Ozonides 1,2,4-Trioxolans

Ozonides react with catalytic quantities of chlorosulfonic acid (0.3 equivalents) in dichloromethane at 20 °C to yield 3,6-dialkyl-1,2,4,5-tetraoxans and/or 1,4-dialkyl-2,3,5,6,ll-pentaoxabicyclo[5.3.1]undecanes. The reaction of ozonides with chlorosulfonic acid has been extensively investigated by Miura and co-work-ers. The reaction pathways appear to vary with different substituents the proposed mechanism involves heterolytic fission of the carbon-oxygen bond of the peroxide bridge. For example, methylcyclopentene ozonide 472 reacted stereo-selectively with the reagent in dichloromethane to give initially compound 473 which subsequently rearranged to form the trans tetraoxan 474 (Equation 151). 

Phenylcyclopentene ozonide reacted similarly with chlorosulfonic acid, although the same ozonide reacted stereoselectively with antimony pentachloride to yield the cis tetraoxan (55%). The conversion of ozonides to tetraoxans by treatment with catalytic amounts of chlorosulfonic acid appears to be a fairly general reaction thus l,2-diphenylethylene(stilbene) ozonide 475 yields the corresponding tetraoxan 476 41% (Equation 152). 

All with excess chlorosulfonic acid (three equivalents, 3 hours) gave the ester 480 in quantitative yield.  

The reaction of ozonides with carbonyl compounds and hydrogen peroxide is catalysed by the presence of chlorosulfonic acid and provides a new synthetic route to the corresponding 2,3,5,6,ll-pentaoxabicyclo[5.3.1]undecanes in 3-35% yield. As an illustration, l-phenyl-6,7,8-trioxabicyclo[3.2.1]octane 481 reacted with p-tolualdehyde, hydrogen peroxide and chlorosulfonic acid (0.03 equivalents) in acetic acid at 20 °C (2 hours) to yield a mixture of the products 482-484 (Equation 154). 

The reaction of a mixture of two kinds of ozonides in the presence of an acid catalyst affords the crossed 2,3,5,6,ll-pentaoxabicyclo[5.3.1]imdecane derivative. For instance, a mixture of 3-phenylindene ozonide 485 and stilbene ozonide 475 reacted with chlorosulfonic acid (0.03 equivalents) to give the crossed 2,3,5,6,11-pentaoxabicyclo[5.3.1]undecane 486, 25%, together with the tetraoxa compound 476, 7%, a cyclic peroxide (Equation 155).  

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Ozonolysis of alkenes in participating solvents such as alcohols often leads to trapping of intermediates. Most commonly, an alcohol will react with the carbonyl oxide zwitterion, generated from cycloreversion of the primary ozonide (Section 4.16.8.2), to give an alkoxy hydroperoxide. The secondary ozonide (1,2,4-trioxolane) is usually more stable to nucleophilic attack from alcohols. 

One of the most important features of the ozonolysis reaction of alkenes is one in which ozone adds to the C=C bond to form a primary ozonide (1,2,3-trioxolane). The Criegee mechanism suggests that this unstable intermediate decomposes into a carbonyl compound and a carbonyl oxide that recombine to form a final isomeric ozonide (1,2,4-trioxolane). Direct spectroscopic evidence for a substituted carbonyl oxide has only recently been reported by Sander and coworkers for the NMR characterization of dimesityl carbonyl oxide. Kraka and coworkers have theoretically modeled dimesityl carbonyl oxide and confirmed the structural aspects reported by Sander and coworkers on the basis of NMR data. 

The carbonyl oxides are similar to ozone in being 1,3-dipolar compounds, and undergo 1,3-dipolar cycloaddition to the carbonyl compounds with the reverse regiochemistry, leading to a mixture of three possible secondary ozonides (1,2,4-trioxolanes) ... 

The Griesbaum Coozonolysis allows the preparation of defined, tetrasubsituted ozonides (1,2,4-trioxolanes) by the reaction of O-methyl oximes with a carbonyl compound in the presence of ozone. In contrast to their traditional role as intermediates in oxidative alkene cleavage, 1,2,4-trioxolanes with bulky substituents are isolable and relatively stable compounds. 

There are six possible five-membered monocycles 1-6 containing three oxygen or sulfur atoms in the 1,2,3-positions <1996CHEC-II(4)545>. 1,2,3-Trioxolane 1 is the parent compound of the so-called primary ozonides, the primary reaction products in the reaction of alkenes with ozone. They are extremely unstable and rearrange to the more stable ozonides (1,2,4-trioxolanes). This rearrangement represents a key step in the reaction of ozonolysis. However, the parent compound 1 and a few derivatives have been characterized at low temperatures (see Section 6.05.10.1). 1,2,3-Trithiolanes have been synthesized (Section 6.05.10.3) some of them undergo slow decomposition at room temperature. Derivatives of 1,2,3-dioxathiolane 3 are unknown, and the other heterocycles of the mixed types 4-6 are known only in the oxidized forms, mostly as -oxides and J -dioxides, and also A-imino and A-thiono derivatives <1996CHEC-II(4)545>. The A-oxides and AA -dioxides of... 

The < a/o-peroxides of aromatic oxygen-containing five-membered heterocycles such as furan and oxazole are actually ozonides (1,2,4-trioxolanes), and by a reverse dipolar [3+2] cycloaddition they can be a source of carbonyl oxides. 

It is the recombination of these fragments, again by 1,3-dipolar addition, that finally leads to the true ozonide (1,2,4-trioxolan) (6). The zwitterion (92) is of primary importance in the ozonization process. 1,2,4,5-Tetroxans ( dimeric alkylidene peroxides ) (7) are formed by their dimerization [Eq. (3)].85,86... 

Ozonides (1,2,4-trioxolanes) are generally obtained by the reaction of fluoroalkenes with ozone Thus, vmyl fluoride is oxidized to monofluoroozomde and formyl fluonde [2J] (equation 15) The same ozomde is formed by ozonolysis of a mixture of cis 1,2-difluoroethylene with ethylene [24]... 

The thermally stable bis-ozonide (1,2,4-trioxolane) of hexamethyl Dewar benzene has been isolated and its X-ray structure determined [94T7625]. Bicyclic oxadithiolane (93) has now been prepared by intramolecular reaction between dithiirane and ketone functions [94AG(E)777]. An efficient synthesis of benzotrithiole oxide (94) has been reported [93SUL5] and the stable benzotriselenole (95) has been prepared [94CC1593]. 

Mechanism of Ozonolysis (Criegee mechanism) The initial step of the reaction involves a 1,3-dipolar cycloaddition of ozone to the alkene leading to the formation of the primary ozonide (molozonide or 1,2,3-trioxolane), which decomposes to give a carbonyl oxide and a carbonyl compound. The carbonyl oxides are similar to ozone in being 1,3-dipolar compounds and undergo 1,3-dipolar cycloaddition to the carbonyl compound with the reverse regio-chemistry, leading to a relatively stable secondary ozonide (1,2,4-trioxolane) (Scheme 5.47). 

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