An improved iron-catalyzed epoxidation of aromatic and aliphatic olefins with hydrogen peroxide as oxidant

Article abstract of DOI:10.1002/ejoc.200800712

A convenient and practical method for the iron-catalyzed epoxidation of aromatic and aliphatic olefins is described. The iron catalyst system is generated in situ from iron trichloride hexahydrate, pyridine-2,6-dicarboxylic acid (H₂pydic), and benzylamines. By variation of the benzylamine ligand, a variety of aliphatic and aromatic olefins were oxidized in high yield (up to 96%) and good-to-excellent selectivity in the presence of hydrogen peroxide as the terminal oxidant. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.

Full text of DOI:10.1002/ejoc.200800712

SHORT COMMUNICATION
DOI: 10.1002/ejoc.200800712
An Improved Iron-Catalyzed Epoxidation of Aromatic and Aliphatic Olefins
with Hydrogen Peroxide as Oxidant
Bianca Bitterlich,[a] Kristin Schröder,[a] Man Kin Tse,[a,b] and Matthias Beller*[a,b]
Keywords: Epoxidation / Alkenes / Iron / Hydrogen peroxide / Homogeneous catalysis
A convenient and practical method for the iron-catalyzed
epoxidation of aromatic and aliphatic olefins is described.
The iron catalyst system is generated in situ from iron trichlo-
ride hexahydrate, pyridine-2,6-dicarboxylic acid (H2pydic),
and benzylamines. By variation of the benzylamine ligand, a
variety of aliphatic and aromatic olefins were oxidized in
high yield (up to 96%) and good-to-excellent selectivity in
the presence of hydrogen peroxide as the terminal oxidant.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2008)
Introduction
Results and Discussion
The epoxidation of olefins is an important synthetic
method in organic chemistry as well as for the chemical
industry. With respect to generality, it still remains challeng-
ing to discover catalytic epoxidations that allow efficient
and selective reactions for both aromatic and aliphatic ole-
fins.[1,2] In general, state-of-the-art epoxidations should run
under environmentally benign reaction conditions with in-
expensive catalysts by using sustainable terminal oxidants
and simple operation protocols.[3] Traditionally, stoichio-
metric oxidants such as organic peracids have been applied
in epoxidation reactions.[4] More recently, hydrogen perox-
ide has become one of the terminal oxidants of choice, be-
cause it produces only water as a byproduct and is advan-
tageous regarding costs, safety, and storage.[5] With regard
to catalysts, the use of Fe- or Mn-based complexes is at-
tractive due to their price and low toxicity.[6,7] On the basis
of ruthenium-catalyzed epoxidation of olefins with hydro-
gen peroxide,[8] we found that FeCl3·6H2O in combination
with pyridine-2,6-dicarboxylic acid and pyrrolidine shows
high reactivity and selectivity towards the epoxidation of
mono- and disubstituted aromatic olefins.[9] Unfortunately,
aliphatic olefins and highly substituted aromatic olefins
were less reactive and selective under the conditions of our
previous system. Hence, we are interested in improved Fe-
catalyzed epoxidations, which can be applied to all classes
of olefins.
The key to the success of the Fe-catalyzed epoxidation is
the use of pyridine-2,6-dicarboxylic acid (H2pydic) as li-
gand. By studying the effect of the organic coligand on the
epoxidation of cyclooctene as a model substrate, we ob-
served a strong influence on the reactivity.
In Table 1 a small selection of the tested amines is shown.
To our delight, the yield of cyclooctene oxide is improved
from 4% (without ligand) up to 89% in the presence of
N-(diphenylmethyl)methylamine (Table 1, entries 1 and 7).
Notably, also our standard base pyrrolidine gave a signifi-
cantly lower yield (16%) and selectivity with respect to
epoxidation (Table 1, entry 2). Interestingly, in comparison
to previous investigations the epoxidation of trans-stilbene
with these amines did not display apparent differences in
reactivity.[10] This can be attributed to the high reactivity of
trans-stilbene. Hence, differences in the amine coligands did
not show a significant influence on the reactivity. De novo
analysis of the structural motif indicates that benzylamine is
the important element in order to achieve high conversion.
Strong coordinative 2-picolylamine gave inferior results
as compared to benzylamine (Table 1, entries 5 and
8).[6a,6b,6d,6e] Slow dosing of hydrogen peroxide to the sys-
tem increased the yield but is not the crucial factor. In fact,
the addition of hydrogen peroxide can be performed within
seconds, and cyclooctene oxide is obtained in 75% yield at
88% conversion. Further investigations on the concentra-
tion of the ligands showed 10 to 15 mol-% of the amine to
be optimum. For better comparison and general applica-
bility, the H2O2 addition time (1 h) and the amine concen-
tration (12 mol-%) were maintained for all experiments. Re-
placement of H2pydic with picolinic acid or quinaldic acid
or the use of other iron sources resulted in a total loss of
reactivity. Apparently, the H2pydic component is essential
in this system.[11]
Herein, we report the development of a general method
for the epoxidation of a broad scope of olefins with hydro-
gen peroxide.
[a] Leibniz-Institut für Katalyse e.V. an der Universität Rostock,
Albert-Einstein-Straße 29a, 18059 Rostock, Germany
Fax: +49-381-1281-5000
E-mail: matthias.beller@catalysis.de
[b] Center for Life Science Automation, Universität Rostock,
Friedrich-Barnewitz-Straße 8, 18119 Rostock, Germany
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B. Bitterlich, K. Schröder, M. K. Tse, M. Beller
SHORT COMMUNICATION
Table 1. Effect of the amine coligand on the epoxidation of cyclooc-
tene.[a]
Scheme 1. Epoxidation of olefins with benzylamine derivatives 1.
Table 2. Epoxidation of aromatic olefins with benzylamine deriva-
tive 1.[a]
[a] Reaction conditions: In a test tube, FeCl3·6H2O (0.025 mmol),
H2pydic (0.025 mmol), tert-amyl alcohol (9 mL), amine
(0.060 mmol), cyclooctene (0.50 mmol), and dodecane (GC in-
ternal standard, 100 µL) were added in sequence at r.t. in air. To
this mixture was added a solution of 30% hydrogen peroxide
(114 µL, 1.0 mmol) in tert-amyl alcohol (886 µL) over a period of
1 h at r.t. by syringe pump. [b] Conversion and yield were deter-
mined by GC analysis. [c] Selectivity refers to the chemoselectivity
of epoxide from olefin. [d] Addition of hydrogen peroxide within
some seconds.
[a] Reaction conditions: In a test tube, FeCl3·6H2O (0.025 mmol),
H2pydic (0.025 mmol), tert-amyl alcohol (9 mL), amine
(0.060 mmol), olefin (0.50 mmol), and dodecane (GC internal stan-
dard, 100 µL) were added in sequence at r.t. in air. To this mixture
was added
a solution of 30% hydrogen peroxide (114 µL,
As shown in Table 1, it appears that benzylamine is a
preferred structural element for the epoxidation of cyclooc-
tene (Table 1, entries 5 to 7). For this reason we tested a
selection of various commercially available benzylamines
for the epoxidation of different classes of aromatic and ali-
1.0 mmol) in tert-amyl alcohol (886 µL) over a period of 1 h at r.t.
by syringe pump. [b] Conversion and yield were determined by GC
analysis. [c] Selectivity refers to the chemoselectivity of epoxide
from olefin.
phatic olefins (Scheme 1). Table 2 shows the epoxidation re- and 2-methyl-1-phenyl-1-propene (Table 2, entry 4; from 16
sults for different substituted aromatic olefins. By applying to 37% yield, respectively) in comparison to our previous
the novel protocol, we could maintain the high reactivity system. However, the tetrasubstituted olefin 2-methyl-3-
and selectivity toward trans-stilbene and styrene as com- phenyl-2-butene gave no corresponding epoxide (Table 2,
pared to our previous pyrrolidine system (Table 2, entries 1 entry 6).
and 3). Even though active catalysts for aliphatic olefins
Aliphatic olefins work particularly well with the new cat-
often lead to subsequent over oxidation reactions of the alyst system (Table 3). Internal olefins like trans-2-octene
much-more reactive aromatic olefins, the benzylamine/ (Table 3, entry 1) and trans-5-decene (Table 3, entry 2) were
H2pydic/FeCl3 system gives a general activity and good oxidized in high yield and selectivity. Trisubstituted 2-
selectivity with respect to epoxidation in both of these methyl-2-heptene (Table 3, entry 3) and cyclic olefins
classes of olefins.
(Table 3, entries 4 and 5) gave the corresponding epoxides
Epoxidation of cis-stilbene proceeded in 24% yield in in good yield. Terminal olefins are intrinsically poorly reac-
comparison to 8% yield with the pyrrolidine-based sys- tive substrates and catalytic methods for their epoxidation
tem.[10] In addition, we could also increase the yields for are limited.[6,7,12] Our system afforded 32% yield of 1-oc-
trisubstituted aromatic olefins such as trans-β-methylstil- tene oxide, whereas 2-methyl-2-heptene was oxidized in
bene (Table 2, entry 5; from 21 to 68% yield, respectively) 58% yield (Table 3, entries 6 and 7). Moreover, the iron cat-
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Iron-Catalyzed Epoxidation of Aromatic and Aliphatic Olefins
alyst system showed good chemoselectivity towards olefins with hydrogen peroxide as the terminal oxidant. The simple
in the presence of hydroxy and carboxyl groups (Table 3, and practical catalyst system consists of iron trichloride
entries 8 and 9).
hexahydrate, pyridine-2,6-dicarboxylic acid, and a benzyla-
mine derivative. It was demonstrated that benzylamine is a
preferred structural element for the coligand in this general
epoxidation of aromatic and aliphatic olefins. The system
showed good-to-excellent reactivity to mono-, di-, and tri-
substituted aromatic olefins, as well as to internal di- and
trisubstituted and functionalized aliphatic olefins. Note-
worthy is that inactive aliphatic olefins can be oxidized in
up to 96% yield. Currently, further efforts are underway
to improve the protocol for tetrasubstituted aromatic and
monosubstituted terminal aliphatic olefins and to investi-
gate the mechanistic aspects of this reaction.
Table 3. Fe-catalyzed epoxidation of aliphatic olefins with benzyl-
amine derivative 1.[a]
Experimental Section
General Remarks: All reagents were used as purchased from com-
mercial suppliers (Aldrich, Fluka, Merck, etc.) without further pu-
rification. 2-Methyl-3-phenyl-but-2-ene (Table 2, entry 6) was syn-
thesized according to literature procedures.[14] “30%” aqueous
H2O2 from Merck was used as received. The peroxide content var-
ied from 30% to 40% as determined by titration. GC analyses were
performed with a Hewlett Packard HP 6890 model spectrometer.
GC calibrations for alkenes and epoxides were carried out with
authentic samples and dodecane as an internal standard.
General Procedure for the Epoxidation of Olefins: In a test tube,
FeCl3·6H2O (0.025 mmol), H2pydic (0.025 mmol), tert-amyl
alcohol (9 mL), amine (0.060 mmol), olefin (0.50 mmol) and do-
decane (GC internal standard, 100 µL) were added in sequence at
r.t. in air. To this mixture was added a solution of 30% hydrogen
peroxide (aqueous, 114 µL, 1.0 mmol) in tert-amyl alcohol (886 µL)
over a period of 1 h at room temperature by syringe pump. Conver-
sion and yield were determined by GC analysis without further
manipulations.
[a] Reaction conditions: In a tube, FeCl3·6H2O (0.025 mmol),
H2pydic (0.025 mmol), tert-amyl alcohol (9 mL), amine
(0.060 mmol), olefin (0.50 mmol), and dodecane (GC internal stan-
dard, 100 µL) were added in sequence at r.t. in air. To this mixture
was added
a solution of 30% hydrogen peroxide (114 µL,
Acknowledgments
1.0 mmol) in tert-amyl alcohol (886 µL) over a period of 1 h at r.t.
by syringe pump. [b] Conversion and yield were determined by GC
analysis. [c] Selectivity refers to the chemoselectivity of epoxide
from olefin.
We thank the State of Mecklenburg-Western Pommerania, the Fed-
eral Ministry of Education and Research (BMBF), and the Deut-
sche Forschungsgemeinschaft (SPP 1118 and Leibniz-prize) for fin-
ancial support. Mrs. M. Heyken, Mr. H.-M. Kaiser, Dr. Feng Shi,
Mr. Naveenkumar Mangu, and Dr. Anirban Khar (LIKAT) are
acknowledged for their valuable support in the laboratory.
Acetic acid is a well-known additive for the epoxidation
of olefins with hydrogen peroxide by in situ formation of
peracetic acid.[13] In contrast, addition of certain amounts
of acetic acid to our catalyst system inhibited the conver-
sion of 1-octene. Furthermore, to exclude the possibility of
in situ formation of the alkyl hydroperoxide from tert-amyl
alcohol, we used tert-BuOOH (70% aqueous) as an oxidant
instead of hydrogen peroxide. Again no reactivity was ob-
served for the epoxidation of cyclooctene. This indicates
that tert-amyl hydroperoxide is not likely to be involved in
the reaction and hydrogen peroxide is the only terminal oxi-
dant in our system.
[1] a) L. P. C. Nielsen, E. N. Jacobsen in Aziridines and Epoxides in
Organic Synthesis (Ed.: A. K. Yudin), Wiley-VCH, Weinheim,
2006, pp. 229–269; b) H. Adolfsson, D. Balan in Aziridines and
Epoxides in Organic Synthesis (Ed.: A. K. Yudin), Wiley-VCH,
Weinheim, 2006, pp. 185–228; c) J.-E. Bäckvall (Ed.), Modern
Oxidation Methods, Wiley-VCH, Weinheim, 2004; d) M. Beller,
C. Bolm (Eds.), Transition Metals for Organic Synthesis Build-
ing Blocks and Fine Chemicals, 2nd ed., Wiley-VCH, Weinheim,
2004, vol. 1 and 2; e) E. N. Jacobsen, M. H. Wu in Comprehen-
sive Asymmetric Catalysis Vol. 3: Ring Opening of Epoxides and
Related Reactions (Eds.: E. N. Jacobsen, A. Pfaltz, H. Yamam-
oto), 1999, pp. 1309–1326.
Conclusions
[2] For recent examples of homogeneous metal-catalyzed epoxid-
ation of olefins, see: a) M. Colladon, A. Scarso, P. Sgarbossa,
R. A. Michelin, G. Strukul, J. Am. Chem. Soc. 2007, 129, 7680–
7689; b) Y. Mahha, L. Salles, J.-Y. Piquemal, E. Briot, A. At-
In conclusion, we developed an improved iron-catalyzed
epoxidation, which can be performed under mild conditions
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B. Bitterlich, K. Schröder, M. K. Tse, M. Beller
SHORT COMMUNICATION
lamsani, J.-M. Brégeault, J. Catal. 2007, 249, 338–348; c) M.
Colladon, A. Scarso, P. Sgarbossa, R. A. Michelin, G. Strukul,
J. Am. Chem. Soc. 2006, 128, 14006–14007; d) K. Kamata, K.
Yonehara, Y. Sumida, K. Yamaguchi, S. Hikichi, N. Mizuno,
Science 2003, 300, 964–966; e) X. Zuwei, Z. Ning, S. Yu, L.
Kunlan, Science 2001, 292, 1139–1141.
Kim, J. Lee, Y. Do, S. Chang, J. Org. Chem. 2006, 71, 6721–
6727; c) A. Murphy, A. Pace, T. D. P. Stack, Org. Lett. 2004,
6, 3119–3122; d) A. Murphy, G. Dubois, T. D. P. Stack, J. Am.
Chem. Soc. 2003, 125, 5250–5251.
[8]
a) M. K. Tse, S. Bhor, M. Klawonn, G. Anilkumar, H. Jiao, C.
Döbler, A. Spannenberg, W. Mägerlein, H. Hugl, M. Beller,
Chem. Eur. J. 2006, 12, 1855–1874; b) M. K. Tse, S. Bhor, M.
Klawonn, G. Anilkumar, H. Jiao, A. Spannenberg, C. Döbler,
W. M ägerlein, H. Hugl, M. Beller, Chem. Eur. J. 2006, 12,
1875–1888; c) M. K. Tse, M. Klawonn, S. Bhor, C. Döbler, G.
Anilkumar, H. Hugl, W. Mägerlein, M. Beller, Org. Lett. 2005,
7, 987–990; d) M. K. Tse, C. Döbler, S. Bhor, M. Klawonn, W.
Mägerlein, H. Hugl, M. Beller, Angew. Chem. Int. Ed. 2004,
43, 5255–5260; e) S. Bhor, G. Anilkumar, M. K. Tse, M. Kla-
wonn, C. Döbler, B. Bitterlich, A. Grotevendt, M. Beller, Org.
Lett. 2005, 7, 3393–3396; f) G. Anilkumar, S. Bhor, M. K. Tse,
M. Klawonn, B. Bitterlich, M. Beller, Tetrahedron: Asymmetry
2005, 16, 3536.
[3] For reviews on metal-catalyzed epoxidation, see: a) G. Grigoro-
poulou, J. H. Clark, J. A. Elings, Green Chem. 2003, 5, 1–7; b)
B. S. Lane, K. Burgess, Chem. Rev. 2003, 103, 2457–2473; c)
K. A. Jørgensen, Chem. Rev. 1989, 89, 431–458; for a commen-
tary, see: d) M. Beller, Adv. Synth. Catal. 2004, 346, 107–108.
[4] Examples using peracids for olefin epoxidation: a) K. Craw-
ford, V. Rautenstrauch, A. Uijttewaal, Synlett 2001, 1127–
1128; b) U. Wahren, I. Sprung, K. Schulze, M. Findeisen, G.
Buchbauer, Tetrahedron Lett. 1999, 40, 5991–5992; c) D. R.
Kelly, J. Nally, Tetrahedron Lett. 1999, 40, 3251–3254.
[5] a) C. W. Jones, Applications of Hydrogen Peroxide and Deriva-
tives, Royal Society of Chemistry, Cambridge, 1999; b) G.
Struku (Ed.), Catalytic Oxidations with Hydrogen Peroxide as
Oxidant, Kluwer Academic, Dordrecht, 1992.
[9]
G. Anilkumar, B. Bitterlich, F. G. Gelalcha, M. K. Tse, M.
Beller, Chem. Commun. 2007, 289–291.
[6] For recent examples of iron-catalyzed epoxidations, see: a) S.
Taktak, W. Ye, A. M. Herrera, E. V. Rybak-Akimova, Inorg.
Chem. 2007, 46, 2929–2942; b) M. R. Bukowski, P. Comba, A.
Lienke, C. Limberg, C. Lopez de Laorden, R. Mas-Ballesté, M.
Merz, L. Que Jr., Angew. Chem. Int. Ed. 2006, 45, 3446–3449;
c) G. Dubois, A. Murphy, T. D. P. Stack, Org. Lett. 2003, 5,
2469–2472; d) K. Chen, M. Costas, J. Kim, A. T. Tipton, L.
Que Jr., J. Am. Chem. Soc. 2002, 124, 3026–3035; e) M. C.
White, A. G. Doyle, E. N. Jacobsen, J. Am. Chem. Soc. 2001,
123, 7194–7195; for an excellent review on iron-based catalysts
see: f) C. Bolm, J. Legros, J. Le Paih, L. Zani, Chem. Rev. 2004,
104, 6217–6254.
[10]
B. Bitterlich, G. Anilkumar, F. G. Gelalcha, B. Spilker, A. Gro-
tevendt, R. Jackstell, M. K. Tse, M. Beller, Chem. Asian J.
2007, 2, 521–529.
K. Schröder, X. Tong, B. Bitterlich, M. K. Tse, F. G. Gelalcha,
A. Brückner, M. Beller, Tetrahedron Lett. 2007, 48, 6339–6342.
M. Klawonn, M. K. Tse, S. Bohr, C. Döbler, M. Beller, J. Mol.
Catal. A 2004, 218, 13.
a) R. Mas-Ballesté, L. Que Jr., J. Am. Chem. Soc. 2007, 129,
15964–15972; b) M. Fujita, L. Que Jr., Adv. Synth. Catal. 2004,
346, 190–194.
[11]
[12]
[13]
[14]
G. A. Olah, A.-h. Wu, O. Farooq, G. K. S. Prakash, J. Org.
Chem. 1990, 55, 1792–1796.
[7] For recent examples of manganese-catalyzed epoxidations, see:
a) I. Garcia-Bosch, A. Company, X. Fontrodona, M. Costas,
Org. Lett. 2008, DOI: 10.1021/ol800329m; b) B. Kang, M.
Received: July 17, 2008
Published Online: September 2, 2008
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Eur. J. Org. Chem. 2008, 4867–4870