Enantioselective Synthesis of Biphenyl‐Bridged ϵ‐Sultams by Organocatalytic Mannich Reactions of Cyclic N‐Sulfonylimines with Unactivated Ketones

Abstract

AbstractA highly enantioselective Mannich reaction of biphenyl‐bridged seven‐membered cyclic N‐sulfonylimines with methyl alkyl ketones is disclosed in this study. The reaction was performed under organocatalysis by using a quinine‐derived primary amine as the catalyst in combination with a Brønsted acid as the co‐catalyst. High yields (up to 89 %) and excellent enantioselectivities (up to 97 % ee) were observed. For methyl alkyl ketones containing a larger alkyl substituent, specific regioselective addition to the C=N bond is favored at the methyl group. On the contrary, ketones containing a smaller alkyl substituent or hydroxyacetone substrates gave major syn selective Mannich products at the methylene group.