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

Abstract

The venerable Mannich reaction using p-anisidine, an aldehyde, and a nucleophile affords a linear α-secondary amine motif. Herein, we report that a slight yet rational modification of the reaction inputs diverts this three-component reaction, providing a cyclic α-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 α-aminoalkyl site is suggested to account for the reaction outcome.