Borane-Catalyzed C3-Alkylation of Pyridines with Imines,Aldehydes, or Ketones as Electrophiles

Achieving C3-selective pyridine functionalization isa longstanding challenge in organic chemistry. The existingmethods, including electrophilic aromatic substitution and C-Hactivation, often require harsh reaction conditions and excesspyridine and generate multiple regioisomers. Herein, we report amethod for borane-catalyzed tandem reactions that result inexclusively C3-selective alkylation of pyridines. These tandemreactions consist of pyridine hydroboration, nucleophilic additionof the resulting dihydropyridine to an imine, an aldehyde, or a ketone, and subsequent oxidative aromatization. Because the pyridineis the limiting reactant and the reaction conditions are mild, this method constitutes a practical tool for late-stage functionalization ofstructurally complex pharmaceuticals bearing a pyridine moiety.