Julia—Kocienski approach

Pan and collaborators [87] reported a more conventional approach to aigialomycin D exploiting a Yamaguchi lactonization for macrocyclization. Key features of the route included a SAE and selective opening of epoxy alcohol 222 to install the C5, C6 -diol and two Julia-Kocienski couplings to establish the -configured double... 

Julia, in a very elegant approach, has used sulfur ylidic 3,2-rearrangements to produce p.y-unsaturated aldehydes (Scheme 46). Following the same idea, Kociensky also used ylidic 3,2-sigmatropic rearrangements to prepare P,7-unsaturated aldehydes he employed sulfur ylides in conjunction with silicon substituents (Scheme 47). In contrast, Mander used the nitrogen ylidic 3,2-rearrangement as an easy route towards the synthesis of P,y-unsaturated aldehydes (Scheme 48). ° It is noteworthy that better... 

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. 

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