Patrick Lutz
Michigan
Nickel-Catalyzed Reductive Coupling of Iminium Ions
Benzhydryl amines are commonly found in bioactive compounds, but their synthesis often requires multiple synthetic steps because aromatic ketones are challenging substrates for reductive amination. We present a Ni-catalyzed, C–C bond-forming analogue of reductive amination in which benzaldehydes, N-trimethylsilyl amines, and aryl halides can be coupled in a modular, three-component fashion to provide access to benzhydryl amine products. Initial results demonstrate that these conditions can be translated to intramolecular contexts and to cross coupling with alkyl halides. Mechanistic studies suggest that the reaction proceeds by a sequential oxidative addition pathway rather than by a mechanism involving α-amino radical generation.
Benzhydryl amines are commonly found in bioactive compounds, but their synthesis often requires multiple synthetic steps because aromatic ketones are challenging substrates for reductive amination. We present a Ni-catalyzed, C–C bond-forming analogue of reductive amination in which benzaldehydes, N-trimethylsilyl amines, and aryl halides can be coupled in a modular, three-component fashion to provide access to benzhydryl amine products. Initial results demonstrate that these conditions can be translated to intramolecular contexts and to cross coupling with alkyl halides. Mechanistic studies suggest that the reaction proceeds by a sequential oxidative addition pathway rather than by a mechanism involving α-amino radical generation.