Diverting the Mannich reaction to access 2,2-disubstituted indolin-3-ones by merging 1,2-aryl migration and copper-catalyzed aerobic oxidation

The venerable Mannich reaction using p-anisidine, an aldehyde, and a nucleophile affords a linear alpha-secondary amine motif. Herein, we report that a slight yet rational modification of the reaction inputs diverts this three-component reaction, providing a cyclic alpha-tertiary amine. 2,2-Disubstituted indolin-3-ones equipped with diverse substitution patterns on their de novo generated quaternary carbon centers are readily accessible through this unprecedented transformation. Mechanistically, a domino sequence involving a kinetically favored intramolecular 1,2-aryl migration and a copper-catalyzed aerobic oxidation of an activated alpha-aminoalkyl site is suggested to account for the reaction outcome. Three typical substrates for the Mannich reaction, p-anisidine, aldehyde, and a nucleophile, did not afford the predictable linear Mannich base under an aerobic copper oxidation condition, but rendering a 2,2-disubstituted indolin-3-one product.