Chiral Amines as Catalysts in Asymmetric Mannich Reactions

1 Chiral Amines as Catalysts in Asymmetric Mannich Reactions 

Based on the mechanistic hypotheses that the nucleophilic addition of chiral enamines, formed from ketones and chiral amines, onto imines is sufficiently faster compared with the 

SCHEME 11.10 Mannich bases—important synthetic intermediates. 

FIGURE 11.2 Application of Mannich bases and derivatives thereof in medicine. 

Although, simple acyclic amino acids, such as L-serine, L-alanine, L-valine, etc., proved to be similarly effective in promoting the asymmetric Mannich reaction [59], since the pioneering work by List and collaborators, L-proline has been the catalyst of choice probably due the fact that it has performed well in a multitude of cases besides its availability and low costs [60-62], However, the apphcation of L-proline is not without its flaws. As with other organocatalysts, typically high catalyst loadings of up to 30mol% are required. Additionally, reactions have to be executed in very polar solvents, snch as DMSO, DMF, MeOH, or H O, due to its poor solubihty. To overcome some of these limitations, novel 

---