An Access to Chiral Phthalides: Enantioselective Synthesis of Escitalopram

Abstract

AbstractA method for the asymmetric synthesis of phthalides containing a stereogenic γ‐carbon has been described. The protocol, based on the arylogous Michael addition to chiral alkenoyl oxazolidinones catalyzed by a crown ether under phase‐transfer conditions does not require anhydrous conditions and uses commercially available materials. A complete syn‐stereocontrol is achieved and facial diastereoselectivities are moderate to excellent (62:38 to 99:1 dr). Purification of the major diastereomer by chromatography and selective cleavage of the chiral auxiliary affords enantiopure Michael products. The protocol has been applied to the formal synthesis of escitalopram.