Highly E-Selective Solvent-Free Horner-Wadsworth-Emmons Reaction for the Synthesis of α-Methyl-α,β-Unsaturated Esters Using Either LiOH·H2O or Ba(OH)2·8H2O

Abstract

Abstract (E)-α-Methyl-α,β-unsaturated esters were prepared by the Horner-Wadsworth-Emmons reaction, which stirs a mixture of aldehyde, phosphonate reagent 1, and a base without solvent. The reaction of aromatic aldehydes and triethyl 2-phosphonopropionate 1a using LiOH·H2O gave 95–99% E-selectivity in 83–97% yield. The reaction of 1a with aliphatic aldehydes gave 92–94% E-selectivity except for α-branched aldehydes, and the selectivity was improved to 97–98% using ethyl 2-(diisopropylphosphono)propionate 1b. The reaction with α-branched aliphatic aldehydes was improved using triisopropyl 2-phosphonopropionate 1c and Ba(OH)2·8H2O to give 98–>99% E-selectivity and high yields. The HWE reaction using Ba(OH)2·8H2O in THF also gave (E)-α-methyl-α,β-unsaturated esters highly selectively in high yields.