The Horner–Wadsworth–Emmons (HWE) reaction is a chemical reaction used in organic chemistry of stabilized phosphonate carbanions with aldehydes (or ketones) to produce predominantly E-alkenes. In 1958, Leopold Horner published a modified Wittig reaction using phosphonate-stabilized carbanions. William S. Wadsworth and William D. Emmons further defined the reaction. In contrast to phosphonium ylides used in the Wittig reaction, phosphonate-stabilized carbanions are more nucleophilic but less basic. Likewise, phosphonate-stabilized carbanions can be alkylated. Unlike phosphonium ylides, the dialkylphosphate salt byproduct is easily removed by aqueous extraction. Several reviews have been published. Reaction mechanism The Horner–Wadsworth–Emmons reaction begins with the deprotonation of the phosphonate to give the phosphonate carbanion 1. Nucleophilic addition of the carbanion onto the aldehyde 2 (or ketone) producing 3a or 3b is the rate-limiting step. If R2 = H, then intermediates 3a and 4a and intermediates 3b and 4b can interconvert with each other. The final elimination of oxaphosphetanes 4a and 4b yield (E)-alkene 5 and (Z)-alkene 6, with the by-product being a dialkyl-phosphate. 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. The electron-withdrawing group (EWG) alpha to the phosphonate is necessary for the final elimination to occur. In the absence of an electron-withdrawing group, the final product is the α-hydroxyphosphonate 3a and 3b. However, these α-hydroxyphosphonates can be transformed to alkenes by reaction with diisopropylcarbodiimide. Stereoselectivity The Horner–Wadsworth–Emmons reaction favours the formation of (E)-alkenes. In general, the more equilibration amongst intermediates, the higher the selectivity for (E)-alkene formation. Disubstituted alkenes Thompson and Heathcock have performed a systematic study of the reaction of methyl 2-(dimethylphosphono)acetate with various aldehydes. While each effect was small, they had a cumulative effect making it possible to modify the stereochemical outcome without modifying the structure of the phosphonate. They found greater (E)-stereoselectivity with the following conditions: Increasing steric bulk of the aldehyde Higher reaction temperatures (23 °C over −78 °C) Li > Na > K salts In a separate study, it was found that bulky phosphonate and bulky electron-withdrawing groups enhance E-alkene selectivity. Trisubstituted alkenes The steric bulk of the phosphonate and electron-withdrawing groups plays a critical role in the reaction of α-branched phosphonates with aliphatic aldehydes. Aromatic aldehydes produce almost exclusively (E)-alkenes. In case (Z)-alkenes from aromatic aldehydes are needed, the Still–Gennari modification (see below) can be used. Olefination of ketones The