C O M M U N I C A T I O N S
Scheme 2. Solvents for the Organocatalyzed Epoxidation of
substituted substrates. This might be due to the fact that there is
no stereocenter formed in the first step, which influences the
formation of the second stereocenter (see Scheme 1). The possibility
for an asymmetric epoxidation of these substrates is an important
4
new development compared to existing methods. We have taken
in advantage this protocol for the direct formation of the sex
pheromone from an acaric mite.12 Epoxidation of citral 1j (3:2 E:Z
ratio was used) under the standard conditions gave the sex
13
pheromone 2j in 73% yield and 85% ee of the major diastereomer
eq 3).
Table 2. Scope of the Organocatalyzed Epoxidation of
(
a
R,â-Unsaturated Aldehydes with Hydrogen Peroxide
entry
R1
R2
yieldb (%)
drc
eed (%)
In summary, we have developed the first organocatalytic
1
2
3
4
5
6
7
8
9
Ph - 1a
H
2a - 80
2b - 90
2c - 65
2d - 63
2e - >90
2f - 75
2g - 84
2h - 60
2i - 65
93:7
91:9
90:10
95:5
97:3
98:2
96:4
90:10
96
97
96
98
96
96
94
96
75
asymmetric epoxidation of R,â-unsaturated aldehydes using a
sterically encumbered chiral pyrrolidine derivative, which is easily
accessible in four steps from L-proline as the catalyst and hydrogen
peroxide as the oxidant. The reactions can take place under
environmentally friendly conditions, and for a series of different
substituted R,â-unsaturated aldehydes, good to high yields and
diastereoselectivities and excellent enantioselectivities of the cor-
responding R,â-epoxy aldehydes were obtained. Furthermore, the
formation of the optically active female sex pheromone from an
acaric mite in one step was presented.
o-NO2-Ph - 1b
o-Me-Ph - 1c
p-Cl-Ph - 1d
Et - 1e
H
H
H
e
H
i-Pr - 1f
H
CH2OBn - 1g
H
CO2Et -1h
H
Me - 1i
Me
a
.3 equiv of H2O2 used. Isolated yield. c The dr was determined by
b
1
d
chiral GC and NMR. The ee was determined by chiral GC and HPLC.
More than 90% conversion was found; however, due to the volatility of
the product, the R,â-epoxy aldehyde was transformed to the corresponding
alcohol, which under nonoptimized conditions, was isolated in 43% yield.
e
Acknowledgment. This work was made possible by a grant
from The Danish National Research Foundation. J.F. thanks The
Wenner-Gren Foundation for a grant.
2 2
cumene hydroperoxide gave the same results as H O and UHP,
while very low conversion was found using m-chloro perbenzoic
acid.
An important aspect of the organocatalytic asymmetric epoxi-
dation catalyzed by 3 is that it proceeds in different solvents. In
Scheme 2, some representative results are presented using UHP as
the oxidant.
The results in Scheme 2 show that the asymmetric epoxidation
proceeds well with high stereoselectivity in a variety of solvents,
with the exception of TBME. Of particular interest is to note that
in methanol (80%) and ethanol (90%), the enantiomeric excess of
epoxide 2a is 92% ee, showing that this process can take place
under benign conditions.
To demonstrate the scope and potential for the organocatalytic
epoxidation, a series of different substituted R,â-unsaturated
2 2
aldehydes were reacted with H O at room temperature in the
presence of 3 (10 mol %) as the catalyst (eq 2). The results are
summarized in Table 2.
R,â-Unsaturated aldehydes having aromatic substituents in the
â-position, 1a-d, are all converted to the corresponding optically
active epoxides in good yields and diastereoselectivities and with
excellent enantioselectivities (96-98% ee) (Table 1, entries 1-4).
For the alkyl-substituted R,â-unsaturated aldehydes 1e-g, a slight
improvement in diastereoselectivity is found, and the high enan-
tioselectivity is maintained (entries 5-7). 4-Oxo-but-2-enoic acid
ethyl ester (1h) containing an ethyl ester functionality in the
â-position gave 60% yield, 90:10 dr, and 96% ee of the corre-
sponding epoxide 2h (entry 8). The results in entries 7 and 8 show
that heteroatom functionalities, a protected alcohol, and an ester
are tolerated in the R,â-unsaturated aldehydes, giving the possibility
for further transformations of this part of the optically active R,â-
epoxy aldehyde.
Supporting Information Available: Complete experimental pro-
cedures and characterization (PDF). This material is available free of
charge via the Internet at http://pubs.acs.org.
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(
(
(
(
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(
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(
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(
2
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(
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(11) The use of L-proline and other chiral pyrrolidine derivatives as the catalyst
gave poor or low conversion, and the epoxide 2a was formed as a
racemate, or with low enantiomeric excess.
The â-disubstituted R,â-unsaturated aldehyde, 4-methyl butenal
1i), is also epoxidized smoothly (entry 9); however, a slight
(12) Mori, N.; Kuwahara, Y.; Kurosa, K. Bioorg. Med. Chem 1996, 4, 289.
(13) The dr (75:25) is higher than the E:Z ratio of 1j.
(
decrease in enantioselectivity is observed compared to the mono-
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