A novel highly stereoselective synthesis of chiral 5-and 4,5-substituted 2-oxazolidinones

A novel highly stereoselective synthesis of chiral mono- and bicyclic 4- and 4,5-substituted 2-oxazolidinones starting from P-keto esters was developed. After bioreduction with S. cerevisiae the resulting homochiral P-hydroxy esters are transformed into their hydrazides. Treatment with NaNO2/H+ then furnishes 2-oxazolidinones in high e.e. (similar to 99%) and d.e. (> 99%). The ring formation proceeds via a highly concerted sextet rearrangement with full retention of configuration at the stereocentres. Enantiopure 1,2-amino alcohols can subsequently be obtained by saponification of the 2-oxazolidinone products. (C) 2001 Elsevier Science Ltd. All rights reserved.