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 trans-alkenes. This reaction was modified from the Wittig reaction by Leopold Horner in 1958. In the Wittig reaction phosphonium ylides were used. However, when the reaction was modified, phosphonate-stabilized carbanions proved to be the better reactant because they are more nucleophilic, less basic, and can be alkylated.
The mechanism for this reaction begins with the deprotonation of the phosphonate to give the phosphonate carbanion. Next the carbanion acts as a nucleophile and adds onto the aldehyde or ketone creating a tetrahedral intermediate. This is the rate-limiting step of the reaction. This intermediate can now react intramolecularly to form a ring. The final step is an elimination reaction that will yield an alkene product. The ratio of the Z-alkene to E-alkene is dependent upon the stereochemical outcome of the initial carbanion addition and the ability of the intermediates to equilibrate. However, the HWE reaction typically favors the formation of the E-alkene.
In the above reaction scheme, the first step depicts the addition of the phosphonate carbanion 1 to molecule 2, which represents either an aldehyde or ketone. The resulting structures, 3a and 3b, are in equilibrium with 4a and 4b, which are the four-membered rings that are common to all HWE reactions. The stereochemistry of the electron withdrawing group on the four-membered ring is what causes the distinction between the final cis product 5 or the trans product 6.
Works Cited:
Wadsworth, W. Org. React. 1977, 25, 73.
Larsen, R. O.; Aksnes, G. Phosphorus Sulfur 1983, 15, 218-219.
Lefèbvre, G.; Seyden-Penne, J. J. Chem Soc., Chem. Commun. 1970, 20, 1308-1309.