A chiral iron-sexipyridine complex as a catalyst for alkene epoxidation with hydrogen peroxide

Article abstract of DOI:10.1039/b804281k

A chiral iron-sexipyridine complex-hydrogen peroxide mixture is a highly efficient catalytic system for styrene epoxidation with excellent reactivity (3 min, 95% yield) and chemoselectivity (98%). The Royal Society of Chemistry.

Full text of DOI:10.1039/b804281k

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A chiral iron-sexipyridine complex as a catalyst for alkene epoxidation
with hydrogen peroxidew
Ho-Lun Yeung, Kiu-Chor Sham, Chui-Shan Tsang, Tai-Chu Lau and
Hoi-Lun Kwong*
Received (in Cambridge, UK) 12th March 2008, Accepted 22nd May 2008
First published as an Advance Article on the web 2nd July 2008
DOI: 10.1039/b804281k
A chiral iron-sexipyridine complex–hydrogen peroxide mixture
is a highly efficient catalytic system for styrene epoxidation with
excellent reactivity (3 min, 95% yield) and chemoselectivity
(98%).
Iron complexes have been extensively studied as models for non-
heme iron oxygenases1 and as catalysts for oxidation of organic
substrates.2 Among the commonly used terminal oxidants,3
hydrogen peroxide has received much attention because it is
environmentally friendly and biologically important.4 Hence the
toluene–MeOH–H2O, 40%; (ii) hydrated NiCl2, PPh3, Zn, DMF, 25%.
Scheme 1 (i) Pd(PPh3)4, 6-bromo-2-pyridineboronic acid, Na2CO3,
development of iron-based catalysts that utilize hydrogen per-
oxide as the terminal oxidant is a very active research area.5
Since iron catalysts bearing 2,20-bipyridine, 1,10-phenan-
throline and their derivatives have been demonstrated to be
active oxidation catalysts,3f,6 we are interested in investigating
iron complexes of oligopyridines. Herein, we report the synth-
esis of a novel chiral sexipyridine ligand L and the use of its
iron complex as an active catalyst for alkene epoxidation using
H2O2 as the terminal oxidant.
Ligand L was readily prepared by a Ni-catalyzed homocoupling
reaction of a bromo-substituted terpyridine, which was obtained
from Pd-catalyzed Suzuki-coupling of 6-bromo-2-pyridineboronic
acid with a bromo-substituted bipyridine (Scheme 1).z Reaction of
FeCl2 with L in a molar ratio of 2 : 1 afforded the binuclear species
[Fe2O(L)Cl4], which was isolated as a deep red air stable solid
(85% yield) and was characterized by elemental analysis and ESI-
Fig. 1 ESI-MS spectrum of [Fe2O(L)Cl4] in CH2Cl2. The insets show
MS. The ESI mass spectrum of [Fe2O(L)Cl4] exhibits a parent
peak at m/z 879 of formula [Fe2O(L)Cl2]+ and there is excellent
experimental and simulated isotopic distribution patterns of
[Fe2O(L)Cl2]+
.
agreement between the experimental and calculated iron isotopic
mass distributions for each peak (Fig. 1).
temperature, showed 75% incorporation of 18O within the
starting complex after 45 min, also suggesting the presence of a
m-oxo species. Although attempts to obtain single crystals
suitable for X-ray crystallography were unsuccessful, preli-
minary MM2 modeling studies suggest that the single-
stranded helical structure for [Fe2O(L)Cl4] is feasible.
The CD spectrum of [Fe2O(L)Cl4] (2.5 ꢁ 10ꢀ5 M) shows
medium to strong absorptions (Cotton effect) at 270–420 nm
(Fig. 3), suggesting a helical nature for the complex. Although
The proposed structure of the [Fe2O(L)Cl4] complex is
shown in Fig. 2. The molar conductivity of [Fe2O(L)Cl4] in
CH3CN is 95 Oꢀ1 cm2 molꢀ1, which is below the range
120–160 Oꢀ1 cm2 molꢀ1 for 1 : 1 electrolytes in CH3CN. This
suggests that the compound is neutral in the solid state but
substantial chloride dissociation occurs in CH3CN to give
[Fe2O(L)Cl3(CH3CN)]+. The UV-vis spectrum (in CH2Cl2)
shows a strong absorption band at 358 nm (e = 11 000 Mꢀ1
cmꢀ1) and a shoulder at 510 nm (e = 450 Mꢀ1 cmꢀ1),w which
are characteristic for diiron(III) (m-oxo) complexes.7,8 An iso-
tope exchange experiment of [Fe2O(L)Cl4] with H218O, carried
out by mixing a 1 : 1 ratio of H218O and CH3CN at ambient
Department of Biology and Chemistry, City University of Hong Kong,
Tat Chee Avenue, Kowloon, Hong Kong SAR, China. E-mail:
bhhoik@cityu.edu.hk; Fax: +852 2788 4706; Tel: +852 2788 7304
w Electronic supplementary information (ESI) available: UV-Vis spec-
trum of iron complex [Fe2O(L)Cl4]. See DOI: 10.1039/b804281k
Fig. 2 Proposed structure of [Fe2O(L)Cl4].
Chem. Commun., 2008, 3801–3803 | 3801
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Table 1 Epoxidations catalyzed by [Fe2O(L)Cl4]a
Entry Time/min Temperature/1C Conversion (%)b Selectivity (%)b
1
2c
3
4
5
6
7
a
3
3
3
3
3
3
3
Rt
Rt
0
ꢀ10
ꢀ20
ꢀ30
ꢀ40
76
70
100
75
64
40
24
79
72
98
64
68
66
68
Fig. 3 CD spectrum of [Fe2O(L)Cl4] in CH2Cl2.
Reaction conditions: olefin (0.14 mmol, 0.22
M in CH3CN),
[Fe2O(L)Cl4] (2.0 mol%), acetic acid (10 equiv. to catalyst), H2O2
b
(aqueous 35 wt%, 0.21 mmol, 1.5 M in CH3CN). Determined by
a double helical complex is formed between Fe(II) and achiral
sexipyridine,9 in this case the ESI-MS result is more consistent
with a single helical structure for [Fe2O(L)Cl4]. A single helical
complex of Zn2+ having a m-oxo and a dimethyl quinque-
pyridine ligand has been reported previously.10
c
GC-FID. No acetic acid added.
Table 2 Asymmetric epoxidations catalyzed by [Fe2O(L)Cl4]a
The efficiency of the iron-sexipyridine complex as a catalyst for
the epoxidation of styrene with H2O2 was investigated using the
conditions reported by Jacobsen et al.,5e i.e. in CH3CN in the
presence of CH3CO2H. Complex [Fe2O(L)Cl4] afforded, within
3 min at room temperature, 76% conversion and 79% selectivity
of styrene oxide, with 12% benzaldehyde and 9% phenylacetal-
dehyde as side products (Table 1, entry 1). The absence of acetic
acid resulted in slightly lower yields and selectivity for the epoxide
(Table 1, entry 2); this effect was also observed in other iron
catalytic systems.5e,11 Remarkably, at 0 1C, the catalytic oxidation
reached 100% conversion in 3 min with 98% epoxide selectivity
(Table 1, entry 3). However, further decrease in temperature to
between ꢀ10 to ꢀ40 1C did not lead to an increase in conversion
and selectivity. The epoxidation was ineffective when CH2Cl2 was
used instead of CH3CN. No epoxide was formed when peracetic
acid was used as the terminal oxidant indicating the in situ
formation of peracetic acid from H2O2 and acetic acid is not
responsible for the oxidation and implying a different role of
acetic acid. Use of benzoic acid (yield: 91%; selectivity: 88%),
propionic acid (yield: 84%; selectivity: 87%) or potassium acetate
(yield: 75%; selectivity: 84%) showed generally good results, but
not as good as acetic acid. Thus, the best conditions are 2 mol%
catalyst, 1.5 equiv. of H2O2, 10 equiv. of acetic acid in CH3CN at
0 1C; under these conditions complete conversion of styrene to
styrene oxide with 98% selectivity occurs within 3 min.
Conversion Selectivity Yield
(%)b
Entry Alkene
1
(%)b
(%)b
% eec
100
98
95
43 (R)
2e
100
100
100
15 (R)
3e
4
100
95
100
95
100
90
30 (R)
42 (R)d
17 (R)d
5
94
85
80
6
7
56
94
57
90
52
96
—
37
(1R,2S)
8
62
53
78
100
55
100
50
40
(1S,2R)d
To improve the practicability of the reaction, the integrity of
ligand L after oxidation was examined. We were able to recover
88% of the ligand by treating the reaction mixture with aqueous
Na2EDTA (EDTA = ethylenediaminetetraacetic acid). Thus,
regeneration of the catalyst is possible by simply adding 2 equiv.
of FeCl2 to a CH3CN solution. Successive epoxidations carried
out with this process gave albeit 10% lower yield in each cycle,
but maintained very high selectivity for epoxide (90–95%).
To explore the substrate scope of this epoxidation reaction,
different terminal alkenes and 1,2-disubstituted alkenes were
examined (Table 2). A wide range of terminal alkenes proved
to be excellent substrates for epoxidation with [Fe2O(L)Cl4]
(53–100% conversion in 3 min). Electron-rich substrates such
as 4-methoxystyrene and 4-methylstyrene were efficiently epox-
idized with TON of up to 83 (Table 2, entries 2 and 3). Good
9
31
(1R,2S)d
10f
75
95
ND
a
Reaction conditions: alkene (0.14 mmol, 0.22 M in CH3CN), [Fe2O(L)-
Cl4] (2.0 mol%), CH3CO2H (10 equiv. to catalyst), H2O2 (aqueous 35
b
wt%, 0.21 mmol, 1.5 M in CH3CN), 0 1C, 3 min. Determined by GC-
FID. Determined by GC with a Cyclodex-B chiral column or HPLC
c
with a Daicel Chiralcel OD column. d The absolute configuration was
determined by comparing the order of elution with that of a sample with
e
f
known configuration. Use 1.2 mol%. No diepoxide product was
detected.
ꢂc
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J = 8.1 Hz), 8.54 (d, 2H, J = 7.8 Hz), 8.66–8.74 (m, 6H); ESI-MS m/z:
681 (M + H)+. Fe2O(L)Cl4: 1H NMR spectrum showed paramagnetic in
nature. IR (KBr) umax (cmꢀ1): 540 (m), 831 (m), 1096 (s), 1564 (s), 2922 (s);
ESI-MS m/z: 879 [Fe2O(L)Cl2]1+; anal. calcd for C46H44N8Fe2OCl4: C,
50.98; H, 4.56; N, 7.34. Found: C, 50.64; H, 4.44; N, 7.38%.
yields of epoxides were also obtained from electron-deficient
styrenes (Table 2, entry 4). On the other hand, the catalytic
oxidation is greatly affected by steric effects, which presumably
is due to the bulkiness of the iron catalyst. For example, a-
methylstyrene gave lower epoxide yield and selectivity than
styrene (Table 2, entry 5), and replacing the a-methyl group
by a phenyl group leads to even lower yield (52%) and selectivity
(57%) (Table 2, entry 6). Similarly, b-substituted styrenes gave
lower yields than styrene (Table 2, entries 7–9). Apart from
aromatic alkenes, cyclooctadiene was also efficiently epoxidized
(Table 2, entry 10). On the other hand, aliphatic alkenes such as
1-heptene were unreactive. All epoxide products were stable
under the acidic conditions used and no acid-catalyzed ring
opening of the epoxides formed was observed.
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9 : 1 preference for the former substrate. A Hammett plot with
good linearity, correlated to s+ with r = ꢀ1.04, was observed,
indicating the electrophilic nature of the active oxidant. Similar
observations have been reported with other diiron (m-oxo)
catalysts.3f,12 The retention in stereochemistry of the epoxide
products of cis-b-methylstyrene and trans-b-methylstyrene sup-
ports a non-radical oxidation process. It is noteworthy that
non-heme iron system, [Fe2(m-O)(m-CH3CO2)(mep)] (mep =
N,N0-dimethyl-N,N0-bis(2-pyridylmethyl)ethane-1,2-diamine),
reported by Jacobsen and co-workers,5e is so far the most efficient
catalyst for epoxidation of aliphatic alkenes using H2O2 as the
terminal oxidant. The results obtained here show that the rate of
epoxidation using [Fe2O(L)Cl4] is comparable to that of [Fe2(m-
O)(m-CH3CO2)(mep)]. Since [Fe2O(L)Cl4] is good for aromatic
substrates, this catalyst is complementary to the Jacobsen catalyst.
A good to high level of enantioselectivities has been achieved in
the asymmetric epoxidation with H2O2 as terminal oxidant.13
However, only a few non-heme iron–H2O2 systems are able to
catalyze asymmetric epoxidation, and in general they give low
enantioselectivities (around 20% ee). The highest enantioselec-
tivity (82%, for a trans-stilbene substrate) was recently reported
by Beller et al.5f A high ee was also observed in Fe-catalyzed
asymmetric sulfur oxidation using H2O2.5h In our studies,
although the ees of the epoxides are modest, (15 to 43%), the
ee for epoxidation of b-methylstyrene (37%) is comparable to
that obtained using Beller’s catalyst (28%).
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In summary, a new class of iron catalyst based on sexipyr-
idines for epoxidation using H2O2 has been explored. The diiron
system shows excellent reactivity and selectivity towards term-
inal and 1,2-disubstituted aromatic alkenes. Further modifica-
tion of the ligand to achieve better enantioselectivities and
understanding of the nature of the active intermediates are
under active investigation in our laboratory.
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Financial support for this research project from the Hong
Kong research grants council CERG grant (CityU 101104)
and CAV grant (8730025) and the City University of Hong
Kong is gratefully acknowledged.
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Notes and references
z L: 1H NMR (300 MHz, CDCl3): d 0.71 (s, 6H), 1.37 (d, 2H), 1.46 (s, 6H),
1.53 (d, 6H), 2.21–2.23 (m, 2H), 2.60–2.64 (m, 2H), 2.85–2.96 (m, 2H), 3.38
(m, 2H), 7.37–7.40 (d, 2H, J = 7.8 Hz), 7.97–8.07 (m, 4H), 8.34 (d, 2H,
ꢂc
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Chem. Commun., 2008, 3801–3803 | 3803