Dearomative Functionalization of Activated Quinolines: Transfer Hydrogenation/Cycloaddition Cascade to Construct α-Tertiary Amines

Cascade dearomative functionalization is a robust protocol to convert flat arenes into medicinally relevant three-dimensional architectures with added new functionality. Herein, a dearomative cycloaddition protocol for synthesizing tetrahydroquinoline-embedded alpha-tertiary amine scaffolds has been developed employing quinolinium salts and sulfonyl azides under metal-free conditions. An underexplored and mechanistically distinct pathway is unveiled, creating quaternary-center-bearing amine skeletons by an amine group migration during the transfer hydrogenation and cycloaddition cascade reaction. This approach provided a broad substrate scope of alpha-tertiary amine scaffolds from a plethora of C3-substituted quinolinium and sulfonyl azides. The post-synthetic modifications have further diversified the alpha-tertiary amine core into interesting scaffolds. Preliminary mechanistic studies suggested the involvement of aziridine ring formation for the amine migration to the C-3 position of quinoline to generate the alpha-tertiary amine core.