Development of a Ruthenium-Catalyzed Asymmetric Epoxidation Procedure with Hydrogen Peroxide as the Oxidant

Full text of DOI:10.1002/anie.200460528

Angewandte
Chemie
Homogeneous Catalysis
For the enantioselective epoxidations of olefins to date
transition-metal complexes based on titanium (Sharpless
[
12]
Development of a Ruthenium-Catalyzed
Asymmetric Epoxidation Procedure with
Hydrogen Peroxide as the Oxidant**
epoxidation) and manganese (Jacobsen–Katsuki epoxida-
[
13]
tion) have been the most successful catalysts. In addition,
significant progress using organic catalysts based on chiral
ketones (ketone catalysts from Shi, Yang, and co-work-
[
14,15]
ers)
was reported recently. However, in spite of extensive
Man Kin Tse, Christian Döbler, Santosh Bhor,
Markus Klawonn, Wolfgang Mägerlein, Herbert Hugl,
and Matthias Beller*
research efforts, the development of a general and catalytic
asymmetric-epoxidation method using H O has not been
2
2
[
16]
achieved.
Herein we report the development of a new
catalytic asymmetric-oxidation method that uses H O in the
2
2
The need of environmentally benign and clean oxidation
reactions remains an important goal of chemical research.
Although oxidation reactions constitute core technologies for
presence of ruthenium complexes, allows for general epox-
idation of olefins in high yield with ee values up to 84%, and is
simple to employ. In addition a novel class of chiral tridentate
ligands (pyboxazines) is presented.
We looked for ruthenium complexes with a combina-
tion of two meridional ligands which should provide the
ability to tune both the activity and the asymmetric induction
of the catalyst separately. Therefore, we chose the ruthenium
[
1]
converting bulk chemicals into useful higher-value products,
[
17]
they are among the more problematic processes with regard
to general usage. Even today most of the known textbook
[
2]
oxidation methods lead to a significant amount of waste and
therefore should be avoided. Criteria for state-of-the-art
oxidation technologies should include high atom economy
and selectivity, broad substrate scope, usage of environ-
mentally benign oxidation reagents, and sufficient catalyst
stability and productivity. By comparing different oxidation
methods, it is apparent that the oxidant used in the respective
transformation defines the quality and applicability of the
method. Clearly, molecular oxygen is the most ideal oxidant
(R pybox)(pyridinedicarboxylate) complex 1 (pybox = 2,6-di-
2
4,5-dihydro-1,3-oxazol-2-yl pyridine) which has been
reported by Nishiyama et al. to catalyze the epoxidation of
trans-stilbene in the presence of PhI(OAc) as the stoichio-
2
[
18]
metric oxidant. Although transition-metal complexes rap-
idly decompose H O , we thought after initial tests with
RuCl /2,6-pyridinedicarboxylic acid that it should be pos-
[
19]
2
2
[
20]
3
[
3]
for a number of oxidation reactions. However, mostly only
one oxygen atom of an oxygen molecule is used productively
sible to tune complex 1 to a more general asymmetric
epoxidation catalyst with H O (Scheme 1).
2
2
[
4,5]
for oxidation (50% atom efficiency),
thus at least stoi-
chiometric amounts of unwanted by-products are generated
during the reactions. One of the few examples in which both
oxygen atoms are used efficiently is the aerobic dihydroxy-
[
6,7]
lation of olefins, which we developed some time ago. Apart
from molecular oxygen, hydrogen peroxide is an environ-
mentally benign oxidant, which theoretically generates only
[
8]
water as a by-product. Also it is advantageous compared to
other oxidants because of the availability and low price
À1
[9]
(
< 0.6 Ekg of 100% H O ). Owing to its characteristic
2 2
physical properties H O is particularly useful for liquid-phase
2
2
oxidations for the synthesis of fine chemicals, pharmaceut-
icals, agrochemicals, and electronic materials. Hence, the
discovery of new catalysts using H O is an important goal in
2
2
[
10,11]
oxidation chemistry.
Scheme 1. Strategy of catalyst design.
[
*] Dr. M. K. Tse, Dr. C. Döbler, Dipl.-Chem. S. Bhor,
Dipl.-Chem. M. Klawonn, Prof. Dr. M. Beller
Leibniz-Institut für Organische Katalyse (IfOK)
Universität Rostock e.V.
Buchbinderstrasse 5–6, 18055 Rostock (Germany)
Fax: (+49)381-466-9324
Clearly, the enantioselective induction could be controlled
by the readily accessible pybox or new pyboxazine type
ligands (pyboxazine = 2,2’-pyridine-2,6-diyl bis(5,6-dihydro-
4H-1,3-oxazine)), which can be synthesized from commer-
[21]
cially available a- or b-amino acids. Changing the donating
E-mail: matthias.beller@ifok.uni-rostock.de
atoms (S, C, N, or O) in the pyridinedicarboxylate ligand
should influence the reactivity and the selectivity of the
catalyst.
Dr. W. Mägerlein, Dr. H. Hugl
Bayer AG
51368 Leverkusen (Germany)
The epoxidation of styrene using hydrogen peroxide is
amongst the more challenging asymmetric epoxidation reac-
tions both with regard to chemo- and enantioselectivity. We
[
**] This work has been financed by the State of Mecklenburg-Western
Pommerania, the Bundesministerium für Bildung und Forschung
(
BMBF), and the Deutsche Forschungs. M.K.T. thanks the Alexander
[
17d,e]
von Humboldt Stiftung for granting him an AvH-fellowship.
used our recently developed in situ catalyst system
and
investigated the influence of different ligands and reaction
conditions (Table 1).
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
Angew. Chem. Int. Ed. 2004, 43, 5255 –5260
DOI: 10.1002/anie.200460528
ꢀ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
5255

Communications
[
a]
Table 1: Effects of ligands on ruthenium catalyzed asymmetric epoxidation of styrene.
known complexes, [Ru{(S,S)-Ph pybox}(py-
2
dic)] (1a) and [Ru{(S,S)-iPr pybox}(pydic)]
2
(
1e) new complexes, [Ru{H -(S,S)-Ph py-
2 2
box}(pydic)] (1b), [Ru{(S,S)-indanol py-
2
box}(pydic)] (1c), and [Ru{(R,R)-Ph2-
2
[b]
[b]
[c]
[d]
(S,S)-Ph pybox}(pydic)]
(1d),
which
2
Entry
1
L
t [h]
Conv. [%]
Yield [%]
20
Selec. [%]
ee [%]
derived from known pybox ligands, were
–
–
12
0
0
[21]
also synthesized.
[
e]
All the [Ru(pybox)(pydic)] complexes
catalyzed the epoxidation of styrene with
2
12
80
49
61
24
3
5
0% H O in good yield (Table 2, entries 1–
2 2
). All reactions were run with 5 mol% of
[
f]
[e]
3
4
5
12
12
12
>99
20
70
8
70
40
50
31
n.d.
n.d.
Ru catalyst. However, a similar level of
efficiency is reached with 0.5 mol% of
catalyst (Table 3, entry 12). Moreover, the
catalytic system had a 67% efficiency with
[
[
g]
g]
20
10
respect to H O2 (Table 3, entry 13). Sub-
2
[
[
e]
e]
6
7
8
12
12
12
40
31
22
22
14
6
55
45
27
9
13
–
stituents on the 4-position of the 4,5-dihy-
drooxazol ring positively influence the
enantioselectivity of the reaction more
than those on the 5-position since the 4-
position is closer to the metal center
(Table 2, entries 1 and 2). Moreover, a
flexible aryl ring in the substituent seems
to be essential (Table 2, entries 1 and 3) for
high enantioselectivity. The presence of the
comparatively sterically bulky iso-propyl
group gave a system that was not as reactive
and showed lower enantioselectivity
–
[
h]
1
[
(
a] Reaction conditions: In a 25-mL Schlenk tube, [{Ru(p-cymene)Cl } ] (0.0125 mmol) and L
2 2
0.025 mmol) were stirred at room temperature in 2-methylbutan-2-ol (2 mL) under Ar for 10 min. A
solution of L (0.025 mmol) and Et N (1.2 equiv per acid group) in 2-methylbutan-2-ol (2 mL) was added
by cannular. The whole reaction mixture was heated at 658C for 1 h. After cooling to room temperature,
2
3
the catalyst solution was diluted with 2-methylbutan-2-ol (5 mL), followed by the addition of styrene
(
0.5 mmol) and dodecane (GC internal standard, 100 mL). To this reaction mixture, a solution of 30%
(170 mL, 1.5 mmol) in 2-methylbutan-2-ol (830 mL) was added over 12 h by a syringe pump.
b] Determined by comparing with authentic sample on GC-FID. [c] Chemoselectivity for epoxide
2 2
H O
[
formation. [d] Determined by HPLC. [e] (R)-(+)-styrene oxide was the major enantiomer. [f] The defined
(Table 2, entries 1 and 5). The epoxidation
1
complex 1a was used. [g] Not determined. [h] Performed without L .
of 1-methylcyclohexene in the standard
conditions with 5 mol% 1a led to 100%
conversion with 86% yield, however, with
The reactions were run at room temperature in the
less than 5% ee. This result suggests that a p–p interaction
between the ligand and the substrate may be present.
[
22]
presence of 2.5 mol% of [{Ru(p-cymene)Cl } ] and 5 mol%
2
2
of each ligand. In general all experiments were performed
with three equivalents of H O (30% in water), which was
For the first time we employed pyboxazine ligands, which
are structurally related to pybox, and can be synthesized
easily from b-amino acid derivatives. The b-amino acid was
2
2
slowly dosed into the reaction mixture over 12 h. With
{Ru(p-cymene)Cl } ] alone (Table 1, entry 1), no epoxide was
[
reduced by LiAlH directly or its methyl ester was reduced by
2
2
4
detected, only unspecific decomposition of H O and styrene.
NaBH in the presence of acid to the corresponding b-amino
2
2
4
[
21b]
To our delight, a combination of (S,S)-Ph -pybox and H pydic
alcohol.
pyridine-2,6-dicarboximidate in anhydrous CH Cl gave the
Cyclization of the b-amino alcohol with dimethyl
2
2
(
pydic = pyridine dicarboxylate) led to a remarkable increase
2
2
in activity and chemoselectivity (61%) with a moderate
enantioselectivity (Table 1, entry 2). Using the pre-made
complex 1a gave better yield (70%) as well as a higher
enantioselectivity (31% ee) presumably owing to the higher
concentration of the well-defined catalyst (Table 1, entry 3).
Modification of the pydic ligand resulted in a significant loss
of reactivity (Table 1, entries 2–6). In the presence of only one
of the ligands (pybox or pydic) only a small amount of
epoxide is formed (Table 1, entries 7 and 8). This result
suggests that the combination of these meridional ligands,
pybox and pydic, plays a crucial role in the reactivity and
enantioselectivity and offers the opportunity to epoxidize
olefins with 30% H O .
pyboxazine ligand, which can be used directly for complex
[
21c,e]
formation.
The metal complex, [Ru(S,S)-Ph pyboxa-
2
zine)(pydic)] (2a), was obtained accordingly. Enlargement
of the five-membered ring to a six-membered ring resulted in
a system that increased the ee value to 48% (Table 2, entry 6).
These results show some important factors which can
rationalize the development of a new H O catalyst: 1) the
2
2
combination of pybox and pydic ligands at a ruthenium center
provides the reactivity and enantioselectivity, 2) an aryl group
on the 4-position of the dihydrooxazole ring results in good
ee values with aromatic olefins, 3) a sterically bulky aryl
substituent may further improve the enantioselective induc-
tion, 4) the newly developed six-membered “pyboxazine” is
better than the five-membered “pybox” with respect to
enantioselectivity. Following these principles, we designed
2
2
Different ruthenium complexes were tested in the epox-
idation of styrene (Table 2). All ruthenium catalysts were
directly prepared from the corresponding pybox ligand,
and synthesized [Ru{(R,R)-1-naphthyl pyboxazine}(pydic)]
2
[
18]
Na pydic, and [{Ru(p-cymene)Cl } ].
Apart from the
(2b) and [Ru{(R,R)-2-naphthyl pyboxazine}(pydic)] (2c;
2
2
2
2
5
256
ꢀ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
Angew. Chem. Int. Ed. 2004, 43, 5255 –5260

Angewandte
Chemie
[
a]
Table 2: [Ru(pybox))(pydic)]- and [Ru(pyboxazine)(pydic)]-catalyzed epoxidation of styrene.
Table 2, entries 7 and 8). In the
epoxidization, 2b give a lower
enantioselectivity while 2c gave
the same ee value as 2a under
non-optimized conditions. How-
ever, after optimization 2c was
the best catalyst.
[
b]
[b]
[c]
[d]
Entry Catalyst
t [h] Conv. [%]
Yield [%]
Selec. [%]
ee [%]
Different aromatic olefins were
oxidized in the presence of catalyst
[
[
[
[
e]
f]
e]
f]
1
12
12
20
12
>99
100
91
70
70
31
2
c in good to excellent yield with
good ee values under mild condi-
tions (Table 3). With styrene, in the
presence of acetic acid (HOAc) as
cocatalyst (20 mol%), it was found
that the yield increased to 85%
and the ee value increased to 59%
with 2c as the catalyst (Table 3,
entries 1 and 2). To our knowledge,
this is the highest ee value for
asymmetric epoxidation of styrene
using H O as the oxidant. Mecha-
2
3
4
66
59
78
66
65
78
3
18
18
2
2
nistic studies indicated that HOAc
accelerates the reaction, possibly
by stabilizing the active intermedi-
ates against self-degradation. The
water content increases with the
addition of H O as the oxidant,
100
2
2
this means that the faster the
reaction is, the higher the enantio-
selectivity. We have also demon-
strated that over-dosage of H O in
2
the epoxidation of trans-stilbene
[
[
[
e]
e]
e]
5
6
7
20
12
12
72
81
45
56
65
63
69
65
19
48
38
catalyzed by 1a using PhI(OAc) as
2
the oxidant decreased the ee val-
[
17d]
ue.
So this additive effect is
most prominent with less reactive
substrates and is diminished when
electron-rich olefins are employed.
The highest ee value (84%) was
obtained with 2-methyl-1-phenyl-
1
-propene at 08C with 20 mol%
HOAc and 1.5 equivalents of 50%
H O (Table 3, entry 16). To date
2
2
the new catalytic system has been
applied successfully to mono-, di-,
and trisubstituted olefins (Table 3).
The best results are obtained with
trans disubstituted olefins and tri-
substituted olefins. Hence, the new
procedure complements the known
manganese-catalyzed asymmetric
epoxidations. Apart from differ-
ently substituted aromatic olefins,
allylic acetates and even allylic
chloride could be epoxidized in
high yield (Table 3, entries 15 and
100
[
e]
8
12
82
59
72
48
[
a] In a 25-mL Schlenk tube, the catalyst (0.025 mmol) was stirred at room temperature in 2-
methylbutan-2-ol (9 mL) for 10 min. Styrene (0.5 mmol) and dodecane (GC internal standard, 100 mL)
were added. To this reaction mixture, a solution of 30% H O (170 mL, 1.5 mmol) in 2-methylbutan-2-ol
2
2
1
6).
Preliminary mechanistic stud-
ies of the active species indicate
(
830 mL) was added over 12 h by a syringe pump. [b] Determined by comparing with authentic samples
on GC-FID. [c] Chemoselectivity for epoxide formation. [d] Determined by HPLC. [e] (R)-(+)-styrene
oxide was the major enantiomer. [f] (S)-(À)-styrene oxide was the major enantiomer.
Angew. Chem. Int. Ed. 2004, 43, 5255 –5260
www.angewandte.org
ꢀ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
5257

Communications
[
a]
Table 3: Asymmetric epoxidation catalyzed by 2c.
the so-called pyboxazines. It is expected
that these ligands will complement nicely
the catalytic behavior of the well-known
[
23]
pybox derivatives. The use of two differ-
ent ligands significantly simplifies structural
variations on the catalyst thus allowing easy
tuning of the catalytic properties. This
situation is an important advantage com-
pared to most catalysts and ligands used in
asymmetric oxidation catalysis. Full exper-
imental detail can be found in the Support-
ing Information.
[
b]
[b]
[c]
Entry
Substrate
t [h]
Conv. [%]
Yield [%]
Selec. [%]
ee [%]
1
2
3
R
R
R
[
[
[
[
[
[
[
[
[
[
d]
1
2
3
4
5
6
7
8
9
Ph
Ph
p-Cl-C H4
p-F-C H4
p-CF -C H
4
p-CH -C H
o-CH -C H
o-Cl-C H4
Ph
Ph
Ph
Ph
H
H
H
H
H
H
H
H
Ph
CH3
CH3
CH3
H
H
H
H
H
H
H
H
H
H
H
H
H
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
26
12
12
82
100
100
100
65
100
100
86
100
100
93
100
100
100
100
94
59
85
76
82
57
80
>99
78
100
95
72
85
76
82
88
80
>99
91
100
95
97
48
59
54
60
55
58
64
58
54
72
70
74
53
79
80
84
48
28
d],[e]
e]
6
e]
6
e]
3
6
e]
3
6
4
e]
3
6
4
e]
6
f]
Received: April 30, 2004
d],[g]
10
11
12
13
14
15
16
17
18
[
[
h]
i]
[d],[g]
[d],[g]
90
67
Keywords: asymmetric catalysis ·
.
[j]
67
epoxidations · homogeneous catalysis ·
ruthenium
p-CH O-C H
4
CH3
>99
>99
93
91
83
>99
>99
93
97
99
3
6
Ph
Ph
Ph
Ph
Ph
1,1-cyclohexyl
CH3
CH3
CH3
CH3
H
[
[
[
e][k]
e]
[
1] K. Weissermel, H.-J. Arpe, Industrial
Organic Chemistry, 4th ed., Wiley-VCH,
Weinheim, 2003.
CH OAc
84
79
2
e]
CH Cl
H
68
86
2
[
a] In a 25-mL Schlenk tube, the catalyst (0.025 mmol) was stirred at room temperature in 2-
[2] For example, epoxides can be produced by
cyclization of halohydrins or 1,2-glycols,
epoxidation of olefins by peracids, reaction
of carbonyl compounds with gem-dihalides
and Li or nBuLi, condensation between
methylbutan-2-ol (9 mL) for 10 min. Olefin (0.5 mmol) and dodecane (GC internal standard, 100 mL)
were added. To this reaction mixture, a solution of 30% H O (170 mL, 1.5 mmol) in 2-methylbutan-2-ol
(
2
2
830 mL) was added over 12 h by a syringe pump. [b] Determined by comparing with authentic samples
on GC-FID. [c] Determined by HPLC, absolute configurations were not determined unless mentioned.
[
d] (R)-(+)-styrene oxide was the major enantiomer. [e] 20 mol% of HOAc was added. [f] (S,S)-(À)-
aldehydes
and
a-halo
esters,
stilbene oxide was the major enantiomer. [g] (R,R)-(+)-1-Phenyl-1-propene oxide was the major
enantiomer. [h] In a 25-mL Schlenk tube, 2a (0.0025 mmol) was stirred at room temperature in 2-
methylbutan-2-ol (9 mL) for 10 min. trans-1-Phenyl-1-propene (0.5 mmol), HOAc (5.7 mL, 0.10 mmol)
and dodecane (GC internal standard, 100 mL) were added. Cooled to 08C, a solution of 50% H O
-ketones, or -amides, addition of sulfur
ylides or diazomethane to aldehydes or
ketones, and bimolecular reduction of alde-
hydes or ketones. See: J. March, Advanced
Organic Chemistry, 3rd ed., Wiley, New
Delhi, 1992.
2
2
(
102 mL, 1.5 mmol) in 2-methylbutan-2-ol (898 mL) was added over 12 h by a syringe pump. [i] In a 25-mL
Schlenk tube, 2a (0.025 mmol) was stirred at room temperature in 2-methylbutan-2-ol (9 mL) for
0 min. trans-1-Phenyl-1-propene (0.6 mmol), HOAc (5.7 mL, 0.10 mmol), and dodecane (GC internal
standard, 100 mL) were added. To this reaction mixture, a solution of 50% H O (34 mL, 0.5 mmol) in 2-
1
[3] R. A. Sheldon, J. K. Kochi, Metal-Catalyzed
Oxidations of Organic Compounds, Aca-
demic Press, New York, 1981.
2
2
methylbutan-2-ol (966 mL) was added 12 h by a syringe pump. [j] Yield based on H O . [k] 08C, a solution
2
2
of 50% H O (51 mL, 0.75 mmol) in 2-methylbutan-2-ol (949 mL) was added by syringe pump.
[4] For recent examples see: a) I. E. Markó,
P. R. Giles, M. Tsukazaki, S. M. Brown, C. J.
Urch, Science 1996, 274, 2044 – 2046; b) G.-J.
ten Brink, I. W. C. E. Arends, R. A. Shel-
don, Science 2000, 287, 1636 – 1639; c) B. Betzemeier, M.
Cavazzini, S. Quici, P. Knochel, Tetrahedron Lett. 2000, 41,
2
2
that the corresponding ruthenium dioxo complex is the active
catalyst. In stoichiometric reactions of 1a with PhI(OAc)2,
tBuOOH, and H O , UV/Vis spectroscopy showed that the
same active species are formed. Electrospray ionization mass
spectrometry of the reaction mixture showed molecular ion
2
2
4
343 – 4346; d) Y. Ishii, S. Sakaguchi, T. Iwahama, Adv. Synth.
Catal. 2001, 343, 393 – 427; e) Y. Nishiyama, Y. Nakagawa, N.
Mizuno, Angew. Chem. 2001, 113, 3751 – 3753; Angew. Chem.
Int. Ed. 2001, 40, 3639 – 3641; f) Y. Nishiyama, T. Hayashi, Y.
Nakagawa, N. Mizuno, Stud. Surf. Sci. Catal. 2003, 145, 255 – 258;
g) A. M. Khenkin, L. J. W. Shimon, R. Neumann, Inorg. Chem.
peaks corresponding to [Ru{(S,S)-Ph pybox}pydic)(O)]
2
(
3a) and [Ru{(S,S)-Ph pybox}(pydic)(O) ] (3b), regardless
2
2
of whether or not HOAc was present. While 3b seems to be
quite unstable, 3a could be independently synthesized by
treating 1a with two equivalents of 30% H O in 2-metylbu-
2003, 42, 3331 – 3339; h) T. Nishimura, S. Uemura, Synlett 2004,
2
01 – 216; i) R. Irie, T. Katsuki, Chem. Rec. 2004, 4, 96 – 109.
2
2
[
[
5] a) L. I. Simµndi, Catalytic Activation of Dioxygen by Metal
Complexes, Kluwer Academic, Dordrecht, 1992; b) The Activa-
tion of Dioxygen and Homogeneous Catalytic Oxidation (Eds.:
D. H. R. Barton, A. E. Bartell, D. T. Sawyer), Plenum, New
York, 1993; c) Advances in Catalytic Activation of Dioxygen by
Metal Complexes (Ed.: L. I. Simµndi), Kluwer Academic,
Dordrecht, 2003.
tan-2-ol. Even when using a stoichiometric amount of 3a, no
oxo-transfer from 3a to trans-1-phenyl-1-propene occurred.
Hence, we postulate that 3b is the real active catalyst in
solution.
In summary, a general ruthenium-catalyzed asymmetric
epoxidation procedure of olefins using H O2 has been
2
6] a) C. Döbler, G. Mehltretter, M. Beller, Angew. Chem. 1999, 111,
developed. For the first time high yield and chemoselectivity
have been obtained using H O as the oxidant. Enantiose-
3
211 – 3212; Angew. Chem. Int. Ed. 1999, 38, 3026 – 3028; b) C.
2
2
Döbler, G. Mehltretter, U. Sundermeier, M. Beller, J. Am.
Chem. Soc. 2000, 122, 10289 – 10297; c) G. M. Mehltretter, C.
Döbler, U. Sundermeier, M. Beller, Tetrahedron Lett. 2000, 41,
8083 – 8087; d) C. Döbler, G. M. Mehltretter, U. Sundermeier,
lectivities (typically in between 50–80%) up to 84% were
observed for different aromatic olefins. An important factor
for the success was the introduction of a new class of ligands,
5
258
ꢀ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
Angew. Chem. Int. Ed. 2004, 43, 5255 –5260

Angewandte
Chemie
M. Beller, J. Organomet. Chem. 2001, 621, 70 – 76; e) U.
Sundermeier, C. Döbler, G. M. Mehltretter, W. Baumann, M.
Beller, Chirality 2003, 15, 127 – 134.
9807; c) Z.-X. Wang, Y. Tu, M. Frohn, J.-R. Zhang, Y. Shi, J. Am.
Chem. Soc. 1997, 119, 11224 – 11235; d) D. Yang, M.-K. Wong,
Y.-C. Yip, X.-C. Wang, M.-W. Tang, J.-H. Zheng, K.-K. Cheung,
J. Am. Chem. Soc. 1998, 120, 5943 – 5952, and references therein.
[15] For reviews of asymmetric epoxidation mediated by organic
compounds see: a) P. I. Dalko, L. Moisan, Angew. Chem. 2001,
113, 3840 – 3864; Angew. Chem. Int. Ed. 2001, 40, 3726 – 3748;
b) W. Adam, C. R. Saha-Möller, P. A. Ganeshpure, Chem. Rev.
2001, 101, 3499 – 3548, and references therein.
[
7] For other examples of using oxygen or air, see: a) J. T. Groves, R.
Quinn, J. Am. Chem. Soc. 1985, 107, 5790 – 5792; b) I. R. Paeng,
K. Nakamoto, J. Am. Chem. Soc. 1990, 112, 3289 – 3297;
c) Metalloporphyrins Catalyzed Oxidations (Eds.: F. Montanari,
L. Casella), Kluwer, Dordrecht, 1994; d) I. E. Markó, P. R. Giles,
M. Tsukazaki, I. ChellØ-Regnant, C. J. Urch, S. M. Brown, J. Am.
Chem. Soc. 1997, 119, 12661 – 12662; e) K. P. Peterson, R. C.
Larock, J. Org. Chem. 1998, 63, 3185 – 3189; f) K. S. Coleman,
C. Y. Lorber, J. A. Osborn, Eur. J. Inorg. Chem. 1998, 1673 –
[16] Selected examples of asymmetric epoxidation using H O2 as
2
oxidant: a) R. Sinigalia, R. A. Michelin, F. Pinna, G. Strukul,
Organometallics 1987, 6, 728 – 734; b) T. Schwenkreis, A. Ber-
kessel, Tetrahedron Lett. 1993, 34, 4785 – 4788; c) R. Irie, N.
Hosoya, T. Katsuki, Synlett 1994, 255 – 256; d) P. Pietikäinen,
Tetrahedron Lett. 1994, 35, 941 – 944; e) A. Berkessel, M.
Frauenkron, T. Schwenkreis, A. Steinmetz, J. Mol. Catal. A
1997, 117, 339 – 346; f) C. Bolm, D. Kadereit, M. Valacchi, Synlett
1997, 687 – 688; g) M. B. Francis, E. N. Jacobsen, Angew. Chem.
1999, 111, 987 – 991; Angew. Chem. Int. Ed. 1999, 38, 937 – 941;
h) R. M. Stoop, A. Mezzetti, Green Chem. 1999, 1, 39 – 41;
i) R. M. Stoop, C. Bauer, P. Setz, M. Wörle, T. Y. H. Wong, A.
Mezzetti, Organometallics 1999, 18, 5691 – 5700; j) R. M. Stoop,
S. Bachmann, M. Valentini, A. Mezzetti, Organometallics 2000,
19, 4117 – 4126; k) C. Bolm, N. Meyer, G. Raabe, T. Weyher-
mꢀller, E. Bothe, Chem. Commun. 2000, 2435 – 2436; l) P.
Pietikäinen, J. Mol. Catal. A 2001, 165, 73 – 79; m) L. Shu, Y.
Shi, Tetrahedron 2001, 57, 5213 – 5218; n) R. I. Kureshy, N.-u. H.
Khan, S. H. R. Abdi, S. T. Patel, R. V. Jasra, Tetrahedron:
Asymmetry 2001, 12, 433 – 437.
1675; g) J. Christoffers, J. Org. Chem. 1999, 64, 7668 – 7669.
[
[
8] a) Catalytic Oxidations with Hydrogen Peroxide as Oxidant (Ed.:
G. Strukul), Kluwer Academic, Dordrecht, 1992; b) C. W. Jones,
Applications of Hydrogen Peroxide and Derivatives, Royal
Society of Chemistry, Cambridge, 1999.
th
9] a) Ullmannꢀs Encyclopedia of Industrial Chemistry, 5 Ed.,
Vol. A13 (Eds.: B. Elvers, S. Hawkins, M. Ravenscroft, G.
Schulz), VCH, New York, 1989, p. 443; b) Kirk-Othmer Ency-
clopedia of Chemical Technology, 4th ed., Vol. 13 (Eds.: J. I.
Kroschwitz, M. Howe-Grant), Wiley, New York, 1995, p. 961.
[
10] Selected recent examples using H O as oxidant: a) J. Rudolph,
2 2
K. L. Reddy, J. P. Chiang, K. B. Sharpless, J. Am. Chem. Soc.
1997, 119, 6189 – 6190; b) L. Shu, Y. Shi, J. Org. Chem. 2000, 65,
8807 – 8810; c) M. C. White, A. G. Doyle, E. N. Jacobsen, J. Am.
Chem. Soc. 2001, 123, 7194 – 7195; d) Y. Shi, J. Synth. Org. Chem.
Jpn. 2002, 60, 342 – 349; e) K. A. Srinivas, A. Kumar, S. M. S.
Chauhan, Chem. Commun. 2002, 2456 – 2457; f) M. K. Carter, J.
Mol. Catal. A 2003, 200, 191 – 203; g) D. E. De Vos, B. F. Sels,
P. A. Jacobs, Adv. Synth. Catal. 2003, 345, 457 – 473; h) R.
Noyori, M. Aoki, K. Sato, Chem. Commun. 2003, 1977 – 1986;
i) S. Y. Jonsson, H. Adolfsson, J.-E. Bäckvall, Chem. Eur. J. 2003,
[17] For an excellent review using Ru complexes for epoxidation
reactions, see: a) G. A. Barf, R. A. Sheldon, J. Mol. Catal. A
1995, 102, 23 – 39; for achievements in Ru-based epoxidations
with different oxidants, see: b) N. End, A. Pfaltz, Chem.
Commun. 1998, 589 – 590; c) Z. Gross, S. Ini, Org. Lett. 1999, 1,
2077 – 2080; d) M. K. Tse, S. Bhor, M. Klawonn, C. Döbler, M.
Beller, Tetrahedron Lett. 2003, 44, 7479 – 7483; e) S. Bhor, M. K.
Tse, M. Klawonn, C. Döbler, W. Mägerlein, M. Beller, Adv.
Synth. Catal. 2004, 346, 263 – 267; recent using Ru salen
complexes see: f) T. Takeda, R. Irie, Y. Shinoda, T. Katsuki,
Synlett 1999, 1157 – 1159; g) K. Nakata, T. Takeda, J. Mihara, T.
Hamada, R. Irie, T. Katsuki, Chem. Eur. J. 2001, 7, 3776 – 3782;
h) A. Berkessel, P. Kaiser, J. Lex, Chem. Eur. J. 2003, 9, 4746 –
4756.
[18] H. Nishiyama, T. Shimada, H. Itoh, H. Sugiyama, Y. Motoyama,
Chem. Commun. 1997, 1863 – 1864.
[19] a) P. R. Ortiz de Montellano, Acc. Chem. Res. 1987, 20, 289 –
294; b) M. Yagi, M. Kaneko, Chem. Rev. 2001, 101, 21 – 35;
c) A. J. Wu, J. E. Penner-Hahn, V. L. Pecoraro, Chem. Rev. 2004,
104, 903 – 938.
9, 2783 – 2788; j) G. Maayan, R. H. Fish, R. Neumann, Org. Lett.
2003, 5, 3547 – 3550; k) S. Velusamy, T. Punniyamurthy, Tetrahe-
dron Lett. 2003, 44, 8955 – 8957; l) M. V. Vasylyev, R. Neumann,
J. Am. Chem. Soc. 2004, 126, 884 – 890.
[
11] For reviews of H O as epoxidation oxidant see: a) G. Grigor-
2
2
opoulou, J. H. Clark, J. A. Elings, Green Chem. 2003, 5, 1 – 7;
b) B. S. Lane, K. Burgess, Chem. Rev. 2003, 103, 2457 – 2473; for
a commentary see: c) M. Beller, Adv. Synth. Catal. 2004, 346,
1
07 – 108; for other asymmetric oxidations using H O see: d) N.
2 2
Komatsu, T. Murakami, Y. Nishibayashi, T. Sugita, S. Uemura, J.
Org. Chem. 1993, 58, 3697 – 3702; e) A. Gusso, C. Baccin, F.
Pinna, G. Strukul, Organometallics 1994, 13, 3442 – 3451; f) C.
Bolm, F. Bienewald, Angew. Chem. 1995, 107, 2883 – 2885;
Angew. Chem. Int. Ed. Engl. 1995, 34, 2640 – 2642; g) M. Costas,
A. K. Tipton, K. Chen, D. H. Jo, L. Que, Jr., J. Am. Chem. Soc.
2
001, 123, 6722 – 6723; h) S.-I. Murahashi, S. Ono, Y. Imada,
Angew. Chem. 2002, 114, 2472 – 2474; Angew. Chem. Int. Ed.
002, 41, 2366 – 2368; i) S. A. Blum, R. G. Bergman, J. A.
[20] M. Klawonn, M. K. Tse, S. Bhor, C. Döbler, M. Beller, J. Mol.
Catal. A 2004, 218, 13 – 19.
2
Ellman, J. Org. Chem. 2003, 68, 150 – 155; j) J. Legros, C.
Bolm, Angew. Chem. 2003, 115, 5645 – 4657; Angew. Chem. Int.
Ed. 2003, 42, 5487 – 5489.
[21] a) H. Nishiyama, Enantiomer 1999, 4, 569 – 574; b) S. Liu, J. F. K.
Mꢀller, M. Neuburger, S. Schaffner, M. Zehnder, Helv. Chim.
Acta 2000, 83, 1256 – 1267; c) G. Desimoni, G. Faita, M. Guala, C.
Pratelli, Tetrahedron: Asymmetry 2002, 13, 1651 – 1654; d) G.
Desimoni, G. Faita, P. Quadrelli, Chem. Rev. 2003, 103, 3119 –
3154; e) a close related bisoxazine ligand was reported recently:
C. Mazet, L. H. Gade, Inorg. Chem. 2003, 42, 210 – 215.
[22] a) K. B. Sharpless, S. S. Woodard, M. G. Finn, Pure Appl. Chem.
1983, 55, 1823 – 1836; b) E. J. Corey, Y. Matsumura, Tetrahedron
Lett. 1991, 32, 6289 – 6292; c) A. Loupy, A. Zaparucha, Tetrahe-
dron Lett. 1993, 34, 473 – 476; d) T. Hamada, R. Irie, T. Katsuki,
Synlett 1994, 479 – 481; e) L. Cai, Y. Han, H. Mahmoud, B. M.
Segal, J. Organomet. Chem. 1998, 568, 77 – 86; f) R. Noyori, M.
Yamakawa, S. Hashiguchi, J. Org. Chem. 2001, 66, 7931 – 7944;
g) K. Jitsukawa, A. Katoh, K. Funato, N. Ohata, Y. Funahashi, T.
Ozawa, H. Masuda, Inorg. Chem. 2003, 42, 6163 – 6165; h) H.
[
12] Reviews for Ti: a) R. A. Johnson, K. B. Sharpless in Catalytic
Asymmetric Synthesis (Ed.: I. Ojima), VCH, New York, 1993,
Chapter 4.1; b) T. Katsuki, V. S. Martin, Org. React. 1996, 48, 1 –
299.
[
13] Reviews for Mn: a) E. N. Jacobsen in Catalytic Asymmetric
synthesis (Ed.: I. Ojima), VCH, New York, 1993, Chapter 4.2;
b) T. Katsuki in Catalytic Asymmetric Synthesis, 2nd ed. (Ed.: I.
Ojima), Wiley-VCH, New York, 2000, pp. 287 – 325; c) T.
Katsuki, Adv. Synth. Catal. 2002, 344, 131 – 147.
14] For examples of asymmetric epoxidation mediated by chiral
ketones see: a) D. Yang, Y.-C. Yip, M.-W. Tang, M.-K. Wong, J.-
H. Zheng, K.-K. Cheung, J. Am. Chem. Soc. 1996, 118, 491 – 492;
b) Y. Tu, Z.-X. Wang, Y. Shi, J. Am. Chem. Soc. 1996, 118, 9806 –
[
Angew. Chem. Int. Ed. 2004, 43, 5255 –5260
www.angewandte.org
ꢀ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
5259

Communications
Ait-Haddou, O. Hoarau, D. Cramailere, F. Pezet, J.-C. Daran,
G. G. A. Balavoine, Chem. Eur. J. 2004, 10, 699 – 707; i) T. C.
Wabnitz, J.-Q. Yu, J. B. Spencer, Chem. Eur. J. 2004, 10, 484 –
493.
[
23] For examples of catalysis with pybox derivatives, see: a) A.
Pfaltz, Acc. Chem. Res. 1993, 26, 339 – 345; b) H. Nishiyama, Y.
Itoh, H. Matsumoto, S.-B. Park, K. Itoh, J. Am. Chem. Soc. 1994,
116, 2223 – 2224; c) A. K. Ghosh, P. Mathivanan, J. Cappiello,
Tetrahedron: Asymmetry 1998, 9, 1 – 45; d) G. Sekar, A. Datta-
Gupta, V. K. Singh, J. Org. Chem. 1998, 63, 2961 – 2967; e) J. S.
Johnson, D. A. Evans, Acc. Chem. Res. 2000, 33, 325 – 335; f) C.-
X. Zhao, M. O. Duffey, S. J. Taylor, J. P. Morken, Org. Lett. 2001,
3, 1829 – 1831; g) J. Zhou, G. C. Fu, J. Am. Chem. Soc. 2004, 126,
1340 – 1341; h) D. Cuervo, M. P. Gamasa, J. Gimeno, Chem. Eur.
J. 2004, 10, 425 – 432, and references in [21a] and [21d].
5
260
ꢀ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
Angew. Chem. Int. Ed. 2004, 43, 5255 –5260