Alkenes hexamethyldisilazide

Z)-OL, -Unsaturated esters,l Wittig-Homer reactions generally show a preference for formation of (E)-alkenes. Thus (E)-a,p-unsaturated esters are obtained preferentially on reaction of aldehydes with trimethyl phosphonoacetate under usual conditions (potassium f-butoxide). Use of a highly dissociated base can favor (Z)-selectivity. The most effective base for this purpose is potassium hexamethyldisilazide, KN[Si(CH3)3]2, in combination with 18-crown-6, although even potassium carbonate with the crown ether is fairly effective. The (Z)-selectivity can be further enhanced by use of 1 as the phos-phonoester. Under these conditions, (Z)-unsaturated esters can be prepared from aliphatic and aromatic aldehydes with Z/E ratios as high as 50 1. The method is also useful for transformation of unsaturated aldehydes to (E,Z)-dienoates and (E,E,Z)-trienoates. 

A similar carbonyl addition with benzaldehyde derivatives having an ortho-allylic ether led to a benzopyranone when treated with potassium hexamethyldisilazide. ° These reactions are not successful when the alkene contains electron-withdrawing groups, such as halo or carbonyl groups. A free-radical initiator is required, usually peroxides or UV light. The mechanism is illustrated for aldehydes but is similar for the other compounds ... 

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. 

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. 

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). 

The Julia reaction is remarkably versatile but it does need three steps to make the alkene addition, acylation, and reduction. A more recent version of the reaction cuts this down to one by using not a phenylsulfone but instead a sulfone carrying an electron-deficient heterocycle, for example a tetrazole. The anion of the sulfone is made with a strong base (here potassium hexamethyldisilazide, KHMDS—see p. 635) and is added to an aldehyde to give an alkene directly. 

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