Iron-Catalyzed Enantioselective Epoxidations with Various Oxidants: Evidence for Different Active Species and Epoxidation Mechanisms

Article abstract of DOI:10.1021/acscatal.6b02851

Iron complexes with chiral bipyrrolidine-derived aminopyridine (PDP) ligands are among the most efficient Fe-based bioinspired catalysts for regio- and stereoselective oxidation of C-H and C=C moieties with hydrogen peroxide. Besides hydrogen peroxide, other oxidants (peroxycarboxylic acids and organic hydroperoxides) can be effectively used. In this work, we have examined the mechanistic landscape of the Fe(PDP) catalyst family with various oxidants: H₂O₂, organic hydroperoxides, and peracids. The combined EPR spectroscopic, enantioselectivity, Hammett, Z-stilbene epoxidation stereoselectivity, and ¹⁸O-labeling data witness that the same oxoiron complexes [(L)Fe^V=O(OC(O)R)]²⁺ are the actual epoxidizing species in both the catalyst systems (L)Fe/H₂O₂/carboxylic acid and (L)Fe/AlkylOOH/carboxylic acid. On the contrary, in the systems (L)Fe/R²C(O)OOH (R² = CH₃ or 3-Cl-C₆H₄), in the presence or in the absence of carboxylic acid, the epoxidation is predominantly conducted by the acylperoxo-iron(III) intermediates [(L)Fe^III(OOC(O)R²)]²⁺, in a concerted fashion.

Full text of DOI:10.1021/acscatal.6b02851

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Article
Iron-Catalyzed Enantioselective Epoxidations with Various Oxidants:
Evidence for Different Active Species and Epoxidation Mechanisms
Alexandra M. Zima, Oleg Y. Lyakin, Roman V. Ottenbacher, Konstantin P. Bryliakov, and Evgenii P. Talsi
ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.6b02851 • Publication Date (Web): 08 Nov 2016
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IronꢀCatalyzed Enantioselective Epoxidations with
Various Oxidants: Evidence for Different Active
Species and Epoxidation Mechanisms
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Alexandra M. Zima, Oleg Y. Lyakin, Roman V. Ottenbacher, Konstantin P. Bryliakov,* and
Evgenii P. Talsi*
Novosibirsk State University, Pirogova 2, Novosibirsk 630090, Russian Federation
Boreskov Institute of Catalysis, Pr. Lavrentieva 5, Novosibirsk 630090, Russian Federation
ABSTRACT: Iron complexes with chiral bipyrrolidineꢀderived aminopyridine (PDP) ligands
are among the most efficient Feꢀbased bioinspired catalysts for regioꢀ and stereoselective
oxidation of C–H and C=C moieties with hydrogen peroxide. Besides hydrogen peroxide, other
oxidants (peroxycarboxylic acids and organic hydroperoxides) can be effectively used. In this
work, we have examined the mechanistic landscape of the Fe(PDP) catalyst family with various
oxidants: H2O2, organic hydroperoxides and peracids. The combined EPR spectroscopic,
enantioselectivity, Hammett, Zꢀstilbene epoxidation stereoselectivity, and 18O labeling data
witness that the same oxoiron complexes [(L)FeV=O(OC(O)R)]2+ are the actual epoxidizing
species in both the catalyst systems (L)Fe/H2O2/carboxylic acid and (L)Fe/AlkylOOH/carboxylic
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acid. On the contrary, in the systems (L)Fe/R2C(O)OOH (R2 = CH3 or 3ꢀClꢀC6H4), in the
presence or in the absence of carboxylic acid, the epoxidation is predominantly conducted by the
acylperoxoꢀiron(III) intermediates [(L)FeIII(OOC(O)R2)]2+, in a concerted fashion.
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KEYWORDS: asymmetric epoxidation, bioinspired catalysis, enantioselectivity, EPR, iron,
mechanism
INTRODUCTION
Iron and manganese catalysts with aminopyridine ligands have been recently shown to promote
the regioꢀ and stereoselective oxidation of C(sp3)–H groups,1–3 and enantioselective epoxidation
of alkenes4–7 with preparatively acceptable efficiencies and yields. Chiral bipyrrolidineꢀderived
aminopyridine structure appeared as simple and versatile ligand framework, the resulting
complexes of the type 1–3 (Chart 1) being among the most extensively studied Feꢀbased
bioinspired catalysts. In most cases, hydrogen peroxide is used as the oxidant. At the same time,
other oxidants, such as peracetic acid and tertꢀbutyl hydroperoxide can also be used for the
asymmetric epoxidation of olefins in the presence of nonꢀheme iron complexes, with comparably
high enantioselectivities.4c,5,6a In contrast to the thoroughly experimentally studied mechanistic
details of epoxidations by catalyst systems Fe complex/H2O2/carboxylic acid,7c,f,g the nature of
the active species and the mechanism of action of the same catalysts with other oxidants remain
rather underexplored.
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Chart 1. Structures of Aminopyridine Iron and Manganese Complexes.
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OCH3
H3CO
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9
N
N
N
OH
OH
N
N
N
N
III
Fe
OTf
OTf
FeII
N
N
FeIII
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N
N
N
(OTf)4
H3CO
OCH3
1
2
N
H3CO
N
N
OTf
OTf
FeII
N
N
N
N
N
OTf
OTf
II
Mn
OTf
OTf
FeII
N
N
N
N
N
N
H3CO
5
3
4
Very recently, mechanistic peculiarities of olefin epoxidations with different oxidants in the
presence of catalytic amounts of manganese complex 4 (Chart 1) have been examined.7h For the
epoxidation with H2O2, the oxometal(V) active species of the type [(L)MnV=O(OH)]2+ has been
proposed, which is corroborated by the observed 18O incorporation from added H2 O into the
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epoxide. Remarkably, catalyst systems 4/H2O2/carboxylic acid and 4/tꢀBuOOH/carboxylic acid
have demonstrated identical stereoselectivities in the epoxidation of Zꢀstilbene and identical
enantioselectivities in the epoxidation of chalcone. These data give evidence that the same
oxygen transferring species (presumably, [(L)MnV=O(OC(O)R)]2+) conducts the epoxidation in
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these systems. At the same time, on the basis of kinetic and O labeling data, the epoxidation
with peroxycarboxylic acids has been assumed to proceed via direct concerted oxygen transfer
from the manganese acylperoxo intermediate to the olefin.7h
In 2011, Sun and coꢀworkers studied the epoxidation of chalcone by iron catalyst systems
5/CH3CO3H and 5/H2O2/CH3COOH (Chart 1). The epoxidations with CH3CO3H and
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H2O2/CH3COOH showed significant differences in terms of yields and enantiomeric excess (ee):
in the first case, the ees were generally lower, which might reflect the occurrence of different
epoxidizing species.6a
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Intriguingly, Costas and coꢀworkers documented the same enantioselectivity level (61% ee) for
the epoxidation of Zꢀβꢀmethylstyrene with the catalyst systems 3/oxidant/CH3COOH, where
oxidant = H2O2, tꢀBuOOH and CH3CO3H.4c This observation was interpreted in favor of the
same oxygenꢀatom transferring species.
Such contradiction between the data of Sun6a and of Costas4c may reflect the fact that different
active intermediates may operate in the catalyst systems Fe complex/CH3CO3H, depending on
the structure of the iron catalyst and/or the substrate. To explore this possibility in the most
rational way, the catalytic data should be brought into correlation with the direct spectroscopic
monitoring of the active epoxidizing species in the reaction solution.
It was shown previously that intermediates of the types [(L)FeIII(OOH)],7b,8 [(L)FeIII(OOtꢀ
Bu)],7b,8 [(L)FeIII(OOC(O)CH3)],9,10 and [(L)FeV=O]2b,f,7f,g could be detected in the related
catalyst systems at low temperature, by EPR and other spectroscopic techniques. Moreover, their
concentrations in solution can be monitored and compared with the yield of the oxygenated
products, thus enabling to discriminate the inactive, catalytically unreasonable Fe species. In this
contribution, we are presenting the combined EPR spectroscopic, enantioselectivity,
stereoselectivity, Hammett and 18O labeling studies of the olefin epoxidation in the catalyst
systems
1,2/H2O2/RCOOH,
1,2/tꢀBuOOH/RCOOH,
1,2/CmOOH/RCOOH
and
1,2/R2C(O)OOH/RCOOH {RCOOH = acetic or 2ꢀethylhexanoic acid, R2 = CH3 or 3ꢀClꢀC6H4,
Cm = cumyl}, and discuss the plausible nature of the oxygenꢀtransferring species.
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RESULTS AND DISCUSSION
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Catalyst systems based on complex 1 and peroxides (tertꢀbutyl hydroperoxide, cumene
hydroperoxide and hydrogen peroxide). The catalyst system 1/tꢀBuOOH shows low (17%)
yield and moderate (52% ee) enantioselectivity in the asymmetric epoxidation of chalcone at 0
°C (Table 1, entry 1). The addition of acetic acid (AA) or 2ꢀethylhexanoic acid (2ꢀEHA)
significantly improves the yield and enantioselectivity of this system, to 64% and 81% ee,
respectively (Table 1, entries 2 and 3).
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Table 1. Asymmetric Epoxidation of Chalcone with Various Oxidants Catalyzed by Complexes
1 and 2 a
additive
(equiv) b
conversion (%) /
epoxide yield (%)
entry catalyst oxidant
ee (%) c
1
2
tꢀBuOOH
tꢀBuOOH
tꢀBuOOH
H2O2
–
AA
17 / 17
70 / 70
76 / 76
77 / 75
90 / 89
22 / 22
43 / 42
44 / 44
7 / 7
52
64
81
63
82
56
65
80
72
71
82
70
83
67
72
1
1
1
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1
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2
2
2
2
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2
2
3
2ꢀEHA
AA
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5
H2O2
2ꢀEHA
–
6
CmOOH
CmOOH
CmOOH
tꢀBuOOH
tꢀBuOOH
tꢀBuOOH
H2O2
7
AA
8
2ꢀEHA
–
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10
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15
AA
73 / 73
78 / 78
74 / 73
73 / 73
6 / 4
2ꢀEHA
AA
H2O2
2ꢀEHA
–
CmOOH
CmOOH
AA
47 / 47
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CmOOH
CH3CO3H
CH3CO3H
2ꢀEHA
–
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AA
CH3CO3H 2ꢀEHA (55)
CH3CO3H 2ꢀEHA (330)
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mꢀCPBA
mꢀCPBA
mꢀCPBA
CH3CO3H
CH3CO3H
CH3CO3H
mꢀCPBA
mꢀCPBA
mꢀCPBA
–
AA
2ꢀEHA
–
AA
2ꢀEHA
–
AA
2ꢀEHA
a Reaction conditions: at 0 °C, chalcone (100 ꢁmol), oxidant, H2O2 (200 ꢁmol), tꢀBuOOH,
CmOOH, CH3CO3H, mꢀCPBA (110 ꢁmol), catalyst load 1 mol.%, oxidant was added by a
syringe pump over 30 min, and the mixture was stirred for an additional 2.5 h followed by LC
analysis. b If not noted, 55 ꢁmol of carboxylic acid was added. Absolute configuration of
c
chalcone epoxide was (2R,3S).
The EPR spectrum (−196 °C)11a of the system 1/tꢀBuOOH exhibits weak resonances of the
alkylperoxo complex [((S,S)ꢀPDP)FeIII(OOtꢀBu)(CH3CN)]2+ (g1 = 2.19, g2 = 2.14, g3 = 1.96,
Table 2, entry 1) and those of tꢀBuOO• radical (g|| = 2.030, g⊥ = 2.005)11b (Figure 1A). The EPR
spectrum of the system 1/tꢀBuOOH/2ꢀEHA displays intense resonances of stable (at 20 °C)
complex [((S,S)ꢀPDP)FeIII(OC(O)R)(RCOOH)]2+ (1b) (g1 = 2.75, g2 = 2.41, g3 = 1.64),7g and
weaker resonances of tꢀBuOO• radical and of the iron complex 1aEHA (g1 = 2.069, g2 = 2.007, g3
= 1.963) (Figure 1B; Table 2, entry 5). 1aEHA was previously observed in the catalyst system
1/H2O2/2ꢀEHA and was assigned to the [((S,S)ꢀPDP)FeV=O(OC(O)R)]2+ species (RCOOH = 2ꢀ
EHA, Figure 1C).7g 1aEHA reacted with cyclohexene at −85 °C to afford the corresponding
epoxide, and displayed EPR spectrum very similar to those of the spectroscopically well
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(L)FeIII–OOtBu
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2.030
2.005
(tBuOO•)
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B)
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tBuOO•
1aEHA
2.14
2.19
1b
1aEHA
2.069
1b
2.75
2.007
1b
1aEHA
2.41
C)
1.64
1.963
1b
2500
3000
3500
4000
4500
H / G
Figure 1. EPR spectra (−196 °C) of the samples (A) 1/tꢀBuOOH ([1]:[ tꢀBuOOH] = 1:3, [1] =
0.04 M) frozen 3 min after mixing the reagents at −60 °C; (B) 1/tꢀBuOOH/2ꢀEHA ([1]:[ tꢀ
BuOOH]:[2ꢀEHA] = 1:3:10, [1] = 0.04 M) frozen 3 min after mixing the reagents at −60 °C; (C)
1/H2O2/2ꢀEHA ([1]:[H2O2]:[2ꢀEHA] = 1:3:10, [1] = 0.04 M) frozen 2.5 min after mixing the
reagents at −65 °C. A 1.8:1 CH2Cl2/CH3CN mixture was used as a solvent. The signal of 1aEHA
at g2 = 2.007 in “B” overlaps with the signals of tꢀBuOO• radical.
characterized FeV=O species (Table 2, entries 3, 4).2g,11 One can see that the same intermediate
[((S,S)ꢀPDP)FeV=O(OC(O)R)]2+ (1aEHA) is formed in the catalyst systems 1/H2O2/2ꢀEHA and
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Table 2. EPR Spectroscopic Data for S = 1/2 Iron Species Formed in the Catalyst Systems Based
on Iron Complexes with N4ꢀdonor Tetradentate Ligands.
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g1
g2
g3
ref
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1 [((S,S)ꢀPDP)FeIII(OOtꢀBu)(CH3CN)]2+
2 [((S,S)ꢀPDP)FeIII(OOCm)(CH3CN)]2+
3 [(PyNMe3)FeV=O(OC(O)CH3)]2+ a
4 [(TMC)FeV=O(NC(O)CH3)]+ b
2.19
2.18
2.07
2.053
2.069
2.66
2.14
1.96
this work
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2f
2.13
1.96
2.01
1.95
2.010
2.007
2.42
1.971
1.963
1.71
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5 [((S,S)ꢀPDP)FeV=O(OC(O)R)]2+ (1aEHA c
)
7g
1aAA
6
7c,g
7f,g
7g
7 [((S,S)ꢀPDP*)FeV=O(OC(O)CH3)]2+ (2aAA) 2.071
2.008
2.008
2.41
1.960
1.958
1.64
8 [((S,S)ꢀPDP*)FeV=O(OC(O)R)]2+ (2aEHA c
)
2.070
2.75
9 [((S,S)ꢀPDP)FeIII(OC(O)R)(RCOOH)]2+
7g
(1b) c
10 [((S,S)ꢀPDP*)FeIII(OC(O)R)(RCOOH)]2+
(2b) d
2.79
2.41
1.62
this work
11 [((S,S)ꢀPDP*)FeIII(κ2ꢀOC(O)R)]2+ (2b′) d
12 [((S,S)ꢀPDP*)FeIII(κ2ꢀOOC(O)CH3)]2+ (2c)
2.54
2.52
2.52
2.41
2.41
2.41
1.79
1.80
1.80
this work
this work
this work
13 [((S,S)ꢀPDP*)FeIII(κ2ꢀOOC(O)C6H4Cl)])]2+
(2c′) e
14 [(TPA*)FeIII(κ2ꢀOOC(O)CH3)]2+ a
2.58
2.38
1.72
9
a PyNMe3, TPA* – N4ꢀdonor aminopyridine ligands. TMC – tetramethylcyclam. c RCOOH =
2ꢀethylhexanoic acid. d RCOOH = acetic or 2ꢀethylhexanoic acid. e ClC6H4C(O)OOH = mꢀ
CPBA (3ꢀchloroperoxybenzoic acid).
b
1/tꢀBuOOH/2ꢀEHA (Figure 1B,C). If this intermediate is the common oxygen transferring
species of these catalyst systems, one can expect identical olefin epoxidation enantioselectivities
from the catalyst systems 1/H2O2/2ꢀEHA and 1/tꢀBuOOH/2ꢀEHA. In agreement with this
prediction, chalcone epoxidation enantioselectivities were the same (within experimental
uncertainty ±1% ee) for the systems 1/H2O2/2ꢀEHA, 1/tꢀBuOOH/2ꢀEHA, and 1/CmOOH/2ꢀEHA
(81±1% ee: Table 1, entries 3, 5, 8). The same picture has been documented for the epoxidation
of benzylideneacetone by the systems 1/H2O2/AA and 1/tꢀBuOOH/AA (Table S1, Supporting
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Information (SI), entries 1 and 4) and by the systems 1/H2O2/2ꢀEHA and 1/tꢀBuOOH/2ꢀEHA
(Table S1, entries 2 and 5).
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The catalyst systems 1/tꢀBuOOH/AA and 1/H2O2/AA display EPR spectrum of the same
highly unstable intermediate 1aAA with large gꢀfactor anisotropy (g1 = 2.66, g2 = 2.42, g3 = 1.71,
Figure S1A,B, SI; Table 2, entry 6). The EPR spectrum of 1aAA is sharply different from that of
1aEHA (Figure 1B,C; Table 2, entry 5), which difference has been recently explained in terms of
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different unpaired spin distribution in the intermediates 1aAA and 1aEHA 7g
Again, the catalyst
.
systems 1/H2O2/AA, 1/tꢀBuOOH/AA, and 1/CmOOH/AA exhibited identical chalcone
epoxidation enantioselectivities (64±1% ee, Table 1, entries 2, 4, 7), in agreement with the
observation of the common intermediate of the type 1aAA. The same picture has been
documented for the epoxidation of benzylideneacetone (Table S1, SI) and dbpcn (Table S2, SI).
The plausible active species of the catalyst system 1/tꢀBuOOH is alkylperoxo complex [((S,S)ꢀ
PDP)FeIII(OOtꢀBu)(CH3CN)]2+. For the related system 1/CmOOH, the observed active species
(presumably [((S,S)ꢀPDP)FeIII(OOCm)(CH3CN)]2+) exhibits a very similar but not identical EPR
parameters (g1 = 2.18, g2 = 2.13, g3 = 1.96; Table 2, entry 2). One might expect that this small
spectral difference, reflecting minor structural distinction, may result in moderately different
enantioselectivities. The experimental data agree with this assumption, the catalyst systems 1/tꢀ
BuOOH and 1/CmOOH demonstrating 52% ee and 56% ee for chalcone epoxidation (Table 1,
entries 1 and 6).
Previously, independent evidence for the similarity/difference of the active species in Mnꢀ
aminopyridine based catalyst systems with different oxidants has been obtained by examining
the stereoselectivity of epoxidation of Zꢀstilbene.7h We would expect that for the structurally
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Table 3. Epoxidation of ZꢀStilbene with Various Oxidants Catalyzed by Complex 1 a
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4
5
6
7
8
9
10
11
12
13
14
15
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27
28
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30
31
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34
35
36
37
38
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48
49
50
51
52
53
54
55
56
57
58
59
60
conversion (%) /
epoxide yield (%)
entry catalyst oxidant
additive
cis : trans
1
2
H2O2
H2O2
–
AA
87 / 75
99 / 84
99 / 91
18 / 14
84 / 69
100 / 89
25 / 21
76 / 63
90 / 80
47 / 38
46 / 37
54 / 44
41 / 40
60 / 50
57 / 48
63 / 54
8 / 7
18
49
65
10
61
63
5
1
1
1
1
1
1
1
1
1
1
1
1
3
H2O2
2ꢀEHA
–
4
tꢀBuOOH
tꢀBuOOH
5
AA
6
tꢀBuOOH 2ꢀEHA
7
CmOOH
CmOOH
–
8
AA
48
59
34
33
37
30
83
82
81
50
9
CmOOH 2ꢀEHA
10
11
12
13
14
15
16
17
mꢀCPBA
mꢀCPBA
–
AA
mꢀCPBA 2ꢀEHA
b
–
mꢀCPBA
CH3CO3H
CH3CO3H
–
–
1
1
1
AA
CH3CO3H 2ꢀEHA
CH3CO3H
c
–
–
a Reaction conditions: at 0 °C, Zꢀstilbene (100 ꢁmol), oxidant, H2O2 (200 ꢁmol), tꢀBuOOH,
CmOOH, CH3CO3H, mꢀCPBA (110 ꢁmol), carboxylic acid additive (55 ꢁmol), catalyst load 2
mol %, oxidant was added by a syringe pump over 30 min, and the mixture was stirred for an
b
additional 2.5 h followed by NMR analysis. Uncatalyzed Prilezhaev reaction, from ref. 7h.
c Uncatalyzed Prilezhaev reaction, this study (for details see SI).
similar Fe catalysts, different active species should also exhibit significantly different cis:trans
epoxidation selectivity with Zꢀstilbene. Indeed, it is seen that for the epoxidation by the systems
1/tꢀBuOOH and 1/CmOOH, the cis:trans ratios for the resulting mixture of epoxides are 10 and
5,
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respectively (Table 3, entries 4 and 7). The addition of 2ꢀEHA, which is expected to result in the
formation of a different active species, improves both the conversion and the stereoselectivity (to
cis:trans = 63 and 59, Table 3, entries 6 and 9). The latter values are very close to that for the
catalyst system 1/H2O2/2ꢀEHA (cis:trans = 65, Table 3, entry 3). In turn, in the catalyst systems
1/tꢀBuOOH/AA and 1/CmOOH/AA, cis:trans ratios of 61 and 48 have been found, (Table 3,
entries 5 and 8), that are close to the value of 49 for the system 1/H2O2/AA (Table 3, entry 2).
These data comply with the hypothesis of the common active species of the catalyst systems
1/H2O2/RCOOH and 1/R1OOH/RCOOH (RCOOH = AA or 2ꢀEHA, R1 = tꢀbutyl or cumyl).
On the basis of the above EPR, enantioꢀ and cis:trans selectivity data, the following mechanisms
for the epoxidation by catalyst systems 1/H2O2/RCOOH and 1/R1OOH/RCOOH can be
suggested (Scheme 1).13 In Scheme 1, it is assumed that the reaction proceeds via acyclic
intermediate, capable of rotating around the single Cα−Cβ bond. This mechanism is similar to
that proposed for the epoxidation by the related catalyst systems Mn aminopyridine
complex/H2O2/AA,7e,h with the evidence in favor of carbocationic nature of the acyclic
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intermediate based on the observed linear correlation between the relative epoxidation rates of pꢀ
+ 7e,h
substituted chalcones and the HammettꢀBrown parameter σp .
Herewith, a similar Hammett
analysis, applied to the epoxidation of pꢀsubstituted chalcones with the system 1/H2O2/2ꢀEHA,
+
has demonstrated a good linear correlation of the epoxidation rates vs. σp , with a negative slope
ρ+ of −2.83 (Figure 2A), indicative of electronꢀdeficient transition state. Moreover, for the
epoxidation of pꢀsubstituted chalcones with the system 1/tꢀBuOOH/2ꢀEHA, a spectacularly
similar slope ρ+ = −2.84 has been found (Figure 2B), which strongly supports the common
epoxidation mechanism, proceeding via the same active species. The observed ρ+ values,
indicating the relatively high positive charge buildup at the aromatic moiety of the substrate in
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A
B
p-Me
p-Me
1,0
0,
1,
0,
p-H
p-H
0,
0,0
p-Cl
p-Cl
p-F
p-F
log (kX/kH)
log (kX/kH)
-0,5
-1,0
-1,5
-2,0
-0,5
-1,0
-1,5
-2,0
y = −2.83x + 0.048
R = 0.995
y = −2.84x + 0.039
R = 0.998
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p-CF3
p-CF3
-0,4
-0,2
0,0
0,2
0,4
0,6
-0,4
-0,2
0,0
0,2
0,4
0,6
+
+
σp
σp
C
D
1,0
0,5
1,0
0,5
p-H
p-Me
p-F
p-F
0,0
0,0
p-Cl
p-Me
p-H
log (kX/kH)
log (kX/kH)
-0,5
-1,0
-1,5
-2,0
-0,5
-1,0
-1,5
-2,0
p-Cl
p-CF3
p-CF3
y = −1.40x + 0.031
R = 0.945
y = −2.64x + 0.085
R = 0.996
-0,4
-0,2
0,0
0,2
0,4
0,6
-0,4
-0,2
0,0
0,2
0,4
0,6
σp
σp
Figure 2. Hammett plots for the oxidation of pꢀsubstituted chalcones by the catalyst systems (A)
1/H2O2/2ꢀEHA, (B) 1/tꢀBuOOH/2ꢀEHA, (C) 1/tꢀBuOOH, (D) 1/mꢀCPBA. See SI for the
experimental details.
Scheme 1. Proposed Reaction Sequence for the Asymmetric Epoxidation of Olefins by Catalyst
Systems 1/H2O2/RCOOH and 1/R1OOH/RCOOH (R1 = tꢀbutyl or cumyl).
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the transition state, are somewhat higher than those typically reported for olefin epoxidations by
electrophilic oxometal complexes (that mostly fit within the range −0.5 to −2.1).7e,h,14 At the
same time, such values are not as large as those sometimes reported for oxidations via electronꢀ
transfer mechanism, mediated by natural metalloenzymes or their synthetic models (ρ+ −3 to
−7).15
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The epoxidations by catalyst systems 1/R1OOH (R1 = tꢀbutyl and cumyl) have demonstrated
substantially lower cis:trans selectivity (Table 3, entries 4 and 7), as compared to those for the
catalyst system 1/H2O2/carboxylic acid, indicating that the proposed active species ((S,S)ꢀ
PDP)FeIII(OOR1) likely operates via different epoxidation mechanism. Previously, two kinds of
reaction mechanisms were discussed for the metalꢀcatalyzed epoxidations with alkyl
hydroperoxides: the concerted oxygen transfer and the radical epoxidation pathway.7h,16 For the
epoxidations with Mn aminopyridine complex/R1OOH (for which formation of radical acyclic
intermediate was concluded), the cisꢀstilbene oxide/transꢀstilbene oxide ratios were in the range
1.5–2.0, which was 6–8 times lower than for the epoxidations with Mn aminopyridine
complex/H2O2 or R1OOH/carboxylic acid (12–13).7h We note that Fe based catalyst systems 1/
R1OOH also demonstrate cisꢀstilbene oxide/transꢀstilbene oxide ratios (5–10, entries 4 and 7 of
Table 3) several times lower than for the epoxidation by catalyst systems
1/H2O2 or R1OOH/carboxylic acid (48–65, Table 3, entries 2, 3, 5, 6, 8 and 9), which may
indicate a similar mechanistic changeover when passing from carboxylic acidꢀcontaining systems
to the carboxylic acidꢀfree ones. Hammett analysis shows that the log (kX/kH) for the epoxidation
of pꢀsubstituted chalcones by the system 1/tꢀBuOOH well correlates with σp, exhibiting ρ of
−1.40 (Figure 2C). The twice smaller slope, as compared with the systems 1/H2O2 or 1/tꢀ
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BuOOH/2ꢀEHA and, particularly, correlation with σp (rather than σp ) supports a different
mechanism, without positive charge buildup at the substrate, while the low cis:trans selectivities
(entries 4, 7 of Table 3) hint at acyclic transition state, capable of rotating around the Cα−Cβ
single bond. Therefore, it is logical to assume that the epoxidations by catalyst systems 1/R1OOH
proceed via the general radical mechanism, similar to that proposed for the analogous Mn
aminopyridine catalysts (Scheme 2).7h
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Scheme 2. Proposed Reaction Sequence for the Asymmetric Epoxidation of Olefins by Catalyst
Systems of the Type 1/Alkyl hydroperoxide.
Independent evidence for different mechanisms has been obtained by 18O labeling data, using
the methodology previously developed for the identification of active species in MnꢀPDP
catalyzed asymmetric epoxidations with different oxidants.7h The epoxidation of Zꢀ
βꢀ
16
18
18
methylstyrene with the system 1/H2 O2/H2 O has resulted in a 15% O incorporation into the
epoxide (Table 4, entry 1), characteristic of the presence of [(L)FeV=O(OH)]2+ active species,
capable of exchanging its oxygen atom with that of labeled water.2b In contrast, the epoxidation
18
18
with the catalyst system 1/tꢀBuOOH/H2 O has demonstrated a much smaller O incorporation
(4%, Table 4, entry 2), indicating that the major epoxidation pathway does not involve the
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[((S,S)ꢀPDP)FeV=O(OH)]2+ intermediate, apparently proceeding with participation of another
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active oxidant.
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Table 4. Isotopic Labeling Results from the Oxidation of ZꢀβꢀMethylstyrene Catalyzed by
Complex 1 a
epoxide epoxideꢀ18O
diol
(TON) diolꢀ16O18O (%)
diolꢀ16O16O (%) /
entry oxidant
(TON)
(%)
1
2
3
H2O2
35
14
14
15
4
7
–
32 / 68 b
tꢀBuOOH
mꢀCPBA
–
0
0.5
53 / 47 b
a Reaction conditions: at 0 °C, ZꢀβꢀMethylstyrene (100 ꢁmol), oxidant, H2O2 (200 ꢁmol), tꢀ
18
18
BuOOH, mꢀCPBA (110 ꢁmol), H2 O containing 97% O (400 ꢁmol for the oxidation with tꢀ
BuOOH and 1000 ꢁmol for H2O2 and mꢀCPBA), catalyst load 2 mol %, H2O2 and tꢀBuOOH
were added by a syringe pump over 30 min, mꢀCPBA was added in one portion, and the resulting
mixtures were stirred for an additional 2.5 h followed by GCꢀMS analysis. Yields of products are
given in catalyst turnover numbers (TON). b Transꢀdiol.
We note that previously characterized lowꢀspin iron(III) alkylperoxo complexes were
considered as sluggish oxidants in electrophilic oxidation reactions.17 It is thus intriguing that
catalyst systems 1/R1OOH and 2/R1OOH demonstrate moderate but nonꢀzero activity, as well as
moderate to good enantioselection in the oxidation of olefins at 0 °C (Table 1, entries 1, 6, 2, 14;
Table S1, entries 3, 14; Table S2, entries 3 and 11), in combination with unique stereoselectivity
pattern (Table 3, entries 4 and 5), clearly exhibiting electrophilic character of the active species
18
and negligible O incorporation. Unfortunately, direct EPR monitoring of the reaction of in situ
generated species [((S,S)ꢀPDP)FeIII(OOtꢀBu)(CH3CN)]2+ with cyclohexene and Zꢀstilbene at −50
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°C has not revealed any dependence of the decay of the alkylperoxo complex on the
concentration of added olefin (Zꢀβꢀmethylstyrene or cyclohexene, [olefin]:[Fe]total = up to 20).
Similarly, the addition of more electronꢀrich substrate thioanisole (10 equiv) did not cause any
effect on the selfꢀdecay profile of the above alkylperoxo intermediate at −50 °C. Such result
agrees with literature precedents17 but does not provide the desirable direct spectroscopic
corroboration for the general radical mechanism in Scheme 2.
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Catalyst systems based on complex 2 and peroxides (tertꢀbutyl hydroperoxide, cumene
hydroperoxide and hydrogen peroxide). With the above preliminary mechanistic proposals in
mind, we have attempted a similar study of the catalyst systems based on Fe complex 2 and
peroxides, either with or without added carboxylic acid. The catalytic data agree with the
hypothesis of common active species in the catalyst systems 2/H2O2/RCOOH and
2/R1OOH/RCOOH (R1 = tꢀBu, Cm). The catalyst systems 2/tꢀBuOOH/2ꢀEHA, 2/CmOOH/2ꢀ
EHA and 2/H2O2/2ꢀEHA show high and identical chalcone epoxidation enantioselectivities (82–
83% ee, Table 1, entries 11, 13, 16). The epoxidation enantioselectivities by catalyst systems 2/tꢀ
BuOOH/AA, 2/CmOOH/AA and 2/H2O2/AA also coincided within experimental uncertainty
(71±1% ee, Table 1, entries 10, 12, 15). Therefore, by analogy with the systems 1/H2O2/RCOOH
and 1/R1OOH/RCOOH, we can expect that the same intermediate should operate in the catalyst
systems
2/H2O2/RCOOH
and
2/R1OOH/RCOOH
(presumably,
[((S,S)ꢀ
PDP*)FeV=O(OC(O)R)]2+).
Previously, it was found that catalyst systems 2/H2O2/AA and 2/H2O2/2ꢀEHA exhibit active
species 2aAA and 2aEHA with EPR spectra identical to that of 1aEHA (Table 2). Unfortunately,
EPR monitoring of the systems 2/tꢀBuOOH/AA and 2/tꢀBuOOH/2ꢀEHA (at −80 °C) did not
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reveal detectable steadyꢀstate concentrations of active species of the type 2aAA and 2aEHA
.
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8
Instead, only the highly unstable tertꢀbutylperoxy radicals, as well as stable ferric complexes 2b
and 2b′ (see below) were detected.
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In the absence of added carboxylic acid, the active species for the catalyst systems 2/tꢀBuOOH
and 2/CmOOH are expected to be different: [((S,S)ꢀPDP*)FeIII(OOtꢀBu)(CH3CN)]2+ and [((S,S)ꢀ
PDP*)FeIII(OOCm)(CH3CN)]2+, respectively. Therefore, one might anticipate that catalyst
systems 2/tꢀBuOOH and 2/CmOOH should exhibit different enantioselectivities. Indeed,
chalcone was epoxidized with 72% ee for 2/tꢀBuOOH vs. 67% ee for 2/CmOOH (Table 1,
entries 9 and 14), which small difference reflects minor structural difference of the active
species.
Previously, we found that chalcone epoxidation enantioselectivity of the system 1/H2O2/2ꢀ
EHA is substantially higher than for the system 1/H2O2/AA.7c This trend has been reproduced
herein for the epoxidation of different substrates by systems 1, 2/H2O2/2ꢀEHA and 1, 2/H2O2/AA
(chalcone: Table 1, entries 5 vs. 4, and 13 vs. 12; benzylideneacetone: Table S1, entries 2 vs. 1,
and 13 vs. 12; dbpcn: Table S2, entries 2 vs. 1, and 10 vs. 9), thus corroborating the documented
ability of the carboxylic acid with tertiary αꢀcarbon atom (2ꢀEHA) to enhance the
stereoselectivity of the proposed active species [(L)FeV=O(OC(O)R)]2+.7c,g
We can conclude that the results of the investigation of catalyst systems based on complex 2
and peroxides agree with the mechanistic conclusions made for complex 1. In particular, while
the epoxidation with alkyl hydroperoxides (in catalyst systems 1,2/tꢀBuOOH and 1,2/CmOOH)
is most likely conducted by ferric alkylperoxo species [(L)FeIII(OOR1)(CH3CN)]2+, the addition
of carboxylic acid triggers the epoxidation mechanism driven by oxoiron(V) intermediates
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[(L)FeV=O(OC(O)R)]2+ – the plausible epoxidizing agents of catalyst systems 1,2/H2O2/RCOOH
and 1,2/R1OOH/RCOOH.
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Catalyst systems based on complexes 1, 2 and peracids. Given the controversial data4c,6a on
the olefin epoxidation on Fe aminopyridine complexes (see Introduction), it would be tempting
to study the epoxidation of different olefinic substrates with peracids in the presence of different
catalysts, and probe the effect of added carboxylic acids on the enantioselectivity. When
implementing such a study, it was discovered that the catalyst systems 1/CH3CO3H,
1/CH3CO3H/AA and 1/CH3CO3H/2ꢀEHA display identical enantioselectivities in chalcone
epoxidation (67% ee, Table 1, entries 17–19). The enantioselectivity of the catalyst system
1/CH3CO3H/2ꢀEHA did not change upon the 6ꢀfold increase of 2ꢀEHA concentration (Table 1,
entries 19 and 20). The systems 1/mꢀCPBA, 1/mꢀCPBA/AA and 1/mꢀCPBA/2ꢀEHA also
demonstrated equal epoxidation enantioselectivities (51–52% ee, Table 1, entries 21–23, mꢀ
CPBA = metaꢀchloroperoxybenzoic acid). The above enantioselectivities noticeably differ from
the value of 67% ee for the epoxidations with CH3CO3H, and from those observed in the systems
1/H2O2/2ꢀEHA and 1/H2O2/AA (82% and 63% ee, respectively, Table 1, entries 4 and 5).
A similar picture has been documented for catalyst 2. The systems 2/CH3CO3H,
2/CH3CO3H/AA and 2/CH3CO3H/2ꢀEHA have exhibited very close enantioselectivities (62–65%
ee, Table 1, entries 24–26), as well as the systems 2/mꢀCPBA, 2/mꢀCPBA/AA and 2/mꢀCPBA/2ꢀ
EHA (59–63% ee, entries 27–29, Table 1). Again the above enantioselectivities noticeably
differed from those observed in the systems 2/H2O2/2ꢀEHA and 2/H2O2/AA (83% and 70% ee,
respectively, Table 1, entries 13 and 12).
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For benzylideneacetone, the trend was the same. The enantioselectivities of the catalyst
systems 1/CH3CO3H, 1/CH3CO3H/AA and 1/CH3CO3H/2ꢀEHA were rather close (25, 28 and
29% ee, Table S1, entries 6, 7, 8), as well as those of the systems 2/CH3CO3H, 2/CH3CO3H/AA
and 2/CH3CO3H/2ꢀEHA (34, 36, 38% ee, Table S1, entries 17, 18, 19). One can see that the
enantioselectivities of epoxidation with peracids were not sensitive to the nature of the added
carboxylic acid, and differed from those for the epoxidation with catalyst system 1/H2O2/2ꢀEHA
(53% ee, Table S1, entry 2), and with 2/H2O2/2ꢀEHA (65% ee, Table S1, entry 13). Epoxidations
of dbpcn as a substrate demonstrated the same regularity (Table S2).
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The Zꢀstilbene epoxidation stereoselectivity pattern was also very much different for the
catalyst systems based on complex 1 and different oxidants. For those systems, associated with
the [(L)FeV=O(OC(O)R)]2+ active species, the cis:trans ratio was in the range 48–65 (Table 3,
entries 2, 3, 5, 6, 8, 9). On the contrary, for the epoxidation with mꢀCPBA, the cis:trans
selectivity level was only 33–37 (Table 3, entries 10–12), which is close (in fact somewhat
higher) to that of uncatalyzed Prilezhaev epoxidation with mꢀCPBA (Table 3, entry 13), known
to proceed via concerted mechanism.18 In turn, for the epoxidations with the catalyst systems
1/CH3CO3H, 1/CH3CO3H/AA and 1/CH3CO3H/2ꢀEHA, the cis:trans ratio was in the range 81–
83 (Table 3, entries 14–16), irrespective of the presence of added carboxylic acid and of its
structure. For comparison, the uncatalyzed Prilezhaev epoxidation of Zꢀstilbene with CH3CO3H
(Table 3, entry 17) showed a cis:trans ratio of 50.
The above data testify that the epoxidations with catalyst systems 1,2/peracid and
1,2/peracid/carboxylic acid demonstrate substantial mechanistic distinctions from the systems
1,2/H2O2/carboxylic acid, that is (1) different levels of enantioselectivity and (2) independence of
the presence and nature of added carboxylic acid, and (3) different Zꢀstilbene epoxidation
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stereoselectivity pattern. It is logical to explain this difference by the occurrence of different
mechanisms of oxygen transfer, conducted by different oxidizing species.
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Previously, the independence of chalcone epoxidation enantioselectivity on the nature of
RCOOH was observed for the structurally similar Mnꢀbased catalyst system 4/R2CO3H/RCOOH,
and was explained by the existence of different active intermediates of the catalyst systems based
on peracids and hydrogen peroxide ([(L)MnIII(OOC(O)R2)]2+ and [(L)MnV=O(OC(O)R)]2+,
respectively).7h In much the same way, one can expect that in the catalyst systems
1,2/R2CO3H/RCOOH and 1,2/H2O2/RCOOH, different active species predominantly operate,
namely, [(L)FeIII(OOC(O)R2)]2+ and [(L)FeV=O(OC(O)R)]2+, respectively. To directly access the
ironꢀoxygen intermediates, the catalyst systems 1,2/R2CO3H/RCOOH were monitored by EPR
spectroscopy.
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The direct method to detect ferric acylperoxo complexes by EPR is to observe changes in the
EPR spectrum of the starting ferric complex upon the addition of peracid to the reaction solution
at low temperature. The systems 1/R2CO3H, 1/R2CO3H/AA and 1/R2CO3H/2ꢀEHA are not
suitable for such experiments since only EPR silent ferrous complexes exist in the starting
solutions before the addition of R2CO3H. In the system 2/R2CO3H, the starting diferric complex
2 is EPR silent, and thus this system is also inappropriate for the detection of ferric acylperoxo
intermediate.
The situation was more fortunate for the systems 2/R2CO3H/2ꢀEHA and 2/R2CO3H/AA. When
complex 2 was combined with 2ꢀEHA in a 1.8:1 CH2Cl2/CH3CN mixture at room temperature,
two types of mononuclear ferric complexes 2b′ and 2b were formed (Figure S2, SI). Complex
2b′ (g1 = 2.54, g2 = 2.41, g3 = 1.79) can be observed at relatively small [2ꢀEHA]/[Fe] ratios
(Figure S2A), while complex 2b (g1 = 2.79, g2 = 2.41, g3 = 1.62) predominates at high [2ꢀ
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EHA]/[Fe] ratios (Figure S2B). Most probably, 2b′ is complex [((S,S)ꢀPDP*)FeIII(κ2ꢀ
OC(O)R)]2+. The related complex [(TPA)FeIII(κ2ꢀacac)]2+ (TPA = tris(2ꢀpyridylmethyl)amine,
acac = acetylacetonate) displays similar EPR spectrum (g1 = 2.57, g2 = 2.35, g3 = 1.71).19 The
increase of the carboxylic acid concentration may favor the formation of a ferric complex with
two carboxylic ligands, so that 2b can be tentatively assigned to the complex [((S,S)ꢀ
PDP*)FeIII(OC(O)R)(RCOOH)]2+.
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(2b′)
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Figure 3. EPR spectra (−196 °C) of the samples (A) 2/2ꢀEHA ([2ꢀEHA]/[Fe] = 10, [Fe] = 0.04
M) frozen 2 min after mixing the reagents at room temperature; (B) 2/CH3CO3H/2ꢀEHA
([Fe]:[CH3CO3H]:[2ꢀEHA] = 1:3:10, [Fe] = 0.04 M) frozen after mixing the sample in “A” with
CH3CO3H solution for 2 min at −70 °C; (C) frozen 2 min after storing the sample in “B” at room
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temperature. A 1.8:1 CH2Cl2/CH3CN mixture was used as a solvent. Resonances denoted by an
asterisk belong to unidentified stable species.
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The addition of 3 equiv of peracetic acid to the sample 2/2ꢀEHA = 1:10 (Figure 3A) and
mixing the reagents during 2 min at −70 °C led to the decrease of signals of species 2b′ and 2b,
and emergence of rhombically anisotropic spectrum (g1 = 2.070, g2 = 2.008, g3 = 1.958),
characteristic of the intermediate 2aEHA with the proposed structure7g [((S,S)ꢀ
PDP*)FeV=O(OC(O)R)]2+ (Figure 3B). At the same time, complexes 2b′ and 2b partially
converted to a new complex 2c. The principal gꢀvalues of 2c (g1 = 2.52, g2 = 2.41, g3 = 1.80) are
similar but not identical to those of 2b′ (g1 = 2.54, g2 = 2.41, g3 = 1.79). Warming the sample in
Figure 3B to room temperature led to the disappearance of the spectra of 2c and 2aEHA, and
recovery of the spectra of 2b′ and 2b (Figure 3C). Apparently, the interaction of 2b′ and 2b with
peracetic acid results in the replacement of κ2ꢀOC(O)R and RCOOH = 2ꢀEHA ligands with κ2
ꢀ
OOC(O)CH3 one to afford acylperoxo complex of the type [((S,S)ꢀPDP*)FeIII(κ2ꢀ
OOC(O)CH3)]2+ (2c). The EPR spectrum of 2c resembles that of the well spectroscopically
characterized acylperoxo complex [(TPA*)FeIII(κ2ꢀOOC(O)CH3)]2+ (g1 = 2.58, g2 = 2.38, g3 =
1.72).9 In contrast to the catalyst system 2/CH3CO3H/2ꢀEHA, exhibiting EPR spectra of unstable
intermediates 2c and 2aEHA, the catalyst system 2/H2O2/2ꢀEHA displays the EPR spectrum of
intermediate 2aEHA (Figures S3, SI), along with the spectra of temperatureꢀstable complexes 2b′
and 2b. A similar picture has been documented for the catalyst systems 2/H2O2/AA and
2/CH3CO3H/AA. The former system exhibits EPR spectrum of only intermediate 2aAA, while the
latter exhibits EPR spectra of both unstable intermediates 2c and 2aAA (Table 2, Figure S4, SI).
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The reason of the formation of oxoiron(V) intermediates (2aEHA and 2aAA) in the systems
2/CH3CO3H/2ꢀEHA and 2/CH3CO3H/AA is rather clear: the solutions of peracetic acid (typically
obtained by reacting acetic acid with excess H2O2 in the presence of appropriate catalyst) always
contain some amounts of H2O2, and H2O2 can react with Fe catalysts 1 or 2, to afford oxoiron(V)
intermediates (in the presence of carboxylic acid).
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2.54
2b′
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Figure 4. EPR spectra (−196 °C) of the samples (A) 2/AA ([AA]/[Fe] = 10, [Fe] = 0.04 M)
frozen 2 min after mixing the reagents at room temperature; (B) 2/mꢀCPBA/AA ([Fe]:[mꢀ
CPBA]:[AA] = 1:3:10, [Fe] = 0.04 M) frozen after mixing the sample in “A” with mꢀCPBA
solution for 2 min at −70 °C. A 1.8:1 CH2Cl2/CH3CN mixture was used as a solvent.
To exclude the poorly controlled contribution of residual H2O2 into the observed picture, one
could use metaꢀchloroperoxybenzoic acid (mꢀCPBA), which is commercially provided as a solid
and usually contains residual hydrogen peroxide in trace amounts. To this end, formation of
active species in catalyst systems 2/mꢀCPBA/2ꢀEHA and 2/mꢀCPBA/AA has been monitored by
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EPR. mꢀCPBA was added at −70 °C to the sample 2/AA = 1:10 (Figure 4A), to afford a 2/mꢀ
CPBA/AA = 1:3:10 mixture (Figure 4B). Predictably, the oxoiron(V) intermediate 2aAA was not
observed in the system 2/mꢀCPBA/AA (cf. Figures 3B and 4B). Instead, formation of only
intermediate 2c′ with EPR spectrum nearly identical to that of 2c was detected (Figure 4B, Table
2). Complex 2c′ (which can be assigned to the [((S,S)ꢀPDP*)FeIII(κ2ꢀOOC(O)R2)]2+ species,
where R2 = 3ꢀClꢀC6H4), is unstable and decays at −60 °C with a halfꢀdecay time of 10 min.
A similar picture was observed for the catalyst system 2/mꢀCPBA/2ꢀEHA. Again 2c′ was the
only observable intermediate, and oxoiron(V) intermediate 2aEHA was not detected (Figure S5,
SI). So, the catalyst systems 2/mꢀCPBA/AA and 2/mꢀCPBA/2ꢀEHA, capable of conducting the
enantioselective epoxidation of chalcone (Table 1, entries 28 and 29) and benzylideneacetone
(Table S1, entries 21 and 22) exhibit only acylperoxo species 2c′ as potential candidate to the
role of active oxygenꢀtransferring species.
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Very recently, Nam, Latour, Sarangi and coworkers have synthesized and spectroscopically
characterized a series of highꢀspin mononuclear nonꢀheme iron(III)ꢀacylperoxo complexes
bearing Nꢀmethylated cyclam ligand (1,4,7,10ꢀtetramethylꢀ1,4,7,10ꢀtetraazacyclotridecane).
These complexes have been found active in C=C epoxidation and C–H hydroxylation
reactions.10 On the basis of these studies, the authors have concluded that mononuclear nonꢀ
heme highꢀspin iron(III)ꢀacylperoxo complexes are strong oxidants capable of oxidizing
hydrocarbons faster than converting into ironꢀoxo species via O–O bond cleavage. Taking into
account our data, both highꢀspin and lowꢀspin nonheme iron(III)ꢀacylperoxo complexes may be
considered as plausible active species of enantioselective epoxidation of olefins.
The relatively high cis:trans ratios in the epoxidation of Zꢀstilbene by catalyst systems based
on complex 1 and mꢀCPBA (33–37, cf. Table 3, entries 10–12) are similar to that for uncatalyzed
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Prilezhaev reaction (30, Table 3, entry 13), that may be evidence for concerted epoxidation
mechanism.
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Epoxidation of Zꢀβ
ꢀmethylstyrene by the catalyst system 1/mꢀCPBA in the presence of 18Oꢀ
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labeled water shows zero incorporation of 18O into the epoxide (Table 4, entry 3), which is
evidence of epoxidation mechanism different from that involving the oxoiron active species.
In combination, the EPR observations, the unique cis:trans selectivity pattern, the Hammett
18
and Oꢀlabelling data can be reasonably interpreted in favor of the concerted mechanism of the
epoxidations by mꢀCPBAꢀbased catalyst systems (Scheme 3). In this scheme, “S” stands for an
auxiliuary ligand (solvent or carboxylic acid additive). According to the catalytic results, the
ligand “S” has very minor effect on the epoxidation enantioselectivity (Table 1) and
stereoselectivity (Table 3).
Scheme 3. Proposed Reaction Sequence for the Asymmetric Epoxidation of Olefins with
Peroxycarboxylic Acids in the Presence of Fe Aminopyridine Complexes 1 or 2.
“S” denotes coordinated molecule of solvent or carboxylic acid.
As to the “epoxidations with peracetic acid”, our data witness that the presence of residual
H2O2 in solutions of CH3CO3H can lead to coꢀexistence of two types of active species, i.e. the
[(L)FeIII(κ2ꢀOOC(O)CH3)]2+ and [(L)FeV=O(OC(O)CH3)]2+, which may affect the epoxidation
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outcome. The indifference of chalcone epoxidation enantioselectivity to the additives of
carboxylic acids (Table 1, entries 17–19 and 24–26) indicates that at 0 °C predominantly the
acylperoxoꢀiron(III) intermediate drives enantioselective epoxidation of chalcone with peracetic
acid (Scheme 3), in spite of the documented formation of oxoiron(V) species at −70 °C. In
principle, the balance between the mechanisms based on these two epoxidizing species could
depend on the proportion of CH3CO3H and H2O2 in the mixture, as well as on their relative
reactivities. Therefore, the results of epoxidations with peracetic acid should be interpreted
carefully, without drawing excessive conclusions.
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CONCLUSIONS
In summary, the nature of active species of the catalyst systems based on mononuclear ferrous
complex 1 and binuclear ferric complex 2 of the Fe(PDP) family, and various oxidants (H2O2,
R1OOH, R1 = tꢀBu and Cm; R2C(O)OOH, R2 = CH3 and 3ꢀClꢀC6H4) has been studied. On the
basis of the obtained EPR, stereoselectivity, Hammett and 18Oꢀlabelling data, as well as on
literature precedents, plausible mechanisms of epoxidations with different oxidants have been
proposed, that are (1) oxygen transfer from the [(L)FeIII(OOR1)(CH3CN)]2+ species to the olefin
with the formation of acyclic, presumably radical intermediate for the systems 1,2/R1OOH, (2)
[(L)FeV=O(OC(O)R)]2+ driven pathway for the epoxidations with 1,2/H2O2/RCOOH and
1,2/R1OOH/RCOOH systems, with the formation of acyclic, presumably cationic intermediate,
and (3) concerted oxygen transfer from the acylperoxoꢀiron(III) intermediates
[(L)FeIII(OOC(O)R2)]2+ to the olefin for the epoxidations with 1,2/R2C(O)OOH/RCOOH.
The observed mechanistic landscape is qualitatively similar to that for the structurally similar
bioinspired Mnꢀaminopyridine catalysts. As a general rule, the Fe based catalysts exhibit lower
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olefin epoxidation enantioselectivities and higher cis:trans selectivities (with Zꢀstilbene), which
may reflect the higher intrinsic reactivity of Feꢀbased systems. Further studies, aimed at the
examination of reactivity of different active intermediates toward oxidation of alkanes are in
progress in our laboratory.
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ASSOCIATED CONTENT
Supporting Information. Experimental procedures, additional data on asymmetric epoxidations
and EPR spectra.
The following files are available free of charge.
Supporting Information.doc
AUTHOR INFORMATION
Corresponding Authors
*Eꢀmail: bryliako@catalysis.ru, talsi@catalysis.ru
ACKNOWLEDGMENTS
Complexes 1 and 2 were synthesized, necessary chemicals were purchased, and catalytic studies
were conducted with the aid of the Russian Foundation for Basic Research (#16ꢀ29ꢀ10666). EPR
spectroscopic studies were performed using the equipment of the Russian Academy of Sciences
and Federal Agency of Scientific Organizations (project V.44.2.4).
REFERENCES
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