Chiral proton catalysis: Enantioselective bronsted acid catalyzed additions of nitroacetic acid derivatives as glycine equivalents

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 alpha-amino acids. In this regard, nitroacetic acid esters provide complementary products, namely, anti-alpha,beta-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.