J . Org. Chem. 1996, 61, 1877-1879
1877
Ch em o- a n d Regioselective Con ver sion of
Ep oxid es to Ca r bon yl Com p ou n d s in 5 M
Lith iu m P er ch lor a te-Dieth yl Eth er
Med iu m
(1a ) gave only phenylacetaldehyde (2a ), which was stable
to the reaction conditions. This product can be directly
8
converted to the corresponding dithioacetal by adding 1
equiv of 1,2-ethanedithiol in the same medium, thus
offering a convenient one-pot conversion of the epoxide
to the corresponding dithioacetal. Among the acyclic
olefin epoxides, the terminal olefin epoxides 1f-i did not
react in 5 M LPDE medium. However, the di- and
trisubstituted epoxides (1c-e and 1p) rearranged smooth-
ly at rt. The bis-epoxide 1e is an interesting example
demonstrating the high chemo- and regioselectivities that
can be achieved in 5 M LPDE medium. Thus, 1e reacted
to yield the epoxy ketone 2e as the only product in which
the terminal epoxide remained intact under the reaction
conditions. Among the cyclic olefin epoxides, cyclohexene
oxide (11) was found to be stable in 5 M LPDE medium.
However, epoxides with a tertiary oxirane center rear-
ranged readily to give the corresponding ketones without
any ring contraction. The case of limonene oxide (1o) is
noteworthy. When a 1:1 mixture of cis and trans-
limonene oxides was reacted, it was found that only the
trans diastereomer [1-methyl-t-4-(2-propenyl)-r-1-cyclo-
hexene oxide] rearranged stereospecifically to give, ex-
clusively, trans-dihydrocarvone [trans-5-(2-propenyl)-2-
methylcyclohexanone) (trans-2o) and the cis isomer
[1-methyl-c-4-(2-propenyl)-r-1-cyclohexene oxide] remained
R. Sudha, K. Malola Narasimhan,
V. Geetha Saraswathy, and S. Sankararaman*
Department of Chemistry, Indian Institute of Technology,
Madras - 600 036, India.
Received October 12, 1995
Epoxides are useful substrates in organic synthesis due
to their high reactivity.1 Conversion of an epoxide to a
carbonyl compound is a synthetically useful reaction, and
BF
3
and its etherate are the most commonly used
2
reagents for this purpose. Unless there is a structural
or a stereochemical bias, generally multiple products are
obtained due to the lack of regioselectivity in the ring
opening step. Moreover, lack of chemoselectivity among
various substituted epoxides limits the synthetic utility
of this reaction in multistep synthesis. In fact, no epoxide
2
has been reported to be insensitive to BF
3
.
Lithium and
magnesium halides have been used for epoxide ring
opening reaction.2 Recently, chemo and regioselective
isomerization of epoxides to carbonyl compounds by a
palladium catalyst has been reported.5 Lithium perchlo-
rate in refluxing benzene has been reported to be a very
useful reagent for the rearrangement of several epoxides
-4
intact. With strong Lewis acids such as ZnBr
no stereoselectivity has been reported for limonene oxide
2 3
and BF ,
and other structurally related epoxides.1
0,11
Finally,
as it shows higher product selectivity compared to strong
norbornene oxide (1q) gave only 2-norbornanone (2q), in
Lewis acids.2
,3,6
Recently, 5 M lithium perchlorate in
sharp contrast to the formation of two products in
3
diethyl ether (LPDE) has been shown to be an excellent
medium for several synthetic transformations, and high
chemo-, regio-, and stereoselectivities have been re-
ported.7 In our efforts to use this medium for selective
LiClO
4
-benzene medium arising from the involvement
of a nonclassical carbenium ion.
Based on the observed chemo- and regioselectivities
and the products of rearrangement, it is inferred that the
rearrangement of epoxides in LPDE medium could
proceed by the coordination of the lithium ion to the
epoxide oxygen followed by the cleavage of a C-O bond
to give the most stable carbenium ion and subsequent
hydride migration (except in the case of 1b) to give the
observed product. We attribute the observed chemo- and
8
,9
synthetic transformations, we have investigated the
ring opening reaction of epoxides, and herein we report
our results.
Resu lts a n d Discu ssion
The results from the rearrangement of various ep-
oxides are summarized in Table 1. Benzylic epoxides
from both acyclic and cyclic olefins (1a , 1b, 1k , and 1n )
rearranged with high regiospecificity to give a single
product in each case. The reactions of the oxides of
styrene and trans-stilbene were highly exothermic, and
hence they were carried out either at 0 °C in 5 M LPDE
or at rt in 1 M LPDE. It is noteworthy that styrene oxide
regioselectivities to the mild Lewis acidity of the lithium
ion in ether.8 The stereoselectivity in the case of li-
monene oxide (1o) can be explained by invoking the rule
11
of diaxial ring opening or the Furst-Plattner rule. The
trans-limonene oxide could undergo antiperiplanar ring
opening with ease to give directly a chair conformer of
the tertiary carbenium ion where as such a ring opening
in the case of the cis isomer will initially lead to a twist
boat conformer.2 The small differences in the activation
barriers for the ring opening of these two diastereomers
is manifested in LPDE medium. Such a highly diaste-
reoselective ring opening is not possible with strong
,11
(
1) Smith, J . G. Synthesis 1984, 629. Rao, A. S.; Pakinkar, S. K.;
Kirtane, J . G. Tetrahedron 1983, 39, 2323.
2) Rickborn, B. In Comprehensive Organic Synthesis; Trost, B. M.,
Fleming, I., Eds.; Pergamon Press: New York, 1991; Vol. 3, pp 733-
75.
3) Rickborn, B.; Gerkin, R. M. J . Am. Chem. Soc. 1968, 90, 4193.
Rickborn, B.; Gerkin, R. M. J . Am. Chem. Soc. 1971, 93, 1693.
4) Naqvi, S. M.; Horwitz, J . P.; Filler, R. J . Am. Chem. Soc. 1957,
9, 6283. Hudrlik, P. F.; Misra, R. N.; Withers, G. P.; Hudrlik, A. M.;
(
7
1
1
Lewis acids such as BF
3
.
Similarly, the small differ-
(
ences in the activation barriers for the rearrangement
of monosubstituted and higher substituted epoxides (as
in 1e) is also exemplified in this medium leading to very
high chemoselectivity.
(
7
Rona, R. J .; Arcoleo, J . P. Tetrahedron Lett. 1976, 1453. Obayashi,
M.; Utimoto, K.; Nozaki, H. Tetrahedron Lett. 1977, 1807.
(
(
5) Kulasegaram, S.; Kulawiec, R. J . J . Org. Chem. 1994, 59, 7195.
6) Trost, B. M.; Bogdanowicz, M. J . J . Am. Chem. Soc. 1973, 95,
Exp er im en ta l Section
5
321. McMurry, J . E.; Musser, J . H.; Ahmed, M. S.; Blaszczak, L. C.
J . Org. Chem. 1975, 40, 1829.
7) Grieco, P. A. Aldrichim. Acta 1991, 24, 61. Waldmann, H.
Angew. Chem., Int. Ed. Engl. 1991, 30, 1306.
8) Geetha Saraswathy, V.; Sankararaman, S. J . Org. Chem. 1994,
9, 4665.
Ma ter ia ls. Preparation of 5 M LPDE medium has been
described previously.8 The epoxides were prepared from the
(
(
(10) Lewis, J . B.; Hendrick, G. W. J . Org. Chem. 1965, 30, 4271.
Settine, R. L.; Parks, G. L.; Hunter, G. L. K. J . Org. Chem. 1964, 29,
616.
(11) Barili, P. L.; Berti, G.; Macchia, B.; Macchia, F.; Monti, L. J .
Chem. Soc. C 1970, 1168.
5
6
(
9) Geetha Saraswathy, V.; Sankararaman, S. J . Org. Chem. 1995,
0, 5024. Geetha Saraswathy, V.; Sankararaman, S. J . Chem. Soc.
Perkin Trans. 2, in press.
0
022-3263/96/1961-1877$12.00/0 © 1996 American Chemical Society