Julia-Kocienski olefination, Mitsunobu reaction

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. 

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 best version of the Julia olefin synthesis (so far) is probably that introduced by Kocienski.33 It uses /V-phenyl tetrazolyl sulfones 167 easily prepared from the available thiol 165 by a Mitsunobu reaction with a simple alcohol followed by oxidation. 

A stereoselective construction of the Z)-e/yr/tro-azidosphingosine characteristic trans double bond was accomplished by Panza and co-workers by condensation reaction between tetradecanol and a heterocyclic sulfone derived from diethyl Z)-tartrate, following the Kocienski modification of the Julia-Lythgoe olefination. Alcohol 71 was first converted into the 1-phenyl-l//-tetrazole-5-yl thioether under Mitsunobu conditions and then oxidized to 73 in 80% yields. A solution of sulfone 73 in DME at -55 "C was treated with KHMDS to give a stable anion of compound 73, which was then reacted with tetradecanal to give compound 74 in 53% yield. The compound 74 can be efficiently transformed into the target, 3-(9-(4-methoxybenzyl)-azidosphingosine, with reported procedure. 

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