Julia-Kocienski reaction

The S. Julia olefination reaction modified and optimized by P. Kocien-ski [10] became the premiere fragment linkage reaction in construction of functionally complex targets. It has frequently been referred to as the Julia-Kocienski reaction. 

Scheme 19.30 Julia-Kocienski reactions leading to alkynes.

From an atom economy viewpoint, the RBR involves only loss of hydrogen halide (in the episulfone-forming step) followed by extrusion of sulfur dioxide. This makes it more atom economic than several of the common alternative strategies, such as the popular Mttig and Julia-Kocienski reactions, although the chosen method for forming the RBR precursor also needs to be considered if fully evaluating the synthetic efficiency. 

Beyond the medicinal chemistry sphere, the most striking use of the Smiles rearrangements in synthesis came with the work of Julia and coworkers who transformed the rather tedious two-step olefination developed by his brother, Marc Julia, into an elegant one-step transformation under milder conditions. Further iii5)roved by KociensM and coworkers, this olefination is now recognized as the Julia-Kocienski reaction. An illustrative exaii5)le may be found in the conversion of the tetrazolylsulfone 7 into olefin 8 and tetrazole 9 fScheme 19.41. 

Scheme 19.15 Benzothiazo-2-yl sulfones in Julia-Kocienski reactions.

Scheme 19.20 Methylenation through Julia-Kocienski reactions.

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. 

Prakash GKS, Shakhmin A, Zibinsky M, Ledneczki I, Chacko S, Olah GA. Synthesis of monofluoroalkenes via Julia-Kocienski reaction. J. Fluorine Chem. 2010 131 (11) 1192-1197. 

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