Still-Gennari modification

Still-Gennari modification of the HWE reaction Z-isomers are predominantly formed under conditions of kinetic control, e.g. at low temperatures, in weak polar solvents and under the action of strong bases. The use of phosphonates with an electron-withdrawing... 

HORNER-WADSWORTH-EMMONS OLEFINATION - STILL-GENNARI MODIFICATION... 

Horner-Wadsworth-Emmons Olefination (Still-Gennari modification) 214... 

Related reactions , Horner-Wadsworth-Emmons olefination - Still-Gennari modification, Julia-Lithgoe olefination, Peterson... 

Horner-Wadsworth-Emmons Oiefination - Still-Gennari Modification.214... 

Related reactions Horner-Wadsworth-Emmons olefination, Homer-Wadsworth-Emmons olefination - Still-Gennari modification, Julia-Lithgoe olefination, Takai-Utimoto olefination, Tebbe oiefination, Wittig reaction, Wittig reaction - Schiosser modification ... 

Still-Gennari Modification of the Horner-Wadsworth-Emmons Reaction... 

Other references related to the Horner-Wadsworth-Emmons oleflnation and to the Still-Gennari modification are cited in the corresponding literature. 

The stereochemical outcome of the Homer-Wadsworth-Emmons reaction is primarily dependent on the nature of the phosphonate used. In general, bulky substituents at both the phosphoms and the carbon adjacent to the carbanion favor formation of the -alkene. This selectivity has been rationalized in terms of a lowering of steric strain in intermediate SB as compared to intermediate SA. Z-Selectivity in HWE reactions can, however, be achieved using the Still-Gennari modification [20]. Here, the use of a (2,2,2-trifluoroethyl) phosphonate enhances the rate of elimination of the originally formed adduct SA (Scheme 1.6) relative to equilibration of the intermediates 4 and S. An example of the Still-Gennari modification is illustrated in Scheme 1.7. 

Bulky R groups on the phosphonate e.g. (R0)2P(0)-CH(-)-R Bulky R groups adjacent to the carbanion e.g. (R0)2P(0)-CH(—)-R Use of a-fluoro phosphonates Use of bis(2,2,2-trifluoroethyl) phosphonates (Still-Gennari modification) Use of cyclic phosphonates such as 8 Use of (diarylphosphono)acetates (Ando method)/ excess Na+ ions... 

In the Still-Gennari modification, a potassium base is used with crown ether complexation of the cation and the (Z)- product is favored. Even higher Z selectivity is obtained using trifluoroethyl phos-phonoesters (Eq. 7.35) [59]. 

Modifications directly to the alkoxy phosphonate were examined. The Still-Gennari modification of the HWE reaction provided access to (Z)-selective alkenes. In this example, the substituents on the phosphonate were modified as in 51. Executing the standard reaction conditions with aldehyde 52 now resulted in 53. It was postulated that this modification accelerates the elimination of the initial adduct, thus preventing equilibration to the more stable threo intermediate vide supra). 

Synthesis of dienyl chloride 2.349, the dithiane coupling partner for dithiane aldehyde 2.338, was accomplished in five steps from commercially available cis-2-butene-l,4-diol (Scheme 2.72). To this end, monosilylation of 2.344 as the TBS ether and this allyl alcohol was then oxidized with accompanying Zto E isomerization by PCC [122] to afford the enal 2.346 in 73 % yield. a,]S-unsaturated ester 2.347 was accessed by the Still—Gennari modification [219] of the Homer-Wads worth-Emmons olefination in good yield and selectivity (92 %, Z/E — 16 1). Reduction of the resulting ester 2.347 to produce allyl alcohol 2.348, in turn was chlorinated by treatment with LiCl and methanesulfonyl chloride to furnish the requisite dienyl chloride 2.349. 

Fig. 6 Rationale for Z-selectivity in Still-Gennari modification of HWE olefination...

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