Phosphorus catalysis enabling α-sp3-C–H amination of 2-alkylpyridines

Abstract

Phosphorus-catalyzed sp³-C–H amination of 2-alkylpyridines was developed as a notable advancement of a catalytic sp³-C–H functionalization by an organophosphorus compound. Racemic 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (BINAP) acted as a particularly efficient catalyst precursor for the reaction of 2-alkylpyridines with dibutyl azodicarboxylate (DBAD) as an aminating agent in the presence of water and cesium carbonate as promoters in dichloromethane as a critical solvent, allowing the sp³-C–H amination under mild reaction conditions at 0 °C. The reaction proceeded exclusively at the C(α)-position even in the presence of more acidic C–H bonds. A quaternary azaphosphonium cation, generated by the reaction between BINAP and DBAD followed by solvolytic N-chloromethylation, is proposed to be the active catalyst that reacts directly with the alkylpyridine substrate.