Native Amide‐Directed C(sp³)−H Amidation Enabled by Electron‐Deficient Rh^III Catalyst and Electron‐Deficient 2‐Pyridone Ligand

Abstract

Trivalent group-9 metal catalysts with a cyclopentadienyl-type ligand (CpM III ; M = Co, Rh, Ir, Cp = cyclopentadienyl) have been widely used for directed CÀ H functionalizations, albeit that their application to challenging C(sp 3 )À H functionalizations suffers from the limitations of the available directing groups. In this report, we describe directed C(sp 3 )À H amidation reactions of simple amide substrates with a variety of substituents. The combination of an electron-deficient Cp E Rh catalyst (Cp E = 1,3-bis(ethoxycarbonyl)-substituted Cp) and an electron-deficient 2-pyridone ligand is essential for high reactivity.

Triflic Acid-Promoted 1,2-Amino Migration Reactions in α-Arylaminoacrylamides: Access to Substituted β-Aminoamides

“…Kim and co-workers realized a directing group-assisted nickel-catalyzed intermolecular C­(sp 3 )-H amidation of carboxamides using TsN 3 as a nitrogen source as well as an internal oxidant (Scheme e) . Wakikawa and co-workers demonstrated that the combination of an electron-deficient Rh­(III) catalyst and an electron-deficient 2-pyridone ligand enabled amide-directed C­(sp 3 )-H amidation reactions using dioxazolone as a nitrogen source (Scheme e) . Alternatively, ring opening of β-lactams, oxazoles, or pyrazolones was reported to afford various β-aminoamides .…”

Native Amides as Enabling Vehicles for Forging sp3–sp3 Architectures via Interrupted Deaminative Ni-Catalyzed Chain-Walking

“…Driven by the prevalence of alkyl amines in a myriad of biologically relevant molecules and preclinical candidates, we wondered whether we could establish “ a la carte ” site-selective interrupted Ni-catalyzed deaminative chain-walking for forging sp 3 –sp 3 linkages at the always elusive methylene sp 3 C–H bonds with predictable and tunable selectivity by using weakly coordinating native amides (Scheme , bottom) . The choice of the latter is not arbitrary, as these ubiquitous motifs possess an electron-rich carbonyl fragment suitable for metal chelation without the need for decorating the amide backbone with strongly chelating quinoline or pyridine backbones, hence setting the basis for applying these techniques to advanced synthetic intermediates . As part of our interest in the field, we report herein the successful realization of this goal.…”