First highly enantioselective epoxidation of alkenes with aldehyde/Oxone

Article abstract of DOI:10.1016/j.tetlet.2003.08.040

Optically active aldehydes have been successfully used as catalysts for asymmetric epoxidations of unfunctionalized alkenes (ee up to 94%) by using Oxone as the oxygen source. Experimental results indicate that the in-situ-generated aldehyde dioxirane is responsible for this catalytic activity.

Full text of DOI:10.1016/j.tetlet.2003.08.040

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 7403–7406
First highly enantioselective epoxidation of alkenes with
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ꢀ
aldehyde/Oxone
Ghanashyam Bez and Cong-Gui Zhao*
Department of Chemistry, University of Texas at San Antonio, 6900 N. Loop 1604 W., San Antonio, TX 78249-0698, USA
Received 6 August 2003; accepted 11 August 2003
Abstract—Optically active aldehydes have been successfully used as catalysts for asymmetric epoxidations of unfunctionalized
®
alkenes (ee up to 94%) by using Oxone as the oxygen source. Experimental results indicate that the in-situ-generated aldehyde
dioxirane is responsible for this catalytic activity.
©
2003 Elsevier Ltd. All rights reserved.
®
Ketone dioxiranes have been known for decades as
excellent oxidants. Through the efforts of recent years,
optically active aldehydes and Oxone , which, to the best
1
of our knowledge, is the first direct evidence for the
involvement of aldehyde dioxiranes.
chiral ketone dioxiranes have been shown to be promi-
2
,3
nent oxidants for asymmetric epoxidations. They have
also shown their potential in asymmetric CꢀH oxida-
Although ketone dioxirane may be readily prepared from
Oxone oxidation of a ketone, preparation of aldehyde
4
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tions, which is still a challenge of organic chemistry. In
5,6
contrast, although substantiated in theoretical study,
dioxirane by this way was regarded as taboo. This is
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aldehyde dioxiranes (RHCO ), which have been involved
because aldehyde is reportedly prone to Oxone oxida-
2
8
in biological processes, still remain elusive. For example,
the bioluminescent process of bacterial luciferase uses
C4a-flavin hydroperoxide to react with an aldehyde to
generate the corresponding dioxirane as the high-energy
intermediate, which has not been isolated nor character-
tion to give the corresponding acid. However, as shown
in Scheme 1, this is only the major reaction pathway.
Three reaction pathways may be envisaged when alde-
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hyde is allowed to react with Oxone , which rely on the
Criegee intermediate. We reasoned that if both pathways
6
ized. So far the only known aldehyde dioxirane is
a and b are inhibited, for example, through electronic
9
dihydrodioxirane (H CO ), but it was obtained from low
effects, then dioxirane formation is highly possible.
2
2
7
temperature ozonolysis of ethene, rather than from
formaldehyde directly. Herewith we wish to report our
preliminary results on asymmetric epoxidation by using
Recently we synthesized 1-benzyloxy cyclohexanecarb-
aldehyde (1) and found that it catalyzes the epoxidation
of trans-stilbene (Eq. (1)). When 3 equiv. of 1 was used,
3
1% yield of the epoxide was obtained after 2 h of
reaction, while under these conditions the background
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oxidation by Oxone itself is negligible. The possible
involvement of oxidative degradation product of 1 (such
as cyclohexanone) as the actual catalyst in the present
system was ruled out by NMR and GC–MS studies since
neither cyclohexanone nor oxepan-2-one was found in
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the reaction mixture of 1 and Oxone (Scheme 2).
Scheme 1. Possible reaction pathways of aldehyde.
Keywords: aldehyde dioxirane; enantioselective; alkene; epoxidation,
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Oxone .
(1)
ꢀ
Supplementary data associated with this article can be found at
doi:10.1016/j.tetlet.2003.08.040
*
Corresponding author. Tel.: +1-210-458-4464; fax: +1-210-458-7428;
e-mail: czhao@utsa.edu
0
040-4039/$ - see front matter © 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2003.08.040

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G. Bez, C.-G. Zhao / Tetrahedron Letters 44 (2003) 7403–7406
Table 1. Enantioselective epoxidation with chiral alde-
a
hydes 2 and 3 and ketone 4
Scheme 2. Exclusion of cyclohexanone as the catalyst (B.-
V.=Baeyer–Villiger oxidation).
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The intermediates formed by aldehyde and Oxone that
are capable of oxygen transfer are the Criegee interme-
diate and the aldehyde dioxirane (cf. Scheme 1). Since
ketone dioxirane, rather than the Criegee intermediate,
has been proved to be the active oxygen transfer
10
reagent under similar conditions, we favor the alde-
hyde dioxirane mechanism. Of course, more mechanis-
tic scrutiny is still required to verify this.
On the basis of these findings, we explored the possibil-
ity of using optically active aldehyde dioxirane for
asymmetric epoxidations. Chiral aldehydes 2 and 3
were designed and synthesized from fructose. The fruc-
tose backbone was selected because Shi et al. have
11
shown that it is very effective in stereocontrol. The
results of asymmetric epoxidation of unfunctionalized
alkenes by using aldehydes 2 and 3 as catalysts are
summarized in Table 1. For comparison purpose the
results of the corresponding ketone 4 are also included.
hyde 3 also yielded higher enantioselectivity than alde-
hyde 2 for these substrates [67% (entry 9) and 82%
(
entry 10), respectively]. Aldehyde 3 also yielded a good
enantioselectivity (70% ee, entry 11) for a prochiral
allylic alcohol, while aldehyde 2 gave no conversion of
this particular substrate (data not shown). A terminal
alkene (entries 12 and 13) and a cyclic alkene (entries 14
and 15) produce low enantioselectivities with either
aldehydes 2 or 3, albeit with good conversions. It is
clear from Table 1 that aldehyde 3 yields consistently
better enantioselectivity than aldehyde 2, except for the
terminal and cyclic alkenes.
With trans-stilbene as the substrate, a 63.5% ee was
obtained for the epoxide by using aldehyde 2 as the
catalyst (entry 1). The ee value was greatly improved to
9
3.5% by using aldehyde 3 as catalyst, with also
12
The observed enantioselectivity may be explained in
improved conversion of the substrate (entry 2). In
contrast, the corresponding ketone 4 only yielded 39%
ee for the epoxide (entry 3). Under the same conditions,
excellent ee values were obtained for triphenylethylene
epoxide by using both aldehydes 2 (81% ee, entry 4)
and 3 (92% ee, entry 5) as the catalyst, although the
conversions were not so good. Again, much inferior
enantioselectivity was obtained with ketone 4 as the
catalyst (36% ee, entry 6). When 1-phenylcyclohexene
and 1-methyl-trans-stilbene were used as substrates, ee
values of 48% (entry 7) and 53% (entry 9) were
obtained for aldehyde 2, respectively. Similarly, alde-
13
terms of the favored spiro transition states, as shown
for aldehyde 3 in Scheme 3. The lower dioxirane oxy-
gen atom is sterically hindered for the oxygen transfer
by the two nearby acetal functionalities and electroni-
cally deactivated by the hydrogen bonding. Thus, the
upper oxygen atom is favored for oxygen transfer. In
the disfavored transition state, the phenyl group of the
trans-stilbene interacts with the dioxolane ring of the
dioxirane, while in the favored one such steric encum-
brance is absent and, therefore, a high enantioselectiv-
ity is obtained. The favored transition state will

G. Bez, C.-G. Zhao / Tetrahedron Letters 44 (2003) 7403–7406
7405
Acknowledgements
The generous financial support from the University of
Texas at San Antonio (UTSA) is gratefully acknowl-
edged. The authors thank Professor Stephan Bach
(
UTSA) for his help with GC-MS.
References
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6
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favorably interact with the dioxolane ring if it also
adopts similar transition states as aldehyde 3. Appar-
ently, the hydrogen bonding is not forming in this case
and low enantioselectivity is obtained.
2
001, 12, 2779–2781; (i) Seki, M.; Furutani, T.; Imashiro,
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5
It should be pointed out that asymmetric epoxidation
with acyclic chiral ketones is still a challenge in dioxi-
14
rane chemistry (less than 20% ee has been obtained;
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fact that cyclic chiral ketones have been established as
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7
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1
8
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9
®
when anisaldehyde is oxidized by Oxone , only low yield
In summary, we developed the first highly enantioselec-
tive epoxidation protocol with optically active alde-
hydes as the catalysts. Aldehyde dioxirane is proposed
as the active oxygen transfer reagent. We are currently
working on the reaction mechanism and the improve-
ment of the catalytic efficiency of the aldehydes.
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G. Bez, C.-G. Zhao / Tetrahedron Letters 44 (2003) 7403–7406
12. General epoxidation procedure: To a stirred solution of
mL), dried over MgSO and evaporated to give the crude
4
trans-stilbene (0.018 g, 0.1 mmol) and aldehyde 3 (0.086
product. A conversion of 54% of the starting material with
g, 0.3 mmol) in CH CN (3.0 mL) were added tetrabutyl
an ee value of 93.5% for the epoxide were achieved as
indicated by HNMR and HPLC analyses, respectively.
13. For theoretical treatments, see: (a) Miaskiewicz, K.; Smith,
D. A. J. Am. Chem. Soc. 1998, 120, 1872–1875; (b) Jenson,
C.; Liu, J., Houk, K. N.; Jorgensen, W. L. J. Am. Chem.
Soc. 1997, 119, 12982–12983.
3
1
ammonium sulfate (3 mg, 8 mmol) and the buffer (0.05 M
−
4
Na B O in 4×10 M aqueous Na EDTA, 1.0 mL) at 0°C.
2
4
7
2
®
A solution of Oxone (0.085 g, 0.138 mmol) in aqueous
−
4
Na EDTA (4×10 M, 0.65 mL) and an aqueous solution
2
of K CO (0.080 g, 0.58 mmol) in water (0.65 mL) were
2
3
added dropwise simultaneously through syringe over a
period of 2 h. After stirring for additional 2 h the reaction
mixture was quenched by addition of hexane and water.
Then the reaction mixture was extracted with hexane (3×10
14. (a) Curci, R.; Fiorentino, M.; Serio, M. R. J. Chem. Soc.,
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