![drawing a wittig reagent in chemdoodle drawing a wittig reagent in chemdoodle](https://media.springernature.com/m312/springer-static/image/art:10.1038%2Fnchem.458/MediaObjects/41557_2009_Article_BFnchem458_Fig1_HTML.jpg)
Lithium salts can also exert a profound effect on the stereochemical outcome. However, certain reactants do not follow this simple pattern. For many years, the stereochemistry of the Wittig reaction, in terms of carbon-carbon bond formation, had been assumed to correspond directly with the Z/E stereochemistry of the alkene products. Reitz identified the issue about equilibration of Wittig intermediates and termed the process "stereochemical drift". When lithium is present, there may be equilibration of the intermediates, possibly via betaine species 3a and 3b. Under lithium-free conditions, the stereochemistry of the product 5 is due to the kinetically controlled addition of the ylide 1 to the carbonyl 2. In particular, phosphonium ylides 1 react with carbonyl compounds 2 via a cycloaddition that is sometimes described as having topology to directly form the oxaphosphetanes 4a and 4b. For lithium-free Wittig reactions, studies support a concerted formation of the oxaphosphetane without intervention of a betaine. The existence and interconversion of the betaine ( 3a and 3b) is subject of ongoing research. Mechanistic studies have focused on unstabilized ylides, because the intermediates can be followed by NMR spectroscopy. To obtain the ( Z)-enoate, the Still-Gennari modification of the Horner-Wadsworth-Emmons reaction can be used. Ordinarily, the Horner–Wadsworth–Emmons reaction provides the ( E)-enoate (α,β-unsaturated ester), just as the Wittig reaction does. Alternatively, the Julia olefination and its variants also provide the ( E)-alkene selectively. To obtain the ( E)-alkene for unstabilized ylides, the Schlosser modification of the Wittig reaction can be used. The ( E)/( Z) selectivity is often poor with semistabilized ylides (R 3 = aryl). With stabilized ylides (R 3 = ester or ketone), the ( E)-alkene is formed with high selectivity. With unstabilised ylides (R 3 = alkyl) this results in ( Z)-alkene product with moderate to high selectivity. ( doi: 10.For the reaction with aldehydes, the double bond geometry is readily predicted based on the nature of the ylide. "Still–Gennari Olefination and its Applications in Organic Synthesis".