Direct C3‐H Alkylation and Alkenylation of Quinolines with Enones

Conversion of quinoline C‐H bonds to C‐C bonds is essential for obtaining the enormous array of derivatives required for pharmaceutical and agrochemical development. Despite over a century of synthetic efforts, the direct alkylation and alkenylation at C3‐H positions in a wide array of quinoline precursors remain predominantly challenging and elusive. This report outlines the first successful quinoline C3‐H alkylation and alkenylation reactions, exhibiting exceptional regio‐ and stereoselectivity, all achieved under redox‐neutral and transition‐metal‐free conditions. The method involves a three‐step, one‐pot or two‐pot sequence, including 1,4‐dearomative addition, functionalization at C3‐, elimination or transalkylation to produce 3‐alkylated /alkenylated quinolines. The presence of a carbonyl group in these products allows for further synthetic manipulations, enabling the production of cyanides, amides, amines, or simple alkyl derivatives.