Endoperoxides strained

The bicyclic peroxide 11 was prepared via diimide reduction of the endoperoxide derived from spirocyclopentadiene (Eq. 8)21>. As before, at elevated temperature the labile endoperoxide rearranges into diepoxide and ketoepoxide,22) but diimide reduction at —78 °C allows trapping leading to the highly strained bicyclic peroxide 11. 

The strained dienic endoperoxide is readily reduced by diimide, leading to the relatively stable bicyclic peroxide in high yield. Again, aprotic solvents such as CH2C12 or CFClj are essential for the diimide reduction, because in MeOH complex rearrangements take place 30d e>. 

B. Peroxyacetalization of Carbonyl Functions with Strained Endoperoxide... 

A number of semibullvalenes and some barbaralanes, which undergo a facile Cope rearrangement via bicyclooctadienyl diradicals, produce various cyclic peroxides on exposure to triplet oxygen ". Thus, cyclopentano semibullvalene 82a is peroxidated with air to give a mixture of 5-membered 83a and 6-membered endoperoxide 84a in a 1 2 ratio, whereas the cyclohexano derivative 82b yields only the 6-membered cyclic peroxide 84b (Scheme 15). The energy in the highly strained mono(Dewar benzene) isomer of... 

Peroxovanadates, O NMR spectroscopy, 186 PeroxyacetaUzation of carbonyl functions ji-hydroperoxyalcohols, 273-7, 278 strained endoperoxide systems, 277-85... 

Strain, steric strain, 154, 163, 166, 866 Strained endoperoxides, peroxyacetalization, 277-85... 

The same method was also used to derive the standard potential for the concerted reduction of some endoperoxides, these values are also listed in Table 4. The BDE of endoperoxides is smaller than that for aeyclic peroxides, which is reasonable due to the added strain and the eelipsing interactions of the lone pairs on the oxygen. 

The stereoselectivity of the allylic hydroperoxidation also depends on se eral factors. With chiral allylic alcohols or allylic amines 200, a hydrogen is developed between ]02 and the vicinal hydroxyl or amino group. The fac differentiation results from an approach of 102 in the transition state that mi mizes 1,3-allylic strain. 201 and 202 can be obtained with a diastereoisome excess higher than 90% in CCI4. As previously indicated for the formation dioxetanes and 1,4-endoperoxides, the selectivity decreases considerably in presence of hydroxylic solvents [123]. When hydrogen bonding is no more pos ble in 203, the stereofacial differentiation is steered by steric and electronic rep sion effects at the level of the possible diastereoisomeric transition states 204 is formed selectively (Scheme 54). 

Artemisinin with its crucial endoperoxide bridge is not the only natural compound exhibiting antiplasmodial activity. An example of the biosynthesis of antiplasmodial endoperoxidic compounds is plakortin, a simple 1,2-dioxane derivative, which is produced by the marine sponge Plakortis simplex [93]. This compound shows activity against chloroquine-resistant strains of Plasmodium falciparum (R falciparum) at submicromolar level. 

Using catalysis by palladium systems, allylic halides show little tendency to add. However, with nickel(O) catalysts [e.g., Ni(cod)2] allylic halides add to norbornene. in contrast to vinyl and aryl halides9. The palladium system also catalyzes the coaddition of alkynes and benzylic halides to strained bicyclic alkenes10- u. Thus, addition of methyl 2-[3-(chloromethyl)phenoxy]acetate and optically pure (S)-l-octyn-3-ol to norbornene, norbornadiene or 7-oxanorbornene 4 leads to diastereomeric adducts 5, used as precursors of interphenylene prostaglandin endoperoxides, in 34-58% yield. No diastereomeric ratios were reported. 

Photo-oxidation.—Turro and co-workers report the rate constants for quenching of singlet molecular oxygen ( O2) by several strained molecules. The authors also discuss a non-photochemical method for determination of quenching constants of singlet oxygen involving thermolysis of l,4-dimethylnaphthalene-l,4-endoperoxide. 

Since singlet oxygen is a dienophile, such oxidations are believed to involve cycloaddition of oxygen to an endoperoxide (46, Scheme 14), followed by rearrangement to the hydroperoxide. Reduction in steric strain and the formation of a strong intramolecular hydrogen bond (vmax 2800 cm 1) could provide the driving force in the second step.48... 

The strain-free endoperoxide 7 has been obtained in the same way from 1,4-cyclooctadiene (6). ... 

Artemisinin, a sesquiterpene lactone endoperoxide and isolated from aerial parts of Artemisia annua L. plants (family Asteraceae commonly known as sweet wormwood), is popular as a potent, promising, highly effective, safe, and best therapeutic agent against drug-resistant strains of Plasmodium sp. The low yield of artemisinin content, is a serious limitation to its ability and affordablity to the most malaria sufferers. The chemically synthesized artemisinin is also costly due to low yield of the process. The World Health Organization (WHO) recommends the use of artemisinin-based combination therapies (ACTs), for the first-line treatment of malaria. To date, A. annua L. 

Finally, mention must be made of the efforts of R. G. Salomon s group to synthesize several derivatives of 2,3-dioxabicyclo[2.2.1]heptane, the strained bicyclic peroxide nucleus of prostaglandin endoperoxide (206). They are prepared from 2,3-dioxabicyclo[2.2.1]hept-5-ene by selective reduction with diimide or chlorination. 

A strain-free homologue of the nucleus in prostaglandin endoperoxides, namely 8,9-dioxabicyclo[5,2,l]decane can be conveniently prepared from cyclo-octa-1,4-diene (Scheme 22). ... 

---