Various multifunctional enantiomerically pure organocatalysts were synthesized and screened in asymmetric Mannich reaction. The reaction of aromatic imines with malonates in the presence of amino acid-derived catalysts gave Mannich adducts in very high enantiomeric purities (up to 98% ee). It is proposed that a network of hydrogen and halogen bonds with Lewis bases, together with the steric effect of the tert -butyl group of the catalyst, is responsible for the high stereoselectivity of the reaction.
Kriis et al. (2026) studied this question.