Organocatalytic Asymmetric Decarboxylative Mannich Reaction for the Synthesis of Non‐Natural α‐Amino Acids Bearing Alkynyl Groups

Abstract Asymmetric decarboxylative Mannich addition of β ‐keto acids or malonic acid half‐esters to β , γ ‐alkynyl‐ α ‐ketimino esters catalyzed by cinchona alkaloid‐derived squaramide has been developed. The reaction proceeded by forming a nucleophilic enolate after decarboxylation, followed by its addition to β , γ ‐alkynyl‐ α ‐ketimino esters facilitated by the bifunctional catalyst. A broad range of substrates with various substituents are tolerated in this reaction, yielding a series of α , α ‐disubstituted amino acid derivatives bearing alkynyl functional groups in high yields with good to excellent enantioselectivities. The practicality of this method was demonstrated by a gram‐scale reaction and subsequent elaboration of the Mannich adducts.