Synthesis of New Di- and Triamides as Potential Organocatalysts for Asymmetric Aldol Reaction in Water

New di- or triamide organocatalysts derived from ( L )-proline were synthesized and successfully used in the direct asymmetric aldol reaction of aliphatic ketones and aromatic aldehydes in water at 0 o C in the presence of benzoic acid as co-catalyst. ( S )-methyl-2-(( S )-3-hydroxy-2-(( S )-3-pyrrolidine-2-carboxamido)propanamido)-3-phenylpropanoate ( 7c ) as organocatalyst showed best results under these reaction conditions, and good diastereoselectivities (up to 99%), enantioselectivities (up to 98%) and yields (up to 91%) were observed.