Olefination Julia protocol

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. 

An inverse olefination protocol based on the intennediate 6 has appeared in the patent literamre recently (nucleophilic activation for Julia-Kocienski olefination) ... 

In the Kocienski-modified Julia olefination, replacement of the phenylsulfone moiety with a heteroarylsulfone such as the 1-phenyl-l/T-tetrazol-5-yl group (PT), shown below, profoundly alters the course of the Julia coupling. The olefin product is obtained in a one-pot procedure as opposed to the three-step protocol of the classical Julia olefination. ... 

The architecturally novel macrolide (+)-zampanolide was synthesized in the laboratory of A.B. Smith. The C8-C9 ( )-olefin moiety was constructed using the Kocienski-modified Julia oleHnation. The required PT-sulfone was prepared from the corresponding primary alcohol via a two-step protocol employing sequential Mitsunobu reaction and sulfide-sulfone oxidation. The primary alcohol and two equivalents of 1-phenyl-1 H-tetrazolo-5-thiol was dissolved in anhydrous THF at 0 °C and treated sequentially with triphenylphosphine and DEAD. The desired tetrazolo sulfide was isolated in nearly quantitative yield. 

The reaction between a carbanion derived from alkyl 3,5-bis(trifluoromethyl)phenyl sulfones and aldehydes affords, with good yields and stereoselectivities, the corresponding 1,2-disubstituted alkene through the Julia-Kocienski olefination reaction. This one-pot protocol can be performed using the phosphazene base at —78 °C and has been successfully used in a high yielding and stereoselective synthesis of various stilbenes such as resveratrol [47] (Scheme 5.28). 

More recently, the Mitsunobu reaction has been used as part of a two-step process to prepare precursors for the Julia-Kocienski olefination reaction. In this context, a primary or secondary alcohol is treated with thiobenzimidazole or another equivalent sulfiir source to provide a sulfide intermediate which is then oxidized using MOOPh (ammonium heptamolybdate) to provide the sulfone precursor for the Julia-Kocienski reaction. The following figure lists olefination precursors 210 through 213, which were prepared following the two-step protocol mentioned above. ° Information about the final target, if known, is also provided. 

At the outset, it should be noted that the original Julia olefination protocol is mostly usefiil in the synthesis of ( )-olefins. Depending upon the conditions of the reductive eUmination, the E/Z selectivity can be modulated, but in general ( )-alkenes are usually easier to obtain than their (Z)-counterparts. This stereochemical control - which also arises in the preparation of tri- and tetrasubstituted olefins - will be discussed in greater detail in the section on reductive elimination (Section 3.4). 

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