A 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.