1,2-Dioxetanes with electrophiles

Adam, W., Fuchs, R., and Kirchgassner, U., Functionalized 1,2-dioxetanes as potential photogenotoxic agents. 1,2-dioxetanes with electrophilic chemical handles for the functionalization with protic nucleophiles. Chem. Ber. 120, 1565-1571 (1987). 

Hydrolysis of dioxetane 223, or of ketal 10, led to an inseparable mixture of expected product 225, as well as bicyclic isomer 226. The mixture was 1 2 (225 226), and underwent standard acylation reactions to give, for example, 179 on treatment with Ac20/pyridine/CH2Cl2. Carbonates such as 181 were available from 225 upon treatment with various chloroformates in pyridine/CH2Cl2. In other words, the alcohol 225 could be funneled away from the mixture by reaction with electrophiles, providing the desired tricyclic products. The bicyclic aldehyde 10 was isomerized to obtain tricyclic ketal 228 under dehydrating conditions in the presence of an alcohol. 

Intramolecular peroxymercuration (Eq. 18) followed by brominolysis afforded the dioxetane (10). Since the allylic hydroperoxides are readily available via ene-reaction of a suitably alkyl-substituted olefin (Eq. 16), this method has synthetic potential, especially if electrophiles other than bromine can be employed to provide dioxetanes with other substituents. 

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. 

Besides their thermal decompositions into carbonyl fragments, the chemistry of 1,2-dioxetanes is quite limited. Obviously one of the reasons for this is the great lability of the dioxetane ring system. However, a number of reactions with nucleophiles and electrophiles have been performed and will be briefly reviewed here. 

The reaction of divalent metals, such as copper, nickel, and so on, with dioxetanes in methanol leads to clean catalytic decomposition into carbonyl fragments/ The reaction rates increase with increasing Lewis acidity of the divalent metal and indicate, therefore, typical electrophilic cleavage of the dioxetane. On the other hand, univalent rhodium and iridium complexes catalyze the decomposition of dioxetanes into carbonyl fragments via oxidative addition. 

The electrophilic bromination of alkenes, e.g. with l,3-dibromo-5,5-dimethylhydantoin, in the presence of coned hydrogen peroxide, leads to y -bromo hydroperoxides. They are cyclized with bases or with silver acetate to give 1,2-dioxetanes (Kopecki 1973), e.g. ... 

Tetrasubstituted-l,2-dioxetanes (9.26) are electrophilic reagents that form stable adducts with nucleophiles, e. g., with carbanions (Adam and Heil, 1992). Adam and Treiber (1994) demonstrated that the sterically less hindered oxygen atom of these dioxetanes add at the C(a)- and at the N()ff)-atom of diazoalkane to form the 0,N-dipole (9.27) and the 0,C-dipole (9.29), respectively. Dediazoniation and cycliza-tion of 9.27 leads to 1,3-dioxolanes (9.28) and that of 9.29 to fragmentation, i.e., to the ketones 9.30 and 9.31 (9-18). 

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