Asymmetric epoxidation of cis-β-methylstyrenes catalyzed by N-aryl substituted oxazolidinone-containing ketones. A beneficial substituent effect

Article abstract of DOI:10.1016/j.tetlet.2004.08.124

Asymmetric epoxidation of substituted cis-β-methylstyrenes using N-aryl substituted oxazolidinone-containing ketones as catalysts shows that substituents on the phenyl group of the olefin have significant positive effects on the enantioselectivity of the

Full text of DOI:10.1016/j.tetlet.2004.08.124

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 8115–8117
Asymmetric epoxidation of cis-b-methylstyrenes catalyzed by
N-aryl substituted oxazolidinone-containing ketones.
A beneficial substituent effect
Lianhe Shu and Yian Shi*
Department of Chemistry, Colorado State University, Fort Collins, CO 80523, USA
Received 29 July 2004; revised 20 August 2004; accepted 20 August 2004
Available online 17September 2004
Abstract—Asymmetric epoxidation of substituted cis-b-methylstyrenes using N-aryl substituted oxazolidinone-containing ketones
as catalysts shows that substituents on the phenyl group of the olefin have significant positive effects on the enantioselectivity of
the epoxidation, indicating a beneficial interaction between the phenyl group of the olefin and the phenyl group of the ketone
catalyst.
Ó 2004 Elsevier Ltd. All rights reserved.
Asymmetric epoxidation of olefins is an important
method for synthesizing optically active epoxides. Great
success has been achieved for the epoxidation of allylic
alcohols,1 the metal-catalyzed epoxidation of unfunc-
tionalized olefins,2 and the nucleophilic epoxidation of
electron-deficient olefins.3 In recent years, chiral dioxir-
anes have been shown to be powerful asymmetric epoxi-
dation agents.4–6 In our earlier studies, we have shown
that fructose-derived ketone 1 (Scheme 1) gives high
enantioselectivity for the epoxidation of trans- and tri-
substituted olefins.7 Subsequently, we have found that
ketone 2, resulting from the replacement of the spiro ke-
tal of ketone 1 with an oxazolidinone, provides encour-
agingly high eeÕs for the epoxidation of cis-olefins and
styrenes.8 Our earlier studies suggest that the asymmet-
ric induction is likely due to an attraction between the
Rp group and the oxazolidinone moiety of the ketone
catalyst in the transition state (Scheme 2). This elec-
tronic interaction was further illustrated by our recent
studies with N-aryl substituted oxazolidinone ketone
3.9 To further probe this interaction, we have investi-
gated the epoxidation of various substituted cis-b-methyl-
styrenes and have found that the olefin substituent has a
significant effect on the enantioselectivity of the epoxi-
dation. Herein we wish to report our preliminary efforts
on this subject.
The epoxidation was initially investigated using ketone
3a as catalyst. Subjecting cis-b-methylstyrene to the
epoxidation conditions with 10mol% of ketone 3a at
À10°C gave (1R,2S)-cis-b-methylstyrene oxide with
99% conversion and 84% ee (Table 1, entry 1).10 The
epoxidation of cis-b-methylstyrene with 3a was found
Scheme 1.
Keywords: Asymmetric epoxidation; Chiral dioxirane; Chiral ketone;
Phenyl–phenyl interaction.
*
Corresponding author. Tel.: +1 970 491 7424; fax: +1 970 491
1801; e-mail: yian@lamar.colostate.edu
Scheme 2.
0040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.08.124

8116
L. Shu, Y. Shi / Tetrahedron Letters 45 (2004) 8115–8117
Table 1. Asymmetric epoxidation of olefins catalyzed by ketones 3a and 3b
Entry
Substrate
Ketone 3aa
Ketone 3bb
Conv. (%)c
99
ee (%)c
84
Conv. (%)c
100
ee (%)c
90
1
2
3
Me
Me
86
94
88
91
80
92
93
100
X
4
X = Me
X = Et
X = F
100
8790
99
88
96
93
91
92
5
91
6
7X = Cl
87100
9
7
92
90
95
8
X = Br
X = CN
X = NO2
82
94
93
96
98
86
98
91
96
96
97
9
10
86
Me
Me
11
12
72
75
92
91
100
97
97
96
Me
Me
Me
13
14
9791
100
94
Me
Me
98
92
100
94
Me
a All reactions were carried out with olefin (0.2mmol), ketone 3a (0.02mmol), Oxone (0.197g, 0.32mmol), and K2CO3 (0.185g, 1.34mmol) in DME/
DMM (3:1, v/v) (3mL) and buffer (0.1M K2CO3–AcOH, pH9.3) (2mL) at À10°C (bath temperature). The reactions were stopped after 4h.
b The reactions with ketone 3b were carried out in a similar fashion to ketone 3a. All reactions used 15mol% of ketone except entries 11 and 12 where
20mol% was used. For ketone 3b, the epoxides (both cis- and trans-isomers) were isolated in 61–95% yield.
c The conversions and eeÕs were determined by chiral GC (Chiraldex B-DM). For entries 2–14, the olefin substrates contain 16–37% trans-isomers.
The conversions indicated are those for cis-olefins.
to be stereospecific and no trans-b-methylstyrene oxide
was formed during the reaction as judged by GC assays
of the crude reaction mixture. Introducing a methyl
group to ortho, meta, and para positions gave rise to a
4–7% ee increase (Table 1, entries 2–4).11 Further studies
with various para substituted cis-b-methylstyrenes
showed that the eeÕs of the epoxides increased across
the board from the electron-donating Me group to the
electron-withdrawing NO2 group (Table 1, entries 4–
10). Up to 98% ee was attained with the NO2 substituted
olefin (Table 1, entry 10). The eeÕs also increased when
two methyl groups were introduced at various positions
(Table 1, entries 11–14). A similar trend was observed
when the epoxidation was carried out with ketone 3b,
which contained an electron-withdrawing sulfone sub-
stituent on the phenyl group of the ketone catalyst.
The significant substituent effect observed with ketone 3
is rather interesting. The results suggest that there is an
additional phenyl–phenyl interaction between the olefin
and catalyst in the transition state aside from the attrac-
tive interaction between the phenyl group of the olefin
and the oxazolidinone moiety of the catalyst (Scheme
3).8,9 The crystal structure of 3a shows that the phenyl
group in this ketone is coplanar with the oxazolidinone.9
Therefore, this phenyl–phenyl interaction is more likely
to be an Ôedge-to-faceÕ interaction.12 While electron-
withdrawing groups on the phenyl group of the olefin

L. Shu, Y. Shi / Tetrahedron Letters 45 (2004) 8115–8117
8117
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show a stronger effect, electron-donating groups can
also enhance the interaction, suggesting that nonbond-
ing interactions such as van der Waals forces and/or
hydrophobic interactions could be involved in the phe-
nyl–phenyl interaction in addition to electrostatic inter-
actions.12b A precise understanding of the interaction
for the current system awaits further studies.
In summary, asymmetric epoxidation of various substi-
tuted cis-b-methylstyrenes using N-aryl substituted oxazo-
lidinone-containing ketones 3a and 3b has shown that
the substituents on the phenyl group of the olefin have
significant positive effects on the enantioselectivity of
the epoxidation. These results reveal a beneficial interac-
tion between the phenyl group of the olefin and the phe-
nyl group of the ketone catalyst. Although the precise
nature of this phenyl–phenyl interaction is not clear,
such interactions could provide us additional opportuni-
ties to explore asymmetric induction. At the same time,
the current epoxidation system could be used as a tool to
further study such interactions. Synthetically, the ob-
served beneficial substituent effect further enhances the
practical aspect of ketone 3, which is readily available
from glucose.9
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Acknowledgements
We are grateful to the generous financial support from
the General Medical Sciences of the National Institutes
of Health (GM59705-05), the Camille and Henry Drey-
fus Foundation, and the Monfort Foundation (Colo-
rado State University).
7 . (a) Tu, Y.; Wang, Z.-X.; Shi, Y.J. Am. Chem. Soc. 1996,
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References and notes
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10. The epoxidation was carried out under more basic
conditions as compared to the one described in Ref. 9.
The conversion was improved under the current reaction
condition.
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Wittig olefination of substituted benzaldehydes and con-
tained a mixture of cis- and trans-isomers.
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