Palladium-Catalyzed Asymmetric α-Arylation of Alkylamines: A General Strategy for the Synthesis of Chiral α-Aryl Amines

A chiral α-aryl amine motif is commonly presented in pharmaceuticals and functional molecules. We report a palladium-catalyzed highly enantioselective α-arylation of N-arylimidoyl cyanide-protected alkylamines, including benzylamines, with aryl bromides and iodides. This reaction features simple feedstock starting materials, broad scopes with respect to both coupling partners, readily available catalysts, and consistently high enantioselectivities. This approach provides a general and practical strategy for converting simple primary alkylamines into both chiral α-aryl-α-alkyl and α,α-diaryl methylamines. Mechanistic studies revealed that the nitrile group of N-arylimidoyl cyanide plays a dual role: serving both as a directing group via C≡N···Pd coordination and as an electron-withdrawing group, both of which are critical for facilitating the amine α-C–H bond cleavage with a mild base, such as Cs2CO3.