An efficient ketone-catalyzed asymmetric epoxidation using hydrogen peroxide (H2O2) as primary oxidant

Article abstract of DOI:10.1016/S0040-4020(01)00362-3

High enantioselectivities have been obtained for asymmetric epoxidation of olefins using a fructose-derived chiral ketone (5) as catalyst and hydrogen peroxide as primary oxidant.

Full text of DOI:10.1016/S0040-4020(01)00362-3

TETRAHEDRON
Pergamon
Tetrahedron 57 +2001) 5213±5218
An ef®cient ketone-catalyzed asymmetric epoxidation using
hydrogen peroxide ꢀH2O2) as primary oxidant
Lianhe Shu and Yian Ship
Department of Chemistry, Colorado State University, Fort Collins, CO 80523, USA
Dedicated to Professor Barry M. Trost on the occasion of his 60th birthday
Received 10 February 2001;revised 21 February 2001;accepted 22 February 2001
AbstractÐHigh enantioselectivities have been obtained for asymmetric epoxidation of ole®ns using a fructose-derived chiral ketone +5) as
catalyst and hydrogen peroxide as primary oxidant. q 2001 Elsevier Science Ltd. All rights reserved.
Epoxides are very important building blocks in organic
synthesis.1 Dioxiranes, either isolated, or generated in situ,
have been shown to be extremely versatile epoxidation
reagents.2±6 The reaction is rapid, mild, and a variety of
ef®cient protocols for this type of epoxidation have been
developed. Thus far, the ef®cient generation of dioxiranes
primarily uses potassium peroxomonosulfate +KHSO5) as
oxidant +Scheme 1).7,8 Its effectiveness in the formation of
dioxiranes is probably due to the fact that sulfate is a good
leaving group, which facilitates the ring closure of inter-
mediate 3 to form dioxirane 4. Nevertheless, the formation
of dioxiranes for a synthetic purpose using substantially
different oxidants is largely unexplored. It is particularly
of interest whether oxidants with poorer leaving groups
than sulfate are capable of ef®ciently generating dioxir-
anes.9 Herein we wish to report our detailed studies in this
area.10
in other solvents, such as DMF, THF, CH2Cl2, EtOH, or
dioxane, instead of CH3CN, only trace amounts of the
epoxide +,1%) were detected by GC, suggesting that
hydrogen peroxide itself could not effectively generate the
dioxirane and that CH3CN played a role. It is highly likely
that in the case of CH3CN, the actual oxidant responsible for
the formation of the dioxirane was peroxyimidic acid 9
+Scheme 2).13 The reaction pH was found to be a very
important parameter and the optimal pH for both conversion
and ee was determined to be around 11.0. It was found that
K2CO3 was an effective base to control the reaction pH. Fig.
1 shows the reaction results with different concentrations of
K2CO3. High conversion could be obtained when the proper
concentrations of K2CO3 were used, with over 90% ee
obtained when [K2CO3] was above 0.6 M +increasing the
concentration of K2CO3 slightly increased the ee of the
epoxide product).14,15
Among oxidants hydrogen peroxide +H2O2) is quite unique.
It has a high active oxygen content and its reduction product
is water.11 We decided to test whether hydrogen peroxide
itself, or its activated form, could serve as oxidants to
produce dioxiranes. Our investigation started with trans-
b-methylstyrene as substrate and chiral ketone 5 as cata-
lyst.6 When a solution of the ole®n +1 mmol), ketone 5
+0.3 mmol), hydrogen peroxide +30%, 0.5 mL, 5 mmol) in
CH3CN +2 mL)-aqueous buffer +AcOH±K2CO3) +the buffer
pH was adjusted to 10.3 by adding HOAc to 0.1 M K2CO3)
+1 mL) was stirred at room temperature for 2 h, a 40%
conversion was obtained. Analysis of the epoxide product,
using chiral GC +Chiraldex G-TA), showed 86% ee! The
fact that the epoxide was formed with good enantio-
selectivity suggested that the dioxirane was the likely epoxi-
dizing agent.12 However, when the reaction was carried out
p
Corresponding author. Tel.: 11-970-491-7424;fax: 11-970-491-1801;
e-mail: yian@lamar.colostate.edu
Scheme 1.
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020+01)00362-3

5214
L. Shu, Y. Shi / Tetrahedron 57 %2001) 5213±5218
Scheme 2.
After the determination of the optimal reaction pH, the
scope of this epoxidation system was investigated. As
shown in Table 1, a variety of trans- and trisubstituted
ole®ns can be effectively epoxidized giving good yields
and ee's. It was found that the H2O2±CH3CN system
provided similar enantioselectivities to Oxone. The catalyst
loading is somewhat substrate dependent and it can be
reduced to as low as 10 mol% in some cases +Table 1,
entry 7). It was found that the solvent was also very impor-
tant for the reactions. For substrates with poor solubility like
trans-stilbene +Table 1, entry 4), the epoxidation did not
give a high conversion when CH3CN was used as the
organic solvent +Table 1, method A). However, a good
conversion could be obtained by running the epoxidation
in a mixed solvent of CH3CN±DMM +1:2, v/v) +Table 1,
method B). Further studies showed that a mixed solvent
such as CH3CN±EtOH±CH2Cl2 was bene®cial for ole®ns
with poor solubility +Table 1, method C, entries 4±9). These
mixed solvent systems increase the utility of the current
epoxidation method.16
In the present epoxidation system, acetonitrile +CH3CN)
serves not only as a solvent but also as a reagent to react
with H2O2 to form the peroxyimidic acid. It would be inter-
esting to know whether other nitriles could also be used
for the epoxidation. To this end, a variety of nitriles were
investigated +Table 2). These nitriles were used either alone
or with other organic solvents. As shown in Table 2, CH3CN
and CH3CH2CN give the best results. Other H2O2 activators
such as DCC were also investigated +Table 2, entries
18±20),17 however, low conversions were obtained. Some
epoxidation occurred with oxidants such as NaBO3,
Na2CO3´1.5H2O2, mCPBA, CH3COOOH.18 Only trace
amounts of epoxides were obtained when NaClO and
NaClO2 were used. Among all those oxidants tested, it is
clear that peroxyimidic acids generated from nitriles such as
acetonitrile are effective oxidants to react with ketones to
generate dioxiranes. The ef®cient formation of the dioxirane
with this class of oxidant could be due to the fact the nitro-
gen of the peroxyimidic acid acts as an internal base to
facilitate the generation of the dioxirane +Scheme 2).
In summary, we have shown that dioxiranes can be gener-
ated in situ using a combination of nitrile and H2O2 as
oxidant. Among the nitriles tested, acetonitrile is particu-
larly effective and inexpensive. Peroxyimidic acid 9 is
postulated to be the active oxidant. A few appealing features
of the current epoxidation system are worth mentioning.
High yields and ee's were obtained for a number of ole®ns.
The epoxidation was carried out under mild conditions
using inexpensive hydrogen peroxide as primary oxidant.
Also, the amount of salts introduced and volume of solvent
required were signi®cantly reduced compared to our
previous procedures using Oxone. In addition, the current
Figure 1. Plot of the conversion of trans-b-methylstyrene against time +h).
The curves presented are: +A) 0.05 M K2CO3 in 4£1024 M of EDTA +pH
11.1), +B) 0.1 M K2CO3 in 4£1024 M of EDTA +pH 11.3), +C) 0.4 M
K2CO3 in 4£1024 M of EDTA +pH 11.6), +D) 0.6 M K2CO3 in 4£1024
M of EDTA +pH 11.7), +E) 0.8 M K2CO3 in 4£1024 M of EDTA +pH 11.8),
+F) 1.0 M K2CO3 in 4£1024 M of EDTA +pH 11.9). +The pH indicated
above is the pH of the K2CO3 solution. The pH varied upon adding other
reaction components as well as the reaction time. This variation became
smaller when higher concentration of K2CO3 was used.)

L. Shu, Y. Shi / Tetrahedron 57 %2001) 5213±5218
5215
Table 1. Asymmetric epoxidation of ole®ns catalyzed by ketone 5 using H2O2 and CH3CN
Entry
Substrate
Methoda
Cat +mol%)
Time +h)
Yield +%)b
ee +%)
1
2
3
A
A
A
15
30
30
12
24
16
93
75
71
92c
93d
89d
4
B
C
D
30
30
30
24
24
1.5
77
90
78
99d
98d
99
5
6
C
30
10
97
92e
B
C
30
30
24
24
68
94
97d
95d
7
8
A
D
10
30
6
2
90
94
96c
98
C
C
A
30
30
30
16
16
4
88
77
93
89d
92d
95f
9
10
11
A
A
15
30
5.5
3.5
75
76
96d
95g
12
a
Method A: The reactions were carried out at 08C +bath temperature) with substrate +1.0 mmol), ketone 5 +0.1±0.3 mmol), and H2O2 +4.0 mmol) in CH3CN
+1.5 mL)-2.0 M K2CO3 in 4£1024 M of EDTA +1.5 mL). Method B: The reactions were carried out at 08C +bath temperature) with substrate +1.0 mmol),
ketone 5 +0.3 mmol), and H2O2 +4.0 mmol) in CH3CN±DMM +1:2, v/v) +6.0 mL)-2.0 M K2CO3 in 4£1024 M of EDTA +1.5 mL). For entries 4 and 6, the
reactions were carried out at 08C for 10 h then at rt for 14 h. Method C: The reactions were carried out at 08C +bath temperature) with substrate +1.0 mmol),
ketone 5 +0.3 mmol), and H2O2 +4.0 mmol) in CH3CN±EtOH±CH2Cl2 +1:1:2, v/v) +2.0 mL)-2.0 M K2CO3 in 4£1024 M of EDTA +1.5 mL). For entries 4 and
6, the reactions were carried out at 08C for 12 h then at rt for 12 h. Method D: The reactions were carried out with substrate +1 equiv.), ketone +0.3 equiv.),
Oxone +1.38 equiv.), and K2CO3 +5.8 equiv.) in CH3CN±DMM±0.05 M Na2B4O7.10H2O of aqueous EDTA +4£1024 M) solution +1:2:2, v/v). The reactions
were run at 08C for entry 4 and 2108C for entry 7 +taken from Ref. 6c).
b
c
d
e
The epoxides were puri®ed by ¯ash chromatography and gave satisfactory spectroscopic characterization.
Enantioselectivity was determined by chiral GC +Chiraldex G-TA).
Enantioselectivity was determined by chiral HPLC +Chiracel OD).
The epoxide was opened +NaOMe±MeOH), and the resulting alcohol was converted to its acetate;enantioselectivity was determined by 1H NMR shift
analysis of the resulting acetate with Eu+hfc)3.
Enantioselectivity was determined by chiral GC +Chiraldex B-TA) after desilylation with TBAF.
f
g
Enantioselectivity was determined by chiral HPLC +Chiracel OB).
study shows that oxidants other than peroxysulfates can be
used to ef®ciently generate dioxiranes.
satisfactory spectroscopic characterization. The correspond-
ing references for these epoxides are included.
1.1. Representative epoxidation procedures
1. Experimental
1.1.1. Method A. To a solution of trans-b-methylstyrene
+0.118 g, 1.0 mmol) and ketone 5 +0.0387 g, 0.15 mmol) in
CH3CN +1.5 mL) was added a solution of 2.0 M K2CO3 in
4£1024 M of EDTA +1.5 mL) followed by H2O2 +30%,
0.4 mL, 4 mmol) at 08C. Upon stirring at 08C for 12 h, the
reaction mixture was extracted with hexane, washed with
1 M aqueous Na2S2O3 and brine, dried +Na2SO4), ®ltered,
concentrated, and puri®ed by chromatography +silica gel
The general experimental information is similar to those
recently described.6c Hydrogen peroxide +H2O2) is poten-
tially explosive although no incidents occurred by our
experience, care must be taken in handling this compound.
In the epoxidation reaction, EDTA is used to minimize the
decomposition of H2O2 catalyzed by any trace metals. All
the epoxides in Table 1 are known compounds and give

5216
L. Shu, Y. Shi / Tetrahedron 57 %2001) 5213±5218
Table 2. Asymmetric epoxidation of trans-b-methylstyrene with 10±
30 mol% ketone 5, H2O2, and various nitriles and activators
was buffered with 1% Et3N in hexane, using hexane/ether
50/1 as eluent) to afford the epoxide product as a white solid
+0.196 g, 88% yield, 89% ee) +Table 1, entry 8).
Entry
nitrile
Conv.+%)
ee +%)
1a
CH3CN
73
52
13
0.6
14
9
94
92
27
4
11
0.7
13
50
17
1
92
94
95
nd
91
6
93
94
94
93
13
26
68
92
84
91
12
93
93
70
1.1.4. ꢀR,R)-trans-b-Methylstyrene oxide ꢀTable 1, entry
2a
CH3CH2CN
CH3CH2CH2CN
t-BuCN
PhCN
CCl3CN
CH3CN
CH3CH2CN
CH3CH2CH2CN
t-BuCN
1
1).6c [a]25 ˆ144.7 +c 0.47, CHCl3); H NMR d 7.38±7.23
D
3a
+m, 5H), 3.58 +d, Jˆ2.6 Hz, 1H), 3.04 +qd, Jˆ5.1, 2.6 Hz,
1H), 1.47 +d, Jˆ5.1 Hz, 3H).
4a
5a
6a
7b
1.1.5. ꢀR,R)-2-[ꢀtert-Butyldimethylsiloxy)methyl]-3-phenyl-
8b
oxirane ꢀTable 1, entry 2).6c [a]25 ˆ140.0 +c 0.47,
9b
D
1
10b
11b
12b
13b
14b
15b
16b
17b
18c
19c
20c
CH2Cl2); H NMR d 7.40±7.20 +m, 5H), 3.97 +dd, Jˆ
12.0, 3.0 Hz, 1H), 3.82 +dd, Jˆ12.0, 3.9 Hz, 1H), 3.80 +d,
Jˆ1.8 Hz, 1H), 3.14 +ddd, Jˆ3.9, 3.0, 1.8 Hz, 1H), 0.92 +s,
9H), 0.13 +s, 3H), 0.12 +s, 3H).
CCl3CN
HOCH2CN
CH3OCH2CN
PhCN
o-F-PhCN
o-CH3O-PhCN
F5-PhCN
DCC
+MeO)2CO
+t-BuOCO)2O
1.1.6. ꢀR,R)-3-Phenyloxiranemethanol ꢀTable 1, entry
1
3).6e [a]25 ˆ146.0 +c 0.55, CHCl3). H NMR d 7.40±7.25
7
17
2
D
+m, 5H), 4.06 +ddd, Jˆ12.6, 5.1, 2.1 Hz, 1H), 3.94 +d, Jˆ
2.1 Hz, 1H), 3.82 +ddd, Jˆ12.6, 7.8, 3.9 Hz, 1H), 3.24 +m,
1H), 1.78 +m, 1H).
8
a
The reactions were carried out at 08C +bath temperature) with substrate
+0.5 mmol), ketone 5 +0.05 mmol), and 30% H2O2 +2 mmol) in RCN
+0.75 mL) and 2.0 M K2CO3 in 4£1024 M of EDTA +0.75 mL). The
conversion and ee were determined by chiral GC +Chiraldex G-TA)
after the reaction mixture was stirred for 10 h.
1.1.7. ꢀR,R)-trans-Stilbene oxide ꢀTable 1, entry 4).6c
1
[a]25 ˆ1357.2 +c 1.10, benzene). H NMR d 7.44±7.31
D
+m, 10H), 3.88 +s, 2H).
b
The reactions were carried out at 08C +bath temperature) with substrate
+0.5 mmol), ketone 5 +0.05 mmol), and 30% H2O2 +2 mmol) in RCN±
EtOH±CH2Cl2 +1:1:1 v/v, 0.75 mL) and 2.0 M K2CO3 in 4£1024 M of
EDTA +0.75 mL). The conversion and ee were determined by chiral GC
+Chiraldex G-TA) after the reaction mixture was stirred for 10 h.
The reactions were carried out at 08C +bath temperature) with substrate
+1.0 mmol), ketone 5 +0.3 mmol), activator +4.0 mmol), and 30% H2O2
+4 mmol) in EtOH±CH2Cl2 +1:1 v/v, 1.5 mL) and 2.0 M K2CO3 in 4£1024
M of EDTA +1.5 mL). The conversion and ee were determined by chiral
GC +Chiraldex G-TA) after the reaction mixture was stirred for 10 h.
1.1.8. ꢀR,R)-2,3-Dihexyloxirane ꢀTable 1, entry 5).6c
1
[a]25 ˆ126.2 +c 0.65, CHCl3); H NMR d 2.66 +m, 2H),
D
1.60±1.20 +m, 20H), 0.89 +t, Jˆ6.8 Hz, 6H).
c
1.1.9. ꢀR,R)-trans-Methylstilbene oxide ꢀTable 1, entry
1
6).6c [a]25 ˆ1114.3 +c 0.63, EtOH) H NMR d 7.52±7.24
D
+m, 10H), 3.96 +s, 1H), 1.47 +s, 3H).
1.1.10. ꢀR,R)-1-Phenylcyclohexene oxide ꢀTable 1, entry
1
7).6c [a]25 ˆ1113.5 +c 1.71, benzene); H NMR d 7.41±
D
was buffered with 1% Et3N in hexane, using hexane/
ether 1/0±50/1 as eluent) to afford the epoxide product
as a colorless oil +0.124 g, 93% yield, 92% ee) +Table 1,
entry 1).
7.22 +m, 5H), 3.08 +m, 1H), 2.29 +ddd, Jˆ14.7, 8.4, 5.4 Hz,
1H), 2.13 +dt, Jˆ14.7, 5.4 Hz, 1H), 2.04 +m, 2H), 1.68±1.42
+m, 3H), 1.31 +m, 1H).
1.1.11. ꢀ1S,2R)-1-Phenyl-3,4-dihydronaphthalene oxide
1
1.1.2. Method B. To a solution of trans-stilbene +0.180 g,
1.0 mmol) and ketone 5 +0.0774 g, 0.30 mmol) in CH3CN±
DMM +1:2, v/v) +6.0 mL) was added a solution of 2.0 M
K2CO3 in 4£1024 M of EDTA +1.5 mL) followed by H2O2
+30%, 0.4 mL, 4 mmol) at 08C. Upon stirring at 08C for 10 h
and rt for 14 h, the reaction mixture was extracted with
hexane, washed with 1 M aqueous Na2S2O3 and brine,
dried +Na2SO4), ®ltered, concentrated, and puri®ed by
chromatography +silica gel was buffered with 1% Et3N in
hexane, using hexane/ether 50/1 as eluent) to afford the
epoxide product as a white solid +0.151 g, 77% yield, 99%
ee) +Table 1, entry 4).
ꢀTable 1, entry 8).6c [a]25 ˆ243.7 +c 0.75, CHCl3); H
D
NMR d 7.49±6.98 +m, 9H), 3.63 +d, Jˆ3.3 Hz, 1H), 2.95
+ddd, Jˆ15.3, 13.2, 6.6 Hz, 1H), 2.70 +dd, Jˆ15.3, 5.4 Hz,
1H), 2.49 +dddd, Jˆ14.7, 6.6, 3.3, 1.8 Hz, 1H), 2.04 +ddd,
Jˆ14.7, 13.2, 5.4 Hz, 1H).
1.1.12. ꢀR)-9-Ethylidene¯uorene oxide ꢀTable 1, entry
9).19 [a]25 ˆ138.4 +c 0.5, CDCl3); H NMR d 7.74 +m,
1
D
2H), 7.47±7.35 +m, 3H), 7.34±7.22 +m, 3H), 3.88 +q, Jˆ
5.4 Hz, 1H), 1.70 +d, Jˆ5.4 Hz, 3H).
1.1.13. ꢀR,R)-1-ꢀTrimethylsilylethynyl)cyclohexene oxide
1
ꢀTable 1, entry 10).6i [a]25 ˆ19.53 +c 0.64, CHCl3); H
D
1.1.3. Method C. To a solution of 1-phenyl-3,4-dihydro-
naphthalene +0.206 g, 1.0 mmol) and ketone 5 +0.0774 g,
0.30 mmol) in CH3CN±EtOH±CH2Cl2 +1:1:2, v/v)
+2.0 mL) was added a solution of 2.0 M K2CO3 in 4£1024
M of EDTA +1.5 mL) followed by H2O2 +30%, 0.4 mL,
4 mmol) at 08C. Upon stirring at 08C for 16 h, the reaction
mixture was extracted with hexane, washed with 1 M
aqueous Na2S2O3 and brine, dried +Na2SO4), ®ltered,
concentrated, and puri®ed by chromatography +silica gel
NMR d 3.31 +t, Jˆ2.4 Hz, 1H), 2.10 +dt, Jˆ15.2, 6.2 Hz,
1H), 1.99 +ddd, Jˆ15.2, 7.5, 5.7 Hz, 1H), 1.88 +m, 2H),
1.44±1.16 +m, 4H), 0.14 +s, 9H).
1.1.14. ꢀR,R)-1-Benzoyloxy-1,2-epoxycyclooctane ꢀTable
1, entry 11).6g [a]25 ˆ17.03 +c 0.91, CHCl3); H NMR d
1
D
8.01 +m, 2H), 7.57 +tt, Jˆ7.4, 1.6 Hz, 1H), 7.43 +m, 2H),
3.20 +ddd, Jˆ10.0, 4.6, 0.8 Hz, 1H), 2.88 +m, 1H), 2.27
+ddd, Jˆ13.1, 7.8, 4.5 Hz, 1H), 1.92±1.20 +m, 10H).

L. Shu, Y. Shi / Tetrahedron 57 %2001) 5213±5218
5217
Tang, M.-W. J. Am. Chem. Soc. 1996, 118, 11311. +g) Song,
C. E.;Kim, Y. H.;Lee, K. C.;Lee, S. G.;Jin, B. W. Tetra-
1.1.15. ꢀR,R)-2-[ꢀE)-2-ꢀEthoxycarbonyl)-2-methylvinyl]-
3-ethyl-2-methyloxirane ꢀTable 1, entry 12).6d [a]25
296.79 +c 0.66, CHCl3); H NMR d 6.83 +m, 1H), 4.19
+q, Jˆ7.1 Hz, 2H), 2.85 +t, Jˆ6.3 Hz, 1H), 1.92 +d, Jˆ
1.2 Hz, 3H), 1.77±1.50 +m, 2H), 1.39 +s, 3H), 1.29 +t Jˆ
7.1 Hz, 3H), 1.08 +t, Jˆ7.5 Hz, 3H).
ˆ
D
1
hedron: Asymmetry 1997, 8, 2921. +h) Adam, W.;Zhao, C.-G.
Tetrahedron: Asymmetry 1997, 8, 3995. +i) Ref. 4j. +j) Wang,
Z.-X.;Shi, Y. J. Org. Chem. 1997, 62, 8622. +k) Armstrong,
A.;Hayter, B. R. Chem. Commun. 1998, 621. +l) Yang, D.;
Wong, M.-K.;Yip, Y.-C.;Wang, X.-C.;Tang, M.-W.;Zheng,
J. H.;Cheung, K. K. J. Am. Chem. Soc. 1998, 120, 5943.
+m) Yang, D.;Yip, Y.-C.;Chen, J.;Cheung, K.-K.
J. Am.
Acknowledgements
Chem. Soc. 1998, 120, 7659. +n) Adam, W.;Saha-Moller,
C. R.;Zhao, C.-G. Tetrahedron: Asymmetry 1999, 10, 2749.
+o) Wang, Z.-X.;Miller, S. M.;Anderson, O. P.;Shi, Y. J. Org.
Chem. 1999, 64, 6443. +p) Carnell, A. J.;Johnstone, R. A. W.;
Parsy, C. C.;Sanderson, W. R. Tetrahedron Lett. 1999, 40,
8029. +q) Armstrong, A.;Hayter, B. R. Tetrahedron 1999, 55,
11119. +r) Armstrong, A.;Hayter, B. R.;Moss, W. O.;Reeves,
J. R.;Wailes, J. S. Tetrahedron: Asymmetry 2000, 11, 2057.
+s) Solladie-Cavallo, A.;Bouerat, L. Org. Lett. 2000, 2, 3531.
6. For examples of asymmetric epoxidation mediated in situ by
fructose-derived ketones see: +a) Tu, Y.;Wang, Z.-X.;Shi, Y.
J. Am. Chem. Soc. 1996, 118, 9806. +b) Wang, Z.-X.;Tu, Y.;
Frohn, M.;Shi, Y. J. Org. Chem. 1997, 62, 2328. +c) Wang,
We are grateful to the generous ®nancial support from the
General Medical Sciences of the National Institutes of
Health +GM59705-02), Arnold and Mabel Beckman
Foundation, the Camille and Henry Dreyfus Foundation,
Alfred P. Sloan Foundation, DuPont, Eli Lilly, Glaxo-
Wellcome, and Merck.
References
1. For reviews see: +a) Smith, Gorzynski J. Synthesis 1984, 629.
+b) Besse, P.;Veschambre, H. Tetrahedron 1994, 50, 8885.
2. +a) Murray, R. W. Chem. Rev. 1989, 89, 1187. +b) Adam, W.;
Curci, R.;Edwards, J. O. Acc. Chem. Res. 1989, 22, 205. +c)
Curci, R.;Dinoi, A.;Rubino, M. F. Pure & Appl. Chem. 1995,
67, 811. +d) Clennan, E. L. Trends in Organic Chemistry 1995,
5, 231. +e) Adam, W.;Smerz, A. K. Bull. Soc. Chim. Belg.
1996, 105, 581. +f) Denmark, S. E.;Wu, Z. Synlett 1999, 847.
+g) Frohn, M.;Shi, Y. Synthesis 2000, 1979.
Z.-X.;Tu, Y.;Frohn, M.;Zhang, J.-R.;Shi, Y.
J. Am. Chem.
Soc. 1997, 119, 11224. +d) Frohn, M.;Dalkiewicz, M.;Tu, Y.;
Wang, Z.-X.;Shi, Y. J. Org. Chem. 1998, 63, 2948. +e) Wang,
Z.-X.;Shi, Y. J. Org. Chem. 1998, 63, 3099. +f) Cao, G.-A.;
Wang, Z.-X.;Tu, Y.;Shi, Y. Tetrahedron Lett. 1998, 39, 4425.
+g) Zhu, Y.;Tu, Y.;Yu, H.;Shi, Y. Tetrahedron Lett. 1998,
39, 7819. +h) Tu, Y.;Wang, Z.-X.;Frohn, M.;He, M.;Yu, H.;
Tang, Y.;Shi, Y. J. Org. Chem. 1998, 63, 8475. +i) Wang, Z.-
3. Murray, R. W.;Singh, S. Org. Synth. 1996, 74, 91.
4. For examples of in situ generation of dioxiranes see:
+a) Edwards, J. O.;Pater, R. H.;Curci, R.;Di Furia, F. Photo-
chem. Photobiol. 1979, 30, 63. +b) Curci, R.;Fiorentino, M.;
Troisi, L.;Edwards, J. O.;Pater, R. H. J. Org. Chem. 1980, 45,
4758. +c) Gallopo, A. R.;Edwards, J. O. J. Org. Chem. 1981,
46, 1684. +d) Cicala, G.;Curci, R.;Fiorentino, M.;
Laricchiuta, O. J. Org. Chem. 1982, 47, 2670. +e) Corey,
P. F.;Ward, F. E. J. Org. Chem. 1986, 51, 1925. +f) Adam,
W.;Hadjiarapoglou, L.;Smerz, A. Chem. Ber. 1991, 124, 227.
+g) Kurihara, M.;Ito, S.;Tsutsumi, N.;Miyata, N.
Tetrahedron Lett. 1994, 35, 1577. +h) Denmark, S. E.;Forbes,
D. C.;Hays, D. S.;DePue, J. S.;Wilde, R. G. J. Org. Chem.
1995, 60, 1391. +i) Yang, D.;Wong, M. K.;Yip, Y. C. J. Org.
Chem. 1995, 60, 3887. +j) Denmark, S. E.;Wu, Z.;Crudden,
C. M.;Matsuhashi, H. J. Org. Chem. 1997, 62, 8288.
+k) Denmark, S. E.;Wu, Z. J. Org. Chem. 1997, 62, 8964.
+l) Boehlow, T. R.;Buxton, P. C.;Grocock, E. L.;Marples,
B. A.;Waddington, V. L. Tetrahedron Lett. 1998, 39, 1839.
+m) Denmark, S. E.;Wu, Z. J. Org. Chem. 1998, 63, 2810.
+n) Frohn, M.;Wang, Z.-X.;Shi, Y. J. Org. Chem. 1998, 63,
6425. +o) Yang, D.;Yip, Y.-C.;Jiao, G.-S.;Wong, M.-K.
J. Org. Chem. 1998, 63, 8952. +p) Yang, D.;Yip, Y.-C.;
Tang, M.-W.;Wong, M.-K.;Cheung, K.-K. J. Org. Chem.
1998, 63, 9888.
X,;Cao, G.-A.;Shi, Y.
J. Org. Chem. 1999, 64, 7646.
+j) Warren, J. D.;Shi, Y. J. Org. Chem. 1999, 64, 7675.
+k) Frohn, M.;Zhou, X.;Zhang, J.-R.;Tang, Y.;Shi, Y.
J. Am. Chem. Soc. 1999, 121, 7718.
7. Oxone +2KHSO5´KHSO4´K2SO4) is currently the common
source of potassium peroxomonosulfate +KHSO5).
8. As close analogues of potassium peroxomonosulfate, arene-
sulfonic peracids generated from +arenesulfonyl)imidazole/
H2O2/NaOH have also been shown to produce dioxiranes
from acetone and tri¯uoroacetone as illustrated by 18O-label-
ling experiments see: Schulz, M.;Liebsch, S.;Kluge, R.;
Adam, W. J. Org. Chem. 1997, 62, 188.
9. The formation of dioxiranes have also been reported when
a ketone reacts with an oxidant such as CH3COOOH,
HOF, and ONOO2 +a) for CH3COOOH see: Murray, R. W.;
Ramachandran, V. Photochemistry and Photobiology 1979,
30, 187. +b) for HOF see: Rozen, S.;Bareket, Y.;Kol, M.
Tetrahedron 1993, 49, 8169. +c) for ONOO2 see: Yang, D.;
Tang, Y.-C.;Chen, Y.;Wang, X.-C.;Bartberger, M. D.;Houk,
K. N.;Olson, L. J. Am. Chem. Soc. 1999, 121, 11976.
10. For a preliminary report of a portion of this work, see: Shu, L.;
Shi, Y. Tetrahedron Lett. 1999, 40, 8721.
11. For a general reference on hydrogen peroxide see: Strukul, G.
Catalytic Oxidations with Hydrogen Peroxide as Oxidant,
Kluwer Academic Publishers, 1992.
5. For leading references on asymmetric epoxidation mediated in
situ by chiral ketones see: +a) Curci, R.;Fiorentino, M.;Serio,
M. R. J. Chem. Soc., Chem. Commun. 1984, 155. +b) Curci, R.;
12. The dioxirane is highly likely to be responsible for the
asymmetric epoxidation. However, other non-dioxirane
species can not completely ruled out at this moment.
13. For leading references on epoxidation using H2O2 and RCN
see: +a) Payne, G. B.;Deming, P. H.;Williams, P. H. J. Org.
Chem. 1961, 26, 659. +b) Payne, G. B. Tetrahedron 1962, 18,
763. +c) McIsaac Jr., J. E.;Ball, R. E.;Behrman, E. J. J. Org.
Chem. 1971, 36, 3048. +d) Bach, R. D.;Knight, J. W. Org.
D'Accolti, L.;Fiorentino, M.;Rosa, A.
Tetrahedron Lett.
1995, 36, 5831. +c) Ref. 4h. +d) Brown, D. S.;Marples,
B. A.;Smith, P.;Walton, L. Tetrahedron 1995, 51, 3587.
+e) Yang, D.;Yip, Y. C.;Tang, M. W.;Wong, M. K.;
Zheng, J. H.;Cheung, K. K. J. Am. Chem. Soc. 1996, 118,
491. +f) Yang, D.;Wang, X.-C.;Wong, M.-K.;Yip, Y.-C.;

5218
L. Shu, Y. Shi / Tetrahedron 57 %2001) 5213±5218
Synth. 1981, 60, 63. +e) Arias, L. A.;Adkins, S.;Nagel, C. J.;
Bach, R. D. J. Org. Chem. 1983, 48, 888.
18. For NaBO3, the epoxide was obtained in 52% conversion
and 76% ee when the reaction was carried out at room
temperature for 24 h with trans-b-methylstyrene +1 mmol),
ketone 5 +0.3 mmol), and NaBO3 +3 mmol) in CH3CN. For
Na2CO3´1.5H2O2, trans-b-methylstyrene oxide was obtained
in 20% conversion and 84% ee using 10 mol% ketone 5 and
2.7 equiv. of Na2CO3´1.5H2O2 in CH3CN at 08C for 10 h. For
mCPBA, trans-b-methylstyrene oxide was obtained in 28%
conversion and 89% ee when the reaction was carried out at
08C +bath temperature) with ole®n +1 mmol), ketone 5
+0.3 mmol), mCPBA +4 mmol in 6 mL of ethanol), and
K2CO3 +10 mmol in 6 mL of H2O) in CH2Cl2±EtOH +1:1,
v/v, 15 mL) +mCPBA and K2CO3 were added dropwise over
5 h via syringe pump).
14. A control experiment showed that at 1.0 M K2CO3, only 1%
conversion was obtained after 5 h stirring at 08C in the absence
of ketone.
15. In addition to ketone 5, other ketones are also able to catalyze
the epoxidation with the H2O2±CH3CN system, see: Shu, L.;
Shi, Y. J. Org. Chem. 2000, 65, 8807.
16. Other mixed solvent systems such as CH3CN-n-PrOH-CH2Cl2,
CH3CN-n-PrOH-PhCH3, CH3CN-n-PrOH-PhH, are also effec-
tive in many cases.
17. +a) Coates, R. M.;Williams, J. W. J. Org. Chem. 1974, 39,
3054. +b) Krishnan, S.;Kuhn, D. G.;Hamilton, G. A.
Tetrahedron Lett. 1977, 1369. +c) Bach, R. D.;Klein, M. W.;
Ryntz, R. A.;Holubka, J. W. J. Org. Chem. 1979, 44, 2569.
+d) Majetich, G.;Hicks, R. Synlett 1996, 649. +e) Murray,
R. W.;Iyanar, K. J. Org. Chem. 1998, 63, 1730.
19. Reddy, K. S.;Sola, L.;Moyano, A.;Pericas, M. A.;Riera, A.
Synthesis 2000, 165.