Synthesis of Azetidinones from L-Threonine: Formation of Unusually Stable Bicyclic Hemiketals and<i>cis</i>-Azetidinones

Abstract

L-Threonine-based synthesis of azetidinones/penems leads to the desired trans-azetidinones as well as novel, unusually stable bicyclic hemiketals/cis-azetidinones. The latter compounds are resistant to Baeyer-Villiger oxidation, and hence they can not be used towards penem synthesis. Structures of the bicyclic hemiketal, (1S,2R, 4R,5R)-4-(4-chlorophenyl)-4-hydroxy-6-(4-methoxyphenyl)-2-methyl-3-oxa-6-azabicyclo[3.2.0]heptan-7-one, and the cis-azetidione, (3S, 4R)-3-[(R)-1-(acetoxy)ethyl]-4-(4-chlorobenzoyl)-1-(4-methoxyphenyl)-2-azetidinone, were established by x-ray crystallography.