Enantioselective Synthesis of Chiral Amides by Phosphoric Acid-Catalyzed Asymmetric Wolff Rearrangement

The enantioselective addition of potent nucleophilic reagents to ketene compounds poses challenges due to the presence of significant background reactions, along with simultaneous stereoselectivity and enantioselectivity issues in the reaction process. We present a method for enantioselective amination of ketenes employing α-aryl-α-diazoketones as ketene precursors and phosphoric acids as catalysts. Upon exposure to visible light, diazoketones undergo Wolff rearrangement to gradually generate ketenes. Subsequently, the phosphoric acid not only accelerates capture of ketenes by amines, forming a singular configuration of aminoenol intermediates, but also promotes the enantioselective proton transfer of the intermediates to yield product. Mechanism studies elucidate the reaction pathways and explain how the catalysts expedite this transformation and control enantioselectivity.