Asymmetric 1,4-Addition of Oxazolones to Nitroalkenes by Bifunctional Cinchona Alkaloid Thiourea Organocatalysts: Synthesis of alpha,alpha-Disubstituted alpha-Amino Acids

An easy and simple synthetic approach to optically active a,a-quaternary a-amino acids using asymmetric organocatalysis is presented. The addition of oxazolones to nitroalkenes catalyzed by thiourea cinchona derivatives provides the corresponding a,a-quaternary a-amino acid derivatives with good yields, excellent diastereoselectivities (up to 98% dr), and from moderate to good enantioselectivities (up to 92% ee). The reaction can be performed on a large scale. The optically active oxazolone-nitroalkene addition products can be opened in a one-pot reaction to the corresponding ester-amide derivatives. Additional transformations are also presented, such as the synthesis of amino esters, amino acids, and transformation into 3,4-disubstituted pyrrolidin-2-ones.