Enantioselective Meerwein–Ponndorf–Verley reduction of β,γ-unsaturated α-keto esters by asymmetric binary-acid catalysis in the green solvent iPrOH

Abstract

Enantioselective Meerwein–Ponndorf–Verley reduction of β,γ-unsaturated α-keto esters in iPrOH alone was achieved by using asymmetric binary-acid catalysts. The presence of 0.2 mol% of a chiral phosphoric acid and 0.5 mol% Sc(OTf)₃ is sufficient to obtain synthetically relevant β,γ-unsaturated α-hydroxy esters in excellent yields (up to 98%) and enantioselectivities (up to 99% ee). By DFT studies on the transfer hydrogenation of 2-oxo-3-enoates, we have proposed a possible mechanism to elucidate binary acid synergistic effects and a plausible model for enantiocontrol via the π–π stacking interaction between the vinyl benzene moiety of the substrate and the benzene ring of the chiral phosphoric acid.