Nickel-catalyzed C-N bond activation: activated primary amines as alkylating reagents in reductive cross-coupling

Nickel-catalyzed reductive cross coupling of activated primary amines with aryl halides under mild reaction conditions has been achieved for the first time. Due to the avoidance of stoichiometric organometallic reagents and external bases, the scope regarding both coupling partners is broad. Thus, a wide range of substrates, natural products and drugs with diverse functional groups are tolerated. Moreover, experimental mechanistic investigations and density functional theory (DFT) calculations in combination with wavefunction analysis have been performed to understand the catalytic cycle in more detail. The reductive cross coupling of pyridinium salts derived from readily available primary alkyl amines with aryl halides has been achieved under mild reaction conditions using a nickel catalyst.