Asymmetric Mannich Reactions of Ketones with Isatin-Derived N -Unprotected Ketimines Catalyzed by Amine Derivatives

Abstract Enantioselective Mannich reactions of ketones, including functionalized ketones, with N-unprotected ketimines of isatin derivatives are reported. These reactions are catalyzed by amine-based catalysts and afford highly enantiomerically enriched 3-substituted 3-aminooxindole derivatives as single regioisomers under mild conditions. The use of N-unprotected imines minimizes the need for protection and deprotection steps. The reactions enabled the enantioselective construction of tetrasubstituted carbon centers and generated unprotected primary amine groups upon C–C bond formation with the N-unprotected ketimines. The primary amine groups generated in the products did not interfere with the aminocatalysis. The reactions did not require either a decarboxylative strategy (i.e., the use of β-ketoacid derivatives as reactants) or preformed enol ether derivatives to obtain the Mannich reaction products with high regio- and enantioselectivities.