M. Kamata et al. / Tetrahedron Letters 42 (2001) 9203–9206
Table 2. Deoxygenation of trioxolanes 7 by triphenylphosphine.a
9205
Run
Substrate
Time (min)
Conv. (%)
Yields of products (%)b
8
9
11
1
2
7a
7b
90
90
98
100
96
81
94
93
94
99
a 7=0.2 mmol, PPh3=0.2 mmol, CH2Cl2=10 ml, 20–25°C.
b Isolated yield.
3b. Thus, trioxolane 7b was also obtained in moderate
yield along with 4,4%-dimethylbenzophenone 8b and 3,3-
di(p-methylphenyl)-2-propenal 9b (runs 4–5 in Table 1),
which may extend the generality of the DCA-sensitized
conversion of the vinyl oxiranes 3 to trioxolanes 7.§
In summary, we have discovered that the DCA-sensi-
tized PET oxygenation of arylvinyl oxiranes 3 afforded
1,2,4-trioxolanes 7. We are now conducting the studies
on the relationship between the Fe(II)-mediated frag-
mentation, the antimalarial intermediates, and the anti-
malarial activities for 7 and other cyclic peroxides.
On the basis of the above results, we propose a plausi-
ble mechanism involving a peroxy cation radical 12 for
the formation of trioxolane 7 (Scheme 4). Thus, single
electron oxidation of 3 produces the radical cation of 3
(3+) which reacts with molecular oxygen to generate 12.
The resulting peroxy radical cation 12 undergoes
cyclization to give a trioxolane cation radical (7+),
which would be reduced to afford 7. Molecular orbital
calculations (PM3) strongly support the preferential
formation of 7+ rather than 4+. Thus, the heats of
formation of 12, 7+, and 4+ were calculated to be
275.6, 261.2, and 294.4 kcal/mol, respectively, which
indicates that conversion of 12 to 4+ is endothermic
but that of 12 to 7+ is highly exothermic.¶
Acknowledgements
We are grateful to Professor Eietsu Hasegawa (Faculty
of Science, Niigata University), Professor Tsutomu
Miyashi and Dr. Hiroshi Ikeda (Faculty of Science,
Tohoku University) for their helpful comments and
assistance.
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¶ The geometries of 12, 4+, and 7+ were fully optimized and the
details will be reported elsewhere.