Enantioselective Anion‐Binding‐Catalyzed Nucleophilic Addition to 4‐Quinolones

Chiral quinolones and their derivatives are predominant synthetic building blocks and pharmacological agents. Nevertheless, their synthesis mostly relies on transition‐metal‐catalyzed enantioselective 1,4‐additions of organometallic reagents such as Grignard, organozinc, or organoboron species for alkylation, arylation, and alkynylation reactions. Herein, the first organocatalytic enantioselective formal 1,4‐addition to challenging 4‐quinolones is reported, upon in situ silylation to the corresponding quinolinium ions, followed by asymmetric nucleophilic attack to this type of substrates. This method complements previous metal‐catalyzed approaches by enrolling enol nucleophiles and relies on anion‐binding catalysis using a chiral triazole‐based anion binder. The enantioenriched 2‐substituted 2,3‐dihydro‐4‐quinolones were thus obtained in good yields (up to 97% yield) and enantioselectivities up to 89:11 e.r. Finally, the easy access to 4‐amino and γ –amino alcohol derivatives by post‐functionalization, as well as to enantiopure compounds (>99:1 e.r.), was showcased. The notable features of this protocol include its mild reaction conditions, avoiding the use of transition metals, broad functional group tolerance, and potential application toward the synthesis of chiral 2,3‐dihydro‐4‐quinolones and tetrahydroquinolines as important skeletons of bioactive and natural products.