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

An easy and simple synthetic approach to optically active alpha,alpha-quaternary alpha-amino acids using asymmetric organocatalysis is presented and additional transformations are presented, such as the synthesis of amino esters, amino acids, and transformation into 3,4-disubstituted pyrrolidin-2-ones.

Abstract

An easy and simple synthetic approach to optically active alpha,alpha-quaternary alpha-amino acids using asymmetric organocatalysis is presented. The addition of oxazolones to nitroalkenes catalyzed by thiourea cinchona derivatives provides the corresponding alpha,alpha-quaternary alpha-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.