Amine-catalyzed site- and stereo-selective coupling of epoxy amines and carbon dioxide to construct oxazolidinones

Abstract

A non-metal catalyzed coupling of epoxy amines and CO₂ was achieved using readily available tertiary amines, under atmospheric pressure of CO₂ in the absence of any co-catalyst or additive. A high selectivity was obtained, as oxazolidinones were formed almost exclusively in most cases, while negligible amounts of cyclic carbonates were detected. Overall 22 oxazolidinones bearing alkyl, halo, nitro, and methoxy-substituted aryl groups were produced in 75–99% yields under mild conditions (1 bar CO₂, 60–80 °C). This strategy led to 100% configuration inversion and was applied to synthesize the chiral antibiotic drug linezolid. With the aid of kinetic and DFT studies, the role of tertiary amines was found as a nucleophile to cause ring-opening of epoxides, which forms alkoxides as key intermediates.