Twisted Amides: From Obscurity to Broadly Useful Transition‐Metal‐Catalyzed Reactions by N−C Amide Bond Activation

Abstract

The concept of using amide bond distortion to modulate amidic resonance has been known for more than 75 years. Two classic twisted amides (bridged lactams) ingeniously designed and synthesized by Kirby and Stoltz to feature fully perpendicular amide bonds, and as a consequence emanate amino-ketone-like reactivity, are now routinely recognized in all organic chemistry textbooks. However, only recently the use of amide bond twist (distortion) has advanced to the general organic chemistry mainstream enabling a host of highly attractive N-C amide bond cross-coupling reactions of broad synthetic relevance. In this Minireview, we discuss recent progress in this area and present a detailed overview of the prominent role of amide bond destabilization as a driving force in the development of transition-metal-catalyzed cross-coupling reactions by N-C bond activation.

2‐Methyltetrahydrofuran (2‐MeTHF): A Green Solvent for Pd−NHC‐Catalyzed Amide and Ester Suzuki‐Miyaura Cross‐Coupling by N−C/O−C Cleavage

“…[1][2][3] 2-MeTHF has been regarded as a very attractive solvent for organometallic reactions. [1][2][3] 2-MeTHF has been regarded as a very attractive solvent for organometallic reactions.…”

“…[3,8] It should be noted that the acyl-cross-coupling manifold is fundamentally different from decarbonylative cross-coupling amides. Thus, this green protocol allows one to take advantage of different amide bond precursors and activation mechanisms.…”

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 .…”

Synthesis of Symmetric and Unsymmetric Secondary Amines from the Ligand-Promoted Ruthenium-Catalyzed Deaminative Coupling Reaction of Primary Amines

“…4 A few remarkably efficient amide-to-ester conversion methods via amide C–N bond cleavage have been achieved by using Ni catalysts. 5 A number of Pd-catalyzed C–N cleavage methods have also been developed, including intramolecular Heck-type coupling reactions 6 and allylamine coupling reactions. 7 Selective catalytic C–C coupling methods via sp 3 C–N bond activation of allyl- and benzylic amines have been achieved.…”