Iron-Catalyzed Enantioselective Epoxidations with Various Oxidants

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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 Downloaded from http://pubs.acs.org on November 8, 2016

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ACS Catalysis

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* 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 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

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O 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 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)FeIII(OOC(O)R2)]2+, in a concerted fashion.

KEYWORDS: asymmetric epoxidation, bioinspired catalysis, enantioselectivity, EPR, iron, mechanism

INTRODUCTION Iron and manganese catalysts with aminopyridine ligands have been recently shown to promote the regio- and stereoselective oxidation of C(sp3)–H groups,1–3 and enantioselective epoxidation of alkenes4–7 with preparatively acceptable efficiencies and yields. Chiral bipyrrolidine-derived 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 Fe-based bioinspired catalysts. In most cases, hydrogen peroxide is used as the oxidant. At the same time, other oxidants, such as peracetic acid and tert-butyl hydroperoxide can also be used for the asymmetric epoxidation of olefins in the presence of non-heme 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. OCH3

H3CO

N N

N

N

N II

N N

OTf

Fe

III

Fe

OH

III

Fe OH

OTf

N

N

N

N

N

(OTf)4 OCH3

H3CO

1

2

N H3CO N N N

II

OTf

Fe

OTf N

N

3

N II N Mn N N

N

OTf N N

OTf

II

OTf

Fe

OTf N

H3CO

5

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

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O incorporation from added H218O into the

epoxide. Remarkably, catalyst systems 4/H2O2/carboxylic acid and 4/t-BuOOH/carboxylic acid have demonstrated identical stereoselectivities in the epoxidation of Z-stilbene 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 these systems. At the same time, on the basis of kinetic and

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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 co-workers 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 Intriguingly, Costas and co-workers documented the same enantioselectivity level (61% ee) for the epoxidation of Z-β-methylstyrene with the catalyst systems 3/oxidant/CH3COOH, where oxidant = H2O2, t-BuOOH and CH3CO3H.4c This observation was interpreted in favor of the same oxygen-atom 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(OOtBu)],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 systems

1,2/H2O2/RCOOH,

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O labeling studies of the olefin epoxidation in the catalyst 1,2/t-BuOOH/RCOOH,

1,2/CmOOH/RCOOH

and

1,2/R2C(O)OOH/RCOOH {RCOOH = acetic or 2-ethylhexanoic acid, R2 = CH3 or 3-Cl-C6H4, Cm = cumyl}, and discuss the plausible nature of the oxygen-transferring species.


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RESULTS AND DISCUSSION Catalyst systems based on complex 1 and peroxides (tert-butyl hydroperoxide, cumene hydroperoxide and hydrogen peroxide). The catalyst system 1/t-BuOOH 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 2-ethylhexanoic acid (2-EHA) significantly improves the yield and enantioselectivity of this system, to 64% and 81% ee, respectively (Table 1, entries 2 and 3).

Table 1. Asymmetric Epoxidation of Chalcone with Various Oxidants Catalyzed by Complexes 1 and 2 a

entry catalyst 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

1 1 1 1 1 1 1 1 2 2 2 2 2 2 2

oxidant

additive (equiv) b

conversion (%) / epoxide yield (%)

ee (%) c

t-BuOOH t-BuOOH t-BuOOH H2O2 H2O2 CmOOH CmOOH CmOOH t-BuOOH t-BuOOH t-BuOOH H2O2 H2O2 CmOOH CmOOH

– AA 2-EHA AA 2-EHA – AA 2-EHA – AA 2-EHA AA 2-EHA – AA

17 / 17 70 / 70 76 / 76 77 / 75 90 / 89 22 / 22 43 / 42 44 / 44 7/7 73 / 73 78 / 78 74 / 73 73 / 73 6/4 47 / 47

52 64 81 63 82 56 65 80 72 71 82 70 83 67 72


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16 17 18 19 20 21 22 23 24 25 26 27 28 29

2 1 1 1 1 1 1 1 2 2 2 2 2 2

CmOOH CH3CO3H CH3CO3H CH3CO3H CH3CO3H m-CPBA m-CPBA m-CPBA CH3CO3H CH3CO3H CH3CO3H m-CPBA m-CPBA m-CPBA

2-EHA – AA 2-EHA (55) 2-EHA (330) – AA 2-EHA – AA 2-EHA – AA 2-EHA

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53 / 53 54 / 54 49 / 49 53 / 53 57 / 57 48 / 48 39 / 39 46 / 46 41 / 41 52 / 52 69 / 69 28 / 28 41 / 41 38 / 38

83 67 67 67 67 51 52 52 65 64 62 59 62 63

a

Reaction conditions: at 0 °C, chalcone (100 µmol), oxidant, H2O2 (200 µmol), t-BuOOH, CmOOH, CH3CO3H, m-CPBA (110 µmol), 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 µmol of carboxylic acid was added. c Absolute configuration of chalcone epoxide was (2R,3S).

The EPR spectrum (−196 °C)11a of the system 1/t-BuOOH exhibits weak resonances of the alkylperoxo complex [((S,S)-PDP)FeIII(OOt-Bu)(CH3CN)]2+ (g1 = 2.19, g2 = 2.14, g3 = 1.96, Table 2, entry 1) and those of t-BuOO• radical (g|| = 2.030, g⊥ = 2.005)11b (Figure 1A). The EPR spectrum of the system 1/t-BuOOH/2-EHA 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 t-BuOO• 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/H2O2/2-EHA and was assigned to the [((S,S)-PDP)FeV=O(OC(O)R)]2+ species (RCOOH = 2EHA, 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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III

t

(L)Fe –OO Bu 2.030 t • 2.005 ( BuOO )

A) 2.19

1b

2.14 1.96 (L)FeIII–OOtBu

1b

t

BuOO

•

EHA

1a

B)

1b

2.14 2.19

2.75

1b

1b 2.41

1aEHA

2.069 2.007

1aEHA

C)

1.64

1.963

1b

2500

3000

3500

4000

4500

H/G

Figure 1. EPR spectra (−196 °C) of the samples (A) 1/t-BuOOH ([1]:[ t-BuOOH] = 1:3, [1] = 0.04 M) frozen 3 min after mixing the reagents at −60 °C; (B) 1/t-BuOOH/2-EHA ([1]:[ tBuOOH]:[2-EHA] = 1:3:10, [1] = 0.04 M) frozen 3 min after mixing the reagents at −60 °C; (C) 1/H2O2/2-EHA ([1]:[H2O2]:[2-EHA] = 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 t-BuOO• 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/H2O2/2-EHA 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 N4-donor Tetradentate Ligands.

no species 1 2 3 4 5 6 7 8 9 10 11 12 13 14

[((S,S)-PDP)FeIII(OOt-Bu)(CH3CN)]2+ [((S,S)-PDP)FeIII(OOCm)(CH3CN)]2+ [(PyNMe3)FeV=O(OC(O)CH3)]2+ a [(TMC)FeV=O(NC(O)CH3)]+ b [((S,S)-PDP)FeV=O(OC(O)R)]2+ (1aEHA) c 1aAA [((S,S)-PDP*)FeV=O(OC(O)CH3)]2+ (2aAA) [((S,S)-PDP*)FeV=O(OC(O)R)]2+ (2aEHA) c [((S,S)-PDP)FeIII(OC(O)R)(RCOOH)]2+ (1b) c [((S,S)-PDP*)FeIII(OC(O)R)(RCOOH)]2+ (2b) d [((S,S)-PDP*)FeIII(κ2-OC(O)R)]2+ (2b′) d [((S,S)-PDP*)FeIII(κ2-OOC(O)CH3)]2+ (2c) [((S,S)-PDP*)FeIII(κ2-OOC(O)C6H4Cl)])]2+ (2c′) e [(TPA*)FeIII(κ2-OOC(O)CH3)]2+ a

g1

g2

g3

ref

2.19 2.18 2.07 2.053 2.069 2.66 2.071 2.070 2.75

2.14 2.13 2.01 2.010 2.007 2.42 2.008 2.008 2.41

1.96 1.96 1.95 1.971 1.963 1.71 1.960 1.958 1.64

this work this work 2f 12 7g 7c,g 7f,g 7g 7g

2.79

2.41

1.62

this work

2.54 2.52 2.52

2.41 2.41 2.41

1.79 1.80 1.80

this work this work this work

2.58

2.38

1.72

9

a

PyNMe3, TPA* – N4-donor aminopyridine ligands. b TMC – tetramethylcyclam. c RCOOH = 2-ethylhexanoic acid. d RCOOH = acetic or 2-ethylhexanoic acid. e ClC6H4C(O)OOH = mCPBA (3-chloroperoxybenzoic acid).

1/t-BuOOH/2-EHA (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/H2O2/2-EHA and 1/t-BuOOH/2-EHA. In agreement with this prediction, chalcone epoxidation enantioselectivities were the same (within experimental uncertainty ±1% ee) for the systems 1/H2O2/2-EHA, 1/t-BuOOH/2-EHA, and 1/CmOOH/2-EHA (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/t-BuOOH/AA (Table S1, Supporting


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Information (SI), entries 1 and 4) and by the systems 1/H2O2/2-EHA and 1/t-BuOOH/2-EHA (Table S1, entries 2 and 5). The catalyst systems 1/t-BuOOH/AA and 1/H2O2/AA display EPR spectrum of the same highly unstable intermediate 1aAA with large g-factor 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 different unpaired spin distribution in the intermediates 1aAA and 1aEHA.7g Again, the catalyst systems 1/H2O2/AA, 1/t-BuOOH/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/t-BuOOH is alkylperoxo complex [((S,S)PDP)FeIII(OOt-Bu)(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/tBuOOH 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 Mnaminopyridine based catalyst systems with different oxidants has been obtained by examining the stereoselectivity of epoxidation of Z-stilbene.7h We would expect that for the structurally


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Table 3. Epoxidation of Z-Stilbene with Various Oxidants Catalyzed by Complex 1 a

entry catalyst 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17

1 1 1 1 1 1 1 1 1 1 1 1 –b 1 1 1 –c

oxidant

additive

conversion (%) / epoxide yield (%)

cis : trans

H2O2 H2O2 H2O2 t-BuOOH t-BuOOH t-BuOOH CmOOH CmOOH CmOOH m-CPBA m-CPBA m-CPBA m-CPBA CH3CO3H CH3CO3H CH3CO3H CH3CO3H

– AA 2-EHA – AA 2-EHA – AA 2-EHA – AA 2-EHA – – AA 2-EHA –

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 48 59 34 33 37 30 83 82 81 50

a

Reaction conditions: at 0 °C, Z-stilbene (100 µmol), oxidant, H2O2 (200 µmol), t-BuOOH, CmOOH, CH3CO3H, m-CPBA (110 µmol), carboxylic acid additive (55 µmol), catalyst load 2 mol %, oxidant was added by a syringe pump over 30 min, and the mixture was stirred for an additional 2.5 h followed by NMR analysis. b 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 Z-stilbene. Indeed, it is seen that for the epoxidation by the systems 1/t-BuOOH 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 2-EHA, 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/H2O2/2-EHA (cis:trans = 65, Table 3, entry 3). In turn, in the catalyst systems 1/t-BuOOH/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 2-EHA, R1 = t-butyl or cumyl). On the basis of the above EPR, enantio- 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 intermediate based on the observed linear correlation between the relative epoxidation rates of psubstituted chalcones and the Hammett-Brown parameter σp+.7e,h Herewith, a similar Hammett analysis, applied to the epoxidation of p-substituted chalcones with the system 1/H2O2/2-EHA, has demonstrated a good linear correlation of the epoxidation rates vs. σp+, with a negative slope ρ+ of −2.83 (Figure 2A), indicative of electron-deficient transition state. Moreover, for the epoxidation of p-substituted chalcones with the system 1/t-BuOOH/2-EHA, 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

1,0 0, 0,0

B

p-Me

-1,5 -2,0 -0,4

p-Me

1, 0,

p-H p-Cl

p-F

p-H

0,

log (kX/kH) -0,5 -1,0

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p-Cl

p-F

log (kX/kH) -0,5 -1,0

y = −2.83x + 0.048 R = 0.995 -0,2

0,0

0,2

0,4

p-CF3

-1,5

0,6

-2,0 -0,4

y = −2.84x + 0.039 R = 0.998 -0,2

0,0

σp+

C

D

0,0

log (kX/kH)

p-H

0,2

0,4

1,0 0,5

p-F

p-Me

p-F

0,0

p-Me

log (kX/kH)

-0,5

p-Cl

p-H -0,5

p-Cl -1,0 -1,5 -2,0 -0,4

0,0

-1,0

p-CF3

y = −1.40x + 0.031 R = 0.945 -0,2

0,6

σp+

1,0 0,5

p-CF3

-1,5

0,2

0,4

0,6

p-CF3 y = −2.64x + 0.085 R = 0.996

-2,0 -0,4

-0,2

0,0

σp

0,2

0,4

0,6

σp

Figure 2. Hammett plots for the oxidation of p-substituted chalcones by the catalyst systems (A) 1/H2O2/2-EHA, (B) 1/t-BuOOH/2-EHA, (C) 1/t-BuOOH, (D) 1/m-CPBA. 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 = t-butyl 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 electrontransfer mechanism, mediated by natural metalloenzymes or their synthetic models (ρ+ −3 to −7).15 The epoxidations by catalyst systems 1/R1OOH (R1 = t-butyl 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 metal-catalyzed 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 cis-stilbene oxide/trans-stilbene 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 cis-stilbene oxide/trans-stilbene 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 acid-containing systems to the carboxylic acid-free ones. Hammett analysis shows that the log (kX/kH) for the epoxidation of p-substituted chalcones by the system 1/t-BuOOH well correlates with σp, exhibiting ρ of −1.40 (Figure 2C). The twice smaller slope, as compared with the systems 1/H2O2 or 1/t-


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BuOOH/2-EHA 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

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 Mn-PDP catalyzed asymmetric epoxidations with different oxidants.7h The epoxidation of Z-βmethylstyrene with the system 1/H216O2/H218O has resulted in a 15% 18O 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 with the catalyst system 1/t-BuOOH/H218O has demonstrated a much smaller

18

O incorporation

(4%, Table 4, entry 2), indicating that the major epoxidation pathway does not involve the


14

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[((S,S)-PDP)FeV=O(OH)]2+ intermediate, apparently proceeding with participation of another active oxidant.

Table 4. Isotopic Labeling Results from the Oxidation of Z-β-Methylstyrene Catalyzed by Complex 1 a

entry

oxidant

1 2 3

H2O2 t-BuOOH m-CPBA

epoxide epoxide-18O (TON) (%) 35 14 14

15 4 0

diol (TON)

diol-16O16O (%) / diol-16O18O (%)

7 – 0.5

32 / 68 b – 53 / 47 b

a

Reaction conditions: at 0 °C, Z-β-Methylstyrene (100 µmol), oxidant, H2O2 (200 µmol), tBuOOH, m-CPBA (110 µmol), H218O containing 97% 18O (400 µmol for the oxidation with tBuOOH and 1000 µmol for H2O2 and m-CPBA), catalyst load 2 mol %, H2O2 and t-BuOOH were added by a syringe pump over 30 min, m-CPBA was added in one portion, and the resulting mixtures were stirred for an additional 2.5 h followed by GC-MS analysis. Yields of products are given in catalyst turnover numbers (TON). b Trans-diol.

We note that previously characterized low-spin 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 non-zero 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 and negligible 18O incorporation. Unfortunately, direct EPR monitoring of the reaction of in situ generated species [((S,S)-PDP)FeIII(OOt-Bu)(CH3CN)]2+ with cyclohexene and Z-stilbene 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 (Z-β-methylstyrene or cyclohexene, [olefin]:[Fe]total = up to 20). Similarly, the addition of more electron-rich substrate thioanisole (10 equiv) did not cause any effect on the self-decay 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.

Catalyst systems based on complex 2 and peroxides (tert-butyl 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 = t-Bu, Cm). The catalyst systems 2/t-BuOOH/2-EHA, 2/CmOOH/2EHA and 2/H2O2/2-EHA show high and identical chalcone epoxidation enantioselectivities (82– 83% ee, Table 1, entries 11, 13, 16). The epoxidation enantioselectivities by catalyst systems 2/tBuOOH/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/H2O2/2-EHA exhibit active species 2aAA and 2aEHA with EPR spectra identical to that of 1aEHA (Table 2). Unfortunately, EPR monitoring of the systems 2/t-BuOOH/AA and 2/t-BuOOH/2-EHA (at −80 °C) did not


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reveal detectable steady-state concentrations of active species of the type 2aAA and 2aEHA. Instead, only the highly unstable tert-butylperoxy radicals, as well as stable ferric complexes 2b and 2b′ (see below) were detected. In the absence of added carboxylic acid, the active species for the catalyst systems 2/t-BuOOH and 2/CmOOH are expected to be different: [((S,S)-PDP*)FeIII(OOt-Bu)(CH3CN)]2+ and [((S,S)PDP*)FeIII(OOCm)(CH3CN)]2+, respectively. Therefore, one might anticipate that catalyst systems 2/t-BuOOH and 2/CmOOH should exhibit different enantioselectivities. Indeed, chalcone was epoxidized with 72% ee for 2/t-BuOOH 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/H2O2/2EHA 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/H2O2/2-EHA 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 α-carbon atom (2-EHA) 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/t-BuOOH 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.

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/2-EHA display identical enantioselectivities in chalcone epoxidation (67% ee, Table 1, entries 17–19). The enantioselectivity of the catalyst system 1/CH3CO3H/2-EHA did not change upon the 6-fold increase of 2-EHA concentration (Table 1, entries 19 and 20). The systems 1/m-CPBA, 1/m-CPBA/AA and 1/m-CPBA/2-EHA also demonstrated equal epoxidation enantioselectivities (51–52% ee, Table 1, entries 21–23, mCPBA = meta-chloroperoxybenzoic 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/H2O2/2-EHA 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/2-EHA have exhibited very close enantioselectivities (62–65% ee, Table 1, entries 24–26), as well as the systems 2/m-CPBA, 2/m-CPBA/AA and 2/m-CPBA/2EHA (59–63% ee, entries 27–29, Table 1). Again the above enantioselectivities noticeably differed from those observed in the systems 2/H2O2/2-EHA and 2/H2O2/AA (83% and 70% ee, respectively, Table 1, entries 13 and 12).


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ACS Catalysis

For benzylideneacetone, the trend was the same. The enantioselectivities of the catalyst systems 1/CH3CO3H, 1/CH3CO3H/AA and 1/CH3CO3H/2-EHA 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/2-EHA (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/H2O2/2-EHA (53% ee, Table S1, entry 2), and with 2/H2O2/2-EHA (65% ee, Table S1, entry 13). Epoxidations of dbpcn as a substrate demonstrated the same regularity (Table S2). The Z-stilbene 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 m-CPBA, 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 m-CPBA (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/2-EHA, 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 Z-stilbene 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 Z-stilbene epoxidation


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Page 20 of 33

stereoselectivity pattern. It is logical to explain this difference by the occurrence of different mechanisms of oxygen transfer, conducted by different oxidizing species. Previously, the independence of chalcone epoxidation enantioselectivity on the nature of RCOOH was observed for the structurally similar Mn-based 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 iron-oxygen intermediates, the catalyst systems 1,2/R2CO3H/RCOOH were monitored by EPR spectroscopy. 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/2-EHA 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/2-EHA and 2/R2CO3H/AA. When complex 2 was combined with 2-EHA 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 [2-EHA]/[Fe] ratios (Figure S2A), while complex 2b (g1 = 2.79, g2 = 2.41, g3 = 1.62) predominates at high [2-


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EHA]/[Fe] ratios (Figure S2B). Most probably, 2b′ is complex [((S,S)-PDP*)FeIII(κ2OC(O)R)]2+. The related complex [(TPA)FeIII(κ2-acac)]2+ (TPA = tris(2-pyridylmethyl)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+.

2.54 (2b′) 2.79 (2b) 1.79

2.41 (2b′) 2.008 2.070

A)

2b′

2aEHA

2aEHA

2.52

2c

2c 2.41

1.958 1.80

B)

2c

2b′

2aEHA

*

2b

2500

3000

3500

C)

4000

4500

H/G

Figure 3. EPR spectra (−196 °C) of the samples (A) 2/2-EHA ([2-EHA]/[Fe] = 10, [Fe] = 0.04 M) frozen 2 min after mixing the reagents at room temperature; (B) 2/CH3CO3H/2-EHA ([Fe]:[CH3CO3H]:[2-EHA] = 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.

The addition of 3 equiv of peracetic acid to the sample 2/2-EHA = 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 g-values 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 κ2-OC(O)R and RCOOH = 2-EHA ligands with κ2OOC(O)CH3 one to afford acylperoxo complex of the type [((S,S)-PDP*)FeIII(κ2OOC(O)CH3)]2+ (2c). The EPR spectrum of 2c resembles that of the well spectroscopically characterized acylperoxo complex [(TPA*)FeIII(κ2-OOC(O)CH3)]2+ (g1 = 2.58, g2 = 2.38, g3 = 1.72).9 In contrast to the catalyst system 2/CH3CO3H/2-EHA, exhibiting EPR spectra of unstable intermediates 2c and 2aEHA, the catalyst system 2/H2O2/2-EHA displays the EPR spectrum of intermediate 2aEHA (Figures S3, SI), along with the spectra of temperature-stable 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/2-EHA 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).

2.54

2b′

2b′ 1.79

2.41

A)

2b′ 2.52

2c′ 2c′ 2.41

*

1.80

B)

2c′

2500

3000

3500

4000

4500

H/G

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/m-CPBA/AA ([Fe]:[mCPBA]:[AA] = 1:3:10, [Fe] = 0.04 M) frozen after mixing the sample in “A” with m-CPBA 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 meta-chloroperoxybenzoic acid (m-CPBA), 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/m-CPBA/2-EHA and 2/m-CPBA/AA has been monitored by


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EPR. m-CPBA was added at −70 °C to the sample 2/AA = 1:10 (Figure 4A), to afford a 2/mCPBA/AA = 1:3:10 mixture (Figure 4B). Predictably, the oxoiron(V) intermediate 2aAA was not observed in the system 2/m-CPBA/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(κ2-OOC(O)R2)]2+ species, where R2 = 3-Cl-C6H4), is unstable and decays at −60 °C with a half-decay time of 10 min. A similar picture was observed for the catalyst system 2/m-CPBA/2-EHA. Again 2c′ was the only observable intermediate, and oxoiron(V) intermediate 2aEHA was not detected (Figure S5, SI). So, the catalyst systems 2/m-CPBA/AA and 2/m-CPBA/2-EHA, 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 oxygen-transferring species. Very recently, Nam, Latour, Sarangi and coworkers have synthesized and spectroscopically characterized a series of high-spin mononuclear non-heme iron(III)-acylperoxo complexes bearing N-methylated cyclam ligand (1,4,7,10-tetramethyl-1,4,7,10-tetraazacyclotridecane). 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 nonheme high-spin iron(III)-acylperoxo complexes are strong oxidants capable of oxidizing hydrocarbons faster than converting into iron-oxo species via O–O bond cleavage. Taking into account our data, both high-spin and low-spin 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 Z-stilbene by catalyst systems based on complex 1 and m-CPBA (33–37, cf. Table 3, entries 10–12) are similar to that for uncatalyzed


24

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Prilezhaev reaction (30, Table 3, entry 13), that may be evidence for concerted epoxidation mechanism. Epoxidation of Z-β-methylstyrene by the catalyst system 1/m-CPBA in the presence of labeled water shows zero incorporation of

18

18

O-

O 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 and 18O-labelling data can be reasonably interpreted in favor of the concerted mechanism of the epoxidations by m-CPBA-based 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 co-existence of two types of active species, i.e. the [(L)FeIII(κ2-OOC(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 acylperoxo-iron(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.

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 = t-Bu and Cm; R2C(O)OOH, R2 = CH3 and 3-Cl-C6H4) has been studied. On the basis of the obtained EPR, stereoselectivity, Hammett and

18

O-labelling 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

acylperoxo-iron(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 Mn-aminopyridine catalysts. As a general rule, the Fe based catalysts exhibit lower


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olefin epoxidation enantioselectivities and higher cis:trans selectivities (with Z-stilbene), which may reflect the higher intrinsic reactivity of Fe-based systems. Further studies, aimed at the examination of reactivity of different active intermediates toward oxidation of alkanes are in progress in our laboratory.

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 *E-mail: [email protected], [email protected]

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 (#16-29-10666). 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).

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ENTRY FOR THE TABLE OF CONTENTS


33

Iron-Catalyzed Enantioselective Epoxidations with Various Oxidants

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