Julia olefination approach

An advanced example of this simple approach was used by Danishefsky in the synthesis of the antibiotic indolizomycin.30 This example illustrates the compatibility of the Julia olefination with many sensitive functional groups. The enal 154 was combined with the lithium derivative of an allylic sulfone and the adduct acylated to give a mixture of isomers of the adduct 155. Elimination with sodium amalgam gave a good yield of the , , -triene 156. [The R s are protecting groups.]... 

The Julia reductive elimination is a good choice when trying to prepare mono-, 1,1-di- and E-l,2-disubstituted alkenes. This application has been demonstrated, for example, in the preparation of a key intermediate in the synthesis of calciferol (Eq. 167).305 The alternative Wittig olefination approach failed due to the difficulties encountered in the preparation of the corresponding sterically hindered phosphonium halide.305... 

The coupling of 77 and 84 was performed via the Julia-Julia olefination [50] to construct the ( )-olefin 85 EjZ => 20) at the C14-C15 bond. This approach is slightly more efficient than that of the Kocienski-Julia protocol in the case of Lee s synthesis. As a macrocyclization, the intramolecular Horner-Emmons reaction was adopted, because macrolactonization of the hydroxy (E, )-dienylcarboxylic acid was difficult. The phosphonate 86, derived from 85, was exposed to K2CO3 and 18-crown-6 [51-53] to provide the macrolactone 87 in good yield. Finally, the side chain was introduced via the Wittig reaction like Lee s method, and the second total synthesis was accomplished. 

Among the different methods for the synthesis of alkenes, none matches the versatility of carbonyl olefination.290 It has been extensively studied since the discovery of the Wittig reaction,291292 and a wide variety of approaches to transform carbonyl compounds into alkenes have been developed. Besides the classical Julia reaction,94 the most generally applicable methods for direct olefination of carbonyl compounds include the Wittig,291,293,294 Homer-Wittig,295,293,296 Homer-Wadsworth-Emmons,297,298,293 Peterson,299 301 Johnson,302 and Julia-Kocienski303,304 reactions. All of these methods involve the addition of a... 

Beckwith concluded that bond formation occurs at the terminus of the olefinic linkage most readily approached vertically by the radical and he thus rationalized the preferred formation of the (Cy 5) radical. This view has been further discussed in a review and developed in later work. " In fact, examination of models does not lead, in our hands, to such an obvious conclusion as advanced by Beckwith, unless one takes into account the same C(2)-H / interactions discussed by Julia (Scheme 7). 

This approach has since been extended by Julia et al. to the synthesis of trisub-stituted olefins by replacing the sulfone moiety with an alkyl group. Some examples are collected in Table 3.10 [58]. 

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