Modular and diverse synthesis of amino acids via asymmetric decarboxylative protonation of aminomalonic acids

Stereoselective protonation is a challenge in asymmetric catalysis. The small size and high rate of transfer of protons mean that face-selective delivery to planar intermediates is hard to control, but it can unlock previously obscure asymmetric transformations. Particularly, when coupled with a preceding decarboxylation, enantioselective protonation can convert the abundant acid feedstocks into structurally diverse chiral molecules. Here an anchoring group strategy is demonstrated as a potential alternative and supplement to the conventional structural modification of catalysts by creating additional catalyst–substrate interactions. We show that a tailored benzamide group in aminomalonic acids can help build a coordinated network of non-covalent interactions, including hydrogen bonds, π – π interactions and dispersion forces, with a chiral acid catalyst. This allows enantioselective decarboxylative protonation to give α-amino acids. The malonate-based synthesis introduces side chains via a facile substitution of aminomalonic esters and thus can access structurally and functionally diverse amino acids. Asymmetric decarboxylation can transform abundant carboxylic acids into valuable chiral molecules but faces major limitations due to the challenging enantiocontrol of proton transfer. Now the use of Brønsted acid catalysis in conjunction with an anchoring group strategy has enabled the decarboxylative protonation of aminomalonic acids to access diverse amino acids.