1.2- Dioxetanes intermediates

The mechanism involves attack by singlet oxygen on the carbon-carbon double bond, followed by a two-step cleavage of the 1,2-dioxetane intermediate. Formation of polar intermediates such as a 1,4-zwitterion (ZWI) has been proposed in order to account for the fact that radical inhibitors have no effect on the reaction rate, whereas the intermediates can be trapped by alcohols4,7-11. 

In a number of groundbreaking explorations,46 Wudl, Hummelen, and coworkers showed that photoinduced [2 + 2] cycloaddition of singlet oxygen to one of the electron-rich enamine-type double bonds of azahomo [60] fullerene derivative 53 (Scheme 1.8), followed by decomposition of the 1,2-dioxetane intermediate (not shown), led to ketolactam ( )-54, the first cluster-opened fullerene with a free orifice.153 Under synthetic conditions mimicking events observed in the gas phase,154 acid-induced loss of 2-methoxyethanol from... 

Hydroperoxides obtained by autoxidation of 2,3-disubstituted indoles have long been known to undergo facile rearrangement to ketoamides, presumably via thermal decomposition of 1,2-dioxetane intermediates (Scheme 31) [8, 63]. 

A C(carbonyl)-C bond of aldehydes can be cleaved under oxidative reaction conditions [31]. For example, when a mixture of aldehyde 55 and aniline was treated with Mn(0Ac)3-2H20 under an oxygen atmosphere, formanilide was obtained, presumably through fragmentation of the 1,2-dioxetane intermediate 56 (Scheme 7.22). Treatment of the aldehyde 57 with KCl and HjOj in the presence of a vanadium peroxo complex promoted a decarbonylative chlorination reaction to produce aryl chloride 58 (Scheme 7.23) [32]. 

A number of chemiluminescent reactions may proceed through unstable dioxetane intermediates (12,43). For example, the classical chemiluminescent reactions of lophine [484-47-9] (18), lucigenin [2315-97-7] (20), and transannular peroxide decomposition. Classical chemiluminescence from lophine (18), where R = CgH, is derived from its reaction with oxygen in aqueous alkaline dimethyl sulfoxide or by reaction with hydrogen peroxide and a cooxidant such as sodium hypochlorite or potassium ferricyanide (44). The hydroperoxide (19) has been isolated and independentiy emits light in basic ethanol (45). 

One is the concerted decomposition of a dioxetanone structure that is proposed for the chemiluminescence and bioluminescence of both firefly luciferin (Hopkins et al., 1967 McCapra et al., 1968 Shimomura et al., 1977) and Cypridina luciferin (McCapra and Chang, 1967 Shimomura and Johnson, 1971). The other is the linear decomposition mechanism that has been proposed for the bioluminescence reaction of fireflies by DeLuca and Dempsey (1970), but not substantiated. In the case of the Oplopborus bioluminescence, investigation of the reaction pathway by 180-labeling experiments has shown that one O atom of the product CO2 derives from molecular oxygen, indicating that the dioxetanone pathway takes place in this bioluminescence system as well (Shimomura et al., 1978). It appears that the involvement of a dioxetane intermediate is quite widespread in bioluminescence. 

Enaminoketones undergo a clean oxidative cleavage to a-diketones, presumably through a dioxetane intermediate.180... 

As mentioned earlier (see p. 122) the previously postulated dioxetane intermediate in firefly bioluminescence has been challenged as no 180 is in-corporated in the carbon dioxide released during oxidation of firefly luciferin with 18C>2. In view of the crucial significance of the 180. experiments De Luca and Dempsey 202> rigorously examined the reliability of their tracer method. They conclude from their experiments that all available evidence is in favour of a linear, not a cyclic peroxide intermediate — in contrast to Cypridina bioluminescence where at least part of the reaction proceeds via a cyclic peroxide (dioxetane) as concluded from the incorporation of 180 into the carbon dioxide evolved 202,203). However, the dioxetane intermediate is not absolutely excluded as there is the possibility of a non-chemiluminescent hydrolytic cleavage of the four-membered ring 204>. 

Figure 5 Chemiluminescent reaction of lucigenin proceeding via a dioxetane intermediate.

CL is produced during the decomposition of excited dioxetane intermediate Luc02. Recently, Okajima and Ohsaka [29] confirmed that simultaneously electrogenerated 02 and Luc+ produced CL by the decomposition of Luc02. 

The reaction mechanism for the aerobic oxidation of the pz to seco-pz can be attributed to a formal 2 + 2 cycloaddition of singlet oxygen to one of the pyrrole rings, followed by cleavage (retro 2 + 2) of the dioxetane intermediate to produce the corresponding seco-pz (160). This mechanism is shown in Scheme 29 for an unsymmetrical bis(dimethylamino)pz. Further photophysical studies show that the full reaction mechanism of the photoperoxidation involves attack on the reactant by singlet oxygen that has been sensitized by the triplet state of the product, 159. As a consequence, the kinetics of the process is shown to be autocatalytic where the reactant is removed at a rate that increases with the amount of product formed. 

Lipid hydroperoxides are also generated in singlet molecular oxygen mediated oxidations and by the action of enzymes such as lipoxygenases and cyclooxygenases. Chemiluminescence (CL) arising from lipid peroxidation has been used as a sensitive detector of oxidative stress both in vitro and in vivo . Several authors have attributed ultra-weak CL associated with lipid peroxidation to the radiative deactivation of O2 and to triplet-excited carbonyls (63, 72) (equations 35 and 36) " . It has been proposed that the latter emitters arise from the thermolysis of dioxetane intermediates (61, 62) (equation 35), endoperoxide (73) (equation 37) and annihilation of aUtoxyl, as well as peroxyl radicals ... 

Cobaltn-Schiff base complexes, e.g. Co(salen),567 Co(acacen)568 and cobalt(II) porphyrins,569 e.g. Co(TPP), are effective catalysts for the selective oxygenation of 3-substituted indoles to keto amides (equation 249), a reaction which can be considered as a model for the heme-containing enzyme tryptophan-2,3-dioxygenase (equation 21).66 This reaction has been shown to proceed via a ternary complex, Co-02-indole, with probable structure (175), which is converted into indolenyl hydroperoxide (176). Decomposition of (176) to the keto amide (174) readily occurs in the presence of Co(TPP), presumably via formation of a dioxetane intermediate (177).569,56 Catalytic oxygenolysis of flavonols readily occurs in the presence of Co(salen) and involves a loss of one mole of CO (equation 251).570... 

The oxidation of vitamin K hydroquinone monoanion (17) with labelled, 802 in THF leads to vitamin K oxide (18) in which the epoxide oxygen is fully labelled, hi addition, partial incorporation of 180 at the carbonyl oxygen is observed (on the basis of the mass spectrum).215 This is most readily explained by invoking a dioxetane intermediate (19) as opposed to the alternative intermediacy of a 2-hydroperoxide (20), where only the epoxide oxygen would be expected to be labelled. 

Benzaldehyde is formed in the liquid-phase oxidation of f-butyl phenylacetate via a hydroperoxide and also by a non-radical pathway, probably via a dioxetane intermediate both reactions are catalysed by benzoic acid. The kinetic parameters have been calculated by solving an inverse kinetic equation.258... 

Over the years several different mechanisms for the singlet oxygen ene reaction have been considered as depicted in Sch. 2. Biradical (mechanism B in Sch. 2) [10,11] and zwitterionic (mechanism C in Sch. 2) mechanisms have been considered as very unlikely for a variety of reasons including the facts that Markovnikov directing effects are not observed [4], radical scavengers have no influence on the reaction, only minor solvent effects are observed [12-14], and cis-trans isomerizations of the substrates do not occur [6], A dioxetane intermediate (mechanism D in Sch. 2) was considered very early [6] but this suggestion was dismissed when isolated dioxetanes were shown to cleave to the carbonyl compounds rather than rearrange to the allylic... 

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