Chiral Proton Catalysis: Enantioselective Brønsted Acid Catalyzed Additions of Nitroacetic Acid Derivatives as Glycine Equivalents

Abstract

An unsymmetrical, bifunctional chiral proton catalyst (2) has been developed to enable the highly diastereo- and enantioselective synthesis of epimerizable addition products from nitroacetic acid esters. The strategy is analogous to O'Donnell's glycine Schiff base alkylations that have been broadly applied to the synthesis of α-amino acids. In this regard, nitroacetic acid esters provide complementary products, namely, anti-α,β-diamino acids, derived from addition reactions. Products are obtained with high diastereoselection (generally 6−12:1) and enantioselection (generally >90% ee) using 5 mol% catalyst loading.