Horner-Wadsworth-Emmons reactions, lithiated

The format of this chapter is similar to that used in previous volumes. The first section deals with methylene phosphoranes and their Wittig reactions, the second looks at the Horner-Wadsworth-Emmons reaction of phosphonate anions and the third the structure and reaction of lithiated phosphine oxides - an area which continues to receive particular attention. The majority of reports concerning ylides relate to their use in synthesis and in the final section some of these applications are reviewed. 

Reactions of lithiated ethyl 6-(dimethoxyphosphoryl)cyclohex-l-enecarboxylate with aliphatic, aromatic, and unsaturated aldehydes have been studied and determined to proceed with a or 5 regioselectivity. Such an unusual regioselectivity resulted from the contribution of two allylic carbanions one, stabilized by the phosphonate moiety and the other stabilized by the carboethoxy group. The course of the reaction depends mainly on the stmcture of the aldehyde and the reaction conditions. The products of Horner-Wadsworth-Emmons reaction were formed under kinetic conditions, whereas the 5-adducts were obtained as thermodynamic products. 

The Horner-Wadsworth-Emmons (HWE) reaction of a carbonyl compound with an a-lithiated phosphonate is an extremely useful method for introducing a double bond. In order to create a chiral compound having a double bond, 4-substituted cyclohexanones, 3-substituted cyclohexanones, 2,2-disubstituted cyclohexane-l,3-diones, or ketenes would be potential carbonyl substrates for the enantioselective HWE reaction, as Rein and coworker proposed [Fig. (15)] [69]. Only 4-substituted cyclohexanones have so far been applied to the enantioselective HWE reaction. 

---