Ruthenium-catalyzed asymmetric epoxidation of olefins using H 2O2, part II: Catalytic activities and mechanism

Article abstract of DOI:10.1002/chem.200501262

Asymmetric epoxidation of olefins with 30% H₂O₂ in the presence of [Ru(pybox)(pydic)] 1 and [Ru(pyboxazine)(pydic)] 2 has been studied in detail (pybox = pyridine-2,6-bisoxazoline, pyboxazine = pyridine-2,6-bisoxazine, pydic = 2,6-pyridinedi-carboxylate). 35 Ruthenium complexes with sterically and electronically different substituents have been tested in environmentally benign epoxidation reactions. Mono-, 1,1-di-, cis- and trans-1,2-di-, tri-, and tetra-substituted aromatic olefins with versatile functional groups can be epoxidized with this type of catalyst in good to excellent yields (up to 100%) with moderate to good enantioselectivies (up to 84% ee). Additive and solvent effects as well as the relative rate of reaction with different catalysts have been established. It is shown that the presence of weak organic acids or an electron-withdrawing group on the catalyst increases the reactivity. New insights on the reaction intermediates and reaction pathway of the ruthenium-catalyzed epoxidation are proposed on the basis of density functional theory calculation and experiments.

Full text of DOI:10.1002/chem.200501262

FULL PAPER
DOI: 10.1002/chem.200501262
Ruthenium-Catalyzed Asymmetric Epoxidation of Olefins Using H2O2,
Part II: Catalytic Activities and Mechanism
Man Kin Tse,[a] Santosh Bhor,[a] Markus Klawonn,[a] Gopinathan Anilkumar,[a]
Haijun Jiao,[a] Anke Spannenberg,[a] Christian Dçbler,[a] Wolfgang Mägerlein,[b]
Herbert Hugl,[b] and Matthias Beller*[a]
Abstract: Asymmetric epoxidation of
di-, tri-, and tetra-substituted aromatic
olefins with versatile functional groups
can be epoxidized with this type of cat-
alyst in good to excellent yields (up to
100%) with moderate to good enantio-
selectivies (up to 84% ee). Additive
and solvent effects as well as the rela-
tive rate of reaction with different cata-
lysts have been established. It is shown
that the presence of weak organic acids
or an electron-withdrawing group on
the catalyst increases the reactivity.
New insights on the reaction intermedi-
ates and reaction pathway of the ruthe-
nium-catalyzed epoxidation are pro-
posed on the basis of density functional
theory calculation and experiments.
olefins with 30%H O2 in the presence
2
of
[Ru(pyboxazine)(pydic)]
studied in detail (pybox=pyridine-2,6-
bisoxazoline, pyboxazine=pyridine-
[Ru(pybox)(pydic)]
1
and
2
has been
2,6-bisoxazine, pydic=2,6-pyridinedi-
carboxylate). 35 Ruthenium complexes
with sterically and electronically differ-
ent substituents have been tested in en-
vironmentally benign epoxidation reac-
tions. Mono-, 1,1-di-, cis- and trans-1,2-
Keywords: asymmetric oxidation ·
epoxidation
·
homogeneous
catalysis · mechanism · olefins ·
ruthenium
Introduction
ly for oxidation (this corresponds to only 50%atom effi-
ciency) in most of the cases and such processes produce sig-
nificant amount of waste from the co-reductant.[3,4] Apart
from molecular oxygen, hydrogen peroxide (H2O2) has been
shown to be environmentally benign by a similar atom-econ-
omy with its side product being water. In addition, it is read-
ily available, has a comparably low price (<0.6 EkgÀ1 of
One of the core technologies to convert bulk raw materials,
such as alkanes and olefins, to value-added products is, un-
doubtedly, oxidation reactions.[1] On the one hand, high se-
lectivity, broad substrate scope, and sufficient catalyst stabil-
ity and productivity are in high priority of any chemical pro-
cess. On the other, 100%atom-economy, usage of environ-
mentally benign reagents, and minimizing or eliminating the
use of dangerous chemicals are the major concerns for the
general application of oxidation reactions.[2] Among the
readily available oxidants, molecular oxygen seems to be the
perfect reagent for an oxidation reaction. However, only
one oxygen atom of an oxygen molecule is used productive-
100%H O2) and can be used safely without much precau-
2
tions.[5,6] In general, it is particularly useful for liquid-phase
oxidation for the synthesis of fine chemicals, pharmaceuti-
cals, agrochemicals, and electronic materials. Clearly, the de-
velopment of new catalytic systems using H2O2 is still an im-
portant and challenging goal in oxidation chemistry.[7,8]
With regard to enantioselective epoxidation of olefins, ti-
tanium (Sharpless epoxidation)[9] and manganese (Jacobsen–
Katsuki epoxidation)[10] based catalysts are still in the state-
of-the-art. Significant progress using organic catalysts based
on chiral ketones has been reported by Shi, Yang, and
others recently.[11,12] Besides, polypeptide-catalyzed epoxida-
tion of enones under basic phase-transfer conditions is prob-
ably one of the most applicable processes in this context.[13]
Our interest in the past years has been aroused by ruthe-
nium-catalyzed oxidation reactions with its wide range of
applicability and broad variation of ligand type especially in
the asymmetric epoxidation of olefins (1, 6–14).[14] Mono-,
[a] Dr. M. K. Tse, Dr. S. Bhor, Dr. M. Klawonn, Dr. G. Anilkumar,
Dr. H. Jiao, Dr. A. Spannenberg, Dr. C. Dçbler, Prof. Dr. M. Beller
Leibniz-Institut für Organische Katalyse
an der Universität Rostock e.V.
Albert-Einstein-Strasse 29a, 18059 Rostock (Germany)
Fax : (+49)381-1281-5000
E-mail: matthias.beller@ifok-rostock.de
[b] Dr. W. Mägerlein, Prof. Dr. H. Hugl
LANXESS Deutschland GmbH, BU Fine Chemicals
51369 Leverkusen (Germany)
Chem. Eur. J. 2006, 12, 1875 – 1888
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1875

have
been
reported
(Scheme 1).
We chose (pyridine-2,6-bi-
soxazoline)(2,6-pyridinedicar-
boxylate)ruthenium
([Ru-
(pybox)(pydic)] 1) as the start-
ing point for our research on
novel epoxidation catalysts as
it contains two different meri-
dional ligands (see preceeding
article).[16] It is apparent that
by varying the chiral pybox
and the achiral pydic separate-
ly, the reactivity as well as the
(enantio)selectivity of the cata-
lyst should be easily tuned.
Initially, we demonstrated
that 1 becomes a more practi-
cal oxidation catalyst by add-
ing a defined amount of water
to the reaction mixture.[29a]
This also led to the develop-
ment of enantioselective epoxi-
dation protocols applying alkyl
peroxides[29b] and hydrogen
bi-, tri-, and tetradentate ligands as well as macrocyclic por-
phyrins have been found useful ligands for this reaction.
Moreover, various coordinating atoms such as N, O, S, or P
can all be beneficial for a given Ru catalyst. In some of the
cases combination of ligands has also been applied. Howev-
er, in spite of extensive research efforts, the development of
a general and catalytic asymmetric epoxidation method with
peroxide.[29d–g] In this paper we describe a full account of our
work on ruthenium-catalyzed asymmetric epoxidation with
H2O2 as the oxidant as well as the mechanistic studies. Sys-
tematic variation of the ligands led to the development
of (pyridine-2,6-bisoxazine)(2,6-pyridinedicarboxylate)ruthe-
nium ([Ru(pyboxazine)(pydic)] 2) as novel epoxidation cat-
alysts.
high
enantioselectivity
by
using hydrogen peroxide has
not yet been achieved.[15] Gen-
erally, there are several draw-
backs in asymmetric epoxida-
tion utilizing H2O2.[8] For in-
stance more than the stoichio-
metric amount of H2O2 is
needed to solve the problem
of unproductive decomposition
of H2O2 to O2 by the used
transition-metal catalyst.
Evidently, the stability of
the catalyst and the ligands in
high concentration of H2O2 as
well as the selectivity, especial-
ly enantioselectivity, in the
presence of water can be prob-
lematic. It is also not uncom-
mon that oxidative cleavage of
the olefin competes with the
productive epoxidation. There-
fore only a handful of exam-
ples of asymmetric epoxidation
of simple styrene using H2O2
Scheme 1. Catalysts for asymmetric epoxidation of styrene.
1876
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Chem. Eur. J. 2006, 12, 1875 – 1888

Homogeneous Catalysis
FULL PAPER
Results and Discussion
slowly dosed into the reaction mixture. In general, after 12 h
of addition of H2O2 good yield for the epoxidation of sty-
rene and an excellent yield for that of trans-stilbene are ob-
tained. It is worth noting that aryl groups on the C4-position
generally gave a better reactivity towards styrene than alkyl
groups (Table 1, entries 1–16 and entries 18–22). When a
highly sterically demanding group is introduced, either on
the C4- or C5-position, the reactivity dropped tremendously
(Table 1, entries 17 and 20). However, functional groups like
amine, alkoxy, ester, halogen, hydroxy, and silylether did not
affect the reactivity much (Table 1). In general,
As a starting point for our systematic investigation, we syn-
thesized and tested some [Ru(pybox)(pydic)] (1aa, 1na, and
1pa) complexes from commercially available chiral pybox li-
gands and found that the substitutions on the C4- and C5-
positions of the oxazoline ring affect both the reactivity and
selectivity of the catalyst.[29] We then identified the possibili-
ties of variation of the catalyst according to the availability
of starting materials, literature knowledge, and the ease of
synthesis. These versatile electronic and steric substitution
effects are valuable for a further development of the catalyst
by rational design.[30] Hence, more than 30 different [Ru-
(pybox)(pydic)] 1 and [Ru(pyboxazine)(pydic)] 2 complexes
were synthesized (Scheme 2) and tested in the asymmetric
[Ru(pyboxazine)(pydic)]
2 were less reactive than its
“pybox cousins” for trans-stilbene as well as styrene
(Table 1, entries 1 and 19; Table 2, entries 1, 2, and 9).[32]
From these initial reactivity patterns, we thought that modi-
fication of the catalyts should
be possible to increase the ee
without losing much reactivity.
Indeed, the substituents on
both the C4- and C5-positions
have a large influence on the
ee of the prototypical reac-
tions. The ee of styrene oxide
ranged from 0–37%and 25–
48%in 1 and 2, respectively
(Tables 1 and 2).[33] Aryl sub-
stituents on the C4-position
generally gave higher ee than
the alkyl groups (Table 1, en-
Scheme 2. Synthesis of [Ru(pybox)(pydic)] 1 and [Ru(pyboxazine)(pydic)] 2.[31]
tries 1, 12, and 18–22; Table 2,
epoxidation of styrene (Scheme 3, Tables 1 and 2).[31] For a
better understanding of the generality of a specific catalyst,
we also tested these catalysts with trans-stilbene as substrate
(Scheme 3, Tables 1 and 2).
entries 1, 2, and 4–9). This positive effect is attributed to a
p–p interaction between the ligand and the aryl substrates.
Among the different aryl substituents, the larger 2-naphthyl
group was beneficial in 1 with respect to a phenyl group
(Table 1, entry 1 versus 12). However, a higher ee is not ob-
tained in the case of 2 under standard reaction conditions
(Table 2, entries 2, 5, vide infra). The more sterically hin-
dered 1-naphthyl group in 2 turned out to be inferior to the
ee (Table 2, entry 4). Furthermore, phenyl substitution on
the C5-position in 1 has interesting effects on the enantiose-
lectivity.
Scheme 3. [Ru(pybox)(pydic)] 1- or [Ru(pyboxazine)(pydic)] 2-catalyzed
epoxidation of styrene and trans-stilbene.
On the one hand it had no significant asymmetric induc-
tion to the product when there was no substituent at the C4-
position (Table 1, entry 13). On the other hand it dominated
the asymmetric induction when a methyl group is trans to it
(Table 1, entries 18 and 21). However, when two phenyl
groups were on both C4- and C5-positions, to our surprise,
the trans-orientation gave a positive influence to the ee of
styrene oxide, while the cis-orientation resulted in a reduc-
tion of ee (Table 1, entries 1, 14 and 15). This clearly is a co-
operative effect and the reasons are difficult to understand.
Evidently, one has to consider the effects of the substitution
on the ligands as a whole rather than as single additive ef-
fects.
The applied [Ru(pybox)(pydic)] 1 catalysts have a broad
coverage of substitution pattern, including 4-, 5-, cis-4,5-di-,
trans-4,5-di-, and 4,5,5-tri-substitution on the oxazoline ring;
para-substitution on the pyridine ring on both pybox and
pydic; ortho- or meta- substitution on the phenyl ring at the
C4-position of the oxazoline; and a wide range of functional
groups, such as halogen, alcohol, amine, silyl ether, ester,
aryl, and alkyl groups. Complementary to [Ru(pybox)-
(pydic)] 1, the six-membered pyboxazine derivatives 2 con-
tain also aryl and alkyl group at the C4-positions and para-
substitution on the phenyl ring at C4 as well.
For convenience the catalytic reactions were run at room
temperature in the presence of 5 mol%of Ru complex
using three equivalents of H2O2 (30%in water), which was
The influence of the size of the alkyl group at the C4-po-
sition to the ee of styrene oxide was not significant (10–
19% ee; Table 1, entries 18, 19, and 22). The yield of styrene
Chem. Eur. J. 2006, 12, 1875 – 1888
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1877

M. Beller et al.
Table 1. [Ru(pybox)(pydic)] 1-catalyzed epoxidation of styrene and trans-stilbene with H2O2.[a]
n=0, [Ru(pybox)(pydic)] 1
Entry
R1
R2
R3
R4
X
Y
Yield
[%]
ee[b]
[%]
Yield
[%]
ee[c]
[%]
1
2
3
4
5
6
7
8
9
1aa
1ab
1ac
1ad
1ae
1af
1ba
1ca
1da
1ea
H
H
H
H
H
H
H
H
H
H
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
Cl
NMe2
Ph
1-Np
H
OH
Cl
Br
OMe
Ph
H
H
H
H
70
77
65
65
62
65
61
74
64
–
+31
+27
+43
+44
+24
+36
+23
+26
+33
–
100
100
93
97
95
97
93
99
97
98
À67
À45
À66
À66
À52
À65
À71
À34
À69
À63
10
11
1 fa
H
59
+18
93
À46
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
1ga
1ha
1ia
1ja
1ka
1la
1ma
1na
1oa
1pa
1qa
1ra
1 sa
1ta
2-Np
H
Ph
Ph
H
Ph
H
H
H
H
H
H
H
H
H
H
H
H
Ph
H
H
Me
H
H
H
Ph
H
H
Ph
H
Ph
H
Me
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
69
66
78
68
59
32
52
45
32
64
51
48
–
À37
À3
99
93
100
94
95
29
100
100
35
94
87
+70
À1
À18
À35
+24
+12
+12
+19
0
+14
+65
À50
À32
À51
À54
À29
+42
À35
+25
+50
À36
+25
2-ClC6H4
H
Me
iPr
tBu
Me
Bn
CH2OH
À14
+10
À10
–
H
H
H
H
H
H
H
H
91
100
85
CH2OTBS
H
CO2Me
H
CH(CH3)OTBS
H
–
–
–
–
1ua
92
[a] See Experimental Section. [b] “+” sign means (R)-(+)-styrene oxide is the major enantiomer. [c] “À” sign means (S,S)-(À)-trans-stilbene oxide is the
major enantiomer.
Table 2. [Ru(pybox)(pydic)] 1-catalyzed epoxidation of styrene and trans-stilbene with H2O2.[a]
The para-positions of the
pyridine ring of the pybox-
(azine) and pydic ligands also
n=1, [Ru(pyboxazine)(pydic)] 2
R1
R2
R3
R4
X
Y
Yield
[%]
ee[b]
[%]
Yield
[%]
ee[c]
[%]
influenced the ee of styrene
oxide. Electron-deficient
Entry
groups on pydic increased the
ee up to 44%, while the elec-
tron-donating groups reduced
the ee (Table 1, entries 1–5).
The weak electron-withdraw-
ing phenyl group has a positive
effect to the ee as well possibly
owing to additional p–p inter-
actions with the substrate.
However, the electronic effects
on the pybox side seem to be
1
2
3
4
5
6
7
8
9
(R)-2aa
(S)-2aa
(R)-2ac
(R)-2ba
(S)-2ba
(R)-2ca
(S)-2da
(S)-2ea
(R)-2 fa
H
Ph
H
H
Ph
H
Ph
1-Np
H
2-Np
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
Cl
H
H
H
H
H
H
56
61
66
65
71
59
69
54
59
+48
À46
+47
+38
À44
+48
À48
À31
+25
93
86
49
92
95
99
99
88
60
-53
+51
À43
À30
+32
À54
+51
+52
À30
1-Np
H
4-ClC6H4
4-MeOC6H4
H
iPr
[a] See Experimental Section. [b] “+” sign means (R)-(+)-styrene oxide is the major enantiomer. [c] “À” sign
means (S,S)-(À)-trans-stilbene oxide is the major enantiomer.
oxide and ee were both very low for the tert-butyl derivative
1oa, possibly due to decomposition of the catalyst (Table 1,
entry 20). The steric effect of the substituents on the cata-
lysts to the ee in the case of trans-stilbene oxide follows the
same trend as styrene oxide. However, the effect diminishes
when the ee reached around 70%in 1.
controversial both in styrene and trans-stilbene cases
(Table 1, entries 7–10). With a para-chloro group, the ee in-
creased for trans-stilbene oxide and decreased for styrene
oxide (Table 1, entry 7). However, in case of NMe2 and Ph
groups, the ee for trans-stilbene oxide and styrene oxide had
the same trend (Table 1, entries 8, 9). Since the absolute
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Chem. Eur. J. 2006, 12, 1875 – 1888

Homogeneous Catalysis
FULL PAPER
configuration of trans-stilbene oxide and styrene oxide are
always the opposite with the same catalyst, we believe that
the two test reactions pass through different major transition
states. At this point we did not have any conclusive explana-
tion of the electronic effects. But as we shall see below
(mechanistic studies), it is suggested that the difference of
ee is due to the difference of the rate of reaction and the in-
fluence of water content in the reaction mixture (vide infra).
Clearly, solvent effects plays an important role in asym-
metric catalysis.[34] Therefore, we tested the asymmetric ep-
oxidation of trans-stilbene in ten different reaction media.
As shown in Table 3 protic solvents gave best results in this
20 mol%of HOAc was added, the epoxide yield increased
from 71 to 75%and the ee increased from 31 to 42%. Fur-
ther increasing the amount of HOAc did not give positive
effects. When para-substituted benzoic acids with electron-
donating or -withdrawing groups were used as the additives,
similar results are obtained. It is questionable whether the
acid is acting as a ligand in the reaction mixture in contrast
to the iron-catalyzed sulfur oxidation demonstrated by Bolm
and co-workers.[8k]
To understand the effect of the organic acid in more
detail we traced the 1aa-catalyzed epoxidation of trans-stil-
bene with 30%H O2 with time in the presence and absence
2
of 20 mol%HOAc (Figure 1).
Table 3. Solvent effects in the [Ru(S,S-Ph2-pybox)(pydic)] 1aa-catalyzed epoxidation of trans-stilbene with
In the initial stage of the reac-
tion, the conversion of trans-
stilbene was more or less the
same in both cases. As the re-
action went further, the one
with 20 mol%HOAc kept the
rate of reaction, while the one
without HOAc decelerated.
This indicates that HOAc ac-
celerates the reaction, possibly
by slowing down the self-deg-
radation of the active catalyst.
Since the water content in-
creases during the addition
when H2O2 is used as the oxi-
dant, the faster the reaction
the higher the ee is.[29e] Thus,
the positive effect of added
carboxylic acid is the best ap-
plicable to a less reactive cata-
lyst with less reactive sub-
H2O2.[a]
Entry
Solvent
Conversion [%][b]
Yield [%][b]
Selectivity [%][c]
ee [%][d]
1
2
3
tAmOH
tBuOH
iPrOH
100
100
91
100
93
87
100
93
96
À67[e]
À65
À57
4
83
80
96
À66
5
100
0
0
n.d.[f]
6
7
8
9
toluene
CH3CN
[Bmim]PF6
1,4-dioxane
6
100
trace
44
5
86
trace
38
100
86
–
n.d.[f]
À39
n.d.[f]
À28
86
10
trace
trace
–
n.d.[f]
[a] Reaction conditions: In a 25 mL Schlenk tube, 1aa (0.025 mmol) was stirred at room temperature in the
solvent (9 mL) for 10 min. trans-Stilbene (0.5 mmol) and dodecane (GC internal standard, 100 mL) were
added. A solution of hydrogen peroxide (170 mL, 1.5 mmol) in the solvent (830 mL) was added over a period
of 12 h by a syringe pump to this reaction mixture. [b] Determined by comparing with authentic samples on
GC-FID. [c] Chemoselectivity for epoxide formation. [d] Determined by HPLC. [e] “À” sign means (S,S)-(À)-
trans-stilbene oxide was the major enantiomer. [f] Not determined.
reaction (Table 3, entries 1–4). Hence, excellent yield and
good ee have been achieved with tertiary alcohols. Use of
the secondary alcohol 2-propanol gave a lower ee, since the
competitive reaction of oxidation of 2-propanol occurred,[35]
which increased the water content of the reaction mixture
during the addition of H2O2. Previously, we have demon-
strated that over-dosage of H2O in the epoxidation of trans-
stilbene catalyzed by 1aa with PhI(OAc)2 as the oxidant
also decreased the ee.[29a] In the presence of the more acidic
1,1,1,3,3,3-hexafluoro-2-propanol high conversion of the
olefin is observed, without any epoxide detected due to the
decomposition of the stilbene oxide in the reaction medium
(Table 3, entry 5). Other nonpolar solvents and one example
of an ionic liquid showed to be inferior to the model reac-
tion.
strates. Accordingly, this effect diminishes when electron-
rich olefins are employed.
Next, we applied both 1aa and (R)-2ca to 24 different
olefins with versatile functional groups and substitution pat-
terns (Table 4). In general, both catalysts showed good activ-
In addition to the variation of solvents we also tested 30
different additives to the epoxidation catalyzed by 1aa.
They included amines (four examples), pyridines (four ex-
amples), pyridine oxides (six examples), phosphine oxides
(two examples), ammonium salts (four examples), and or-
ganic acids (ten examples). To our delight, organic acids
generally increased the epoxide yield and the ee when a less
reactive substrate is employed. In a typical reaction, when
Figure 1. Conversion of trans-stilbene against time with 20 mol%HOAc
(pink) and without HOAc (blue) in the epoxidation of trans-stilbene with
H2O2 catalyzed by 1aa.
Chem. Eur. J. 2006, 12, 1875 – 1888
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1879

M. Beller et al.
Table 4. Scope of [Ru(S,S-Ph2-pybox)(pydic)] 1aa- and [Ru{(R,R)-(2-Np)2-pyboxazine}(pydic)] (R)-2ca-catalyzed asymmetric epoxidation.[a]
1aa
Yield [%][b]
(R)-2ca
Yield [%][b]
Entry
Substrate
Conv. [%][b]
Selec. [%]
ee [%][c]
Conv. [%][b]
Selec. [%]
ee [%][c]
1
2
100
100
71
75
71
75
+31
+42[e]
82
59
85
72
85
+48[d]
+59[e]
100
3
4
5
–
–
–
–
–
–
–
–
–
–
–
–
100
100
65
76
82
57
76
82
88
54[e]
60[e]
55[e]
6
7
8
100
100
85
52
74
70
52
74
82
32[e]
33
100
100
86
80
>99
78
80
99
91
58[e]
64[e]
58[e]
31[e]
9
100
100
100
82
100
82
À67[f]
+58[g]
100
100
100
95
100
95
À54[f]
+72[g]
10
11
100
95
95
48
100
>99
>99
53
12
73
65
89
41
84
83
99
48[e]
13
14
15
100
–
72
–
72
–
42
–
97
100
100
79
72
77
81
72
77
41[e]
49
100
79
79
8[e]
6[e]
16
100
55
55
17
100
25
25
13[e]
17
18
100
66
71
56
71
85
32[e]
21
100
79
81
68
81
86
30[e]
28[e]
19
20
88
–
77
–
88
–
30[h]
100
68
96
37
96
54
60[e][h]
–
49[e]
21
22
100
100
52
99
52
99
13
68
100
100
65
65
13[i]
79
>99
>99
23
24
100
–
91
–
91
–
72
–
94
91
97
84[e][j]
10
100
100
100
25
–
–
–
–
100
92
92
52[e]
[a] Reaction conditions: In a 25 mL Schlenk tube, the catalyst (0.025 mmol) was stirred at room temperature in tert-amyl alcohol (9 mL) for 10 min.
Olefin (0.5 mmol) and dodecane (GC internal standard, 100 mL) were added. A solution of 30%hydrogen peroxide (170 mL, 1.5 mmol) in tert-amyl alco-
hol (830 mL) was added over a period of 12 h by a syringe pump to this reaction mixture. [b] Determined by comparing with authentic samples on GC-
FID. [c] Determined by HPLC and 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)-stilbene oxide was the major enantiomer. [g] (1R,2R)-(+)-1-Phenyl-1-propene oxide was the major enan-
tiomer. [h] (1R,2S)-(À)-1-Phenyl-1-propene oxide was the major enantiomer. [i] (S)-2aa was used as the catalyst. [j] 08C, a solution of 50%hydrogen
peroxide (51 mL, 0.75 mmol) in tert-amyl alcohol (949 mL) was added by a syringe pump.
1880
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Chem. Eur. J. 2006, 12, 1875 – 1888

Homogeneous Catalysis
FULL PAPER
ities under mild reaction conditions, but 1aa was more reac-
tive than (R)-2ca as shown in the conversion of less reactive
substrates. However, (R)-2ca is more selective towards ep-
oxide formation relative to 1aa. Mono-, cis- and trans-di-,
and trisubstituted olefins have been realized in 1aa and (R)-
2ca with good to excellent yields and moderate to good ee.
A tetrasubstituted olefin also showed good reactivity to-
wards epoxidation with good yield and moderate ee in the
case of (R)-2ca (Table 4, entry 25). The best results were ob-
tained with trans-disubstituted olefins and trisubstituted ole-
fins. It is worth noting that our catalysts have been applied
to all six classes of olefins in good yields, in which five of
them gave moderate to good ee with (R)-2ca. By the intro-
duction of the new pyboxazine ligands through systematic
variation of ligands on 1, a significant improvement of both
chemoselectivity and enantioselectivity have been achieved.
Hence, this type of catalyst is complementary to both Mn–
salen[10] and chiral ketone[11] epoxidation catalysts in trans-
disubstituted and monosubstituted olefins, respectively.
Apart from different substituted aromatic olefins, functional
groups such as amine, ether, halogens, silylether, allylic ace-
tates, and even allylic chloride, could be epoxidized in high
yields. However, high eeꢁs have not yet been obtained with
1,1-disubstituted olefins (Table 4, entry 21) and olefins with
large substituents (Table 4, entries 21 and 24). Further im-
provement of the reaction through ligand modification is
therefore still in progress.
Figure 2. 1H NMR spectra of 1na a) in CDCl3 and b) in CD3OD.
For a more detailed understanding of this reaction, mech-
anistic studies were performed. We first addressed the effect
1
of the solvent to this epoxidation reaction. H NMR studies
of 1na in different solvents showed that a protic solvent is
important to provide a vacant coordination site for the oxi-
dation of the pseudo-octahedral 18-electron ruthenium com-
plex. In CDCl3, 1na retained its C2 symmetry in solution,
while the meta-protons of the 2,6-pyridinedicarboxylate of
1na splits into two sets of doublets and the para-proton into
to a doublet of doublets in CD3OD (Figure 2). However,
when only a stoichiometric amount of MeOH (with respect
to Ru) was added in the solution of 1na in CDCl3, no signif-
icant change in the 1H NMR spectrum could be observed
compared with Figure 2a. This implies that strong coordina-
Scheme 4. Proposed equilibrium between “close”-1na and “open”-1na in
CD3OD.
lents of hydrogen peroxide in tert-amyl alcohol, after remov-
al of solvent under reduced pressure, the residue showed
molecular ion peaks for [Ru(S,S-Ph2-pybox)(pydic)(O)] and
[Ru(S,S-Ph2-pybox)(pydic)(O)2] along with some undefined
peaks in the electrospray ionization mass spectra (ESI-MS).
Isolation of the intermediates by crystallization or column
chromatography were in vein. Hence, we tried to isolate the
intermediate in the lower oxidation state by reacting
[Ru(S,S-Ph2-pybox)(pydic)] 1aa with two equivalents of hy-
drogen peroxide in the presence of an excess of olefin
(10 equiv). To our surprise, the ESI-MS of this reaction mix-
ture showed also molecular ion peaks corresponding to
[Ru(S,S-Ph2-pybox)(pydic)(O)] and [Ru(S,S-Ph2-pybox)-
(pydic)(O)2]. From this mixture we were able to isolate one
suspected [Ru(S,S-Ph2-pybox)(pydic)(O)] complex in low
yield (<10%). The 1H NMR spectrum of this complex
showed diamagnetic behaviour and is not explainable. The
other complex was found to be unstable.
1
tion of MeOH did not occur and the change of the H NMR
spectrum could be assigned to a polar solvent favourable
equilibrium on the “open”-1na (Scheme 4). A closely relat-
ed ruthenium complex with this “open” form has been re-
ported.[36]
Clearly, all catalytic reactions reported here were started
with a RuII pre-catalyst. However, in the active catalyst the
central metal should be in a higher oxidation state. To deter-
mine the active species, [Ru(S,S-Ph2-pybox)(pydic)] 1aa was
treated with 50%H 2O2 in the presence and absence of
trans-b-methylstyrene in tert-amyl alcohol in an NMR tube.
Unfortunately, only paramagnetic species are observed. UV-
visible spectroscopic studies of these reactions showed no
isosbestic point in the spectra, indicating that more than one
ruthenium complex is formed during the oxidation of 1aa
with H2O2. Indeed, when 1aa was treated with ten equiva-
Next, the suspected [Ru(S,S-Ph2-pybox)(pydic)(O)] was
treated with trans-b-methylstyrene in tert-amyl alcohol at
Chem. Eur. J. 2006, 12, 1875 – 1888
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1881

M. Beller et al.
room temperature. Here, no
oxygen transfer to the olefin is
observed! This suggests that
the
[Ru(S,S-Ph2-pybox)-
(pydic)(O)] is not an active
catalyst, but could be an inter-
mediate in lower oxidation
state. This assumption has
been proven in a catalytic re-
action of the [Ru(S,S-Ph2-
pybox)(pydic)(O)] with olefin
(trans-b-methylstyrene)
with
Scheme 5. Competitive epoxidations of trans-stilbene with 30%H O2.
2
hydrogen peroxide under stan-
dard reaction conditions and
Table 5. Relative activity of [Ru(pybox)(pydic)] 1 and [Ru(pyboxazine)-
(pydic)] 2.
resulted in 100%conversion and 98%yield of the epoxide.
However, compared with the original catalyst 1aa (58% ee),
a significantly lower enantioselectivity (19% ee) was ob-
tained for trans-b-methylstyrene oxide. Thus, it is clear that
the reaction pathway through this intermediate is not re-
sponsible for the major reaction and there should be at least
two reaction pathways that give different enantioselectivity.
So far we believe that the “[Ru(S,S-Ph2-pybox)(pydic)(O)]”
is a mixture of ligand-oxidized ruthenium(ii) complexes (see
modeling studies below).
As the active intermediates could not be isolated, we
turned our interest to kinetic methods to probe the transi-
tion state of this reaction. There are some special features
that standard kinetic techniques could not be easily applied
to our epoxidation protocol.[37] Firstly, the rate of reaction
depends on the amount of water in the reaction mixture.[29e]
The rate of water production correlates not only with the
olefin consumption with respect to a certain catalyst, but
also the rate of H2O2 decomposition to oxygen by the cata-
lyst. We solved this problem in the catalytic reaction by lim-
iting the rate of addition of H2O2 with a syringe pump and
this proved to be applicable. However, under these condi-
tions the dosage of H2O2 turned out to be the limiting factor
of the reaction rate. Moreover, high concentrations of H2O2
were counterproductive for epoxide formation and decom-
position of the catalyst occurred. By using spectroscopic
techniques such as UV-visible and NMR spectroscopy it was
not possible to quantify the amount of the catalyst in the re-
action mixture (vide supra). In spite of all these problems,
we were able to establish a relative rate scale of our cata-
lysts with the aid of catalyst competitive reactions.
Entry
Catalyst
n
R1
X
Y
Relative
activity
1
2
3
4
5
6
7
8
1aa
1ab
1ac
1ad
1ae
1af
1ba
1na
2aa
2ba
2ca
2 fa
0
0
0
0
0
0
0
0
1
1
1
1
Ph
Ph
Ph
Ph
Ph
Ph
Ph
iPr
Ph
H
H
H
H
H
H
Cl
H
H
H
H
H
H
1.00
0.83
1.31
1.41
1.01
1.09
1.14
0.82
0.87
2.00
0.92
0.93
OH
Cl
Br
MeO
Ph
H
H
H
H
H
9
10
11
12
1-Np
2-Np
iPr
H
effect to the activity (Table 5, entries 1–6). Normally, the
faster the reaction, the higher the ee of stilbene oxide was,
at least partially due to the effect of water content.[29e] It
may also be attributed to electronic effects on the asymmet-
ric induction.[39] A similar trend has been observed in a
ruthenium–porphyrin-catalyzed asymmetric epoxidation
with 2,6-dichloropyridine N-oxide.[17a] However, the trend
observed here is reversed with respect to the well-known
Mn–salen system, in which ligands with electron-deficient
groups gave a higher ee.[39c]
Next, we evaluated the transition state by competitive ep-
oxidations of styrene, a-deuteriostyrene, and b-dideuterio-
styrene with H2O2 in the presence of 1aa. An inverse secon-
dary kinetic isotope effect (KIE) is observed for the b-ole-
finic carbon atom (kD/kH =0.87), while the a-olefinic carbon
atom showed no KIE (kD/kH =1.00).[40] The observed values
fall in good agreement with a nonsymmetric transition state
We first confirmed that the ee of trans-stilbene oxide by
epoxidation of trans-stilbene with 30%H 2O2 was directly
proportional to the optical purity of catalyst 1aa. This sug-
gests that a monomeric catalytic center dominates in the ep-
oxidation of trans-stilbene.[38] Then, the relative activity of a
given catalyst was determined by the ee of trans-stilbene
oxide in the model catalytic reaction with this catalyst and
the opposite isomer of 1aa (Scheme 5). The relative activi-
ties of catalysts are shown in Table 5. In general, all the cat-
alysts have activities within the same order of magnitude.
Functional groups with different electronic properties on the
para-position of “pydic” side show a more pronounced
À
and imply that C O bond formation is more advanced at
the b-carbon atom (sp2 to sp3) than the a-carbon atom (sp2
to sp2; Scheme 6).
Further investigation of competitive reactions of styrenes
with electron-releasing or electron-withdrawing substituents
revealed that the relative rates of the formation of styrene
oxides catalyzed by 1aa correlated with the Hammett s+
parameter (Figure 3).[41] This is contrary to the Hammett
logkrel versus (1mbsmb +1ÁjjsjÁj) in [RuVI(por)O2] (H2por=por-
phyrin),[39e,42] but coincides with [FeIV(TMPC+)O] (H2TMP=
1882
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Chem. Eur. J. 2006, 12, 1875 – 1888

Homogeneous Catalysis
FULL PAPER
stable oxidation product, while
both A and B are higher in
energy by ~20 kcalmolÀ1. It
should also be noted that A
and
B are close in energy
(~0.3 kcalmolÀ1).
Following the most popular
Scheme 6. Inverse secondary KIE for the epoxidation of styrene.
oxidation reaction mechanism
and our observed secondary ki-
netic isotope effect, it is most likely that structure B should
be the active catalyst for epoxidation.[39c,e] Hence, we pro-
pose that the pre-catalysts in our catalytic reactions are ini-
tially oxidized to the RuIII species C. This most stable com-
plex C will isomerize subsequently into structure B by
À
breaking the N O bond. In structure B, the ruthenium
center has a distorted octahedral conformation, and the oxa-
zoline ring rotates away from the Ru=O group allowing
thereby for further interaction of the upcoming olefin with
the Ru=O bond. This proposal is further supported by the
previously discussed ESI-MS studies, which showed that dif-
ferent [Ru(S,S-Ph2-pybox)(pydic)(O)] complexes are present
in the reaction mixture. In this context it is worth noting
that the related ruthenium(ii) complex [Ru(terpyridine)-
(pydic)] oxidizes easily in solution to give a paramagnetic
RuIII species.[48] Also in NMR experiments 1 and 2 gave rise
to paramagnetic metal complexes.
Regarding the origin of the enantioselectivity we believe
that p–p interactions between the ligand and the substrate
are the dominating factor for the asymmetric induction.[49]
This is clearly shown in the epoxidations of styrene in the
presence of [Ru{S,S-(p-ClC6H4)2-pyboxazine}(pydic)] ((S)-
2da) and [Ru{S,S-(p-MeOC6H4)2-pyboxazine}(pydic)] ((S)-
2ea) as catalysts (Table 2, entries 7 and 8). As the absolute
configurations of styrene oxide and trans-stilbene oxide for
1aa are R and S respectively, the major p–p interaction be-
tween the ligand and the substrate should be in different ge-
Figure 3. Hammett s+ correlation for the 1aa-catalyzed epoxidation of
para-substituted styrenes.
tetramesitylporphyrin),[43] [CrV(Br8TPP)(O)X] (H2TPP=tet-
raphenylporphyrin),[44] and [RuVI(N4)O2]2+ (N4 =macrocyclic
tertiary amines) complexes.[45] The 1+ (À2.45) found here is
consistent with an initial charge transfer from the metal
center. However, there was no KIE observed in the report-
ed case.[43] Other electrophilic addition to styrenes showed
even larger values of 1+ (À3.5 to À4.1).[46] It is worth noting
that the s+ values also correlate well with radical type reac-
tions when the polar effect dominates the spin effect or the
radical coordinates to the metal center or metal ion.[47]
Because isolation of active catalyst species was unsuccess-
ful we also performed modeling studies of potential inter-
mediates. On the basis of the core structures of the pre-cata-
lysts, there are several possibil-
ities of the active catalyst for
the oxygen-transfer reaction.
The three thermodynamically
most stable structures are
shown in Figure 4. The first
two are oxidation of pybox
and pydic ligands by yielding
new -NO (C) and -COOO (A)
ligands, and the third one is
the direct oxidation of metal
center with the formation of
Ru=O bond (B). The opti-
mized structures are shown in
Figure 4. At the B3LYP/
LANL2DZ density functional
level of theory, all four opti-
mized structures are found to
be energy minima on the po-
tential-energy surface. Interest-
ingly, structure C is the most
Figure 4. B3LYP/LANL2DZ structures and relative energies.
Chem. Eur. J. 2006, 12, 1875 – 1888
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1883

M. Beller et al.
added over a period of 12 h through a syringe pump to this reaction mix-
ture. After the addition, aliquots were taken from the reaction mixture
and subjected to GC analysis for determination of yield and conversion
data.
ometry in these cases. Further mechanistic studies on the
asymmetric induction are under investigation.
In summary, a general ruthenium-catalyzed asymmetric
epoxidation procedure of olefins with hydrogen peroxide
has been developed. For the first time high yield and che-
moselectivity have been obtained for all six classes of olefins
by using hydrogen peroxide as oxidant. Enantioselectivities
(typically in between 50–80%) up to 84% were observed by
applying different aromatic olefins. It is worth noting that
the usage of two different ligands significantly simplifies
structural variations on the catalyst electronically and steri-
cally. Mechanistic studies were performed experimentally
and theoretically with high-level density functional theory
General procedure for deuterated styrene competitive asymmetric epoxi-
dation with hydrogen peroxide: In
a 25 mL Schlenk tube, 1aa
(0.025 mmol) was stirred at room temperature in tert-amyl alcohol
(9 mL) for 10 min. Styrene (2.5 mmol), b-[D2]styrene (2.5 mmol), and do-
decane (GC internal standard, 100 mL) were added. A solution of 30%
hydrogen peroxide (57 mL, 0.5 mmol) in tert-amyl alcohol (276 mL) was
added over a period of 12 h through a syringe pump to this reaction mix-
ture. After the addition, aliquots were taken from the reaction mixture
and subjected to GC analysis for determination of yield and conversion
data. The reaction mixture was then quenched with aqueous Na2SO3 so-
lution (~10 mL), extracted with dichloromethane (10 mL”2), and
washed with water (~20 mL). The combined organic layers were dried
over MgSO4 and evaporated to give the crude epoxides. These were then
subjected to chromatography on silica gel (70–230 mesh, neutralized with
1%Et 3N) with hexane to hexane/ethyl acetate 100:3 as the gradient
calculations. Inverse secondary KIE suggested a nonsym-
+
À
metric C O bond formation, while the Hammett s relation
showed the possibility of a charge-transfer complex or coor-
dination of the respective radical. More insight into the
nature of the active catalyst was revealed by DFT calcula-
tions. Instead of the normal preception of a metal–oxo com-
plex perpendicular to the chiral C2 pybox(azine) as in the
case of N,N,N,N-porphyrin, a novel N-oxide type intermedi-
ate parallel to the pybox(azine) is suggested. Through the
systematic catalyst variation, mechanistic studies, and calcu-
lations, a new generation of asymmetric epoxidation cata-
lysts are under development.
1
eluent. The selectivity was determined by H NMR spectroscopy.
Phenyloxirane: 1H NMR (400.1 MHz, CDCl3): d=2.72 (dd, J=5.6,
2.6 Hz, 1H), 3.06 (dd, J=5.6, 4.2 Hz, 1H), 3.78 (dd, J=4.2, 2.6 Hz, 1H),
7.16–7.29 ppm (m, 5H); 13C NMR (100.6 MHz, CDCl3): d=51.3, 52.5,
125.6, 128.3, 128.6, 137.7 ppm; MS (EI, 70 eV): m/z (%): 120 (41) [M]+,
119 (65), 92 (37), 91 (100), 90 (64), 89 (79); HPLC (Chiralcel OD-H (02),
hexane/EtOH 99.95:0.05, flow rate 0.5 mLminÀ1): tR =6.27, 7.13 min.
4-Chlorophenyloxirane: 1H NMR (400.1 MHz, CDCl3): d=2.68 (dd, J=
5.6, 2.6 Hz, 1H), 3.07 (dd, J=5.6, 4.0 Hz, 1H), 3.76 (dd, J=4.0, 2.6 Hz,
1H), 7.12–7.26 ppm (m, 4H); 13C NMR (100.6 MHz, CDCl3): d=51.4,
51.9, 127.0, 128.8, 134.1, 136.3 ppm; MS (EI, 70 eV): m/z (%): 156 (9)
[M+2]+, 155 (10) [M+1]+, 154 (28) [M]+, 153 (23) [MÀ1]+, 125 (53),
119 (74), 89 (106); HPLC (Chiralcel OB-H, hexane, flow rate
1.0 mLminÀ1): tR =14.47, 17.18 min.
4-Fluorophenyloxirane: 1H NMR (400.1 MHz, CDCl3): d=2.67 (dd, J=
5.6, 2.6 Hz, 1H), 3.04 (dd, J=5.6, 4.0 Hz, 1H), 3.75 (dd, J=4.0, 2.6 Hz,
1H), 6.91- 6.96 (m, 2H), 7.12–7.17 ppm (m, 2H), 13C NMR (100.6 MHz,
CDCl3): d=51.6, 52.2, 115.9 (d, J=20 Hz), 127.6 (d, J=7 Hz), 133.7 (d,
J=2 Hz), 163.1 ppm (d, J=24 Hz); MS (EI, 70 eV): m/z (%): 138 (34)
[M]+, 137 (48) [MÀ1]+, 122 (86), 109 (100), 96 (31); HPLC (Chiralcel
AD-151, hexane/EtOH, 99:1, flow rate 1.1 mLminÀ1): tR =15.31,
18.08 min.
(4-Trifluoromethyl)phenyloxirane: 1H NMR (400.1 MHz, CDCl3): d=
2.77 (dd, J=5.6, 2.6 Hz, 1H), 3.19 (dd, J=5.6, 4.0 Hz, 1H), 3.92 (dd, J=
4.0, 2.6 Hz, 1H), 7.4 (d, J=8.1 Hz, 2H), 7.6 ppm (d, J=8.1 Hz, 2H);
13C NMR (100.6 MHz, CDCl3): d=51.4, 51.6, 125.4 (q, J=3.8 Hz), 125.9,
141.9 ppm; MS (EI, 70 eV): m/z (%): 188 (14) [M]+, 187 (20), 159 (49),
158 (48), 119 (100), 91 (37); HPLC (Chiralcel AD-151, hexane, flow rate
0.5 mLminÀ1): tR =12.30, 13.40 min.
2-(p-Tolyl)oxirane: 1H NMR (400.1 MHz, CD2Cl2): d=2.33 (s, 3H), 2.77
(dd, J=5.5, 2.6 Hz, 1H), 3.09, (dd, J=5.5, 4.1 Hz, 1H), 3.79, (dd, J=4.1,
2.6 Hz, 1H), 7.06–7.26 ppm (m, 5H); 13C NMR (100.6 MHz, CD2Cl2): d=
20.9, 50.9, 52.1, 125.5, 129.2, 134.8, 138.1 ppm; GC-MS: m/z: 134 [M]+;
HPLC (Chiralpak AD-H, hexane/EtOH, 99.95:0.05, flow rate
1.5 mLminÀ1): tR =4.53, 4.79 min.
2-(o-Tolyl)oxirane: 1H NMR (400.1 MHz, CD2Cl2): d=7.14–7.22 (m,
4H), 3.98 (dd, J=3.97, 2.58 Hz, 1H), 3.13 (dd, J=5.75, 3.97 Hz, 1H),
2.65 (dd, J=5.75, 2.58 Hz, 1H), 2.42 ppm (s, 3H); 13C NMR (100.6 MHz,
CD2Cl2): d=136.4, 136.2, 129.8, 127.6, 126, 124, 50.3, 50.1 ppm; MS (EI,
70 eV): m/z (%): 134 (53) [M]+, 119 (44), 118 (42), 117 (64), 105 (100),
103 (48), 91 (52)78 (33), 77 (35); HPLC (Chiralpak AD-H, hexane/
EtOH, 99.95:0.05, flow rate 1.5 mLminÀ1): tR =16.70, 19.84 min.
Experimental Section
General procedure for asymmetric epoxidation with hydrogen peroxide:
In a 25 mL Schlenk tube, the catalyst (0.025 mmol) was stirred at room
temperature in tert-amyl alcohol (9 mL) for 10 min. Olefin (0.5 mmol)
and dodecane (GC internal standard, 100 mL) were added. A solution of
30%hydrogen peroxide (170 mL, 1.5 mmol) in tert-amyl alcohol (830 mL)
was added over a period of 12 h through a syringe pump to this reaction
mixture. After the addition, aliquots were taken from the reaction mix-
ture and subjected to GC analysis for determination of yield and conver-
sion data. The reaction mixture was then quenched with aqueous Na2SO3
solution (~10 mL), extracted with dichloromethane (10 mL”2), and
washed with water (~20 mL). The combined organic layers were dried
over MgSO4 and evaporated to give the crude epoxides. It was then dis-
solved in n-hexane for HPLC measurement.
General procedure for catalyst competitive asymmetric epoxidation with
hydrogen peroxide: In a 25 mL Schlenk tube, catalyst A (0.0125 mmol)
and the opposite isomer of 1aa (0.0125 mmol) were stirred at room tem-
perature in tert-amyl alcohol (9 mL) for 10 min. trans-Stilbene (0.5 mmol)
and dodecane (GC internal standard, 100 mL) were added. A solution of
30%hydrogen peroxide (170 mL, 1.5 mmol) in tert-amyl alcohol (830 mL)
was added over a period of 12 h through a syringe pump to this reaction
mixture. After the addition, aliquots were taken from the reaction mix-
ture and subjected to GC analysis for determination of yield and conver-
sion data. The reaction mixture was then quenched with aqueous Na2SO3
solution (~10 mL), extracted with dichloromethane (10 mL”2), and
washed with water (~20 mL). The combined organic layers were dried
over MgSO4 and evaporated to give the crude epoxides. It was then dis-
solved in n-hexane for HPLC measurement.
General procedure for para-substituted styrene competitive asymmetric
epoxidation with hydrogen peroxide: In a 25 mL Schlenk tube, 1aa
(0.025 mmol) was stirred at room temperature in tert-amyl alcohol
(9 mL) for 10 min. Styrene (0.5 mmol), p-methylstyrene (0.5 mmol), and
dodecane (GC internal standard, 100 mL) were added. A solution of 30%
hydrogen peroxide (57 mL, 0.5 mmol) in tert-amyl alcohol (276 mL) was
2-(2-Chlorophenyl)oxirane: 1H NMR (400.1 MHz, CDCl3): d=2.67 (dd,
J=5.6, 2.6 Hz, 1H), 3.20 (dd, J=5.6, 4.1 Hz, 1H), 3.20 (dd, J=4.1,
2.6 Hz, 1H), 7.21–7.28 (m, 3H), 7.35–7.38 ppm (m, 1H); 13C NMR
(100.6 MHz, CDCl3): d=50.00, 50.68, 125.64, 127.03, 128.88, 129.10,
133.24, 135.56 ppm; MS (EI, 70 eV): m/z: 154 [M]+; HPLC (Chiralpak
1884
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Chem. Eur. J. 2006, 12, 1875 – 1888

Homogeneous Catalysis
FULL PAPER
AD-H [126], hexane/EtOH, 99.95:0.05, flow rate 0.5 mLminÀ1): tR =
12.49, 13.18 min.
HRMS calcd for C16H17NO3S: 303.09293; found: 303.09398; HPLC
(Whelk01 [R,R], hexane/EtOH, 90:10, flow rate 1.0 mLminÀ1): tR =10.01,
11.38 min.
trans-2-Chloromethyl-3-phenyloxirane: 1H NMR (400.1 MHz, CDCl3):
d=3.28 (ddd, J=5.8, 4.8, 1.9 Hz, 1H), 3.66 (dd, J=11.8, 5.8 Hz, 1H),
3.72 (dd, J=11.8, 4.8, Hz, 1H), 3.82 (d, J=1.9 Hz, 1H), 7.26–7.38 ppm
(m, 5H); 13C NMR (100.6 MHz, CDCl3): d=44.3, 58.5, 60.9, 116.6, 125.6,
128.6, 135.9 ppm; GC-MS: m/z: 168 [M]+; HPLC (Chiralpak AD-H,
hexane/EtOH, 95:5, flow rate 1.0 mLminÀ1): tR =7.62, 9.09 min.
cis-2-Methyl-3-phenyloxirane: 1H NMR (400.1 MHz, CDCl3): d=1.07 (d,
J=5.4 Hz, 3H), 3.33 (dd, J=5.4, 4.3 Hz, 1H), 4.05 (d, J=4.3 Hz, 1H),
7.25–7.36 ppm (m, 5H); 13C NMR (100.6 MHz, CDCl3): d=12.5, 55.1,
57.5, 126.5, 127.4, 128.0, 135.5 ppm; MS (EI, 70 eV): m/z: 134 [M]+;
HPLC (Chiralcel OD-H, hexane/EtOH, 99.95:0.05, flow rate
1.0 mLminÀ1): tR =11.64 (2S,3R), 15.56 min (2R,3S).
trans-2,3-Diphenyloxirane: 1H NMR (400.1 MHz, CDCl3): d=7.24–7.31
(m, 10H), 3.87 ppm (s, 2H); 13C NMR (100.6, MHz, CDCl3): d=137.1,
128.6, 128.6, 125.5, 62.8 ppm; MS (EI, 70 eV): m/z (%): 197 (18) [M+1]+,
196 (100) [M]+, 195 (72), 178 (28), 167 (85), 90 (66), 89 (65); HPLC
(Chiralcel OD-H, hexane/EtOH, 98:2, flow rate 0.5 mLminÀ1): tR =14.10
(2S,3S), 4.79 min (2R,3R).
trans-2-Methyl-3-phenyloxirane: 1H NMR (400.1 MHz, CDCl3): d=1.44
(d, J=5.2 Hz, 3H), 3.03 (dq, J=5.2, 2.0 Hz, 1H), 3.57 (d, J=2.0 Hz, 1H),
7.23–7.4 ppm (m, 5H); 13C NMR (100.6 MHz, CDCl3): d=18.0, 59.2,
59.6, 125.7, 128.1, 128.5, 137.9 ppm; MS (EI, 70 eV): m/z (%): 134 (52)
[M]+, 133 (65), 105 (51), 91 (42), 90 (100), 89 (77), 77 (23); HPLC (Chir-
alcel OD-H (069), hexane/EtOH, 99.95:0.05, flow rate 1.0 mLminÀ1): tR =
11.90 (2S,3S), 13.48 min (2R,3R).
1
1H NMR
(400.1 MHz,
3-Phenyl-allyl ester of acetic acid: H NMR (400.1 MHz, CDCl3): d=2.07
trans-2-(p-methoxyphenyl)-3-methyloxirane:
(s, 3H), 4.83 (dd, J=6.6, 1.7 Hz, 2H), 5.80 (dt, J=11.8, 6.6 Hz, 1H), 6.65
(d, J=11.8 Hz, 1H), 7.20–7.22 (m, 2H), 7.24–7.28 (m, 1H), 7.32–
7.36 ppm (m, 2H); 13C NMR (100.6 MHz, CDCl3): d=20.94, 61.47,
125.75, 127.50, 128.36, 128.69, 132.95, 135.99, 170.88 ppm; MS (EI,
70 eV): m/z: 176 [M]+.
2-Methyl-2-phenyloxirane: 1H NMR (400.1 MHz, CDCl3): d=1.65 (s,
3H), 2.73 (d, J=5.4 Hz, 1H), 2.90 (d, J=5.4 Hz, 1H), 7.17–7.31 ppm (m,
5H); 13C NMR (100.6 MHz, CDCl3): d=56.9, 57.2, 125.4, 127.6, 128.5,
141.3 ppm; MS (EI, 70 eV): m/z (%): 134 (35) [M]+, 133 (87), 105 (100),
104 (41), 103 (58), 91 (23), 79 (37), 78 (54), 77 (49); HPLC (Chiralcel
OD-H, hexane/iso-propanol, 99.95:0.05, flow rate 1.0 mLminÀ1): tR =9.78,
12.77 min.
2-Phenyl-1-oxaspiro[2.5]octane: 1H NMR (400.1 MHz, CDCl3): d=1.22–
1.31 (m, 2H), 1.37–1.85 (m, 8H), 3.85 (s, 1H), 7.23–7.34 ppm (m, 5H);
13C NMR (100.6 MHz, CDCl3): d=?24.5, 25.3, 25.5, 28.4, 35.4, 64.5, 65.5,
126.3, 127.2, 127.9, 136.3 ppm; MS (EI, 70 eV): m/z: 188 [M]+; HPLC
(Chiralpak AD-H, hexane/EtOH, 90:10, flow rate 1.0 mLminÀ1): tR =
4.34, 4.72 min.
2,2-Dimethyl-3-phenyloxirane: 1H NMR (400.1 MHz, CDCl3): d=1.04 (s,
3H), 1.45 (s, 3H), 3.83 (s, 1H), 7.21–7.33 ppm (m, 5H); 13C NMR
(100.6 MHz, CDCl3): d=17.9, 24.7, 61.0, 64.5, 126.3, 127.3, 128,
136.6 ppm; MS (EI, 70 eV): m/z (%): 148 [M]+; HPLC (Chiralcel OD-H,
hexane/EtOH, 99.95:0.05, flow rate 0.5 mLminÀ1): tR =11.78 (3S),
18.63 min (3R).
CD2Cl2): d=1.41 (d, J=5.2 Hz, 3H), 3.01 (qd, J=5.2, 2.0 Hz, 1H), 3.50
(d, J=2.0 Hz, 1H), 3.79 (s, 3H), 6.87 (d, J=8.9 Hz, 2H), 7.17 ppm (d, J=
8.9 Hz, 2H); 13C NMR (100.6 MHz, CD2Cl2): d=18.0, 58.9, 59.5, 114.1,
127.2, 130.3, 160.0 ppm; MS (EI, 70 eV): m/z (%): 165 (7) [M+1]+, 164
(57) [M]+, 121 (47), 120 (82), 105 (31), 91 (100), 77 (55), 51 (37); HPLC
(Chiralpak AD-H, hexane/EtOH, 99.95:0.05, flow rate 1.5 mLminÀ1):
tR =16.70, 19.84 min.
1
trans-3-Phenyloxiranylmethyl acetate: H NMR (400.1 MHz, CDCl3): d=
2.04 (s, 3H), 3.18–3.20 (m, 1H), 3.73 (d, J=2.0 Hz, 1H), 4.02 (dd, J=
12.3, 6.0 Hz, 1H), 4.41 (dd, J=12.3, 3.4 Hz, 1H), 7.17–7.32 ppm (m, 5H);
13C NMR (100.6 MHz, CDCl3): d=20.7, 56.4, 59.2, 64.2, 125.6, 128.4,
128.5, 136.1, 170.7 ppm; MS (EI, 70 eV): m/z (%): 192 (2) [M]+, 150 (10),
149 (79), 133 (26), 107 (95), 105 (67), 91 (54), 90 (45), 89 (42), 79 (31), 77
(31), 43 (100); HPLC (Chiralcel OD-H, hexane/EtOH, 95:5, flow rate
1.0 mLminÀ1): tR =4.64, 5.88 min.
trans-2-[(tert-Butyldimethylsiloxy)methyl]-3-phenyloxirane:
1H NMR
(400.1 MHz, CDCl3): d=0.09 (s, 3H), 0.10 (s, 3H), 0.91 (s, 9H), 3.12–3.13
(ddd, J=4.4, 2.8, 1.9 Hz, 1H), 3.79 (d, J=1.9 Hz, 1H), 3.81 (dd, J=12.0,
4.4 Hz, 1H), 3.95 (dd, J=12.0, 2.8 Hz, 1H), 7.24–7.35 ppm (m, 5H);
13C NMR (100.6 MHz, CDCl3): d=À5.3, 18.4, 25.9, 55.9, 62.7, 64.0, 125.7,
128.1, 128.4, 137.2 ppm; MS (EI, 70 eV): m/z: 249 [MÀCH3]+; HPLC
(Whelk01 [R,R], hexane/2-propanol, 99:1, flow rate 0.5 mLminÀ1): tR =
6.30, 8.19 min.
trans-2-Methoxymethyl-3-phenyloxirane: 1H NMR (400.1 MHz, CDCl3):
d=3.19 (ddd, J=5.2, 3.1, 2.1 Hz, 1H), 3.43 (s, 3H), 3.52 (dd, J=11.4,
5.2 Hz, 1H), 3.76 (dd, J=11.4, 3.1 Hz, 1H), 3.78 (d, J=2.1 Hz, 1H),
7.25–7.35 ppm (m, 5H); 13C NMR (100.6 MHz, CDCl3): d=55.7, 59.2,
60.9, 72.1, 125.6, 128.2, 128.4, 136.8 ppm; MS (EI, 70 eV): m/z: 164 [M]+;
HPLC (Chiralcel OD-H, hexane/EtOH, 98:2, flow rate 1.0 mLminÀ1):
tR =4.53, 5.53 min.
2-Methyl-2,3-diphenyloxirane: 1H NMR (400.1 MHz, CDCl3): d=1.48 (s,
3H), 3.98 (s, 1H), 7.30–7.34 (m, 2H), 7.37–7.42 (m, 6H), 7.45–7.48 ppm
(m, 2H); 13C NMR (100.6 MHz, CDCl3): d=16.7, 63.0, 67.1, 125.1, 126.5,
127.5, 127.6, 128.2, 128.4, 135.9, 142.3 ppm; MS (EI, 70 eV): m/z: 210
[M]+; HPLC (Whelk 0.1 [R,R], hexane/EtOH, 99:1, flow rate
0.6 mLminÀ1): tR =5.33, 5.97 min.
2,2,3-Trimethyl-3-phenyloxirane: 1H NMR (400.1 MHz, CDCl3): d=0.95
(s, 3H), 1.46 (s, 3H), 1.61 (s, 3H), 7.20–7.23 (m, 1H), 7.27–7.33 ppm (m,
4H); 13C NMR (100.6 MHz, CDCl3): d=20.7, 21.3, 21.7, 63.7, 66.5, 126.0,
126.7, 128.0, 142.2 ppm; MS (EI, 70 eV): m/z: 162 [M]+; HPLC (Chiral-
pak AD-H, hexane, flow rate 1.0 mLminÀ1): tR =6.23, 6.74 min.
trans-2-Phenoxymethyl-3-phenyloxirane: 1H NMR (400.1 MHz, CDCl3):
d=3.40 (ddd, J=5.2, 3.2, 2.0 Hz, 1H), 3.91, (d, J=2.0 Hz, 1H), 4.14 (dd,
J=11.2, 5.2 Hz, 1H), 4.32 (dd, J=11.2, 3.2 Hz, 1H), 6.94–7.00 (m, 3H),
7.27–7.38 ppm (m, 7H); 13C NMR (100.6 MHz, CDCl3): d=56.4, 60.2,
67.8, 114.7, 121.3, 125.7, 128.4, 128.5, 129.5, 136.5, 158.4 ppm; MS (EI,
70 eV): m/z: 226 [M]+; HPLC (Chiralcel OD-H, hexane/EtOH, 98:2,
flow rate 1.0 mLminÀ1): tR =5.98, 6.89 min.
Computation: All calculations were carried out by using the Gaussian 98
program.[50] All structures were optimized at B3LYP density functional
level of theory with the LANL2DZ[51] basis set, and characterized as
energy minimum structures without imaginary number of frequencies at
the same level of theory (B3LYP/LANL2DZ).[52]
1
trans-2-(3-Phenyloxiranyl)-[1,3]dioxolane: H NMR (400.1 MHz, CDCl3):
d=3.13 (dd, J=3.8, 2.0 Hz, 1H), 3.89 (d, J=2.0 Hz, 1H), 3.89–3.97 (m,
2H), 4.00–4.06 (m, 2H), 5.00 (d, J=3.8, 1H), 7.25–7.35 ppm (m, 5H);
13C NMR (100.6 MHz, CDCl3): d=55.2, 61.3, 65.3, 65.5, 102.3, 125.7,
128.3, 128.4, 136.2 ppm; GC-MS: m/z: 192 [M]+; HPLC (Chiralpak AD-
H, hexane/EtOH, 95:5, flow rate 1.0 mLminÀ1): tR =25.57, 28.44 min.
4-Methyl-N-(trans-3-phenyl-oxiranylmethyl)benzenesulfonamide:
M.p.
Acknowledgements
128–1318C; Rf =0.23 (hexane/ethyl acetate=3:1); 1H NMR (400.1 MHz,
CDCl3): d=2.41 (s, 3H), 3.10 (ddd, J=4.6, 3.4, 2.0 Hz, 1H), 3.23 (ddd,
J=14.1, 6.8, 4.6 Hz, 1H), 3.38 (ddd, J=14.1, 6.0, 3.4 Hz, 1H), 3.74 (d, J=
2.0 Hz, 1H), 4.82 (unresolved dd, 1H), 7.14–7.17 (m, 2H), 7.28–7.31 (m,
5H), 7.74 ppm (d, J=8.3 Hz, 2H); 13C NMR (100.6 MHz, CDCl3): d=
21.51, 43.70, 55.55, 60.12, 125.66, 127.06, 128.51, 128.88, 129.84, 131.04,
135.69, 135.89, 136.71, 143.75 ppm; MS (EI, 70 eV): m/z: 303 [M]+;
This work has been financed by the State of Mecklenburg-Western Pom-
merania, the Bundesministerium für Bildung und Forschung (BMBF)
and the Deutsche Forschungsgemeinschaft (SPP “Sekundäre Wechselwir-
kungen”). We thank Prof. Dr. M. Michalik, Dr. W. Baumann, C. Mewes,
H. Baudisch, A. Lehmann, and S. Buchholz (all IfOK) for their excellent
technical and analytical support. Dr. A. Kçckritz (ACA) is thanked for
Chem. Eur. J. 2006, 12, 1875 – 1888
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
1885

M. Beller et al.
general discussions. M.K.T. thanks the Alexander-von-Humboldt-Stiftung
for granting him an AvH-fellowship.
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