Non-Heme Iron Catalysts for Olefin Epoxidation: Conformationally Rigid Aryl–Aryl Junction To Support Amine/Imine Multidentate Ligands

Article abstract of DOI:10.1002/chem.201800447

Atom-transfer chemistry represents an important class of reactions catalyzed by metalloenzymes. As a functional mimic of non-heme iron enzymes that deliver oxygen atoms to olefins, we have designed monoiron complexes supported by new N-donor chelates. These ligands take advantage of heme-like conformational rigidity of the π-conjugated molecular backbone, and synthetic flexibility of tethering non-heme donor groups for additional steric and electronic control. Iron complexes generated in situ can be used to carry out catalytic epoxidation of a wide range of olefin substrates by using mCPBA as a terminal oxidant. The fate of initial iron-peracid adduct and the involvement of iron-oxo species in this process were investigated further by mechanistic probes and isotope exchange studies. Our findings suggest that anilidopyridyl-derived [N,N]-bidentate motif could serve as a versatile structural platform to build non-heme ligands for catalytic oxidation chemistry.

Full text of DOI:10.1002/chem.201800447

A Journal of
Accepted Article
Title: Non-Heme Iron Catalysts for Olefin Epoxidation:
Conformationally Rigid Aryl-Aryl Junction to Support Amine/Imine
Multidentate Ligands
Authors: Hyunchang Park, Hye Mi Ahn, Ha Young Jeong, Cheal Kim,
and Dongwhan Lee
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Non-Heme Iron Catalysts for Olefin Epoxidation:
Conformationally Rigid Aryl–Aryl Junction to Support
Amine/Imine Multidentate Ligands
Hyunchang Park,[a] Hye Mi Ahn,[b] Ha Young Jeong,[b] Cheal Kim,*[b] and Dongwhan Lee*[a]
Abstract: Atom transfer chemistry represents an important class of
reactions catalyzed by metalloenzymes. As a functional mimic of
non-heme iron enzymes that deliver oxygen atom to olefin, we have
designed monoiron complexes supported by new N-donor chelates.
These ligands take advantage of heme-like conformational rigidity of
-conjugated molecular backbone, and synthetic flexibility of
tethering non-heme donor groups for additional steric and electronic
control. Iron complexes generated in situ carry out catalytic
epoxidation of a wide range of olefin substrates by using mCPBA as
a terminal oxidant. The fate of initial iron-peracid adduct and the
involvement of iron-oxo species in this process were investigated
further by mechanistic probes and isotope exchange studies. Our
findings suggest that anilidopyridyl-derived [N,N]-bidentate motif
could serve as a versatile structural platform to build non-heme
ligands for catalytic oxidation chemistry.
ligands have been studied extensively. Ligands developed for
non-heme iron complexes typically have nitrogen donor groups
connected by flexible alkyl linkers.[7–12] By providing two adjacent
cis-coordination sites that can readily exchange with exogenous
ligands, these ligands facilitate the formation of iron-oxo
species.[13–18] One major deactivation pathway of such high-
valent iron intermediate, however, is degradation of the catalyst
itself,[19] which becomes more pronounced with increasing the
length of the alkyl linkers.[20] In addition, conformationally flexible
ligand skeleton often results in the formation of undesired
multinuclear clusters or polymeric products. We wished to
develop
a new ligand system that accommodates these
seemingly conflicting factors: conformational flexibility (to allow
for mechanistically required geometrical changes in the
coordination sphere) and chemical stability (to suppress
undesired de-metallation or oxidative damage in the catalytic
cycle).
As shown in Figure 1, our ligand design features
amine/imine mixed-donors built around rigid aryl–aryl junction.
By restricting torsional motions around the C–C bond, the
anilido-pyridyl scaffold 1 serves as a conformationally more rigid
ligand backbone than simple alkyl-linked ligand donors.
Introduction
Efforts to mimic enzymatic catalysis continue to inspire
mechanism-based design of their synthetic surrogates. One
prominent class of metalloenzyme-catalyzed reactions is
oxygenation/oxidation of organic molecules. In addition to heme
enzymes such as cytochrome P450 (cP450),[1] an increasing
number of non-heme iron enzymes have been identified that
directly couple activation of O2 with hydroxylation, desaturation,
or epoxidation of small molecule substrates.[2] Prominent
examples
include
soluble
methane
monooxygenase
(sMMO),[2c,3] toluene monooxygenase (ToMO),[4] -ketoglutarate
dioxygenase (TauD),[2b,5] and alkane ω-monooxygenase
(AlkB).[6]
To reproduce the coordination geometry of non-heme iron
active sites, a wide range of amine/imine-based multidentate
[a]
[b]
H. Park, Prof. Dr. D. Lee
Figure 1. Structural analogy between -conjugated ligands motifs 1–4, and
chemical structures of anilido-pyridine-derived ligands L1 and L2.
Department of Chemistry, Seoul National University
1 Gwanak-ro, Gwanak-gu, Seoul 08826, Korea
E-mail: dongwhan@snu.ac.kr
H. M. Ahn, H. Y. Jeong, Prof. Dr. C. Kim
Department of Fine Chemistry, Seoul National University of Science
and Technology
A structural analogy can also be drawn between 1 and the
-diketiminine 2,[21] dipyrromethene 3,[22] as well as the
porphyrin ligand 4,[1,23] all sharing similar -conjugated backbone
(Figure 1, top). Here, the absence of scissile C–H bond along
the π-conjugated backbone precludes deleterious oxo-transfer
reaction to the ligand itself.[1e,20b,20e,22d-e] In addition, steric
constraints around the conformationally rigid six-membered
chelate ring effectively suppress the formation of undesired
bis(chelate) complex having coordinately saturated metal center
(vide infra).
232 Gongneung-ro, Nowon-gu, Seoul 01811, Korea
E-mail: chealkim@seoultech.ac.kr
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.2018xxxxx. CCDC 1819240
and 1819241 contain the supplementary crystallographic data for
this paper. These data can be obtained free of charge from The
Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data%5Frequest/cif
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The primary amine group of 1 could serve as a convenient
anchoring point to install additional ligand tethers to build
crescent-shaped multidentates (Figure 1, bottom). As a proof-of-
concept, we decided to install a 2-pyridylmethyl group to
combine the heme-like -conjugation and non-heme-like
flexibility in coordination geometry. For a direct comparison of
electronic and steric factors of the amine donor group on the
oxo-transfer reactivity, ligands L1 and its N-methylated analogue
L2 were chosen as synthetic targets (Figure 1).
complexes and determined single-crystal X-ray structures. As
shown in Figure 2, both L1 and L2 support five-coordinate iron
complexes with distorted trigonal bipyramidal geometry, with all
three nitrogen atoms coordinated to the metal center.
Results and Discussion
Ligand Synthesis
As summarized in Scheme 1, ligand L1 was prepared in three
steps from readily available materials. A Negishi cross-coupling
of the arylzinc reagent, generated in situ from 2-bromo-5-
methylpyridine, and 1-iodo-2-nitrobenzene furnished 5.
Subsequent reduction with NaBH4 produced the desired
anilidopyridine 6, which was transformed to the tridentate ligand
L1 by reaction with picolyl bromide. The low yield (~25%) of this
particular reaction apparently reflects the poor nucleophilicity of
the aryl amine group, which is also sterically congested by an
ortho-substituent. An alternative synthetic route of reductive
amination with picolyl aldehyde was unsuccessful, due to the
nucleophilic attack of the pyridine nitrogen onto the Schiff base
intermediate to produce undesired cyclization product.[24] The N-
methylated derivative L2 was prepared by reaction of L1 with
methyl iodide in a straightforward manner.
Figure 2. ORTEP diagrams of (a) [(L1)FeBr2] and (b) [(L2)FeBr2] with thermal
ellipsoids at 50% probability.
To accommodate the six-membered chelate ring, the aryl–
aryl junction of the anilidopyridyl ligand fragment adjusted the
torsional angles to 37.57˚ (for L1) and 39.03˚ (for L2). Except for
a slightly elongated Fe–Namine bond distance (2.305(2) Å) of
[(L2)FeBr2] relative to that (2.191(2) Å) of [(L1)FeBr2], both
structures are essentially superimposable, with two pyridyl N-
donors in the axial and the amine N-donor in the equatorial
positions. The remaining two equatorial sites are occupied by
bromide ligands.
The overall spatial arrangements of the iron complexes
establish that the crescent-shaped L1 and L2 function as mer-
type, rather than fac-type, tridentate ligands. The remaining
coordination sites that can potentially exchange with exogenous
ligands, either oxidant or substrate, should be placed in close
proximity, either in cis- (for 5-coordinate system) or mer-
positions (for 6-coordinate system). To probe the functional
relevance of this coordination geometry, we proceeded to carry
out reactivity studies.
Olefin Epoxidation Reactions
Using mCPBA as a terminal oxidant and iron complexes as oxo-
transfer catalysts, epoxidation reactions were carried out for a
wide range of olefin substrates (Table 1). Iron complexes were
generated in situ from an equimolar mixture of iron(II)
perchlorate hydrate salt and the ligand, either L1 or L2, in MeCN.
Independent Job plot analysis with UV–vis spectroscopy
revealed sharply defined features that are consistent with the
formation of 1:1 ligand-metal adducts with either iron(II) (Figure
S1) or iron(III) sources in MeCN (Figure S2). With this metal–
ligand combination, the exchangeable equatorial sites of the
resulting complex (Figure 2) would be taken up by either weakly
coordinating perchlorate anion or MeCN solvent molecule to
facilitate binding and activation of the oxidant mCPBA (vide
infra).
Scheme 1. Synthetic route to L1 and L2.
Metallation and Structural Confirmation of Coordination
Geometry
One important structural requirement to access the iron-oxo
species is the availability of ligand exchangeable coordination
sites.[13–17] To assess the preferred coordination geometry to be
supported by the ligands L1 and L2, we prepared their iron(II)
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Table 1. Olefin Epoxidation Reactions with Iron Catalysts Supported by L1 and L2.[a]
L1
L2
Entry
Substrate
Product
Conversion (%)[b]
Yield (%)[b]
Conversion (%)[b]
Yield (%)[b]
1
2
3
cyclopentene
cycloheptene
cyclooctene
epoxide
epoxide
epoxide
71.7±4.0
81.8±3.4
84.9±0.8
44.8±0.4
79.8±3.9
62.5±0.4
51.1±0.4
80.8±5.1
70.3±0.1
39.3±1.6
77.3±0.9
54.3±0.1
4
cyclohexene
epoxide
2-cyclohexene-1-one
2-cyclohexene-1-ol
epoxide
85.3±1.2
63.0±3.4
2.9±0.1
71.5±0.3
40.2±1.0
2.3±0.1
3.0±0.3
1.6±0.1
5
6
7
1-hexene
1-octene
38.6±3.7
44.0±2.3
69.8±0.2
11.7±0.3
14.8±0.6
42.3±0.7
6.2±0.1
34.6±9.9
37.2±4.7
66.3±1.3
11.3±0.9
10.0±0.4
40.6±0.6
8.8±0.4
epoxide
cis-2-hexene
cis-oxide
trans-oxide
8
9
trans-2-hexene
cis-2-octene
trans-oxide
40.2±1.3
69.8±0.3
35.3±1.4
43.2±1.0
7.6±0.2
35.2±6.0
65.1±0.9
32.2±0.5
44.5±0.4
5.8±0.2
cis-oxide
trans-oxide
10
11
trans-2-octene
trans-oxide
56.5±0.6
45.2±1.5
39.1±2.8
29.7±2.1
1.7±0.2
51.7±0.4
54.2±1.1
36.7±0.1
21.9±0.3
20.0±0.1
8.4±0.1
styrene
epoxide
benzaldehyde
phenylacetaldehyde
cis-stilbene oxide
trans-stilbene oxide
benzaldehyde
2-phenylacetophenone
trans-stilbene oxide
benzaldehyde
2-phenylacetophenone
12.0±1.5
19.3±0.7
14.7±0.5
20.6±0.5
6.8±0.0
12
13
cis-stilbene
80.4±0.1
88.5±1.7
78.8±1.6
80.0±0.4
15.9±0.5
15.1±0.4
31.5±0.0
5.4±0.3
trans-stilbene
44.4±0.3
20.8±0.1
4.0±0.0
33.2±1.4
19.2±0.1
3.7±0.1
[a] Reaction conditions: olefins (0.035 mmol), ligand (0.001 mmol), iron(II) perchlorate hydrate (0.001 mmol), mCPBA (0.07 mmol), solvent (1 mL, MeCN), T = 25
˚C. [b] Based on the substrate.
Under standard reaction conditions (see Table 1 footnote for
details), the reaction was complete within 1 min. Control
experiments in the absence of the iron catalysts confirmed that
mCPBA alone cannot effectively oxidize olefins under this
condition (Table S1). With the catalyst supported by L1, cyclic
olefins (entries 1–3) were converted to the corresponding
epoxides in moderate to good yields (44.8–79.8%). Oxidation of
cyclohexene produced cyclohexene oxide (63.0%) as the major
product; only small amounts of cyclohexanone (2.9%) and
cyclohexanol (3.0%) were obtained as byproducts. This result
suggests a negligible involvement of free radical reaction
pathway in the oxo-transfer mechanism.[25–27] Terminal olefins,
employed. These substrates were oxidized mainly to cis-2-
hexene oxide and cis-2-octene oxide (42.3% and 43.2%,
respectively), along with trans-2-hexene oxide and trans-2-
octene oxide (6.2% and 7.6%, respectively) as minor products
(entries 7 and 9). For trans-2-hexene and trans-2-octene, the
corresponding trans-epoxides were obtained exclusively (entries
8 and 10). Styrene was oxidized to styrene epoxide (29.7%;
entry 11) with a small amount of benzaldehyde (1.7%). For cis-
stilbene (entry 12), a mixture of cis-stilbene oxide (19.3%), trans-
stilbene oxide (14.7%), benzaldehyde (20.6%), and 2-
phenylacetophenone (6.8%) were obtained. For trans-stilbene
(entry 13), the reaction was more selective toward the trans-
epoxide (44.4%), with the formation of benzaldehyde (20.8%)
and 2-phenylacetophenone (4.0%) as byproducts.
such as 1-hexene and 1-octene (entries
5 and 6), are
considered as challenging substrates to oxidize.[10,28] Our results
also show their low conversion (11.7% and 14.8%, respectively)
to the corresponding epoxides.
Under the same reaction conditions, iron complex of L2
showed similar reactivity patterns (Table 1; columns 5 vs 7) but
with somewhat lower efficiency. We tentatively conclude that the
effect of amine donor ligand, i.e. secondary amine for L1 vs
To investigate the stereochemical outcome of the
epoxidation reaction, cis-2-hexene and cis-2-octene were
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tertiary amine for L2, is negligible as far as the olefin epoxidation
reactivity is concerned.
To establish the metal–ligand stoichiometry of the
catalytically relevant species, we carried out control experiments
with three representative olefins: cyclohexene, 1-octene, and
styrene. As summarized in Tables S2 and S3, comparable
substrate conversion and product selectivity were observed
when the metal-to-ligand ratio was varied from 1:1 to 1:2. This
observation, in conjunction with the 1:1 binding stoichiometry
established by Job plot analysis (Figures S1 and S2), supports
the notion that the mono-adduct, rather than the coordinatively
saturated bis(chelate) adduct, is responsible for the catalytic
activity.
Figure 3. Hammett plots for the epoxidation reactions of para-substituted
styrene derivatives by iron catalysts supported by (a) L1 and (b) L2.
Oxidative stability of the catalytic system was also studied by
a combination of UV–vis spectroscopy (Figure S3) and HPLC
analysis (Figure S4). Under the conditions that simulate olefin
epoxidation reactions, the UV–vis spectra of the mixture
containing iron catalyst (of either L1 or L2) and mCPBA
remained unchanged (Figure S3). HPLC analysis of the reaction
products also confirmed that > 85% of the ligand L1 and > 57%
of the ligand L2 remained intact after de-metallation with TFA-
containing eluent (Figure S4).
A number of non-heme iron catalysts have previously been
employed for epoxidation of olefins using peracids, such as
mCPBA[25,29] or peroxyacetic acid,[14,28a,28n,29–31] as terminal
oxidants. While the catalytic performance and reactivity pattern
of certain tetradentate N-donor systems are comparable to
ours,[10,13,15,25,28m,n,30–39] the efficiency and selectivity vary widely
Oxygen Atom Transfer: Isotope Exchange Studies
The electrophilic nature of the oxygen-transferring species
(Figure 3) prompted us to investigate the mechanism of its
formation and subsequent transformation in the catalytic cycle.
For this purpose, we carried out isotope labeling studies with
H218O. Metal-bound oxo ligand can exchange with exogenously
added H218O.[42] With fast ligand exchange kinetics of the long-
lived [M=O]n+ species, the 18O label could end up in the final
product(s) to establish the source of the oxygen atom as well as
the existence of solvent-exchangeable oxygen ligand in the
active oxidant.[14,15,17,43]
Epoxidation of cyclohexene was conducted with iron
catalysts and mCPBA in the presence of an excess amount (>
25 equiv with respect to mCPBA) of H218O in MeCN. For the iron
catalyst of L1, the incorporation of H218O-derived oxygen atom in
the epoxide product increased from 4.1% to 8.5% with an
increasing amount of H218O present (Table 2). This result
supports the notion that iron-oxo species derived from the initial
iron-peracid adduct, rather than the peracid itself, functions as
the active oxidant toward the olefin substrate.
from substrate to substrate, making
comparison less than straightforward.
a
comprehensive
Electronic Nature of Active Oxidant
To examine the electronic properties of the reactive intermediate
involved in the oxo-transfer chemistry, we conducted
competition experiments on five styrene derivatives p-X-
C6H4CHCH2 having electronically disparate para-substituent X (=
–OCH3, –CH3, –H, –Cl, and –CN). A mixture of styrene
substrates was subjected to epoxidation reaction with mCPBA in
the presence of the iron catalyst, and the relative rate of reactant
consumption was determined by GC analysis.
The Hammett plots shown in Figure 3 are fitted with the
reaction constants of –0.68 for the iron complex of L1; –0.91 for
the iron complex of L2. Such trends point toward an electrophilic
nature of the active oxidants involved in the oxo transfer
chemistry. While these values are smaller than that reported for
the iron(IV)-oxo complex [(N3S2)FeIV(O)(ClO4)]+ ( = –2.0),[40]
they are comparable to those of high-spin iron(III)-acylperoxo
species [(13-TMC)FeIII(OOC(O)CH2Ph)]2+ ( = –0.79)[29] and
iron(V)-oxo complex [(biuret-TAML)FeV(O)]– ( = –0.56).[41]
Table 2. Percentage of 18O-Incorporated Cyclohexene Oxide Generated by
Isotope Exchange with H218O in the Epoxidation Reaction.[a]
18O in Cyclohexene Oxide (%)
Cyclohexene
(M)
mCPBA
(M)
H218O
(M)
Entry
L1
L2
1
2
3
0.005
0.005
0.005
0.01
0.01
0.01
0.278
0.556
1.111
4.1
6.6
7.7
11.4
12.0
15.3
4
5
0.005
0.005
0.01
0.01
2.222
4.444
7.8
8.5
18.0
20.4
[a] Reaction conditions: olefins (0.005 mmol), ligand (0.001 mmol), iron(II)
perchlorate hydrate (0.001 mmol), mCPBA (0.01 mmol), solvent (1 mL,
MeCN), T = 25 ˚C.
Apparently, the rate of oxygen atom transfer to the olefin
substrate is faster than the exchange between metal-bound oxo
ligand and exogenously added H218O, so that the isotope
incorporation is less than quantitative. We note that the
exchange of oxo ligand here should benefit from the two
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adjacent coordination sites (Scheme 2) that are made available
by mer-type binding of the tridentate ligand (Figure 2). The
availability of such open coordination sites requires a 1:1-adduct
between metal and ligand, which, again, is consistent with the
Job plot analysis (Figures S1 and S2) and reactivity studies with
varying metal-to-ligand ratio (Tables S2 and S3).
product PAA (63.3% based on the PPAA starting material) was
obtained, along with the homolytic cleavage products
benzaldehyde (17.8%) and benzyl alcohol (8.9%). The relative
ratio of 70.3:29.7 observed for the heterolytic vs homolytic
reaction products suggests that the initially formed FeIII-
OOC(O)R species diverges into two parallel pathways:
heterolytic (70.3%) O–O bond cleavage leading to putative
FeV=O (or its valence tautomer such as FeIV-O·); homolytic
(29.7%) O–O bond cleavage leading to putative FeIV=O species.
Scheme 2. Mechanism of ligand exchange between metal-bound oxo and
exogenously added H2O.
For the catalytic system employing ligand L2, the percentage
of 18O incorporation into the cyclohexane product ranges from
11.4% to 20.4% (Table 2), which is higher than that observed for
the L1-based system under similar reaction conditions. This
result might reflect a faster ligand exchange rate, an enhanced
formation and longer life-time of the iron-oxo species, or a
combination of both. An increased amount of the heterolytic O–
O cleavage product of the L2-derived catalytic system (vide
infra) is consistent with this interpretation. Such difference,
however, does not seem to fundamentally affect either catalytic
activity or selectivity (Table 1).
Scheme 3. Mechanistic Pathways for the Activation of Metal-Bound Peracid.
To probe whether the FeIII-OOC(O)R species could function
directly as an active oxidant (Pathway B, Scheme 3), we carried
out the reaction between PPAA and iron complex in the
presence of varying amounts of olefin substrate.[44i,j] According to
the mechanistic scenario outlined in Scheme 3, both Pathway A
and Pathway B produce PAA as the reaction product. As such, if
Pathway B is also involved in the epoxidation reaction, the
relative amount of PAA would increase as the amount of the
olefin substrate is increased.
Indeed, with increasing concentration of cyclohexene (as a
substrate that is easy to oxidize; see Table 1) from 0 to 160 mM,
the relative % ratio of the PAA product increases systematically
from 70.3 to 85.2 (entries 1–5, Table 3). A similar trend was
observed for 1-octene (as a substrate that is difficult to oxidize;
see Table 1): increasing % ratio of PAA from 70.3 to 77.2
(entries 1–5, Table S5) is observed with increasing substrate
concentration. Similar results were obtained for the iron catalyst
supported by L2 (entries 1–5, Tables S4 and S6).
Mechanism of O–O Bond Cleavage to Access Catalytically
Relevant Iron-Oxo Species
With experimental evidence obtained for the participation of iron-
oxo species in the epoxidation reaction (Table 2; Scheme 2), we
proceeded to investigate possible reaction pathways leading to
its formation from the initial iron-peracid adduct. As shown in
Scheme 3, peroxyphenylacetic acid (PPAA) is a convenient
mechanistic probe for such study, and serves as an ideal
surrogate to probe the reaction pathways taken by
mCPBA.[10,25,28,44]
Upon heterolytic O–O bond cleavage (Pathway A, Scheme
3), metal-bound PPAA fragments into phenyl acetic acid (PAA).
In contrast, a homolytic O–O cleavage of PPAA produces an
acyloxyl radical (Pathway C, Scheme 3), which undergoes a
rapid -scission to furnish a mixture of toluene (I), benzyl
alcohol (II), and benzaldehyde (III). Alternatively, a direct
reaction between iron-bound acylperoxo species and olefin
substrate should produce PAA (Pathway B, Scheme 3).
These findings suggest that iron-bound acylperoxo could
also function as an oxidant that directly delivers oxygen atom to
the C=C double bond. The contribution of this Pathway B
(Scheme 3), however, seems to be diminished for the substrate
To track the fate of the initially formed iron-peracid adduct,
we investigated the reaction between PPAA and the iron
complex supported by L1. In the control experiment with no
olefin substrate added (entry 1, Table 3), heterolytic cleavage
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that is difficult to oxidize, when a side-by-side comparison is
made between cyclohexene and 1-octene (Tables 3 and S5).
This finding further highlights the importance of O–O activation
to access the iron-oxo species as an active oxidant (Pathway A
or C, Scheme 3). The 18O isotope-exchange studies (Scheme 2)
further corroborate this notion. Efforts to trap and obtain direct
evidence for the reaction intermediates, either by low-
temperature UV–vis or EPR spectroscopy, were less successful,
presumably due to their high reactivity and short lifetime.
Table 3. Analysis of the Products Derived from the Reaction between PPAA and Iron Catalyst of L1 in the Absence and the Presence of Cyclohexene.[a]
Heterolysis[b]
PAA
Homolysis[b]
Heterolysis/Homolysis
Oxidation Products[c]
Cyclohexene
(mM)
Entry
I
-
-
-
-
-
II
III
PAA/(I + II + III)
oxide
-
-one
-
-ol
1
2
3
4
5
0
20
63.3±6.8
73.0±3.0
75.7±6.3
78.8±2.9
81.8±11.2
8.9±1.3
8.3±0.4
8.0±0.3
6.7±0.1
5.2±0.4
17.8±0.3
16.2±0.0
14.3±0.2
11.5±0.1
9.0±0.2
2.37
2.98
3.39
4.33
5.76
-
40.6±0.0[d]
33.9±0.8[b]
47.1±2.8[b]
73.0±3.7[b]
4.9±0.2[d]
3.2±0.1[b]
3.5±0.3[b]
3.6±0.3[b]
4.7±0.1[d]
4.0±0.1[b]
6.2±0.7[b]
6.5±1.0[b]
40
80
160
[a] Reaction conditions: substrate (0–0.16 mmol), ligand (0.001 mmol), iron(II) perchlorate hydrate (0.001 mmol), PPAA (0.04 mmol), solvent (1 mL,
MeCN), T = 25 ˚C. [b] Based on PPAA; PAA = phenylacetic acid; see Scheme 3 for the designation of the compounds I (toluene), II (benzyl alcohol),
and III (benzaldehyde). [c] Oxide, -one, and -ol indicate cyclohexene oxide, 2-cyclohexen-1-one, and 2-cyclohexen-1-ol, respectively. [d] Based on the
substrate.
Mechanism of Olefin Epoxidation
Summary and Outlook
From the studies described above, a coherent mechanistic
model emerges. As proposed in Scheme 4, the iron(II) precursor
complex is oxidized by the peracid to the corresponding iron(III)
species. A subsequent reaction with another equiv of peracid
forms an iron(III)-acylperoxo intermediate, which undergoes
either heterolytic or homolytic O–O bond cleavage to afford
putative FeV=O or FeIV=O species, respectively. A high-yielding
epoxidation with stereochemical retention might be ascribed to
oxo transfer from FeV=O, whereas FeIV=O could be responsible
for radical-type oxidation with loss of stereospecificity (Table 1).
The peracid-derived oxo ligand in either species can exchange
with H218O added exogenously, and ends up in the epoxide
product (Table 2). Alternatively, metal-bound peracid could react
directly with olefin to produce epoxide, although such "shortcut"
becomes less viable for less reactive substrate.
A new amine/imine multidentate ligand platform was developed
to support non-heme iron centers for catalytic oxo-transfer
chemistry. In addition to restricting torsional motions to support
a robust chelate ring, the anilido-pyridyl fragment serves as a
convenient starting point to tether additional ligand donor groups
for structural diversity. Iron complexes of these non-heme
ligands effect catalytic epoxidation of olefins using peracid-
derived oxygen atom. Studies with mechanistic probes have
unveiled the involvement of iron-oxo species, derived by
heterolytic O-O cleavage of the initial iron-acylperoxo adduct, as
the catalytically relevant species for epoxidation with high yield
and stereochemical retention. Efforts are currently underway in
our laboratory to develop structurally more elaborate
anilidopyridyl-derived ligands for atom-transfer chemistry of both
fundamental and practical relevance.
Experimental Section
See Supporting Information.
Acknowledgements
This work was supported by the Basic Science Research
Program 2016M3D3A1A01913239 (C1 Gas Refinery R&D
Center) and 2017R1A2B2006605 through the National
Research Foundation of Korea (NRF). H.P. is grateful for the
Predoctoral Fellowship awarded through the BK21 Plus Program.
Keywords: Non-heme • Ligand design • Iron • Epoxidation •
Scheme 4. Olefin Epoxidation via Branched Reaction Pathways.
Reaction mechanisms
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Entry for the Table of Contents
FULL PAPER
Rigid yet Flexible: Built upon
Hyunchang Park, Hye Mi Ahn, Ha
torsionally restricted aryl–aryl junction,
crescent-shaped N-donor ligands
support non-heme iron catalysts that
effect epoxidation of olefins via
electrophilic intermediate having
solvent-exchangeable oxo group.
Young Jeong, Cheal Kim,* and
Dongwhan Lee*
Page No. – Page No.
Non-Heme Iron Catalysts for Olefin
Epoxidation: Conformationally Rigid
Aryl–Aryl Junction to Support
Amine/Imine Multidentate Ligands
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