Ozonides stereochemistry

The above pathway accounts satisfactorily for the main features of ozonolysis but requires modification in detail to account for the observed stereochemistry of the reaction. Thus while a trans- (or cis-) alkene is often found to lead to a mixture of cis- and trans-ozonides as might have been expected, the trans-alkene (55) leads only to the trans-ozonide (57). The latter example demands a high degree of stereoselectivity in both the decomposition of (54) to aldehyde + peroxyzwitterion and in their subsequent recombination to (57) a demand that is not implicit in the pathway as we have written it. 

Several 1,2,4-trioxolanes are known which contain a double bond linked in some way to the ring, with interest focusing on furan endoperoxides. The alkene moiety of 2,5-dimethylfuran endoperoxide (41) can be selectively functionalized in the presence of the 1,2,4-trioxolane ring. Reaction with diimide gives the saturated ozonide <81TL3509> and a single addition product was obtained with p-nitrophenylazide, although the stereochemistry of the reaction was not determined. 

Following this work on NMR spectra of ozonides, there is an extensive paper by the Griesbaum group" where 35 ozonides (6-14 with different stereochemistries) have been studied. The widely different structures examined allowed the influences of structural features on "O NMR spectra of ozonides to be shown. Five structurally different types of ozonides can be recognized symmetrically tetrasubstituted (type 6), unsymmetrically tetrasubstituted (type 7), unsymmetrically tri- and tetrasubstituted (type 8), unsymmetrically disubstituted (type 9-13) and bicyclic ozonides (type 14). "O NMR chemical shifts of peroxidic and ethereal oxygens are collected in Table 3. All spectra were obtained at natural isotopic abundance, in benzene-dg solution mainly at 25 °C, although in some cases higher temperatures had to be used. These experimental conditions make for an easy comparison with the previously discussed data. 

Also inconsistent with the mechanism is that cis alkenes give higher yield of ozoni-des than do the trans isomers. The bulk of alkene susbstituents was also observed to strongly affect the ozonide cis trans ratio. These observations made necessary the incorporation of stereochemistry into the Criegee mechanism. 

The carbonyl component can be externally supplied as in the co-ozonolysis reactions (see Section 6.06.8.2) and other dipolarophiles can be used to trap the intermediate CO. Two types of rotations of the carbonyl component can take place relative to the CO <1997JOC2757> one type is in the plane of the heavy atoms which leads to the same stereochemistry as in the original alkene the other type is a rotation in a plane perpendicular to it leading to inversion. The preference of trans-alkenes to furnish in the gas phase the /raar-ozonides indicates a preference for the in-plane rotation and geminate pair recombination within the dipolar complex. At low temperatures this complex appears to be stabilized. 

Both 2-butyne and 3-hexyne in the presence of various aldehydes or ketones gave isolable ozonides as one diastereoisomer only. However, the stereochemistry is uncertain as neither NMR chemical shifts nor HPLC retention factors give conclusive assignments <1997JOC6129>. 

The complex 100 is calculated to be more stable than the separated aldehyde and carbonyl oxide by 9 kcal mol-1 and the formation of complex 100 from ethylene and ozone is endothermic by only 3.1 kcal mol-1 <1991CPL(187) 491 >. Cycloaddition then leads to the secondary ozonide 101 (1,2,4-trioxolane). subsequent study of the stereochemistry of ozonation reactions using the AMI method provides further support for the modified Criegee mechanism C1997JOC2757, CHEC-III(6.06.2)193>. 

T he Criegee (1) mechanism of ozonolysis postulates that unsymmetrical olefins should give two zwitterions and two carbonyl compounds and hence postulates the possible formation of three different ozonides. This prediction has now been realized in a number of cases (2-9). It has also been shown that in many cases the ozonide stereoisomer ratio depends upon olefin stereochemistry in both normal (3, 6-12) and cross (6-9) ozonides. Since the original Criegee mechanism did not provide for these stereochemical results, a number of additional suggestions for the mechanism have been made (6,9,13, 14), all of which retain the fundamentals of the Criegee mechanism. 

We have shown that cross diperoxides can be formed by various ozonolysis procedures. We now hope to parallel the work done where cross ozonides were produced—i.e., to examine the influence of olefin stereochemistry and other reaction variables. 

Heptene ozonide has been produced by ozonizing mixtures of 3-hexene and 4-octene. The 3-heptene ozonide cis-trans ratio has been determined for a number of sources of this ozonide and found to depend on the stereochemistry of the olefin or pairs of olefins used to generate it. The effect of varying concentrations of added butyraldehyde on the ozonolysis of 3-hexene has been determined. The yields and cis-trans ratios of 3-hexene and 3-heptene ozonides depend on the butyraldehyde concentration. 

The observations of symmetrical cross ozonides from unsymmetrical olefins suggest that unsymmetrical cross ozonides ought to be produced from pairs of symmetrical olefins. Criegee had examined this point earlier (2) and found that no detectable amounts of 3-heptene ozonide were produced when a mixture of 3-hexene and 4-octene was ozonized. Again, this may have been a result of the particular olefin concentrations used. The recent observations that ozonide cis-trans ratios in both cross ozonides (5, 10, 11) and normal ozonides 4-14) can depend on olefin stereochemistry as well as steric factors in the olefin 11) prompted us to reinvestigate the possibility of obtaining unsymmetrical ozonides from pairs of symmetrical olefins. Such an investigation presents an opportunity to examine ozonide cis-trans ratios and yields where several new reaction variables are possible. 

According to Refs. [2, 10] two isomeric forms of 1,2,4-trioxolanes exist. The ratio between them is a function of the double bond stereochemistry, steric effect of the substituents, and the conditions of ozonolysis. It was found out only on the low molecular weight alkenes [19, 21]. The H-NMR spectroscopy is the most powerful method for determination of the cis/tram ratio of ozonides (in the case of pol5miers it is practically the only one method that can be applied). The measuring is based on the differences in the chemical shifts of the methine protons of the two isomers the respective signal of the cis form appears in lower field as compared to the trans one [19, 21]. 

The addition of ozone (O3) to alkenes to give a primary ozonide (molozonide), which rearranges to an ozonide and eventually leads, on reduction, to carbonyl compounds (aldehydes and/or ketones), has already been mentioned and the reaction itself is shown in Scheme 6.11. However, it is important to recognize that this is only one example of a 4th- 2n electrocyclic addition and that orbital overlap for many sets of these reactions dictates their courses as well. Thus, to show the similarity of some of these dipolar 3 -f 2 addition reactions Equations 6.53-6.56 are provided. Although any alkene might be used as an example, (Z)-2-butene is used in each to emphasize that aU of them occur with retention of stereochemistry and, in the first (Equation 6.53), the reaction with ozone to form the primary ozonide (molozonide) is presented again (i.e., see Scheme 6.11). In a similar way, with a suitable azide, R-N3, readily prepared from an alkyl halide (Chapter 7), the same alkene forms a triazoline (Equation 6.54) and with nitrous oxide (N2O) the heterocycle (Chapter 13) cis -4,5-dimethyl-A -l,2,3-oxadiazoline (ds-4,5-dihydro-4,5-dimethyl-l,2,3-oxadiazole) (Equation 6.55). Finally, with a nitrile oxide, such as the oxide derived from ethanenitrile (acetonitrile [CH3ON]), the same alkene yields a different heterocycle, the dihydroisoxazole, 3,4,5-trimethyl-4,5-dihydroisoxazole (Equation 6.56). 

Ozonolysis of lycopadiene followed by oxidative cleavage of the ozonide afforded 6,10,14-trimethylpentadecan-2-one thus establishing the C(14)-C(15) and C(18)-C(19) location of the unsaturations. Moreover, the optical rotation of this ketone was identical with that observed for the 6(R),10(R), 14-trimethylpentadecan-2-one obtained from ozonolysis of natural phytol this result allowed assignment of stereochemistry to the asymmetric centers. Therefore, lycopadiene (45) was identified as... 

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