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

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.