Catalyst- and solvent-free aminolysis of the asymmetric derivatives of Evans’ chiral N-acyloxazolidinones: enantioselective synthesis of chiral amides and its applications†‡

Abstract

The green formation of the amide bond was identified as one of the key green chemistry research areas for the pharmaceutical industry. Here, we report a catalyst- and solvent-free protocol for the aminolysis of the asymmetric derivatives of Evans’ N-acyloxazolidinones to deliver enantioenriched secondary amides. This constitutes an extension of the Evans asymmetric methodology for the enantioselective synthesis of chiral common amides. The reaction features simplicity (without using any catalyst, solvent, or additive), mildness (running at room temperature), versatility (viable for different types of N-acyloxazolidinone-based asymmetric products and for α-branched primary amines), and high efficiency and selectivity (high yield and high ee). The additional value of the method was demonstrated by the one-pot conversion of the amides into other classes of compounds.