Enantioselective α-Hydroxylation of β-Keto Esters Catalyzed by Cinchona Alkaloid Derivatives

Abstract

A highly efficient α-hydroxylation of β-keto esters catalyzed by cupreidine in the presence of cumyl hydroperoxide (CHP) was achieved. The reaction was applied to a wide variety of β-keto esters to give products in high yields (up to 95%) with excellent enantioselectivities (up to 97% ee). The reaction had been successfully scaled up to a gram quantity and (<i>S</i>)-5-chloro-2-hydroxy-1-oxo-2,3-dihydro-1<i>H</i>-indene-2-carboxylate – the important intermediate of Indoxacarb were obtained in 96% yield with 86% ee. The enantiomeric excess could be improved to 99% by crystallization, and this method has prospect of industrial application for its advantages of enantioselectivity, ease of catalyst preparation and reclamation of catalyst.