A One-Pot Synthesis of N -α-Functionalized Amides via Oxidative Four-Component Reaction of Alcohols, Amines, Carboxylic Acids, and Nucleophiles

Abstract N-α-Functionalized amides represent a class of privileged molecular frameworks in both organic chemistry and medicinal chemistry. Nevertheless, the oxidative four-component synthesis of N-α-functionalized amides from alcohols, amines, carboxylic acids, and nucleophiles remains highly challenging, mainly due to the fact that this reaction involves multiple potentially oxidizable intermediates and reactants. Herein, this four-component reaction has been developed by employing a catalytic loading of TPAP alongside stoichiometric quantities of NMO serving as a terminal oxidant. The multicomponent approach demonstrates broad substrate scope and good functional group compatibility. The practicality of the protocol has been illustrated by the scalable synthesis and the late-stage functionalization of pharmaceuticals.