Highly Efficient Asymmetric Synthesis of Enantiopure Dihydro-1,2-oxazines: Dual-Organocatalyst-Promoted Asymmetric Cascade Reaction

A one-pot dual-organocatalyst-promoted asymmetric α-aminoxylation/aza-Michael/aldol consendation cascade reaction is presented. The targeted optically active 1,2-oxazine derivatives are synthesized in moderate yields (up to 70%), excellent enantioselectivities (ee >99% in all cases), and excellent diastereoselectivities (dr up to >99:1) under mild conditions. To further elucidate the synthetic utility of the cascade products, cleavage of the N–O bond is demonstrated and an enantiopure syn-1,4-amino alcohol derivative is achieved in excellent yield.