Nucleophilic Dearomatization of Pyridines under Enamine Catalysis: Regio‑, Diastereo‑, and Enantioselective Addition of Aldehydes to Activated <i>N</i>‑Alkylpyridinium Salts

Catalytic addition of chiral enamines to azinium salts is a powerful tool for the synthesis of enantioenriched heterocycles. An unprecedented asymmetric dearomative addition of aldehydes to activated N-alkylpyridinium salts is presented. The process exhibits complete C-4 regioselectivity along with high levels of diastereo- and enantiocontrol, achieving a high-yielding synthesis of a broad range of optically active 1,4-dihydropyridines. Moreover, the presented methodology enables the synthesis of functionalized octahydropyrrolo­[2,3-c]­pyridines, the core structure of anticancer peptidomimetics.