Regioselective and diastereoselective dimethyldioxirane epoxidation of substituted norbornenes and hexamethyl Dewar benzene

Article abstract of DOI:10.1016/S0040-4039(99)02113-9

Various substituted norbornenes, such as endo-dicyclopentadiene 1, exo- dicyclopentadiene 5, 5-methylenebicyclo[2.2.1]hept-2-ene 8 and hexamethyl Dewar benzene 10 were transformed into the corresponding mono- and bis- epoxides by epoxidation with dimethyldioxirane (as an acetone solution).

Full text of DOI:10.1016/S0040-4039(99)02113-9

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 539–542
Regioselective and diastereoselective dimethyldioxirane
epoxidation of substituted norbornenes and hexamethyl Dewar
benzene
Amalia Asouti and Lazaros P. Hadjiarapoglou ∗
Section of Organic Chemistry and Biochemistry, Department of Chemistry, University of Ioannina, 45110 Ioannina, Greece
Received 30 September 1999; accepted 10 November 1999
Abstract
Various substituted norbornenes, such as endo-dicyclopentadiene 1, exo-dicyclopentadiene 5, 5-
methylenebicyclo[2.2.1]hept-2-ene 8 and hexamethyl Dewar benzene 10 were transformed into the corresponding
mono- and bis-epoxides by epoxidation with dimethyldioxirane (as an acetone solution). © 2000 Elsevier Science
Ltd. All rights reserved.
Keywords: dimethyldioxirane; epoxidation; diastereoselectivity; regioselectivity; substituted norbornenes.
Dimethyldioxirane, either as a solution in acetone or generated in situ, is a well known and powerful
oxidizing agent.1 The dimethyldioxirane reagent is advantaged by efficiency, convenience of preparation
and isolation, and also on its performance under strictly neutral conditions. This reagent was further
enhanced by achievements in diastereoselective and enantioselective oxidation by chiral dioxiranes,2
generated in situ from a chiral ketone-catalyst and potassium monoperoxysulfate.3 Despite all its
synthetic applications, little is known about the regioselectivity of dimethyldioxirane epoxidations,
especially when two similar alkenes are present. To this end, some remarkable examples are the
regioselective epoxidation4 of a disubstituted double bond over a trisubstituted enol ether moiety, and
the exclusive epoxidation5 (at an endocyclic double bond) of the pentafulvenes.
A great number of studies6 have been devoted to epoxynorbornane derivatives due to the fact that these
compounds are readily produced from cyclopentadiene, which is a large scale side-product of the coke
and petroleum processing industries. In particular, dicyclopentadiene diepoxide has found application for
the industrial manufacture of various polymeric materials with valuable properties. Since this oxidation
is usually carried out with peracetic, peroxyphthalic and monoperoxymaleic acids, it was of interest
to examine the behaviour of such substrates towards dimethyldioxirane. Herein we report preliminary
results of the dimethyldioxirane epoxidation of substituted norbornenes and hexamethyl Dewar benzene.
∗
Corresponding author. E-mail: lxatziar@cc.uoi.gr (L. P. Hadjiarapoglou)
0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(99)02113-9
tetl 16041

540
Dimethyldioxirane epoxidation7 of endo-dicyclopentadiene 1 gave a mixture of epoxides 28 and 38
(Scheme 1), which were separated9 by flash column chromatography in 35% and 40% yield, respectively.
In contrast, mCPBA epoxidation9 of 1 leads to a 1.5:1 mixture of epoxides 2 and 3. Treatment of either
epoxide 2 or 3 with another batch of dimethyldioxirane afforded bis-epoxide 4, which was also isolated in
66% yield when endo-dicyclopentadiene 1 was treated with 2.5 equiv. of dimethyldioxirane. Of the four
possible stereoisomers, only epoxide 4, characterized by the syn arrangement of each epoxide function
to the subsequent bridge, was produced.
Scheme 1.
However, epoxidation of exo-dicyclopentadiene 510 with stoichiometric amounts of dimethyldioxirane
gave only epoxide 6 in 45% yield (Scheme 2). The treatment of epoxide 6 with dimethyldioxirane or
exo-dicyclopentadiene 5 with 2.5 equiv. of dimethyldioxirane gave bis-epoxide 7 in ca. 100% and 51%
yield, respectively. Again, of the four possible stereoisomers, only epoxide 7 is produced.
Scheme 2.
The reaction of 5-methylenebicyclo[2.2.1]hept-2-ene 8 with 1 equiv. of dimethyldioxirane afforded
epoxide 911 (Scheme 3). Further treatment of epoxide 9 with dimethyldioxirane or diene 8 with 2.5
equiv. of dimethyldioxirane yielded bis-epoxide 1011 as a 72:28 mixture of diastereomers. The typical
exo-selectivity6,12 of the epoxidation of norbornene derivatives is also observed for the double bond
which resides in the ring. However, as the second double bond moves away from the norbornene group,
the influence of the methylene bridge becomes less significant, and attack at the double bond occurs
from both sides. For dicyclopentadienes 1 and 5, where the C4–C5 double bond is also moved away
from the norbornene group, there is a second bridge between the C2 and C6 atoms which controls the
face-selectivity of the epoxidation at the subsequent double bond.

541
Scheme 3.
Dimethyldioxirane epoxidation of hexamethyl Dewar benzene 11 yields a mixture of the mono-
epoxide 128 and bis-epoxide 138 (Scheme 4), the ratio of which depends on the amount of dioxirane
employed. Quite surprisingly, with 1 equiv. of dimethyldioxirane, epoxide 12 was isolated in 97% yield
while, with excess of dimethyldioxirane, the bis-epoxide 13 was quantitatively isolated instead. Epoxide
12 had been previously postulated13 as the labile intermediate in the peracid epoxidation of 11, which
was not even detected due to rapid acid hydrolysis. The stereochemistry of the two oxygen atoms in bis-
epoxide 13 is syn according to the observed symmetry of the NMR signals. No NOE effect was observed
between the epoxide and the bridge’s methyl groups.
Scheme 4.
In summary, we have demonstrated that dimethyldioxirane (as an acetone solution) serves as a
convenient and diastereoselective oxidant for the preparation of various mono- and bis-epoxides of
substituted norbornenes and hexamethyl Dewar benzene. We are presently examining the optimization
of these reactions, employing various in situ techniques, and our results will be presented in due course.
Acknowledgements
We thank Prof. Dr. Waldemar Adam (University of Wuerzburg) and Drs. George Pilidis, and George
Varvounis (University of Ioannina) for their generous support. The donation of Curox by Interox Peroxid
Chemie (Muenchen, Germany) is greatly appreciated.

542
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1
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