Breaking Amides using Nickel Catalysis

Abstract

Amides have been widely studied for decades, but their synthetic utility has remained limited in reactions that proceed with rupture of the amide C–N bond. Using Ni catalysis, we have found that amides can now be strategically employed in several important transformations: esterification, transamidation, Suzuki–Miyaura couplings, and Negishi couplings. These methodologies provide exciting new tools to build C–heteroatom and C–C bonds using an unconventional reactant (i.e., the amide), which is ideally suited for use in multi-step synthesis. It is expected that the area of amide C–N bond activation using nonprecious metals will continue to flourish and, in turn, will promote the growing use of amides as synthons in organic synthesis.

Catalytic C−H/C−F Coupling of Azoles and Acyl Fluorides

“…Transition‐metal‐catalyzed cross‐coupling reactions of acyl electrophiles with aryl nucleophiles represent a powerful and reliable synthetic strategy for the introduction of acyl fragments into aromatic rings to provide aromatic ketones, and a large variety of carboxylic acid derivatives are currently used as acyl electrophiles . Among these, acyl fluorides have recently gained much attention as valuable carbon‐based electrophiles in cross‐coupling reactions, especially in acyl coupling and decarbonylative coupling reactions .…”

“…Among these, acyl fluorides have recently gained much attention as valuable carbon‐based electrophiles in cross‐coupling reactions, especially in acyl coupling and decarbonylative coupling reactions . Due to the moderate electrophilicity of acyl fluorides, they exhibit a good balance between stability and reactivity with respect to their compatibility under nucleophilic conditions, that is, they are more stable than the commonly employed acyl chlorides, yet more reactive than the corresponding esters and amides . In fact, acyl fluorides are isolable using column chromatography on silica gel and can be used without any special precautions against moisture.…”

Nickel-Catalyzed Reduction of Secondary and Tertiary Amides

“…1–4 Interest in this field has been driven in part by the stability of amides and their consequential promise for applications in multistep synthesis. 5,6 The high abundance, low cost, and minimal CO 2 footprint associated with nickel also render these transformations highly attractive.…”

Transition‐Metal‐Catalyzed Decarbonylative Coupling Reactions: Concepts, Classifications, and Applications

“…Following the recent breakthrough on acyl C−N bond activation and functionalization by nickel catalysis, an intriguing decarbonylative cross‐coupling of amides with boronic acids was reported by Szostak and co‐workers . It is worth noting that the utilization of a sterically distorted amide was the key to success for this Suzuki–Miyaura type cross‐coupling, resulting in 83 % yield of the desired product, while the use of less distorted amides gave rather unsatisfactory results (Scheme ).…”