Nucleophilic Dearomatization of Pyridines under Enamine Catalysis: Regio-, Diastereo-, and Enantioselective Addition of Aldehydes to Activated N-Alkylpyridinium Salts

• DOI: 10.1021/acs.orglett.6b03824
• Publication Date: 2017-01-27T20:16:10Z
• Authors: Giulio Bertuzzi; Alessandro Sinisi; Daniel Pecorari; Lorenzo Caruana; Andrea Mazzanti; Luca Bernardi; Mariafrancesca Fochi
• Keywords: Biochemistry; Physical and Theoretical Chemistry; Organic Chemistry; 01 natural sciences; 0104 chemical sciences

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.