Ruthenium-catalyzed asymmetric alkene epoxidation with tert-butyl hydroperoxide as oxidant

Article abstract of DOI:10.1002/adsc.200303142

A ruthenium-catalyzed asymmetric epoxidation of various olefins using tert-butyl hydroperoxide (TBHP) as the oxidant is reported. By applying ruthenium(pyridinebisoxazoline)-(pyridinedicarboxylate) complexes 1 [Ru(pybox)(pydic), 1] as catalysts, aromatic and aliphatic olefins yielded the corresponding epoxides at room temperature in good to excellent yields and enantioselectivities up to 65% ee. Slow addition of the stoichiometric oxidant significantly improved the yield and the chemoselectivity of the reaction.

Full text of DOI:10.1002/adsc.200303142

FULL PAPERS
Ruthenium-Catalyzed Asymmetric Alkene Epoxidation with
tert-Butyl Hydroperoxide as Oxidant
a
a
a
a
Santosh Bhor, Man Kin Tse, Markus Klawonn, Christian Dˆbler, Wolfgang
b
a,
M‰gerlein, Matthias Beller *
Leibniz-Institut f¸r Organische Katalyse (IfOK) an der Universit‰t Rostock e.V., Buchbinderstr. 5 ± 6, 18055 Rostock,
a
Germany
Fax: ( ‡ 49)-381-4669324; e-mail: matthias.beller@ifok.uni-rostock.de
b
Bayer AG, 51368 Leverkusen, Germany
Received: September 8, 2003; Revised: January14, 2004; Accepted: January18, 2004
Abstract: A ruthenium-catalyzed asymmetric epox- Slow addition of the stoichiometric oxidant signifi-
idation of various olefins using tert-butyl hydroper- cantly improved the yield and the chemoselectivity of
oxide (TBHP) as the oxidant is reported. By applying the reaction.
ruthenium(pyridinebisoxazoline)-(pyridinedicarboxy-
late) complexes 1 [Ru(pybox)(pydic), 1] as catalysts,
aromatic and aliphatic olefins yielded the correspond- Keywords: asymmetric catalysis; tert-butyl hydroper-
ing epoxides at room temperature in good to ex- oxide; epoxidation; homogeneous catalysis; N,O li-
cellent yields and enantioselectivities up to 65% ee. gands; ruthenium
Introduction
however the use of PhI(OAc) as the stoichiometric
oxidant remained as a major disadvantage. Therefore
2
Chiral epoxides are versatile building blocks for syn- we were interested in the behavior of ruthenium(pyr-
theses of numerous natural products and biological idinebisoxazoline)(pyridinedicarboxylate) complexes 1
active substances.[ Among the various possibilities for (Figure 1) in the presence of more practical oxidants
their preparation, asymmetric catalysis constitutes an such as alkyl peroxides.
1]
elegant and efficient tool for the synthesis of enantio-
To utilize tert-butyl hydroperoxide (TBHP) is signifi-
merically pure epoxides. In the past transition metal cantly advantageous compared with PhI(OAc) with
2
complexes based on titanium[ and manganese have
been used most successfully as catalysts for the enantio-
selective epoxidation of olefins. In spite of extensive
research efforts up-to-date, the development of a
general, highly selective epoxidation method is still
one of the major goals in asymmetric catalysis.
2]
[3]
For some time we have been involved in the develop-
ment of improved procedures for asymmetric dihydrox-
[4]
ylation reactions. More recently, we set out to develop
new catalytic asymmetric methods for the synthesis of
epoxides.[ We focused our attention initially on opti-
5]
[
6,7]
cally active ruthenium catalysts,
which are less well
[
8]
studied compared with manganese salen complexes.
As a starting point of our investigations we chose
Nishiyama×s ruthenium-(pyridinebisoxazoline)(pyridi-
nedicarboxylate) complex [Ru(pybox)(pydic)], which
catalyzes the epoxidation of trans-stilbene with approx-
imately 70% ee.[ Unfortunately this system has also
6b]
several drawbacks such as the low reactivity (96 h were
needed for full conversion) and the limited scope of the
catalyst. We were able to solve these problems by adding Figure 1. Structure of ruthenium(pyridinebisoxazoline)
a defined amount of water to the reaction mixture,[5] (pyridinedicarboxylate).
Adv. Synth. Catal. 2004, 346, 263 ± 267
DOI: 10.1002/adsc.200303142
¹ 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
263

FULL PAPERS
Santosh Bhor et al.
regards to the percentage of active oxygen, the nature of reaction by the catalyst. Hence, an excess of oxidant was
the by-product, environmentally friendliness and price. necessary for full conversion. However, in the presence
Here, we report the asymmetric catalytic epoxidations of 6 equivalents of TBHP the oxidation of the co-solvent
of various olefins in the presence of 1 using TBHP as the toluene to benzaldehyde was observed as side reaction.
final oxidant.
Applying tert-amyl alcohol or tert-butanol as the solvent
gave a cleaner reaction with good yield (up to 86%) and
chemoselectivity of the epoxide (Table 1, entries 4 ± 6).
Results and Discussion
Apart from 1a, Ru(S,S-Ph -pybox)(pydic) 1b, Ru(S,S-
2
Me -pybox)(pydic) 1c, Ru(S,S-Me -S,S-ph -pybox)(py-
2
2
2
By comparing the UV-VIS spectra of the reaction of 1a dic) 1d and Ru(S,S-Indanol -pybox)(pydic) 1e were also
2
and PhI(OAc) with that of 1a and TBHP, it appeared used as the catalysts (Table 1, entries 9, 10, 11 and 13).
2
that the same oxidized ruthenium species is formed. All ruthenium catalysts were directly prepared from the
Hence, the usage of tert-butyl hydroperoxide should be corresponding pybox ligand and [Ru(p-cymene)Cl ] . I n
2
2
possible as a stoichiometric oxidant for this reaction. case of 1c and 1e the ligand was synthesized according to
[
9,10]
Firstly, we examined the epoxidation of trans-stilbene previously described procedures.
The best epoxide
with TBHP(70% in water) in the presence of 5 mol % of yield (97%) and enantioselectivity (60%; 1S,2S-trans-
1
a at room temperature using previously optimized stilbene oxide as the major enantiomer) were obtained
[
5,6b]
reaction conditions (Table 1, entry 1).
using 1b as the catalyst. Interestingly, the trans-phenyl
To our delight, it was indeed possible to obtain a group alpha to the oxygen of the oxazoline ring of 1d
significant amount of trans-stilbene epoxide, albeit with induced a reversed enantioselectivity (Table 1, en-
low ee (28%).[ By varying the amount of the oxidant try 13).
6b]
(
Table 1, entries 1 ± 3), it became clear that a major
In addition to the catalyst, the concentration of the
amount of TBHP is destroyed during the course of the oxidant and the solvent have major influences on the
Table 1. Epoxidation of trans-stilbene[a]
Entry
Oxidant [equiv.]
Catalyst
Solvent
Conversion [%]
Yield [%][c]
ee [%][d]
[
b]
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
1.5
1a
1a
1a
1a
1b
1b
1b
1a
1c
1e
1b
1b
1d
1b
1b
1b
1b
1b
1b
toluene/tert-amyl alcohol
toluene/tert-amyl alcohol
toluene/tert-amyl alcohol
tert-amyl alcohol
tert-amyl alcohol
tert-BuOH
tert-amyl alcohol
tert-BuOH
tert-BuOH
tert-BuOH
tert-BuOH
tert-BuOH
tert-BuOH
30
91
27
86
72
86
85
77
91
80
28
25
17
17
24
42
55
28
44
38
59
60
[
[
[
[
[
b]
3
6
6
6
6
3
3
3
3
3
1.5
3
3
3
3
b]
b]
b]
b]
100
100
100
100
100
100
100
100
100
100
100
91
100
100
18
99
76
[
g]
h]
88
1
1
1
1
1
1
1
1
1
1
84[
93
97
88
71
84
88
15
90
45
[
e]
À 39
isopropanol
acetonitrile
3,7-dimethyl-3-octanol
THF
59
23
57
n.d.[
f]
3
3
3
isobutyl methyl ketone
CH Cl
29
17
2
2
[
[
[
[
[
[
[
[
a]
Reaction condition: 0.5 mmol substrate, solvent (10 mL), TBHP added over a period of 12 h, room temperature.
TBHP added in one portion.
GC yield.
Determined by HPLC, the major enantiomer was S,S-trans-stilbene oxide.
R,R-trans-Stilbene oxide was the major enantiomer.
Not determined.
Reaction time 14 h.
Reaction time 16 h.
b]
c]
d]
e]
f]
g]
h]
264
¹ 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
Adv. Synth. Catal. 2004, 346, 263 ± 267

Ruthenium-Catalyzed Asymmetric Alkene Epoxidation
FULL PAPERS
Table 2. Scope and limitations of the Ru-catalyzed asymmetric epoxidation of olefins.[a]
Entry
1
Olefin
Time [h]
12
Conversion [%]
100
Epoxide yield [%][b]
ee [%][c]
60
97
90
2
12
100
51
3
4
12
12
100
100
95
93
65
22
5
6
12
12
100
100
90
88
8
10
7
8
36
36
100
100
56
48
30
34
9
36
91
54
34
1
0
1
24
12
84
80
70
n.d.[d]
n.d.[d]
1
100
[
a]
Reaction condition: 0.5 mmol olefin, 5 mol % Ru(S,S-Ph -pybox)(pydic), tert-BuOH (10 mL), 1.5 equivs. TBHP added
2
over a period of 12 h, room temperature.
GC yield.
Determined by HPLC.
Not determined.
[
[
[
b]
c]
d]
epoxide yield and the enantioselectivity. The best aliphatic olefins reacted with tert-butyl hydroperoxide
enantioselectivities are observed at low concentration in moderate to very good yields (48 ± 97%) under mild
of the oxidant in tert-butanol. The negative influence of conditions (room temperature). The catalyst showed the
a larger excess of oxidant on the enantioselectivity is best reactivity towards 1,2-disubstituted and trisubsti-
explained by the increased amount of water in the tuted aromatic olefins (Table 2, entries 1 ± 6). Styrene
[
5]
reaction mixture. Variation of the solvent (Table 1, and substituted styrenes were obtained in significantly
entries 7, 11, 14 ± 19) showed that alcohols were best lower yields (48 ± 56%) due to unspecified side-reactions
suited as the reaction medium. Isobutyl methyl ketone of the olefin. These substrates also needed longer
and acetonitrile gave good yields, but low ees. Besides, reaction time in order to get completed (Table 2, entries
dichloromethane and THF led to both low yield and ee. 7 ± 9). In addition to aromatic olefins, we tested also
All reactions shown in Table 1 were run with 5 mol % aliphatic olefins, e.g., 1-methylcyclohexene and 2-meth-
of Ru catalyst. In addition we also performed reactions yl-1-heptene. The corresponding epoxides were ob-
with lower catalyst concentration. In the presence of 2.5 tained in 70% and 80% yield respectively (Table 2,
and 1.0 mol % Ru catalyst 95% and 79% yield of entries 10, 11). Moderate enantioselectivities (50 ± 65%
epoxide (54% and 49% ee) were obtained after 15 and ee) were observed with 1-phenyl-2-methylpropene,
3
6 h respectively.
The ™best∫ catalyst 1b was then applied to other styrenes gave mediocre ees (30 ± 34%).
olefins, too. As shown in Table 2 different aromatic and
stilbene and b-methylstyrene. Styrene and substituted
Adv. Synth. Catal. 2004, 346, 263 ± 267
asc.wiley-vch.de
¹ 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
265

FULL PAPERS
Conclusion
Santosh Bhor et al.
d, J ˆ 7.7 Hz), 7.65 (1H, t, J ˆ 7.7 Hz), 7.54 (3H, m), 7.12 ± 7.16
(
(
2H, m), 7.02 ± 7.05 (4H, m), 6.68 (4H, d, J ˆ 6.8 Hz), 5.15 ± 5.21
13
2H, m), 4.59 ± 4.68 (4H, m); C NMR (100.6 MHz, CDCl ):
In summary, we showed that Ru(pybox)(pydic) com-
plexes can be used as general catalysts for the epox-
idation of olefins with TBHP in good to excellent yield
3
d ˆ 171.1, 167,4, 149.2, 147.1, 136.0, 135.6, 133.7, 129.1, 128.6,
‡
1
27.3, 125.9, 124.0, 78.5, 67.8; FAB-MS: m/z ˆ 636 (M ); UV-
VIS (CH Cl ): l
(log e) ˆ 375 (3.36), 484 nm (4.47); anal.
2
2
max
(
up to 97%) with reasonable ees (up to 65%) under mild
calcd. for C H N O Ru ¥ 0.5 CH Cl (%): C 54.03, H 3.42, N
3
0
22
4
6
2
2
reaction conditions (room temperature). Compared
8
.26; found: C 54.37, H 3.79, N 8.50.
Ru(S,S-Me -pybox)(pydic) (1c): R ˆ 0.07 (CH Cl /MeOH,
with previously known reactions using PhI(OAc) as
2
2
f
2
2
1
the stoichiometric oxidant, this procedure represented a 100:5); H NMR (400 MHz, CD Cl ): d ˆ 8.30 (2H, d, J ˆ
2
2
significant improvement with regard to practicability 7.7 Hz), 8.08 (1H, t, J ˆ 7.7 Hz), 7.83 (2H, t, J ˆ 7.7 Hz), 7.60
and generality. Further studies towards improvements (1H, t, J ˆ 7.7 Hz), 4.87 ± 4.92 (2H, unresolved dd), 3.77 ± 3.86
1
3
(
2H, m), 0.74 (6H, d, J ˆ 6.6 Hz); C NMR (100.61 MHz,
of the enantioselectivities by varying pybox ligands are
currently in progress.
CDCl ): d ˆ 171.45, 166.61, 150.97, 147.27, 134.75, 127.03,
3
‡
1
26.65, 123.64, 59.96, 33.81, 18.88; FAB-MS: m/z ˆ 512 (M );
UV-VIS (CH Cl ): l
(log e) ˆ 381 (3.57), 480 nm (4.30);
102 ‡
2
2
max
HRMS (ESI ‡ ): m/z calcd. for C H N O Ru ‡ H :
2
0
19
4
6
5
13.03380; found: 513.03479.
Ru(S,S-Me -S,S-Ph -pybox)(pydic) (1d): R ˆ 0.16 (CH Cl /
Experimental Section
2
2
f
2
2
1
MeOH, 100:5); H NMR (400.1 MHz, CD Cl ): d ˆ 8.23 (2H,
2
2
d, J ˆ 7.5 Hz), 8.08 (1H, t, J ˆ 7.5 Hz), 8.00 (2H, d, J ˆ 7.9 Hz),
General information
7
5
.69 (1H, t, J ˆ 7.9 Hz), 7.38 ± 7.41 (6H, m), 7.33 ± 7.37 (4H, m),
1
13
H and C NMR spectra were recorded on a Bruker ARX 400
.51 (2H, d, J ˆ 9.7 Hz), 3.75 (2H , dd, J ˆ 9.7, 6.7 Hz), 0.84 (6H,
1
13
spectrometer ( H: 400.1 MHz, C 100.6 MHz). Chemical shifts
d) are given in ppm and refer to the residual solvent as the
13
d, J ˆ 6.7 Hz); C NMR (100.6 MHz, CD Cl ): d ˆ 171.3,
2
2
(
1
1
(
66.5, 151.3, 147.4, 136.7, 135.8, 135.1, 129.1, 126.9, 126.5,
internal standard. Gas chromatography was performed on a
Hewlett Packard HP 6890 chromatograph with a HP5 column
‡
24.1, 92.5, 68.1, 18.2; FAB-MS: m/z ˆ 664 (M ); UV-VIS
CH Cl ): l
(log e) ˆ 382 (3.81), 482 nm (4.53); analysis
2
2
max
(
5% phenyl methyl siloxane, 30 m, 250 mm, 0.25 mm). Mass
calcd. (%) for C H N O Ru: C 57.91, H 3.95, N 8.44; found: C
3
2
26
4
6
spectra were recorded on an AMD 402/3 mass spectrometer.
High-performance liquid chromatography was carried out
using a Hewlett Packard HP 1090 liquid chromatograph
equipped with a DAD. Enantiomeric excess values were
determined by HPLC. Chemicals and solvents were purchased
from Fluka and Aldrich and used as received.
5
7.86, H 3.84, N 8.27.
Ru(S,S-indanol -pybox)(pydic) (1e): R ˆ 0.11 (CH Cl /
2
f
2
2
1
MeOH, 100:5); H NMR (400 MHz, CDCl ): d ˆ 8.57 (2H, d,
3
J ˆ 7.7 Hz), 8.31 (1H, t, J ˆ 7.7 Hz), 7.86 (2H, d, J ˆ 7.7 Hz),
7
5
8
1
.59 (1H, t, J ˆ 7.7 Hz), 7.12 ± 7.18 (4H, m), 7.00 ± 7.03 (2H, m),
.95 (2H, d, J ˆ 7.7 Hz), 5.83 ± 5.87 (2H, m), 4.99 (2H, d, J ˆ
.1 Hz), 3.50 (2H, dd, J ˆ 7.3, 18.2 Hz), 3.37 (2H, dd, J ˆ 2.2,
1
3
8.2 Hz); C NMR (100.61 MHz, CDCl ): d ˆ 192.67, 171.33,
3
Synthesis of the Ruthenium Complexes
152.14, 147.36, 139.22, 136.75, 135.08, 129.70, 127.87, 127.47,
1
25.27, 124.22, 125.11, 116.45, 87.71, 78.60, 73.68; FAB-MS:
To a solution of the corresponding pybox ligand (0.34 mmol)
and [Ru(p-cymene)Cl2]2 (104 mg, 0.17 mmol) in MeOH
‡
m/z ˆ 660 (M ); UV-VIS (CH Cl ): l (log e) ˆ 383 (3.62),
2
2
max
4
84 nm (4.39); HRMS (ESI ‡ ): m/z calcd. for
(
(
2 mL), disodium pyridine-2,6-dicarboxylate, Na pydic,
102
2
C H N O Ru: 661.06538; found: 661.06610.
3
6
23
4
6
72 mg, 0.34 mmol) in MeOH/H O 1:1 (2 mL) was added
2
under Ar. The whole reaction mixture was heated to 658C for
h. After cooling to room temperature the mixture was diluted
1
with CH Cl (30 mL) and washed with H O (30 mL). The deep General Procedure for the Catalytic Reactions
2
2
2
orange organic layer was dried over MgSO , filtered and
concentrated under reduced pressure. The reaction mixture
was then purified by silica gel column chromatography (70 ±
4
All prepared oxiranes are known compounds.[11] The prepara-
tion of trans-stilbene oxide is shown as a typical example of the
catalytic reactions.
2
30 mesh), using CH Cl /MeOH (100:2 to 100:5). After
2 2
removal of solvent under reduced pressure, the products can be
crystallized from CH Cl /n-hexane.
2
2
Ru(S,S-i-Pr -pybox)(pydic) (1a):[6b] R ˆ 0.33 (CH Cl /
2
f
2
2
Preparation of trans-Stilbene Oxide (Table 1 and
Table 2, entry 1)
1
MeOH, 10:1); H NMR (400.1 MHz, CDCl ): d ˆ 8.30 (2H,
3
d, J ˆ 7.7 Hz), 8.08 (1H, t, J ˆ 7.7 Hz), 7.85 (2H, d, J ˆ 7.8 Hz),
7
4
.61 (1H, t, J ˆ 7.8 Hz), 4.64 ± 4.68 (2H, unresolved dd), 4.56 ± In a 25-mL Schlenk tube, substrate (0.5 mmol) and Ru (S,S-
.60 (2H, unresolved dd), 3.66 ± 3.71 (2H, m), 1.03 ± 1.10 (2H,
Ph -pybox)(pydic) (15.9 mg, 0.025 mmol) were dissolved in
2
1
3
m), 0.59 (6H, d, J ˆ 7.2 Hz), 0.44 (6H, d, J ˆ 6.8 Hz); C NMR
tert-butanol (9 mL). Then dodecane (100 mL) was added as an
internal standard for GC and a solution of TBHP (103 mL,
0.75 mmol, 1.5 equivs.) in tert-butanol (1 mL) was added over a
period of 12 h by a syringe pump. After completion of the
reaction (monitored by GC-FID), the mixture was quenched
with saturated Na SO solution ( ꢀ 10 mL), extracted with
(
1
(
(
100.6 MHz, CDCl ): d ˆ 171.5, 166.5, 150.9, 147.1, 134.7,
3
27.0, 126.6, 123.8, 71.0, 68.9, 18.8, 13.8; FAB-MS: m/z ˆ 568
‡
M ); UV-VIS (CH Cl ): l
(log e) ˆ 382 (3.56), 480 nm
2
2
max
4.30).
Ru(S,S-Ph -pybox)(pydic) (1b):[6b] R ˆ 0.08 (CH Cl /
2
f
2
2
2
3
1
MeOH, 100:5); H NMR (400.1 MHz, CDCl ): d ˆ 7.95 (2H,
dichloromethane (10 mL Â 2) and washed with water
3
266
¹ 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
Adv. Synth. Catal. 2004, 346, 263 ± 267

Ruthenium-Catalyzed Asymmetric Alkene Epoxidation
FULL PAPERS
(
ꢀ 20 mL). The combined organic layers were dried over
New York, 1993, Chapter 4.1; b) T. Katsuki, V. S. Martin,
Org. React. 1996, 48.
MgSO and analyzed by HPLC. The epoxide was further
4
purified by silica gel column chromatography (70 ± 230 mesh),
saturated with triethylamine ( ꢀ 3%), and n-hexane/ethyl
acetate (100:1) as the eluent.
[3] Reviews for Mn: a) E. N. Jacobsen, In: Catalytic Asym-
metric Synthesis, (Ed.: I. Ojima), VCH: New York, 1993,
Chapter 4.2; b) T. Katsuki, In: Catalytic Asymmetric
1
trans-Stilbene oxide: Colorless solid; H NMR (400.1 MHz,
nd
Synthesis, 2 edn., (Ed.: I. Ojima), Wiley-VCH: New
York, 2000, pp 287 ± 325; c) T. Katsuki, Adv. Synth. Catal.
1
3
CDCl ): d ˆ 7.24 ± 7.31 (10H, m), 3.87 (2H, s); C NMR (100.6,
3
MHz, CDCl ): d ˆ 137.1, 128.6, 128.6, 125.5, 62.8; EIMS
3
2
002, 344, 131 ± 147.
‡
(
70 eV): m/z ˆ 196 (M ); HPLC (Chiralcel AD-114; hexane/
[
4] a) C. Dˆbler, G. Mehltretter, M Beller, Angew. Chem.
Int. Ed. 1999, 38, 3026 ± 3028; b) C. Dˆbler, G. M.
Mehltretter, U. Sundermeier, M. Beller, M. J. Am.
Chem. Soc. 2000, 122, 10289 ± 10297; c) C. Dˆbler, G.
Mehltretter, U. Sundermeier, M. Beller, J. Organomet.
Chem. 2001, 621, 70 ± 76; d) C. Dˆbler, G. M. Mehltret-
ter, U. Sundermeier, M. Beller, M. Eckert, H.-C.
Militzer, Tetrahedron Lett. 2001, 42, 8447 ± 8449; e) U.
Sundermeier, C. Dˆbler, G. M. Mehltretter, W. Bau-
mann, M. Beller, Chirality 2003, 15, 127 ± 134; f) G. M.
Mehltretter, S. Bhor, S. M. Klawonn, C. Dˆbler, M.
Eckert, H.-C. Militzer, M. Beller, Synthesis 2003, 295 ±
301.
EtOH, 99:1, flow rate 1.0 mL/min): t ˆ 7.12 min, 16.63 min.
R
2
,2-Dimethyl-3-phenyloxirane (Table 2, entry 3): Colorless
1
oil; H NMR (400.1 MHz, CDCl ): d ˆ 7.37 ± 7.27 (5H, m), 3.88
3
1
3
(
1H, s), 1.09 (3H, s), 1.49 (3H, s); C NMR (100.6 MHz,
CDCl ): d ˆ 137.0, 128.4, 127.8, 126.8, 61.6, 25.2, 18.4; EIMS
3
‡
(
70 eV): m/z ˆ 148 (M ); HPLC (Chiralcel AD-114; hexane/
EtOH, 99:1, flow rate 0.5 mL/min ): t ˆ 9.25 min, 10.25 min.
R
trans-a-Methylstilbene oxide (Table 2, entry 4): White
1
solid; H NMR (400.1 MHz, CDCl ): d ˆ 7.30 ± 7.46 (10H, m),
3
1
3
3
1
.96 (1H, s), 1.64 (3H, s); C NMR (100.6 MHz, CDCl ): d ˆ
3
42.8, 136.3, 129.2, 128.6, 127.9, 126.9, 125.5, 67.5, 63.5, 17.1;
‡
EIMS (70 eV): m/z ˆ 210 (M ); HPLC (Whelk 01 (R,R);
hexane/EtOH, 99:1, flow rate 0.6 mL/min ): t ˆ 5.33 min,
R
5
.97 min.
[5] M. K. Tse, S. Bhor, M. Klawonn, C. Dˆbler, M. Beller,
Tetrahedron Lett. 2003, 44, 7479 ± 7483.
[6] Recent achievements in Ru-based asymmetric epoxida-
tion see: a) R. I. Kureshy, N. H. Kahn, S. H. R. Abdi,
K. N. Bhatt, Tetrahedron: Asymmetry 1993, 4, 1693 ±
(
4-Chlorophenyl)-oxirane (Table 2, entry 8): Colorless oil;
1
H NMR (400.1 MHz, CDCl ): d ˆ 7.12 ± 7.26 (4H, m), 3.76
3
(
1H, dd, J ˆ 4.0, 2.6 Hz), 3.07 (1H, dd, J ˆ 5.6, 4.0 Hz), 2.68 (1H,
1
3
dd, J ˆ 5.6, 2.6 Hz); C NMR (100.6 MHz, CDCl ): d ˆ 136.3,
3
1
2
1
34.1, 128.8, 127, 51.9, 51.4; EIMS (70 eV): m/z ˆ 156 [(M ‡
1
701; b) H. Nishiyama, T. Shimada, H. Itoh, H. Sugiya-
‡ ‡
) ], 154 (M ); HPLC (Chiralcel OB-H; hexane, flow rate
ma, Y. Motoyama, Chem. Commun. 1997, 1863 ± 1864;
c) N. End, A. Pfaltz, Chem. Commun. 1999, 589 ± 590;
d) Z. Gross, S. Ini, Org. Lett. 1999, 1, 2077 ± 2080 and
references therein; e) R. M. Stoop, S. Bachmann, M.
Valentini, A. Mezzetti, Organometallics 2000, 19, 4117 ±
4126; f) F. Pezet, H. AÔt-Haddou, J.-C. Daran, I. Sadaki,
G. G. A. Balavoine, Chem. Commun. 2002, 510 ± 511.
7] For recent examples using Ru salen complexes, see: a) T.
Takeda, R. Irie, Y. Shinoda, T. Katsuki, Synlett 1999,
.0 mL/min ): t ˆ 14.88 min, 17.61 min.
R
1
,2-Epoxy-1-methylcyclohexane (Table 2, entry 11). Color-
1
less oil; H NMR (400.1 MHz, CDCl ): d ˆ 2.87 (1H, br s),
3
1
.82 ± 1.78 (2H, m), 1.59 (2H, m), 1.36 ± 1.31 (2H, m), 1.22 (5H,
13
m); C NMR (100.6 MHz, CDCl ): d ˆ 59.6, 57.8, 29.9, 25.0,
3
‡
2
2.7, 20.1, 19.7; EIMS (70 eV): m/z ˆ 112 ([M] ).
[
Acknowledgements
1
157 ± 1159; b) K. Nakata, T. Takeda, J. Mihara, T.
Hamada, R. Irie, T. Katsuki, Chem. Eur. J. 2001, 7,
776 ± 3782.
M. K. T. thanks the Alexander-von-Humboldt-Stiftung for an
AvH-fellowship. We acknowledge Prof. Dr. B. L¸cke and Dr. A.
Kˆckritz (both ACA, Berlin) for general discussion. This work
was supported by the Bundesministerium f¸r Bildung und
Forschung (BMBF), Bayer AG, and the Deutsche Forschungs-
gemeinschaft (SPP Sekund‰re Wechselwirkungen).
3
[
[
8] For an excellent review using Ru complexes for epox-
idation reactions see: G. A. Barf, R. A. Sheldon, J. Mol.
Catal. 1995, 102, 23 ± 39.
9] I. W. Davies, L. Garena, N. Lu, R. D. Larsen, P. J. Reider,
J. Org. Chem. 1996, 61, 9629 ± 9630.
[
[
10] G. Desimoni, G. Faita, M. Guala, C. Pratelli, Tetrahe-
dron: Asymmetry. 2001, 13, 1651 ± 1654.
11] a) Z.-X. Wang, Y. Tu. M. Frohn, J.-R. Zhang, Y. Shi, J.
Am. Chem. Soc. 1997, 119, 11224 ± 11235; b) D. Yang, Y.-
C. Yip, G.-S. Jiyo, M.-K. Wong, J. Org. Chem. 1998, 63,
References and Notes
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1] a) R. Noyori, Asymmetric Catalysis in Organic Synthesis,
Wiley: New York, 1994; b) M. Beller, C. Bolm, (Eds.),
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Weinheim, 1999; c) E. N. Jacobsen, A. Pfaltz, H. Yama-
moto, (Eds.), Comprehensive Asymmetric Catalysis,
Springer: Berlin, 1999.
8
952 ± 8956; c) F. Fringuelli, O. Piermatti, F. Pizzo, L.
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Zhang, W.-Y. Yu, K.-Y. Wong, C.-M. Che , J. Org.
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[2] Reviews for Ti: a) R. A. Johnson, K. B. Sharpless, In:
Catalytic Asymmetric Synthesis, (Ed.: I. Ojima), VCH:
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asc.wiley-vch.de
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267