Hydroperoxides zwitterionic

Most ozonolysis reaction products are postulated to form by the reaction of the 1,3-zwitterion with the extmded carbonyl compound in a 1,3-dipolar cycloaddition reaction to produce stable 1,2,4-trioxanes (ozonides) (17) as shown with itself (dimerization) to form cycHc diperoxides (4) or with protic solvents, such as alcohols, carboxyUc acids, etc, to form a-substituted alkyl hydroperoxides. The latter can form other peroxidic products, depending on reactants, reaction conditions, and solvent. 

The model in Fig. 6, specifically the intrazeolite presence of a perepoxide, is supported by an isotope effect of 1.04 0.02 for the photo-oxidation of Z-2,3-dimethyl-l,l,l,4,4,4-hexadeutero-2-butene (Fig. 7). This isotope effect is completely inconsistent with an open zwitterion (Fig. 7), which would be expected to collapse to the hydroperoxide with a significant discrimination for hydrogen abstraction (/ch/ d > ) ... 

Ozonolysis of alkenes in participating solvents such as alcohols often leads to trapping of intermediates. Most commonly, an alcohol will react with the carbonyl oxide zwitterion, generated from cycloreversion of the primary ozonide (Section 4.16.8.2), to give an alkoxy hydroperoxide. The secondary ozonide (1,2,4-trioxolane) is usually more stable to nucleophilic attack from alcohols. 

No cross ozonide was formed from unsymmetrical alkenes. The authors theorized628 that the carbonyl oxide zwitterionic species formed on wet silica gel immediately adds water followed by rapid decomposition of the intermediate hydroxyalkyl hydroperoxide to carboxylic acid and water. It means that water on silica gel acts as participating solvent. In the absence of adsorbed water, rapid recombination of the adsorbed aldehyde and carbonyl oxide due to a favorable proximity effect gives normal ozonide. The low mobility of adsorbed species on the silica surface accounts for the absence of cross ozonides. 

Generation of zwitterion and hydroxy-hydroperoxide. (From Langlais, B. et al., Ozone in Water Treatment Application and Engineering, Lewis Publishers, Boca Raton, FL, 1991. With permission.)... 

Hydroperoxide 7 through reaction of Zwitterion 3 with protic, nucleophilic molecule like ROH, H20, R-COO, NHR. 

In 1989, the irradiation of (E,E)-2,4-hexadiene S3 sensitized by meso-porphyrin IX dimethyl ester led to the formation of cis-3,6-dimethyl-l,2-dioxene (62), which was the major product detected at — 78 °C in Freon 11 [69]. Endoperoxide 62 was purified under vacuum at 0.75 mmHg, and collected in a trap (98% isolated yield). Dienes that can adopt a cisoid conformation, such as 53 or ( , )-l,4-di phenyl butadiene, were photooxidized by the corresponding endoperoxides in high or quantitative yield in a suprafacial Diels-Alder reaction [60, 70], Dienes that cannot readily adopt cisoid conformations, such as (fc, Z)-2,4-hexadienes and (Z, Z)-2,4-hexadienes, lose their stereochemistry in the singlet oxygen [2 + 4]-cyclo-addition [60], (E,Z)- and (Z,Z)-dienes give a complex mixture of hydroperoxides and aldehydes, which suggests the intervention of intermediate zwitterions or 1,4-diradicals [71]. 

Formation of the hydroperoxide 74 is suggested by the authors to involve a proton shift to the zwitterion deriving from the initial addition of singlet oxygen [70c]. This sequence has been successfully used to prepare a,a -bipyrroles, precursors of bioactive natural products in the prodigiosin family and ring A analogs (Sch. 42] [70a],... 

The photo-oxygenation of 2-phenylnorbornene 164 in the presence of hydrogen peroxide leads to the 1,2-fe-hydroperoxide 165 in essentially quantitative yield via trapping of the zwitterionic peroxidic intermediate by the reagent (Sch. 86) [138], Suitable treatment of this compound leads to tricyclic peroxides 166 and 167, some of which [166a and 167 (for R,R1-CH(CH3)(CH2)4-)] have shown moderate antimalarial activity. 

Since [4 + 2]cycloaddition and ene reactions are generally assumed to proceed in a concerted manner via isopolar activated complexes, they should exhibit virtually the same small, often negligible, response to changes in solvent polarity. This is what, in fact, has been found cf. for example [138, 682, 683]. However, two-step [2 + 2]-cycloaddition reactions of singlet oxygen to suitably substituted electron-rich alkenes proceed via dipolar activated complexes to zwitterionic intermediates (1,4-dipoles or perepoxides). In this case, the relative amounts of 1,2-dioxetane and allylic hydroperoxides or e do-peroxides should vary markedly with solvent polarity if two or even all three of the reaction pathways shown in Eq. (5-145) are operative [681, 683, 684]. 

When phenylimidazoles react with singlet oxygen, although there is some evidence that 2,5-endoperoxides or zwitterionic intermediates may be formed initially, the products which are isolated (Scheme 45) appear to arise from the decomposition of hydroperoxides or dioxetanes (8lT(S9)19l). 

In the reaction of cyclopropylidene alkanes with singlet oxygen, the primary product is the hydroperoxide (53) (equation 31). However, in the special case of cyclopropy-lideneadamantane (54) reaction with 02 leads to 55 by a process which most probably involves the zwitterion (56) (equation 32). 

Possible side-reactions, such as the formation of allyl hydroperoxides from compounds having an allylic hydrogen (a competitive ene reaction Section 6.7.3) or 1,4-endoperoxides from 1,3-dienes, may be suppressed by changing the experimental conditions.1359,1438 For example, the extent of [2 + 2] and [4 + 2] photooxygenation in styrenes, such as the propenylanisole 522 (Scheme 6.253), is controlled by solvent polarity and pH, possibly due to protonation of a perepoxide/zwitterion intermediate.1421,1439 The [4 + 2] product 523 is preferentially produced in non-polar benzene or chloroform, whereas the 1,2-dioxetane 524 is almost exclusively formed in methanol or acidified non-polar solvents. 

The papers on simple alkenes [151] and enol ethers [152] discussed above brought the possibility of exciplex intermediacy to the attention of singlet oxygen chemists and since then several papers concerned with reactions involving allylic hydroperoxide, dioxetane and/or endoperoxide formation have invoked their participation [157-165], some as the sole intermediate, some as precursors to perepoxides, open zwitterions or biradicals. The molecules shown in structures 43-51, and relatives thereof, have been... 

Ozonides oxidize A /V -disubstituted PD 11 in weak acid catalyzed reactions into the respective BQDI 53, Scheme 8 [3,4], The intermediary formed Wurster s cation-radical 49 disproportionates. Formation of a-hydroperoxides of the type 160 was proposed for the reaction of 11 with 4. A relinking of the broken rubber chains may arise via the reaction of 160 with the second zwitterion. 

The initial product of the reaction between ozone and most olefins appears to be the 1,2,3-trioxolane ( ozonide ), which then collapses to a carbonyl compound and a zwitterionic intermediate, 68. In the presence of water, the intermediate hydroxy-hydroperoxide, 69, is produced and decomposes to additional carbonyl-containing compounds. 

In the Criegee proposals the initial product is stipulated to have a 1,2,3-trioxolane structure (I) which is also known as a molozonide structure. This undergoes a concerted decomposition to give a zwit-terion (II) and a carbonyl compound (III). The decomposition products (II) and (III) in most cases recombine to give the normal ozonide (IV). Other possible reactions include dimerization of the zwitterion to yield a diperoxide (V) or a higher peroxide (VI) whilst in the presence of methanol as a reactive solvent a methoxy-hydroperoxide (VII) may be produced. 

Schmid and Hofheinz described an important application of this reaction to the total synthesis of the antimalarial drug artemisinin. The key step in the (-)-isopulegol-based synthesis is the ene-reaction of singlet oxygen with an enol ether (Scheme 12). This reaction leads to an allylic hydroperoxide 20 when the reaction is performed in the nonpolar solvent, CHjClj. The use of the more polar, protic methanol inverts the regioselectivity, and the a-hydroperoxy acetal 21 is formed (presumably by trapping of an intermediary 1,4-zwitterion), which is cycHzed to the target molecule 22 by acid catalysis. 

---