Mechanistic details of amino acid catalyzed two-component Mannich reaction: experimental study backed by density functional calculations

• Published in: Amino acids 2019-11, Vol.51 (10-12), p.1609-1621
• Main Authors: Rani, Dixita, Thakur, Lalita, Khera, Mayank, Goel, Neetu, Agarwal, Jyoti
• Format: Article
• Language: English
• Subjects: Acetoacetates - chemistry; Amino acids; Amino Acids - chemistry; Analytical Chemistry; Biochemical Engineering; Biochemistry; Biomedical and Life Sciences; Carbonyl compounds; Carbonyls; Catalysis; Catalysts; Density; Glutamic Acid - chemistry; Hydrogen-Ion Concentration; Imines; Imines - chemistry; Life Sciences; Malonates - chemistry; Mannich Bases - chemical synthesis; Mannich Bases - chemistry; Mathematical analysis; Molecular Structure; Neurobiology; Original Article; pH effects; Proteomics; Stereoisomerism
• ISSN: 0939-4451; 1438-2199
• DOI: 10.1007/s00726-019-02798-z

The role of pH-dependent ionic structures of l -amino acids in catalysis has been investigated for the two-component Mannich reactions between dimethyl malonate (DMM)/ethyl acetoacetate (EAA) and imines. As catalysts, l -amino acids performed well, even better than corresponding base catalysts and provided the β-amino carbonyl compounds in very high yields. Density functional calculations were used to gain the mechanistic insight of the reaction. High catalytic efficiency of amino acids was attributed to the facile formation of carbanion intermediate through barrierless transition state TS1 (− 19.43 kcal/mol) and then its stabilization owing to carbanion interaction with protonated amino acid.