Synthesis of Secondary Amines via Self-Limiting Alkylation of N-Aminopyridinium Salts

Partial amine alkylation to prepare secondary amines is challenging due to the enhanced N-nucleophilicity that accompanies alkylation. Here we introduce N-aminopyridinium salts as ammonia surrogates for the synthesis of secondary amines via self-limiting alkylation chemistry. A one-pot protocol based on N-aminopyridinium arylation followed by N-alkylation and in situ depyridylation provides access to aryl alkyl amines. The method is compatible with complex molecular settings and overcomes classical challenges in selective amine alkylation by accomplishing alkylation via transient pyridinium ylide intermediates. These findings both establish N-aminopyridinium salts as ammonia synthons and provide a new disconnection for the construction of structurally complex secondary amines.