Asymmetric Mannich Reaction Of Cyclic N-Sulfimines With Organocatalysis

Sultams and sulfamidates are key structural motifs in pharmaceuticals and biologically active natural products, and also play an important role in organic synthesis. We have developed the highly enantioselective and regioselective direct Mannich reaction of cyclic N-sulfimines with various methyl alkyl ketones using a primary-tertiary diamine as an organocatalyst(up to 99% yield and 97% ee). The specific regioselective addition preferably occurs at the less-substituted methyl group on unsymmetrical methyl alkyl ketones by steric control.We have also successfully realized highly enantioselective Mannich reaction of aryl methyl ketones with cyclic N-sulfimines. Combination of primary amine and TFA was found to be an efficient organocatalyst for this Mannich addition. A range of different aryl methyl ketones bearing various substituents with different electronic properties and steric hindrance was employed in the highly enantioselective Mannich reactions in up to 99% yield and 98% ee.The Knoevenagel condensation is a classic and efficient method to construct carbon-carbon bond. It has been widely used as important buliding blocks in organic synthesis. Here we demonstrated efficient Knoevenagel condensation reaction of malononitrile with aryl aldehyde derivatives, which is catalyzed by a novel amphoteric ionic type quaternary ammonium salt catalyst with up to 97% yield.