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

• Published in: Advanced synthesis & catalysis 2024-10, Vol.366 (20), p.4219-4227
• Main Authors: Yadav, Suman, Kant, Ruchir, Rao Kuram, Malleswara
• Format: Article
• Language: English
• Subjects: Amines; Aromatic compounds; Cascade chemical reactions; Cycloaddition; Dearomatization; Hydrogenation; Organic compounds; Quaternary center; Quinoline; Scaffolds; Transfer hydrogenation; α-Tertiary amine
• ISSN: 1615-4150; 1615-4169
• DOI: 10.1002/adsc.202400770

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 α‐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 α‐tertiary amine scaffolds from a plethora of C3‐substituted quinolinium and sulfonyl azides. The post‐synthetic modifications have further diversified the α‐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 α‐tertiary amine core.