeIII(OOH)]2+ in
acetone / CF3CH2OH[16]
N
O
FeIII
H
+H2O2
53
53
-121
-68
O
(iv)
TS (iii)
[28]
[(bppc)FeIII(OOH)]2+
H
N
H
H
FeIII
TMC = tetramethylcyclam; TPA = trispyridylamine; PyNMe3 = N,N‘‘-((2,6)-
dimethylpyridyl)-N,N‘,N‘‘-trimethyl-diethylenetriamine; N4py N,N-bis(2-
pyridylmethyl)-N-(bis-2-pyridylmethyl)amine; bppc = N,N′-dibenzyl-N,N′-bis(2-
H
O
H
O
=
O
TS (iv)
O
H
pyridylmethyl)-1,2-cyclohexanediamine
Scheme 3. Proposed decay mechanism for [(L52)FeIII(OOH)]2+ (adapted from
ref. 13) and possible transition states for the evolution of [(mtL42)FeIII(OOH)]2+
Interestingly, when the reaction is carried out in the presence of
300 equiv. benzene, the Eyring plot gives the activation
and [(L42)FeIII(OOH)]2+
.
2
parameters for the [(mtL4 )FeIII(OOH)]2+ decay ΔH2 = 43.5 ± 4
≠
kJ.mol-1 and ΔS2 = -133 ± 1.5 J.K-1.mol-1 (Figure S31). These
≠
parameters are clearly different from those obtained in the
absence of substrate and suggest
a different activation
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10.1002/chem.201903239
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mechanism. On the other hand, under the same conditions (300
example, theoretical studies proposed a homolytic cleavage
along an end-on pathway, with the H atom of FeIII(OOH) being
shared between the proximal and distal O atoms in the transition
state. A similar pathway, associated to the rebinding of the
triazole can thus be proposed (Scheme 4).
2
equiv. benzene), the decay of [(L4 )FeIII(OOH)]2+ is associated to
parameters ΔH2 = 26.3 ± 2kJ.mol-1 and ΔS2 = -178 ± 5 J.K-
≠
≠
1.mol-1 (Figure S35-S36), very close to those obtained in the
absence of substrate (ΔH2 = 32 ± 2kJ.mol-1 ; ΔS2 = -158 ± 7
≠
≠
J.K-1.mol-1, Table 2).
To confirm this, we carried out the benzene oxidation reaction
with 20 equiv. H2O2 starting from a 1:1 mixture of benzene and
D6-benzene and determined a KIE value of 1.07±0.03. If FeV(O)
were the reactive species, an inverse KIE would be expected.[52-
2
Thus, [(L4 )FeIII(OOH)]2+ decays along an analogous path
regardless of the presence or absence of benzene. This path is
2
similar to that of [(mtL4 )FeIII(OOH)]2+ in the absence of benzene
53]
and likely involves a side-on transition state to yield a side-on
Conversely, similar KIE values were reported for a series of
{FeIV(O), OH• ↔ FeV(O), OH-} species, as proposed by Rybak-
complexes involving an {FeIV(O) / OH•} caged pair.[13, 54]
Akimova.[17]
This
leaves
us
with
the
decay
of
The
magnitude
of
the
activation
enthalpy
for
2
2
[(mtL4 )FeIII(OOH)]2+ along
a
new pathway when in the
[(mtL4 )FeIII(OOH)]2+ decay in the absence of substrate is
relatively small, and its activation entropy very negative
compared to most literature parameters. However, literature
systems are not ideal references for the proposed side-on decay
of the intermediate: homolytic cleavage examples correspond to
the cleavage of end-on species, and heterolytic ones involve the
addition of acids, which alter the intrinsic decay of FeIII(OOH).
presence of benzene. The main difference between these two
complexes being the dangling triazole, we hypothesize that it is
likely that it rebinds during the activation process, preventing a
side-on transition state.
2
To summarize, as decay rates of [(mtL4 )FeIII(OOH)]2+ are
poorly dependent on benzene concentration, the substrate does
not react in the TS. However, given the different sets of
activation parameters obtained in the presence and absence of
benzene, it induces a switch in the mechanism. This apparent
paradox can be solved by considering two competitive pathways
for FeIII(OOH) activation that are close in energy (Scheme 4):
one yields a (N4)FeV(O)(OH) species, and the other {(N5)FeIV(O);
OH•}. In support to this proposition, the activation parameters
listed on Table 2 lead to close ΔG≠(293 K) values of (84.5 ± 6)
OH-
HO
FeIV
FeIV
FeIII
+ MeCN
O
O
O
N
H
O
aromatic
rds
hydroxylation
kJ.mol-1 and (82.5
±
5) kJ.mol-1 for the decay of
2
[(mtL4 )FeIII(OOH)]2+ in the absence or presence of benzene,
respectively. None of these proposed FeIII(OOH) activation
pathways involve any substrate, hence reaction rates will not
depend on substrate concentration. For either FeV(O)(OH) or
{FeIV(O); OH•} intermediate obtained, the subsequent step is the
reaction with the aromatic substrate. But if the driving force for
the reaction of aromatic substrates with {(N5)FeIV(O); OH•} is
greater than the driving force for the reaction of substrate with
(N4)FeV(O)(OH), then by equilibrium displacement, the
{(N5)FeIV(O); OH•} pathway will preferentially be picked up. It is a
plausible hypothesis as aromatic hydroxylation by {(N5)FeIV(O);
OH•} intermediates has been shown to be initiated by the fast
interception of OH• by the aromatic ring.[50] Conversely, when
H2O2 is the subtrate for catalase activity (i.e. in the absence of
FeIII
O
O
H
N
[(mtL42)FeIII(OOH)]2+
disproportionation
of H2O2
rds
O
N
H
H
FeV
FeV
+ MeCN
H2O2
H
FeIII
OH
O
O2
+ MeCN
H
O
O
O
OH
N
N
O
N
H
Scheme 4. Proposed mechanisms for the decay of in the absence or
presence of aromatic substrate. Two FeIII(OOH) activation pathways are in
competition and selectively picked up depending on the subsequent reaction
by equilibrium displacement: aromatic oxidation drives the system through the
upper pathway, and H2O2 disproportionation through the lower one in the
absence of benzene. The reaction is independent on benzene concentration
as the FeIIIOOH activation is the slow step of the mechanism (rds).
benzene), (N4)FeV(O)(OH) is
a
structurally more suited
intermediate, as it can form
a transient preorganized 6-
membered ring intermediate with H2O2, and the (N4)FeV(O)(OH)
pathway will preferentially be picked up.[51] This overall scheme
also reflects the two competitive reactions at work (aromatic
hydroxylation vs H2O2 disproportionation).
Discussion
To determine the nature of the O-O bond cleavage, we
compared the activation parameters found in this work with other
literature systems involving well-characterized homo- and
heterolytic pathways (Table 2).
Based on their similar activation parameters, we can conclude
2
that
both
[(mtL4 )FeIII(OOH)(MeCN)]2+
and
2
[(L4 )FeIII(OOH)(MeCN)]2+ evolve through
a
similar side-on
transition state in the absence of aromatic substrates, yielding a
cis Fe(O)(OH) which can be described as two {FeIV(O), OH• ↔
FeV(O), OH-} electromer forms, the relative weight of each is
dependent on the ligand donating ability. In line with this, the
highly reactive species resulting from peracid activation by
2
Interestingly, the activation parameters for [(mtL4 )FeIII(OOH)]2+
decay in the presence of benzene (ΔH2 = 43.5 ± 4 kJ.mol-1 and
≠
ΔS2 = -133 ± 1.5 J.K-1.mol-1 ) are surprisingly close to those
≠
reported for the decay of [(PyNMe3)FeIII(OOH)]2+ in MeCN (ΔH2
= 43 kJ.mol-1 ; ΔS2
= -137 J.K-1.mol-1).[26] In this latter
≠
≠
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2
(N4)FeII precursors has been recently described as a mixture of
FeV(O)(OC(O)R) / FeIV(O)(•OC(O)R) configurations.[55-56]
that is closer to that observed for [(L5 )FeIII(OOH)]2+, where the
2
ligand is pentadentate (Table 1). With L4 , the two oxidizing
However, a difference appears in the presence of aromatic
equivalents are both metal-controlled. The interaction between
the OMe substituent of anisole and the OH ligand of Fe(O)(OH)
will preferentially expose the ortho position to oxidation initiated
by attack of the aromatic π system on the high valent Fe(O), as
shown in Scheme 5. Conversely, the spatial arrangement of
2
substrates: on the one hand, [(L4 )FeIII(OOH)(MeCN)]2+ remains
on the same pathway to yield cis-Fe(O)(OH) which oxidizes the
aromatic substrate. The two oxidative equivalents are both metal
centered, and the active species can be formally described as a
cis-FeV(O)(OH) intermediate, which has been proposed to be the
active species in (N4)FeII / H2O2 catalytic systems.[8, 19, 24, 57]
2
FeIV(O) and OH• gets looser in the mtL4 system and the
regioselectivity becomes altered: aromatic hydroxylation is
initiated by the attack on the π system by the hydroxyl radical
followed the e-/H+ transfer to the FeIV(O), as demonstrated
2
On the other hand, [(mtL4 )FeIII(OOH)(MeCN)]2+ goes through a
new transition state in which triazole rebinds to the metal,
prevents the side-on binding of the hydroperoxo and forces a
homolytic cleavage of the O-O bond in an end-on arrangement.
The resulting reactive species is then a {(N5)FeIV(O), OH•} caged
2
previously for [(L5 )FeIII(OOH)]2+.[13]
Finally, these bifurcated mechanisms from
a
similar
(N4)FeIII(OOH) intermediate are also in line with the kinetic
2
50]
pair, as proposed for [(L5 )FeIII(OOH)]2+,[13,
and for other
isotope effect observed in benzene hydroxylation. A KIE<1 was
FeIII(OOH) intermediates in Fenton[58] and non heme systems.[26]
reported for [(L4 )FeIII(OOH)(MeCN)]2+[17] consistent with the
2
This activation bifurcation between [(L4 )FeIII(OOH)(MeCN)]2+
attack on an electrophilic metal-oxo by the π system.[17,
In
of
2
52]
and [(mtL4 )FeIII(OOH)(MeCN)]2+ directly impacts their catalytic
contrast,
we
found
KIE
>1
in
the
case
2
2
performances
and
selectivities.
Whereas
[(mtL4 )FeIII(OOH)(MeCN)]2+ which has been shown to be the
2
2
[(L4 )FeIII(OOH)(MeCN)]2+ generates a 100% regioselectivity for
signature of {FeIV(O) / OH•} formed from [(L5 )FeIII(OOH)]2+ and
o-hydroxylation
of
anisole
(Table
1),
similar intermediates.[13, 54]
2
[(mtL4 )FeIII(OOH)(MeCN)]2+ shows a distribution of products
R
N
N
N
high
regioselectivity
+ MeCN
+ H2O2
+ MeCN
+ H2O2
N
N
R
N
O
N
N
O
H
N
H
N
N
N
N
N
N
N
N
O
O
FeIII
H
FeIII
FeIII
FeIII
H
OH
N
N
N
OH
H
N
N
N
N
less
regioselectivity
HO
O
O
O
H
H
HO
O
rds
rds
O
N
H
N
N
H
H
O
FeIII
H
O
R
N
N
N
O
O
N
H
O
N
N
O
FeIII
H
H
N
N
O
MeCN
N
N
N
R
N
N
O
N
N
H
H
FeIII
O
MeCN
FeIII
N
TS
O-
O
N
N
H
N
H
N
O
N
O
TS
FeV
O
H
N
O
N
O
High
Preorganization
- MeCN
- MeCN
O
H
O
O
N
R
N
N
N
N
O
N
N
N
R
N
N
N
N
N
N
N
N
N
H
FeIV
FeV
FeIV
FeIV
N
O
O
O
H
H
O
O
O
N
N
N
N
H
H
Less preorganization
Reactive species :
Loose oxidizing pair
Reactive species :
Tight oxidizing pair
Scheme 5. Proposed mechanism for the FeIII(OOH) activation and the reactivity on anisole with [(L42)FeIII(OOH)]2+ (left) and [(mtL42)FeIII(OOH)]2+ (right).
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10.1002/chem.201903239
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FULL PAPER
or {(N5)FeIV(O)/HO•} caged pair), which in turn controls the
reaction selectivity.
Conclusions
2
A new ligand mtL4 was synthesized, in which a pyridyl group
was replaced by the less donating triazole group with respect to
2
2
ligand L5 . Two iron complexes, [(mtL4 )FeCl](PF6) and
Experimental Section
2
[(mtL4 )Fe(OTf)2] , were isolated and characterized in solution
and in the solid state for [(mtL4 )FeCl](PF6). Their catalytic
2
Synthesis and characterization of ligands and complexes, detailed
spectroscopic and kinetic studies of intermediates and additional
information can be found as supplementary material.
properties in the oxidation of aromatics were tested in
acetonitrile using H2O2 and PhIO as oxidants. Spectroscopic
studies indicate the formation of intermediates FeIII(OOH) and
FeIV(O) respectively under these conditions. In particular, the
Fe/H2O2 system is very efficient in aromatic hydroxylation,
reaching an almost quantitative conversion of hydrogen peroxide
Acknowledgements
into anisole oxidation products. The reaction shows
a
This work is supported by a public grant overseen by the French
National Research Agency (ANR) as part of the
“Investissements d’Avenir” program (Labex charmmmat,
reference: ANR-11-LABX-0039-grant).
chemoselectivity ratio of 6.9 (aromatic hydroxylation vs
demethylation) and regioselectivity for o-hydroxylation of 82% in
aromatic hydroxylation. The reaction still occurs with poorer
aromatics like benzene and chlorobenzene.
2
Unlike its pyridyl analogue ([(L5 )Fe(OTf)2]), the FeIII(OOH)
Keywords: non-heme • iron • catalysis • hydrogen peroxide •
2
intermediate derived from [(mtL4 )Fe(OTf)2] can be formed and
aromatic hydroxylation
accumulated in MeCN, which allowed us to study its fate under
catalytic conditions.
[1] I. Bertini, A. Sigel and H. Sigel, Handbook of metalloproteins, Marcel
Dekker, Inc, New York, 2001, p.
2
The intermediate [(mtL4 )FeIII(OOH)]2+ displays a signature
2
close to that of [(L4 )FeIII(OOH)]2+. This suggests triazole acts as
[2] M. Costas, M. P. Mehn, M. P. Jensen and L. Que, Chem. Rev. 2004, 104,
939-986.
a labile ligand during the formation process. Kinetic studies
2
show that the decay rate of [(mtL4 )FeIII(OOH)]2+ is comparable
[3] S. M. Resnick, K. Lee and D. T. Gibson, J. Ind. Microbiol. Biotechnol. 1996,
17, 438-457.
to the formation rate of the phenol product, indicating the
intermediate decay is the rate determining step of the
hydroxylation reaction.
[4] E. Carredano, A. Karlsson, B. Kauppi, D. Choudhury, R. E. Parales, J. V.
Parales, K. Lee, D. T. Gibson, H. Eklund and S. Ramaswamy, J. Mol.
Biol. 2000, 296, 701-712.
In the absence of aromatic substrate, the decay activation
[5] A. Karlsson, J. V. Parales, R. E. Parales, D. T. Gibson, H. Eklund and S.
Ramaswamy, Science 2003, 299, 1039-1042.
2
parameters are similar to those of [(L4 )FeIII(OOH)]2+ and
suggest a side-on arrangement of the hydroperoxo in the
transition state. This type of transition state can lead to a
[6] M. D. Wolfe and J. D. Lipscomb, J. Biol. Chem. 2003, 278, 829-835.
[7] B. Kauppi, K. Lee, E. Carredano, R. E. Parales, D. T. Gibson, H. Eklund
and S. Ramaswamy, Structure with Folding & Design 1998, 6, 571-586.
[8] K. Chen, M. Costas and L. Que Jr, J. Chem. Soc., Dalton Trans. 2002,
672-679.
species described as
a
mixture of two configurations
{FeIV(O)/HO•} and {FeV(O)/(OH-)}. Conversely, in the presence of
2
benzene, whereas [(L4 )FeIII(OOH)]2+ retains a similar activation
[9] I. Prat, A. Company, V. Postils, X. Ribas, L. Que, J. M. Luis and M. Costas,
Chem. Eur. J. 2013, 19, 6724-6738.
2
mechanism, [(mtL4 )FeIII(OOH)]2+ switches to a homolytic O-O
bond cleavage assisted by the rebinding of triazole. This
constitutes one of the rare examples of a substrate-induced
mechanism bifurcation.[59]
[10] J. M. Chen, M. Lutz, M. Milan, M. Costas, M. Otte and R. Gebbink, Adv.
Synth. Catal. 2017, 359, 2590-2595.
[11] V. Balland, D. Mathieu, N. Pons-Y-Moll, J. F. Bartoli, F. Banse, P. Battioni,
J. J. Girerd and D. Mansuy, J. Mol. Cat. A. 2004, 215, 81-87.
[12] A. Thibon, J.-F. Bartoli, R. Guillot, J. Sainton, M. Martinho, D. Mansuy and
F. Banse, J. Mol. Catal. A 2008, 287, 115-120.
Consequently,
the
regioselectivity
obtained
with
2
[(mtL4 )FeIII(OOH)(MeCN)]2+ is altered with respect to that
observed with [(L4 )FeIII(OOH)(MeCN)]2+ and is closer to the one
2
[13] A. Thibon, V. Jollet, C. Ribal, K. Sénéchal-David, L. Billon, A. B. Sorokin
and F. Banse, Chem. Eur. J. 2012, 18, 2715-2724.
observed with pentadentate ligand systems. This can be
rationalized by the formation of a {cis-(N4)FeIV(O)(OH•) ↔ cis-
[14] N. Ségaud, J.-N. Rebilly, K. Sénéchal-David, R. Guillot, L. Billon, J.-P.
Baltaze, J. Farjon, O. Reinaud and F. Banse, Inorg. Chem. 2013, 52,
691-700.
2
(N4)FeV(O)(OH)} species in the case of the (L4 ) system and of a
2
{(N5)FeIV(O)/HO•} caged pair in the case of (mtL4 ). A direct KIE
for benzene oxidation is observed in the case of
[15] Y. M. Kim, K.-B. Cho, J. Cho, B. Wang, C. Li, S. Shaik and W. Nam, J.
Am. Chem. Soc. 2013, 135, 8838-8841.
2
[(mtL4 )FeIII(OOH)(MeCN)]2+, whereas an inverse KIE was
2
[(L4 )FeIII(OOH)(MeCN)]2+,
supporting
the
[16] L. V. Liu, S. Hong, J. Cho, W. Nam and E. I. Solomon, J. Am. Chem. Soc.
2013, 135, 3286-3299.
reported
for
assignement of the respective reactive species.
[17] V. Makhlynets Olga and V. Rybak‐Akimova Elena, Chem. Eur. J. 2010,
16, 13995-14006.
The hemilability of triazole allowed us to accumulate an
FeIII(OOH) intermediate and fully study the mechanism of
aromatic hydroxylation by (N5)Fe non-heme complexes under
catalytic conditions (MeCN) which was previously impossible
with parent systems based on TPEN or L52 ligands.
[18] A. Company, L. Gomez, X. Fontrodona, X. Ribas and M. Costas, Chem.
Eur. J. 2008, 14, 5727-5731.
[19] K. Chen, M. Costas, J. H. Kim, A. K. Tipton and L. Que, J. Am. Chem.
Soc. 2002, 124, 3026-3035.
Finally, this study gives further insight into how ligand denticity
affects the nature of the FeIII(OOH) reactive intermediate in iron-
catalyzed H2O2 oxidations, how it controls its decay pathway
(side-on or end-on TS) and into the nature of the resulting
reactive species ({cis-(N4)FeIV(O)(OH•) ↔ cis-(N4)FeV(O)(OH)}
[20] O. Cusso, X. Ribas and M. Costas, Chem. Commun. 2015, 51, 14285-
14298.
[21] W. N. Oloo, R. Banerjee, J. D. Lipscomb and L. Que, J. Am. Chem. Soc.
2017, 139, 17313-17326.
[22] I. Prat, J. Mathieson, M. Guell, X. Ribas, J. M. Luis, L. Cronin and M.
Costas, nature Chem. 2011 3 788-793.
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[23] S. Xu, J. J. Veach, W. N. Oloo, K. C. Peters, J. Wang, R. H. Perry and L.
Que, Chem. Commun. 2018, 54, 8701–8704.
[55] R. X. Fan, J. Serrano-Plana, W. N. Oloo, A. Draksharapu, E. Delgado-
Pinar, A. Company, V. Martin-Diaconescu, M. Borrell, J. Lloret-Fillol, E.
Garcia-Espana, Y. S. Guo, E. L. Bominaar, L. Que, M. Costas and E.
Munck, J. Am. Chem. Soc. 2018, 140, 3916-3928.
[24] M. Borrell, E. Andris, R. Navrátil, J. Roithová and M. Costas, Nature
Communications 2019, 10, 901-909.
[25] W. N. Oloo and L. Que, Acc. Chem. Res. 2015, 48, 2612-2621.
[26] J. Serrano-Plana, F. Acuna-Pares, V. Dantignana, W. N. Oloo, E. Castillo,
A. Draksharapu, C. J. Whiteoak, V. Martin-Diaconescu, M. G. Basallote,
J. M. Luis, L. Que, M. Costas and A. Company, Chem. Eur. J. 2018, 24,
5331-5340.
[56] J. Serrano-Plana, W. N. Oloo, L. Acosta-Rueda, K. K. Meier, B. Verdejo,
E. Garcia-Espana, M. G. Basallote, E. Munck, L. Que, A. Company and
M. Costas, J. Am. Chem. Soc. 2015, 137, 15833-15842.
[57] A. Company, Y. Feng, M. Güell, X. Ribas, J. M. Luis, L. Que Jr. and M.
Costas, Chem. Eur. J. 2009, 15, 3359–3362.
[27] W. N. Oloo, K. K. Meier, Y. Wang, S. Shaik, E. Munck and L. Que, Nature
Communications 2014, 5, 3046.
[58] R. D. Bach and O. Dmitrenko, J. Org. Chem. 2010, 75, 3705–3714.
[59] C. Wegeberg, F. R. Lauritsen, C. Frandsen, S. Morup, W. R. Browne and
C. J. McKenzie, Chem. Eur. J. 2018, 24, 5134-5145.
[28] Q. Zhang and C. R. Goldsmith, Inorg. Chem. 2014, 53, 5206-5211.
[29] J. Cho, S. Jeon, S. A. Wilson, L. V. Liu, E. A. Kang, J. J. Braymer, M. H.
Lim, B. Hedman, K. O. Hodgson, J. S. Valentine, E. I. Solomon and W.
Nam, Nature 2011, 478, 502-505.
[30] N. Ségaud, C. De Thomasson, C. Daverat, K. Sénéchal-David, A. Dos
Santos, V. Steinmetz, P. Maître, J.-N. Rebilly, F. Banse and O. Reinaud,
Chem. Eur. J. 2017, 2894-2906.
[31] M. Martinho, F. Banse, J. F. Bartoli, T. A. Mattioli, P. Battioni, O. Horner, S.
Bourcier and J. J. Girerd, Inorg. Chem. 2005, 44, 9592-9596.
[32] A. J. Simaan, S. Döpner, F. Banse, S. Bourcier, G. Bouchoux, A. Boussac,
P. Hildebrandt and J. J. Girerd, Eur. J. Inorg. Chem. 2000, 1627-1633.
[33] G. Capocasa, G. Olivo, A. Barbieri, O. Lanzalunga and S. Di Stefano,
Catal. Sci. Technol. 2017, 7, 5677–5686.
[34] M. Martinho, P. Dorlet, E. Riviere, A. Thibon, C. Ribal, F. Banse and J.-J.
Girerd, Chem. Eur. J. 2008, 14, 3182-3188.
[35] M. Martinho, G. Blain and F. Banse, Dalton Trans. 2010, 39, 1630-1634.
[36] S. M. Hölzl, P. J. Altmann, J. W. Kück and F. E. Kühn, Coord. Chem. Rev.
2017, 352, 517–536.
[37] O. V. Makhlynets, W. N. Oloo, Y. S. Moroz, I. G. Belaya, T. D. Pal-luccio,
A. S. Filatov, P. Müller, M. A. Cranswick, L. Que and E. V. Rybak-
Akimova, Chem. Commun. 2013, 50, 645.
[38] A. Mairata i Payeras, R. Y. N. Ho, M. Fujita and L. Que, Chem. Eur. J.
2004, 10, 4944–4953.
[39] G. Roelfes, V. Vrajmasu, K. Chen, R. Y. N. Ho, J.-U. Rohde, C.
Zondervan, R. M. la Crois, E. P. Schudde, M. Lutz, A. L. Spek, R. Hage,
B. L. Feringa, E. Münck and L. Que, Inorg. Chem. 2003, 42, 2639–2653.
[40] J. J. Girerd, F. Banse and A. J. Simaan, Struct. Bond. 2000, 97, 145.
[41] J. Chen, A. Draksharapu, D. Angelone, D. Unjaroen, S. K. Padamati, R.
Hage, M. Swart, C. Duboc and W. R. Browne, ACS Catal. 2018, 8,
9665.
[42] M. Martinho, F. Banse, J. Sainton, C. Philouze, R. Guillot, G. Blain, P.
Dorlet, S. Lecomte and J.-J. Girerd, Inorg. Chem. 2007, 46, 1709-1717.
[43] A. Hazell, C. J. McKenzie, L. P. Nielsen, S. Schindler and M. Weitzer, J.
Chem. Soc., Dalton Trans. 2002, 310-317.
[44] Note: Unlike [(mtL42)FeIII(OOH)]2+
,
[(L52)FeIII(OOH)]2+ cannot be
accumulated in MeCN, but can be in MeOH. To determine these decay
parameters in MeCN, the intermediate was formed in MeOH, isolated
by precipitation at low temperature and redissolved in MeCN.
[45] A. Bassan, M. R. A. Blomberg, P. E. M. Siegbahn and L. Que, J. Am.
Chem. Soc. 2002, 124, 11056-11063.
[46] K. Chen and L. Que, J. Am. Chem. Soc. 2001, 123, 6327-6337.
[47] W. N. Oloo, A. J. Fielding and L. Que, J. Am. Chem. Soc. 2013, 135,
6438-6441.
[48] F. F. Li, K. K. Meier, M. A. Cranswick, M. Chakrabarti, K. M. Van
Heuvelen, E. Munck and L. Que, J. Am. Chem. Soc. 2011, 133, 7256-
7259.
[49] S. Xu, A. Draksharapu, W. Rasheed and L. Que, J. Am. Chem. Soc. 2019.
[50] A. S. Faponle, M. G. Quesne, C. V. Sastri, F. Banse and S. P. de Visser,
Chem. Eur. J. 2015, 21, 1221-1236.
[51] This is in line with the observed [H2O2] dependence of the FeIII(OOH)
decay rate (Figure S23). In that case, the rate determining step (rds)
cannot be fully assigned to the FeIII(OOH) activation step, as the
reaction with the H2O2 subtrate affects the kinetics.
[52] K. H. Mitchell, C. E. Rogge, T. Gierahn and B. G. Fox, Proc. Natl. Acad.
Sci. U S A 2003, 3784–3789.
[53] A. Sorokin and B. Meunier, Eur. J. Inorg. Chem. 1998, 1269–1281.
[54] A. S. Faponle, F. Banse and S. P. de Visser, J. Biol. Inorg. Chem. 2016,
21, 453–462.
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Entry for the Table of Contents (Please choose one layout)
Layout 1:
FULL PAPER
R'
N
2
N
mtL4 FeII(OTf)2 reacts with H2O2 to
Jean-Noël Rebilly*, Wenli Zhang,
N
yield a (N4)FeIII(OOH)(MeCN)
intermediate where triazole remains
dangling. The hemilability of triazole
then allows for a substrate-triggered
switch of the FeIII(OOH) activation
pathway, yielding a reactive
{(N5)FeIV=O; OH•} species instead
(N4)FeV=O(OH) obtained in the
absence of substrate. This
O
Christian Herrero, Hachem Dridi, Katell
Sénéchal-David, Régis Guillot, and
Frédéric Banse*
N
H
N
O
FeIII
N
N
No
substrate
N
Aromatics
Page No. – Page No.
N
O
N
R'
N
N
N
N
N
N
N
N
N
N
FeV
H
R'
FeIV
O
Hydroxylation of aromatics by H2O2
catalyzed by mononuclear non-heme
iron complexes. Role of triazole
hemilability in substrate-induced
bifurcation of the H2O2 activation
mechanism
O
O
N
N
H
O
O
OH
significantly impacts the
regioselectivity in aromatic
hydroxylation.
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