An enhanced stereoselective synthesis of α,β-unsaturated esters through the Horner–Wadsworth–Emmons reaction in deep eutectic solvents

Abstract

A new scalable synthesis of (E)-α,β-unsaturated esters has been developed using protic, non-toxic, and biodegradable deep eutectic solvents through the Horner–Wadsworth–Emmons reaction between triethyl phosphonates and (hetero)aromatic carbonyl compounds, encompassing electron-withdrawing and electron-donating groups. Stereoselective preparation of disubstituted or trisubstituted ethyl cinnamate derivatives is achieved in the presence of LiOH, K₂CO₃, or DBU as bases, at room temperature and under air. Demonstrated with the synthesis of (E)-ethyl 3-(4-bromophenyl)acrylate, the same eutectic mixture (choline chloride/urea) proved to be reusable for three consecutive runs. Gram-scale reactions (10 mmol) can be carried out without the formation of side products, thereby ensuring high atom economy and an EcoScale score of 71.