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

Abstract

The enantioselective addition of potent nucleophiles to ketenes poses challenges due to competing background reactions and poor stereocontrol. Herein, we present a method for enantioselective phosphoric acid catalyzed amination of ketenes generated from α-aryl-α-diazoketones. Upon exposure to visible light, the diazoketones undergo Wolff rearrangement to generate ketenes. The phosphoric acid not only accelerates ketene capture by amines to form a single configuration of aminoenol intermediates but also promotes an enantioselective proton-transfer reaction of the intermediates to yield the products. Mechanistic studies elucidated the reaction pathway and explained how the catalyst expedited the transformation and controlled the enantioselectivity.

Keywords: Asymmetric Catalysis; Brønsted Acids; Chiral Amides; Organocatalysis; Wolff Rearrangement.