Singlet oxygen reaction intermediates perepoxides

Katsumura, Kitaura and their coworkers [74] found and discussed the high reactivity of vinylic vs allylic hydrogen in the photosensitized reactions of twisted 1,3-dienes in terms of the interaction in the perepoxide structure. Yoshioka and coworkers [75] investigated the effects of solvent polarity on the product distribution in the reaction of singlet oxygen with enolic tautomers of 1,3-diketones and discussed the role of the perepoxide intermediate or the perepoxide-Uke transition state to explain their results. A recent review of the ene reactions of was based on the significant intervention of the perepoxide structure [76], which can be taken as a quasi-intermediate. 

Cycloaddition reactions can occur with retention of configuration in the pseudoexcitation band (Sect 1.1) whereas [2jt H-2jtJ reactions are symmetry-forbidden in the delocalization band. Experimental evidence is available for the stereospecific [2-1-2] cycloaddition reactions between A and olefins with retention of configuration (Scheme 14) [82]. A perepoxide intermediate was reported to be trapped in the epoxide form [83] in the reaction of adamantylideneadamantane with singlet oxygen affording dioxetane derivatives [84]. 

Following the discovery of the ene reaction of singlet molecular oxygen ( Ap (Scheme 15) in 1953 by Schenck [88], this fascinating reaction continues to receive considerable mechanistic attention today. The importance of a path via the perepoxide intermediate or a perepoxide-Iike transition state [13] or the perepoxide quasi-intermediate [70] was proposed for the ene reactions of singlet oxygen with alkenes affording allylic hydroperoxides. 

The reactivity order of alkenes is that expected for attack by an electrophilic reagent. Reactivity increases with the number of alkyl substituents.163 Terminal alkenes are relatively inert. The reaction has a low AHl and relative reactivity is dominated by entropic factors.164 Steric effects govern the direction of approach of the oxygen, so the hydroperoxy group is usually introduced on the less hindered face of the double bond. A key mechanistic issue in singlet oxygen oxidations is whether it is a concerted process or involves an intermediate formulated as a pcrcpoxide. Most of the available evidence points to the perepoxide mechanism.165... 

The reaction of cis- and frans-stilbene oxides with phenylphosphonothioic dichloride in the presence of magnesium gives cis- and fra/ts-stilbene and (7).13 Phenylphosphinidene sulphide is postulated as being an intermediate. The zwitterion (8) bears a remarkable similarity to the controversial perepoxides which are thought to be intermediates in the reaction of singlet oxygen with alkenes. 

Gorman and coworkers found ° that the reactions of singlet oxygen with a variety of substrates have negative activation enthalpies and concluded that a reversible formed exciplex is the intermediate. They pointed out that none of the experiments clearly distinguishes between formation of a perepoxide or a geometrically similar exciplex. 

A simple way to rationalize the site selectivity is the formation of a perepoxide between the olefin and singlet oxygen as the rate-determining step of this reaction. The formation of this intermediate is irreversible, at least within the time scale of the ene reaction. The low activation energy ca 10 kcal mol ) provides support for the assumption of irreversibility. This complex is formulated in such a way that Oa is over the monosubstimted side and Ob over the disubstituted side of the olefin (Scheme 4). 

The addition of singlet oxygen to alkenes also gives dioxetanes. A number of mechanisms have been proposed and the literature abounds with theoretical and experimental results supporting one or more possible intermediates (a) 1,4-diradicals, (b) 1,4-dipolar, (c) perepoxides, or (d) concerted (Scheme 95). Both ab initio and semi-empirical calculations have been done and to date the controversy is still not resolved. These mechanisms have been reviewed extensively (77AHC(21)437, 80JA439, 81MI51500 and references therein) and will not be discussed here, except to point out that any one mechanism does not satisfactorily account for the stereospecificity, solvent effects, isotope effects and trapped intermediates observed. The reaction is undoubtedly substrate-dependent and what holds for one system does not always hold for another. 

Ab initio molecular orbital calculations, coupled with activation energies and entropies from experimental data, have been employed to determine the nature of the intermediates in the reaction of singlet oxygen with alkenes, enol ethers, and enamines.214 Allylic alkenes probably react via a perepoxide-like conformation, whereas the more likely pathway for enamines involves a zwitterionic cycloaddition mechanism. The reactions of enol ethers are more complex, since the relative stabilities of the possible intermediates (biradical, perepoxide, and zwitterionic) here depend sensitively on the substituents and solvent polarity. 

Ene reactions of simple alkenes with singlet oxygen have been studied by both computational and experimental methods.56,57,59 The reactions may proceed via a concerted or a stepwise mechanism [Equation (9)]. For a stepwise mechanism, four types of intermediates, biradical, zwitterion, perepoxide,... 

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]. 

Leach, A.G., Houk, K.N., Foote, C.S. Theoretical prediction of a perepoxide intermediate for the reaction of singlet oxygen with trans-cyclooctene contrasts with the two-step no-intermediate ene reaction for acyclic alkenes. J. Org. Chem. 2008, 73, 8511-9. 

Competitive [4 + 2] and ene reactions of 2,4-dimethylpenta-1,3-diene (552) were suggested to occur by either a concerted or a perepoxide intermediate pathway (Scheme 6.265).1460 The major [4 + 2] product 553 is formed in nonpolar solvents nearly exclusively, whereas formation of the ene product (554) via a polar perepoxide intermediate 555 is enhanced in polar solvents, such as methanol. The less stable. v-cw-conformation of 552 is required for the concerted process. Another competing process, physical quenching of singlet oxygen, was found to be at least as efficient as the chemical processes. 

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