Toward design of a practical methodology for stereocontrolled synthesis of χ-constrained pyroglutamic acids and related compounds. Virtually complete control of simple diastereoselectivity in the Michael addition reactions of glycine Ni(II) complexes with N-(enoyl)oxazolidinones

Abstract

A Ni(II) complex of the Schiff base of glycine with o-[ N-α-picolylamino]benzophenone or -acetophenone as a nucleophilic glycine equivalent, and N- trans-enoyloxazolidinones, as a derivative of an α,β-unsaturated carboxylic acid, were found to be the substrates of choice in the corresponding Michael addition reactions. The reactions proceed at room temperature in the presence of catalytic amounts of DBU to afford quantitatively a virtually diastereocomplete formation of the corresponding addition products with (2 R*,3 R*) or (2 R*,3 S*) relative configuration, depending on the nature of the starting N-enoyloxazolidinones. Acidic decomposition of the products followed by treatment of the reaction mixture with NH 4OH gives rise to the corresponding diastereomerically pure 3-substituted pyroglutamic acids.