Horner–Wadsworth–Emmons reaction

[4][5] In contrast to phosphonium ylides used in the Wittig reaction, phosphonate-stabilized carbanions are more nucleophilic but less basic.

Unlike phosphonium ylides, the dialkylphosphate salt byproduct is easily removed by aqueous extraction.

Nucleophilic addition of the carbanion onto the aldehyde 2 (or ketone) producing 3a or 3b is the rate-limiting step.

The ratio of alkene isomers 5 and 6 is not dependent upon the stereochemical outcome of the initial carbanion addition and upon the ability of the intermediates to equilibrate.

Thompson and Heathcock have performed a systematic study of the reaction of methyl 2-(dimethoxyphosphoryl)acetate with various aldehydes.

[23][24] Using phosphonates with electron-withdrawing groups (trifluoroethyl[25]) together with strongly dissociating conditions (KHMDS and 18-crown-6 in THF) nearly exclusive Z-alkene production can be achieved.

The Horner–Wadsworth–Emmons reaction
The Horner–Wadsworth–Emmons reaction
Deprotonation by base (B-) to generate the phosphonate carbanion
The mechanism of the Horner-Wadsworth-Emmons reaction
The mechanism of the Horner-Wadsworth-Emmons reaction
Example of the Horner–Wadsworth–Emmons reaction with branched phosphonates
Example of the Horner–Wadsworth–Emmons reaction with branched phosphonates
The Still modification of the Horner–Wadsworth–Emmons reaction
The Still modification of the Horner–Wadsworth–Emmons reaction