Allyl alcohol ozonolysis

Another example is the cyclization of the racemic allylic alcohol 232 at -80°C which furnished the racemic tetracyclic bis-olefin 233 in 70% yield (89, 90). Ozonolysis of 233 gave the bicyclic triketone aldehyde 234 which underwent under acidic conditions a double intramolecular aldol cyclodehydration to produce racemic 16,17-dehydroprogesterone 235. This represents the first synthesis of a steroid via the now so-called "biomimetic" polyene cyclization method. 

Intramolecular interception of the Criegee carbonyl/carbonyl oxide intermediate was observed in the ozonolysis of steroidal allylic alcohols at — 70 °C. In hexane, the 1,2,4-trioxolane 132 (a mixture of ( Vcpimers) was isolated in 26% yield. Reductive workup afforded the hemiacetal of the dioxolane 133 which could be oxidized to the dioxolane-lactone the hydroperoxide 134 can be isolated in other solvents. When the ozonolysis was carried out in ethyl acetate at —78°C, the yield of the dioxolane-hemiacetal 133 was 95% (Scheme 51) <1990J(P1)1220>. 

The synthetic utility of (i )-enoate 392 is illustrated in the stereoselective synthesis of the bengamide E derivative 399 (Scheme 88). Silyl protection of 392, reduction with DIBAL, and Sharpless epoxidation of the resulting allylic alcohol furnishes epoxy alcohol 396 as a 95 5 anti syn mixture. Conversion of the primary hydroxyl group of 396 to an iodide under neutral conditions followed by a metallation-elimination and subsequent in situ methylation provides the ether 397. Ozonolysis, desilylation with aqueous acetic acid, and a Dess-Martin oxidation supplies the a,jS-dialkoxy aldehyde 398. This, utilizing stannane Se addition, is then converted to 399 [135]. 

Fig. (14). The diol (137) was converted to the ketone (157) by the standard organic reactions. Photoaddition of allene to (157) affords the methylene cyclobutene (158) which is converted to the aldol (162) by ketalization, ozonolysis, reduction and hydrolysis respectively. The derivative (164) prepared from (162) undergoes a chugaev reaction affording the alcohol (165) whose mesyl derivative (166) suffered rearrangement furnishing the allylic alcohol (167) which is converted to the ketone (168). Itis subjected tl lithium ammonia reduction to obtain (169) wich can be converted to aphidicolin (148) by reaction already desccribed.

The allylic alcohol 209 obtained from 3-(m-methoxyphenyl) propanol and isopropenyl magnesium bromide in THE at - 78 C was converted to the ketone 210 by a chloroketal Claisen reaction. ° Reaction with isopropenyllithium followed by reduction of the resulting allylic epoxide (211) resulted in formation of the tetramethyl allylic alcohol 212. Cyclization with stannous chloride" afforded an 85 15 mixture of 213 214 ozonolysis of 213 afforded 215, the route... 

Unexpected products sometimes arise on ozonolysis of alkenes bearing allylic heteroatoms. Draw the structure of the ozonide from the reaction of the allylic alcohol 13 with ozone and suggest an explanation for the formation of the product 14, used in a synthesis of grandisol. 

The structure of the ozonide from the reaction of the allylic alcohol 13 with ozone is shown below. This is the normal product from ozonolysis. Notice that there is no oxidant (such as H2O2) or reductant (such as Mc2S) in the formation of the keto-acid 14. The formation of the product 14 can be explained by fragmentation of the ozonide (see below), which occurs in a similar way to that described for the ozonolysis of a,p-unsaturated carbonyl compounds given in Scheme 5.105. See R. L. Cargill and B. W. Wright, / Org. Chem., 40 (1975), 120. 

When simple aldehydes were converted to allylic alcohols, they could be transformed to the corresponding trichloroacetimidates and subjected to thermal rearrangement to provide aUyl amines. The aUyl amine functionality was also accessible from enantio-selective reduction of propargyl ketones followed by conversion to the phthalamide derivative and reduction of the triple bond. Ozonolysis of these substrates provided the corresponding a-amino methyl esters in good yield (eq 48). As with the allyl alcohols, optically active substrates were treated with ozone without loss of enantiopurity of the chiral center. 

Synthesis of the /3-amino methyl esters was accomplished by Grignard addition to aldehydes or epoxides to deliver the ho-moallylic alcohols. After conversion to the homoamino derivative as prescribed in the allylic alcohol to allylic amine conversion, ozonolysis delivered the targets in good yield, without loss of optical activity or nitrogen protection (eq 49). Numerous additional examples as well as synthetic possibilities exist for the synthesis of natural product fragments utilizing this methodology. 

The synthesis of 252 began with Brown s asymmetric crotylation to aldehyde 261. The resulting homoallyl alcohol was converted benzyl ester 262, which was reduced to give lactol acetate 263. Axial allylation to 263 formed 2,6-trans-tetrahydropyran 264, which was subjected to ozonolysis to give an aldehyde. Addition of alkenylzinc, prepared by hydrozircona-tion of an alkyne 265, to the aldehyde mediated by chiral ligand 266 yielded allyl alcohol 267 with a 5.1 1 diastereoselectivity [110]. The stereochemistry of the major isomer was found, unexpectedly, to be the S-form at Cl7, which rendered the macrolactonization to adopt the Mitsunobu reaction. The iodide 252, prepared from 267 in three steps, reacted with... 

In a non-resolutive approach to chiral compounds. Hart et al. [25] treated the ester 5, derived from the enantiomericaUy pure allylic alcohol 4, with LICA and effected the rearrangement of the enolate so generated at room temperature to get the rearrangement products in good yields. In this way the chirality in the substrate was effectively transferred to the newly formed chiral center. Ozonolysis of the product of rearrangement gave optically pure lactol 6 with the recovery of the chiral auxiliary (Scheme 5.1.14). 

A Claisen-Johnson rearrangement with transfer of chirahty has been used by Pearson in a stereoselective synthesis of A-factor 199, an autoregulator of the production of streptomycin in Streptomyces griseus [42]. Allylic alcohol 200 is prepared in 80% yield and 84% ee by oxazaboroUdine reduction of the corresjxjnding ketone. Orthoester rearrangement afforded ester 201 in 75% yield. Ozonolysis of unsaturated ester 201 is then followed by lactonization (Scheme 6.29). 

Deninno, M. P. "Anomalous ozonolysis of cyclic allylic alcohols Mechanism and synthetic utility. Journal of the American Chemical Society 1995,117(39), 9927-9928. Razumovskii, S. D. Rakovski, S. K. Zaikov, G. E. Influence of the Paraffine Hydrocarbon Structure on its Reaction Rate with Ozone. Izv. Akad. Nauk, ser. khim. 1975, 9,... 

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