Construction of tetrasubstituted stereocenters via asymmetric catalysis using chiral acyclic secondary amines

Catalytic asymmetric reactions of acetaldehyde, an inexpensive and versatile two-carbon nucleophile, still remain a challenge. Herein, chiral acyclic secondary aminocatalysts are developed as a means to address the difficult asymmetric reactions of acetaldehyde. The chiral acyclic secondary aminocatalysts exhibit unique reactivity and selectivity, which are not observable by using chiral cyclic secondary aminocatalysts or primary aminocatalysts. The activity is demonstrated by introducing previously challenging chemical transformations such as asymmetric Mannich reactions and switching enantioselectivity where the same absolute configuration of chiral catalysts are used. In general, the chiral acyclic catalysts improve activity and enantioselectivity, broadening the possible substrate scope. This work lays the foundation for the transformation of acetaldehyde with chiral acyclic secondary aminocatalysis and future work surrounding this class of aminocatalyst.