Precursors, of the Julia reaction

Coupling Between the Tivo Precursors of the Julia Reaction 1109... 

Coupling Between the Two Precursors of the Julia Reaction 1117 a-Sulfonyl anions that lead to 1,4-additions... 

A study carried out by Kocienski and Lythgoe flrst demonstrated the trans selectivity of the Julia coupling process. The authors found the i uctive elimination could best be carried out with the acet-oxy or benzoyloxy sulfones. If the lithio sulfone derivative is used for addition to the carbonyl, the reaction can be worked up with acetic anhydride or benzoyl chloride to obtain the alkene precursor. In cases where enolization of the carbonyl is a complication, the magnesium derivative can frequently be used successfully. A modification of the reductive elimination was found to be most effective. Methanol, ethyl acetate/methanol or THF/methanol were the solvents of choice and a temperature of -20 C was effective at suppressing the undesired elimination of the acetoxy group to produce the vinyl sulfone. With these modifications of the original procedure, the ability of the reaction to produce dienes as well as rran.r-disubstituted alkenes was demonstrated, llie diastereoisomeric erythro- and threo-acetoxy sulfones could be separated and it was demonstrated that both isomers were converted to the rrans-alkene. It... 

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 synthesis of , Z-dienes, 79 and 80, was developed by Charette and co-workers from a,y9-unsaturated aldehydes, 77, and heteroarylsulfones, 78, using the Julia-Lythgoe olefination reaction. The selectivity of the olefination reaction under optimal conditions is better than 88 12 when a pyridylsuofone was used as the precursor. 

The cyclization reaction of the hex-l-en-6-yl radical (5) has been studied fairly extensively in solution by conventional analytical techniques. The amounts of cyclohexane and methylcyclopentane that are formed have been found to vary with the experimental conditions and the radical precursor used, but in the main the results show that cyclization to a five-membered ring is highly favoured (Julia, 1966). 

The Julia olefination reaction is highly regioselective and ( )-stereoselective, providing a valuable alternative to the Schlosser reaction for making rrans -disubstituted olefins. The reaction involves condensation of a metalated alkyl phenyl sulfone with an aldehyde to yield a P-hydroxysulfone, which is then subjected to a reductive elimination to produce the alkene. There are limitations to the preparation of tri- and tetra-substituted alkenes via the sulfone route because the P-alkoxy sulfones derived from addition of the sulfone anion to ketones may be difficult to trap and isolate or they may revert back to their ketone and sulfone precursors. 

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. 

Intramolecular Addition Reactions. Early studies by Julia and his co-workers on the cyclization of hexenyl (eq 11) and hep-tenyl radicals played a key role in the development of radical synthetic methodology, and many of the earher studies were conducted with peroxides as initiators. Cyclization of stabilized radicals such an malonates and cyanoesters are reversible, and the course of ring closure can be controlled by the appropriate choice of precursors and reaction conditions. Thus the cyanoacetate in eq 12 with 2 equiv of DTBP gives the products shown, whereas under kinetic conditions, using the tin hydride method, a different product distribution is obtained (eq 13). 

The Julia-Lythgoe reaction precursors, heteroarylsulfones, were prepared efficiently by using H202/Na2W04 combination oxidation of... 

Vinylcarbonyl compounds are common precursors for the generation of conjugated dienes. Recently, transformations including Wittig or related reactions, Julia or Takai olefination reactions, have been used to access heterosubstituted 1,3-dienes. 

Several groups have made efforts to synthesize these imique natural products [57-59]. Ishihara and Miuai s group constructed the BCD-tricycHc spiroacetal and the EF-bicycHc acetal simultaneously from a tetraketo precursor [60-63]. As shown in Scheme 11, a Julia-coupHng reaction of 115 [60]... 

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