The proline-catalyzed Mannich reactions of N -PMP-protected α-imino ethyl glyoxylate with a variety of ketones afford functionalized α-amino acids (Scheme 9). These reactions can generate two adjacent stereogenic centers simultaneously upon C-C bond formation with complete syn -stereocontrol and can be performed in a gram scale with operational simplicity.

Scheme 9. One-Pot Three-Component Mannich-Type Reaction

The proline-catalyzed reaction of N -PMP-protected α-imino ethyl glyoxylate with aliphatic aldehydes provides a general method for synthesis of β-amino and α-amino acid derivatives (Scheme 10). The diastereoselectivity depends on the bulkiness of the substituents of the aldehyde donor. In most of cases high syn stereoselectivity can be achieved.

Scheme 10. Mannich Reactions of Unmodified Aldehydes with Preformed Aldimines

The synthesis of chiral quaternary amino acid derivatives can be accomplished using proline based catalysis (Scheme 11). The nitrogen is tethered to the α -aryl amine in order to increase the reactivity through ring strain and the products are obtained with high enantioselectivity.

Scheme 11. Mannich Reaction of Unmodified Aldehyde with Ketimines