Insight into C4 Selectivity in the Light‐Driven C−H Fluoroalkylation of Pyridines and Quinolines

Abstract Given the prevalence of pyridine motifs in FDA‐approved drugs, selective fluoroalkylation of pyridines and quinolines is essential for preparing diverse bioisosteres. However, challenges are often faced with conventional Minisci reactions in achieving precise regioselectivity owing to competing reaction sites of pyridine and the limited availability of fluoroalkyl radical sources. Herein, we present a light‐driven, C4‐selective fluoroalkylation of azines utilizing N‐aminopyridinium salts and readily available sulfinates. Our approach employs electron donor‐acceptor complexes, achieving highly C4‐selective fluoroalkylation under mild conditions without an external photocatalyst. This practical method not only enables the installation of CF 2 H groups but also allows for the incorporation of CF 2 ‐alkyl groups with diverse functional entities, surpassing the limitations of previous methods. The versatility of the radical pathway is further demonstrated through straightforward three‐component reactions involving alkenes and [1.1.1]propellane. Detailed experimental and computational studies have elucidated the origins of regioselectivity, providing profound insights into the mechanistic aspects.