Alkenes sodium hexamethyldisilazide

The Julia-Kocienski olefination of heterocyclic sulfones and aldehydes, which is an alternative to the modified Julia olefination, forms alkenes with good -selectivity. First, sulfone 54 is deprotonated in the a-position to the sulfur by sodium hexamethyldisilazide (NaHMDS) and the sulfur-stabilized anion 55 then adds to the alde-... 

Recently, the Homer coupling was utilized by Smith and coworkers in the total synthesis of milbe-mycin (equation 59). In an excellent example of the sensitivity of the alkene stereochemistry to the base utilized, when the phosphine oxide anion (253) was generated with NaH as the base the ( ) (Z) ratio was 7 1, but epimerization occurred at the aldehyde methine (252) and the yield was only 15%. Switching to KHMDS, the yield improved to 74% but virtually a 1 1 ratio of alkenes formed. Use of sodium hexamethyldisilazide solved these difficulties, forming the desired ( )-diene (254) in a 7 1 ratio with the (Z)- in 85-95% yield. Additional examples of the use of phosphine oxides in the synthesis of milbemy-cins and FK-506 are presented in Section 3.1.11.4. 

Phenyl-lff-tetrazol-5-yl sulfones were introduced as another alternative to phenyl sulfones, which led to alkenes in a one-pot procedure from aldehydes. Usually the highest selectivities are obtained while using KHMDS, although higher yields are observed with sodium hexamethyldisilazide. For instance, alkene 4 was obtained in 100% yield and an 84 16 E Z ratio with NaHMDS, whereas the use of KHMDS led to the same product with 59% yield and a 99 1 E Z ratio (eq 41). 

Mitsunobu reaction with alcohols and subsequent oxidation with MCPBA. Deprotonation of such a sulfone with sodium or potassium hexamethyldisilazide in DME followed by reaction with an aldehyde results in an ( )-alkene. 

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