Synthesis of enantiopure 1,3-oxazolidin-2-ones from α-dibenzylamino esters

Adrian Ochoa Teran,Ignacio A Rivero

doi:10.3998/ark.5550190.0009.e30

Abstract

A new method to obtain enantiopure 5-substituted 1,3-oxazolidin-2-ones 1 from α- dibenzylamino esters 2 is reported. This methodology is based on the Lewis acid catalyzed stereoselective addition of trimethylsilyl cyanide to chiral α-dibenzylamino aldehydes 3. Magnesium chloride and zinc iodide were tested to catalyze the addition, obtaining higher stereoselectivity with zinc iodide than with magnesium chloride.

Highlights

In 1981, 4-substituted 1,3-oxazolidin-2-ones were introduced into organic synthesis as chiral auxiliaries by Evans.[1]
N-acyloxazolidinones participate in stereoselective processes as alkylations, αsubstitution reactions, aldol reactions, conjugate additions and pericyclic reactions
We have developed a new methodology for the synthesis of enantiopure 5-substituted 1,3-oxazolidin-2-ones from chiral silylated intermediates prepared from enantiopure α-dibenzylamino esters

Summary

Introduction

In 1981, 4-substituted 1,3-oxazolidin-2-ones were introduced into organic synthesis as chiral auxiliaries by Evans.[1]. N,N-Dibenzylamino esters 2 were prepared from L-phenylalanine, L-alanine, L-valine, L-leucine and L-isoleucine under standard procedures to generate 2a-e, respectively,[17] and reduced with lithium borohydride at reflux temperature in THF, to obtain amino alcohols 11a-e in 44% to 99% yield (Scheme 1). The stereoselective anti addition of trimethylsilyl cyanide to the α-dibenzylamino aldehydes 3 was achieved using zinc iodide (ZnI2) or magnesium chloride (MgCl2) in dichloromethane at 0 oC to give the corresponding trimethylsilylcyanohydrins 12a-e in 72% to 99% yield.

Results

Conclusion