Studies on the synthesis of DMAP derivatives by diastereoselective Ugi reactions

Diastereoselective Ugi reactions of DMAP-based aldehydes with α-amino acids and tert-butyl isocyanide were examined. The reactions of 4-(dimethylamino)-2-pyridinecarboxaldehyde with various α-amino acids afforded 2-substituted DMAP derivatives with low diastereoselectivity. On the contrary, reactions with 4-(dimethylamino)-3-pyridinecarboxaldehyde delivered 3-substituted DMAP derivatives with moderate to high diastereoselectivity. The combination of α-amino acid and DMAP-based aldehyde is thus important to achieve high diastereoselectivity. Kinetic resolution of a secondary alcohol using a chiral DMAP derivative obtained through these reactions was also examined.