Stereoselective synthesis of (E)-α,β-unsaturated esters: triethylamine-catalyzed allylic rearrangement of enol phosphates

Abstract

α,β-Unsaturated esters are key structural motifs widely distributed in various biologically active molecules, and their Z/E-stereoselective synthesis has always been considered highly attractive in organic synthesis. Herein, we present a >99% (E)-stereoselective one-pot synthetic approach towards β-phosphoroxylated α,β-unsaturated esters via a mild trimethylamine-catalyzed 1,3-hydrogen migration of the corresponding unconjugated intermediates derived from the solvent-free Perkow reaction between low-cost 4-chloroacetoacetates and phosphites. Versatile β,β-disubstituted (E)-α,β-unsaturated esters were thus afforded with full (E)-stereoretentivity by cleavage of the phosphoenol linkage via Negishi cross-coupling. Moreover, a stereoretentive (E)-rich mixture of a α,β-unsaturated ester derived from 2-chloroacetoacetate was obtained and both isomers were easily afforded in one operation.