Umpolung Amide Synthesis Using Substoichiometric N-Iodosuccinimide (NIS) and Oxygen as a Terminal Oxidant

Abstract

Umpolung Amide Synthesis (UmAS) provides direct access to amides from an ?-bromo nitroalkane and an amine. Based on its mechanistic bifurcation after convergent C?N bond formation, depending on the absence or presence of oxygen, UmAS using substoichiometric N-iodosuccinimide (NIS) under aerobic conditions has been developed. In combination with the enantioselective preparation of ?-bromo nitroalkane donors, this protocol realizes the goal of enantioselective ?-amino amide and peptide synthesis based solely on catalytic methods.