Studies On Reductive Horner-Wadsworth-Emmons Olefination Using Mixed Silyl Acetals

Abstract

Homologation of esters to α,β-unsaturated esters is a useful transformation in organic synthesis. We have developed a new approach for the Ir-catalyzed reductive Horner-Wadsworth-Emmons olefination of esters; a one-pot method for the transformation of esters to α,β-unsaturated esters utilizing silyl acetals as aldehyde equivalents followed by Horner-Wadsworth-Emmons olefination. Lewis based activation of silyl acetals formed by Ir-catalyzed hydrosilylation of esters initially generates putative penta-coordinate silicate acetals which fragment into aldehydes, silanes and alkoxides in situ. The alkoxides deprotonate phosphonate esters which subsequently react with the aldehydes to furnish α,β-unsaturated esters. This method is operationally simple compared with aluminium hydride-based reductive Horner-Wadsworth-Emmons olefination. Notably, Horner-Wadsworth-Emmons olefination of traditionally challenging substrates such as aryl, alkenyl and alkynl esters furnishes the corresponding α,β-unsaturated esters at room temperature with excellent stereoselectivities (E/Z > 20:1) and moderate to excellent yields (48–91%). This transformation will contribute to enhancing the utility of silyl acetals in synthetic chemistry.