The Z-selective Wittig reaction
المؤلف:
Jonathan Clayden , Nick Greeves , Stuart Warren
المصدر:
ORGANIC CHEMISTRY
الجزء والصفحة:
ص690-691
2025-07-09
459
The Z selectivity observed with simple alkyl R groups is nicely complementary to the E selectivity observed in the Julia olefi nation. This complementarity was exploited by some chemists who wanted to make isomers of capsaicin (the compound that gives chilli peppers their ‘hotness’) to follow up suggestions that capsaicin might be carcinogenic. The key inter mediates in the synthesis of the E and Z isomers of capsaicin were the E and Z unsaturated esters shown below. By using a Wittig reaction with an unstabilized ylid it was possible to make the Z isomer selectively, whilst the Julia olefination gave the E isomer.
How can the Z selectivity in Wittig reactions of unstabilized ylids be explained? We have a more complex situation in this reaction than we had for the other eliminations we considered because we have two separate processes to consider: formation of the oxaphosphetane and decomposition of the oxaphosphetane to the alkene. The elimination step is the easier one to explain—it is stereospecific, with the oxygen and phosphorus departing in a syn-periplanar transition state. Addition of the ylid to the aldehyde can, in principle, produce two diastereo isomers of the intermediate oxaphosphetane. Provided that this step is irreversible, then the stereospecificity of the elimination step means that the ratio of the final alkene geometrical isomers will reflect the stereoselectivity of this addition step. When R is not conjugating or anion-stabilizing, the syn diastereoisomer of the oxaphosphetane is formed preferentially, and the predominantly Z alkene that results reflects this. The Z-selective Wittig reaction therefore consists of a stereoselective first step, to form the syn oxaphosphetane, followed by a stereospecific elimination from this intermediate to give a Z alkene.
Why the syn oxaphosphetane is favoured with unstabilized ylids is the subject of much debate because the mechanism by which the oxaphosphetane is formed is not entirely under stood. One possible explanation relies on rules of orbital symmetry, we need not explain them in detail here but there is good reason to believe that, if the ylid and carbonyl compound react together to give the oxaphosphetane in one step, they will do so by approaching one another at right angles. Here we have drawn the ylid in its phosphorane form, adding to benzaldehyde. Keeping the large substituents apart produces a transition state like that shown below, which (correctly) predicts that the oxaphosphetane will have syn stereochemistry.
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