Wittig Reaction - Reaction Mechanism - Recent Developments

Recent Developments

Recent research has shown that the reaction mechanism presented above does not account for all experimental results. Mechanistic studies have been done mostly on unstablilized ylides, because the intermediates can be followed by NMR spectroscopy. The existence and interconversion of the betaine (3a and 3b) is still under debate and a subject of ongoing research. There is evidence that phosphonium ylides 1 can react with carbonyl compounds 2 via a π²s/π²a cycloaddition to directly form the oxaphosphatanes 4a and 4b. The stereochemistry of the product 5 is due to the addition of the ylide 1 to the carbonyl 2 and to the ability of the intermediates to equilibrate. Maryanoff and Reitz identified the issue about equilibration of Wittig intermediates and termed the process "stereochemical drift". 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. However, certain reactants do not follow this simple pattern. Lithium salts can also exert a profound effect on the stereochemical outcome.

There are distinct differences in the mechanisms of aliphatic and aromatic aldehydes and of aromatic and aliphatic phosphonium ylides. Vedejs et al. have provided evidence that the Wittig reaction of unbranched aldehydes under lithium-salt-free conditions do not equilibrate and are therefore under kinetic reaction control. Vedejs has put forth a theory to explain the stereoselectivity of stabilized and unstabilized Wittig reactions.