Catalytic Nucleophilic Aromatic Substitution Amination of 2-Aminopyridines with Amines

Abstract Nucleophilic aromatic substitution (SNAr) is a powerful strategy for rapid functional group transformations and has been applied extensively in arene functionalization. Electrophilic transition-metal-enabled π-coordination activation has emerged as a unique approach for catalyzing SNAr reactions of benzene derivatives. Traditionally, heteroarenes are considered resistant to π-coordination with transition metals because of preferential binding of the heteroatom to the metal. In our recent work, we demonstrated a π-coordination activation strategy for aminopyridines using a ruthenium(II) catalyst to enable SNAr reactions with amines as nucleophiles. The transient η⁶-pyridine complex serves as an electrophile, facilitating pyridyl C–N bond cleavage and providing access to a diverse array of pyridylamines. Additionally, this method enables the incorporation of chiral and ¹⁵N-labeled amines, expanding its synthetic utility.