Asymmetric Synthesis of 3-Substituted Isoindolinones by Direct Alkylation of Chiral N-tert-Butylsulfinyl-isoindolinones

Abstract

A straightforward, versatile, and efficient method for the asymmetric synthesis of 3-substituted isoindolinones is described. In this method, a series of (S)-2-(tert-butylsulfinyl)-isoindolin-1-ones were synthesized from the corresponding methyl 2-formylbenzoates in two steps with overall yields of 71–78%. Deprotonation of these compounds using LDA and the subsequent alkylation of the resulting carbanions with various alkylating agents afforded a series of 3-substituted isoindolinones in excellent yields and high diastereomeric ratios. This method showcases significant potential for broader applications in organic and medicinal chemistry.