Perepoxide alkene oxygenation

The interaction between the HOMO of alkenes and the LUMO of singlet oxygen O (Scheme 4) is the most favored in the perepoxide structure (Scheme 13). This suggests... 

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. 

In 1999, Clennan and Sram reported a study of the photo-oxidations of a series of tetrasubstituted alkenes (Fig. 5) in methylene blue-doped zeolite Y [11], The ene regiochemistries are very sensitive to the size of the allylic substituent, R, in solution. The A/B ratio increases from 0.49 to 2.4 as the substituent, R, is changed from methyl to ferr-butyl. This phenomenon has been attributed [12] to a sterically induced lengthening of the carbon-2 oxygen bond in the perepoxide intermediate I and subsequent preferred opening of this long bond (Fig. 5). 

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. 

The retention of olefin geometry in the oxidation of cis and trans alkenes408 suggests a one-step concerted [2 + 2]-cycloaddition process, suprafacial in the alkene, and antarafacial in singlet oxygen.363 The strong solvent dependence, however, observed in many cases, points to a stepwise mechanism involving a perepoxide intermediate 403,409... 

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,... 

Many mechanisms had been proposed in the past to rationalize this selectivity (trioxanes, perepoxide, exciplex, dipolar, or biradical intermediates) however, it is now generally accepted [100] that the mechanism proceeds through an intermediate exciplex which has the structural requirements of a perepoxide. This assumption is supported (a) by the lack of stereoselectivity in the reactions with chiral oxazolines [101] and tiglic acid esters [102], (b) by the comparison of the diastereoselectivity of dialkyl-substituted acrylic esters [103] with structurally similar nonfunctionalized alkenes, (c) by intermolecular isotope effects [104] in the photo-oxygenation of methyl tiglate, and (d) by solvent effects on regioselec-tivity [105],... 

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]. 

Further evidence in support of zwitterionic intermediates in the [2 + 2]-cycloaddition of singlet oxygen to electron-rich alkenes has been obtained by Jefford et al. [684]. The photo-oxygenation of 2-(methoxymethylidene)adamantane creates a zwitterionic intermediate (peroxide or perepoxide), which can be captured by acetaldehyde to give 1,2,4-trioxanes in addition to 1,2-dioxetanes cf. Eq. (5-147). 

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