Cross-Coupling of Amides by N–C Bond Activation

Abstract

In recent years, significant conceptual advances have taken place in the field of amide bond cross-coupling. Mild and selective functionalization of amides by transition-metal catalysis has an enormous potential for widespread applications in both industry and academia due to the unparalleled prevalence of amide-containing molecules. However, direct metal insertion into the N–C(O) amide bond is extremely difficult as a consequence of amidic resonance. In this account, we summarize our work on the development of new cross-coupling reactions of amides by N–C bond activation, and briefly discuss other modern developments in this area. 1 Introduction 2 Amide Bond Ground-State Distortion 3 Acyl Amide N–C Cross-Coupling 3.1 Suzuki Cross-Coupling 3.2 Negishi Cross-Coupling 3.3 Esterification and Amidation via N–C Cross-Coupling 4 Decarbonylative Amide N–C Cross-Coupling 4.1 Heck Cross-Coupling 4.2 Suzuki Cross-Coupling 4.3 C–H Activation 4.4 Decarbonylative Borylation 5 Transition-Metal-Free Activation of Amide Bonds 6 Mechanistic Studies 7 Conclusions and Outlook