The Direct Asymmetric Mannich Reaction Of Isatin Imines

A series of chiral amine catalysts were prepared and used in the catalytic asymmetric Mannich reaction of hydroxyacetone with isatin imines. After optimizing the reaction conditions, both of trans and cis-adducts can be obtained in the promotion of catalyst 3f through changing the reaction solvents. The results indicated that the threonine-derived catalyst 3f gave trans-adducts with excellent yields (up to 98%), high enantioselectivities (up to 99% ee) and diastereoselectivities (up to 90:10) in ethyl ether, and gave cis-adducts with excellent yield (up to 99%), high enantioselectivities (up to 90% ee) and diastereoselectivities (up to 83:17) in toluene. The anti-Mannich adducts could be converted into chiral sultams without losing the stereoselectivities.