Sulfides Mitsunobu reaction, alcohol-sulfide

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. 

Other defunctionalizations. Deoxygenation of alcohols via thioxocarbamate derivatives or benzothiazol-2-yl sulfides (formed by Mitsunobu reaction) is readily achieved. 

The Mitsunobu reaction, discovered by Mitsunobu in the late 1960s, has become one of the most widely used reactions in organic chemistry. The reaction has become the standard method for the inversion of secondary alcohols, the conversion of alcohols into amines and sulfides, and many other applications. New uses for this versatile reaction continue to be developed. The Mitsunobu reaction, due to its mild reaction conditions, has found wide application in total synthesis, and heterocyclic and medicinal chemistry. Since the Mitsunobu reaction has been extensively reviewed during the last thirty years, this chapter will focus primarily on applications of the Mitsunobu reaction during the last fifteen years. This review will cover recent examples for the various uses of the Mitsunobu reaction and introduce several new applications of the reaction. Recently developed phosphine and azadicarboxylate reagents will be covered as well. 

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 Mitsunobu reaction (PPhs/DEAD) in the presence of HSTIPS has been used to convert the enediyne primary alcohol in eq 6 to the protected sulfide, which is readily converted upon treatment with CsF/DMF and PhthNSSMe to the corresponding disulfide. ... 

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