Dioxetane alkene oxygenation

Another interesting cycloaddition, the detailed mechanism of which is still under investigation, is the addition of singlet oxygen to alkenes producing 1,2-dioxetanes (Section 5.15.3.3.2). 

Singlet oxygen reacts with electron rich or highly strained alkenes to form 1,2-dioxetanes. These four-membered ring peroxides decompose on warming to two carbonyl compounds (or moieties), usually with appearance of light emission (chemiluminescence). The macrocyclic bis-lactone in (6.17)608>, a musk fragrance, has been synthesized via such a sequence. 

Previous studies have shown that the rate of the O2 ene reaction with alkenes shows neghgible dependence on solvent polarity . A small variation in the distribution of the ene products by changing solvent was reported earlier . However, no mechanistic explanation was offered to account for the observed solvent effects. It is rather difficult to rationahze these results based on any of the currently proposed mechanisms of singlet oxygen ene reactions. Nevertheless, product distribution depends substantially on solvent polarity and reaction temperature only in substrates where both ene and dioxetane products are produced ° . 

In contrast, the a-peroxy lactones, also members of the dioxetane family, display a higher reactivity toward nucleophiles, in view of the inherent polarization of the peroxide bond by the carbonyl functionality. Consequently, the nucleophilic attack is expected to take place at the more sterically hindered but more electrophilic alkoxy-type oxygen atom of the peroxide bond. A recent detailed study of the oxidation of various di-, tri-and tetrasubstituted alkenes 6 with dimethyl a-peroxy lactone (7) revealed, however, much complexity, as illustrated in Scheme 7 for R = CH3, since cycloaddition (8), ene-reaction (9 and 10) and epoxidation (11) products were observed. In the presence of methanol, additionally the trapping products 12 and 13 were obtained, at the expense of the polyester 14. The preferred reaction mode is a sensitive function of the steric demand imposed by the attacking alkene nucleophile. 

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. 

Although 1,2-dioxetanes are excluded as intermediates in the formation of allylic hydroperoxides, they may be formed as primary products in the reaction of singlet oxygen with alkenes not possessing allylic hydrogen 360 363 366 368-370 374... 

In fact, the oxidation with singlet oxygen of alkenes not possessing allylic hydrogens is known to involve a 1,2-dioxetane intermediate15 16 (see Section 9.2.2). 

The addition of singlet oxygen to alkenes gives dioxetanes bisadamantylidene forms an unusually stable dioxetane (Scheme 13) (75JA7110). 

The singlet oxygen ( C ) cycloaddition to electron-rich alkenes is by far the most prevalent method used for the construction of 1,2-dioxetanes. The Kopecky method, which relies on the cyclization of a /3-halo hydroperoxide, is rarely utilized these days but was heavily relied upon in the past. The base-catalyzed cyclization of /3-epoxy hydroperoxides also appears to becoming more popular. There are also several miscellaneous methods that have been utilized for specific dioxetane examples and these are summarized in Section 2.16.7.1.3. 

Despite the fact that singlet oxygen oxidizes tetramethylethylene (16) via the ene pathway, with abstraction of one of the 12 a protons, under electron-transfer photooxidation conditions dioxetane 32 (R = Me) has been generated [29]. The electron-deficient sensitizer 9-mesityl-10-methylacridinium ion (Acr+-Mes) in its excited state Acr"-Mes + was generated, in which the alkene radical cation and... 

More than 40 years later did two different groups [2,3] isolate [2+2]-cycloadducts (1,2-dioxetanes) by photo-oxygenation of alkenes shortly after Kopecky had synthetized the first stable dioxetanes by base-catalyzed cyclization of a-bromohydroperoxides (Schs. 2,3) [4],... 

In the photo sensitized oxygenation reactions of alkenes, not only the influence of the solvent on the reaction rate but also the effect of solvent on product distribution i.e. from competing hydroperoxide, 1,2-dioxetane, and entfo-peroxide formation) is rather small [550, 551],... 

Photo sensitized oxygenation of alkenes with singlet oxygen can, in principle, proceed via three competitive reaction pathways [4 + 2]cycloaddition to e do-peroxides, ene reaction of allylic hydroperoxides, and [2 + 2]cycloaddition to 1,2-dioxetanes (see reference [681] for a review). With suitable olefinic substrates, the chemical outcome of such photo-oxygenation reactions can be strongly influenced by the solvent. This is shown in the somewhat simplified Eq. (5-145). 

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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