Nickel-Catalyzed Reductive Arylation of N-Acyl Hemiaminals

N-Benzyl amides are important structural motifs in pharmaceuticals and natural products. The nucleophilic substitution reactions between aromatic nucleophiles and N-acyliminium ion precursors (N-acyl hemiaminal derivatives) represent one of the most common and powerful approaches. However, these protocols are typically limited by the scope of aromatic substrates or the requirement for air-sensitive reagents. Herein, we report a nickel-catalyzed reductive arylation reaction between N-acyl hemiaminals and readily available aryl halides, which enables the synthesis of a series of structurally diverse N-benzyl amide derivatives under mild conditions through simple operations. Mechanistic studies support a nickel-catalyzed cross-coupling pathway mediated by an N-acyliminium ion intermediate and exclude the participation of an N-acyl α-aminoalkyl radical.