Iridium(III)-Catalyzed Direct Intermolecular Chemoselective α-Amidation of Masked Aliphatic Carboxylic Acids with Dioxazolones via Nitrene Transfer

Abstract

The Ir(III)-catalyzed direct α-C−H amidation of imidazole-masked aliphatic carboxylic acids with dioxazolones is reported. The presence of an imidazole moiety as a directing group is a key to the success of the reaction. The products can be easily converted to esters and amides in a simple procedure. The reaction shows a broad substrate scope for various substituted 2acylimidazoles, as well as a variety of dioxazolone derivatives with important functional groups being tolerated. The reaction mechanism was investigated by deuterium-labeling experiments, Hammett plots, NMR, and FAB-MS, and we propose the generation of an iridium nitrene intermediate.

Theoretical Study on Ir-Catalyzed α-Amidation of 2-Acylimidazoles: Mechanism and Insertion Selectivity

“…In other words, this synthesis strategy via nitrene insertion can be applied to the construction of quaternary amides. On the other hand, the barrier of TS2 Me is apparently higher than that of TS2 (21.3 vs 18.1 kcal/mol), in agreement with an experimentally lower amidation yield of di- vs monosubstituted substrates (31% vs 96%) . As shown in Figure b, the being broken Ir···C α bond in TS2 Me is more elongated to avoid the large steric congestion from the quaternary C α group.…”

Carboxylate-Assisted Iridium (III)-Catalyzed C(sp2)–H Amidation of 2-Aroylimidazoles With Dioxazolones

“…However, there are still a few drawbacks, such as the inapplicability of using a heterocyclic system, difficulties associated with removing the directing group, limited substrate scope, and the use of stoichiometric amounts of catalysts or oxidants . These limitations encouraged us to use an easily removable imidazole directing group that we recently developed , in the ortho C–H amidation with dioxazolones. Despite the remarkable progress made on C–H amidation with dioxazolones, the use of imidazole-masked carboxylic acids in the ortho C–H amidation would be interesting because it has long been known that 2-acylimidazoles are easily converted into the corresponding carboxylic acids, esters, amides, and thioesters .…”

“…These limitations encouraged us to use an easily removable imidazole directing group that we recently developed , in the ortho C–H amidation with dioxazolones. Despite the remarkable progress made on C–H amidation with dioxazolones, the use of imidazole-masked carboxylic acids in the ortho C–H amidation would be interesting because it has long been known that 2-acylimidazoles are easily converted into the corresponding carboxylic acids, esters, amides, and thioesters . We herein report the Ir­(III)-catalyzed C­(sp 2 )–H amidation of 2-aroylimidazoles with 3-aryldioxazolones.…”

Chain Walking as a Strategy for Iridium-Catalyzed Migratory Amidation of Alkenyl Alcohols to Access α-Amino Ketones

“…The vast majority of current strategies often rely on laborious approaches to construct the C–N bonds from carbonyl synthons (Scheme a). − One classical route is the amination of α-halogenated carbonyls via an S N 2-type pathway; − however, this method requires prefunctionalized carbonyl starting materials. , Furthermore, this approach is most efficient with secondary amines and cannot be extended to other synthetically versatile N-nucleophiles such as amides and carbamates, thus limiting the scope of accessible products . On the other hand, a polarity reversal of reacting components has expanded the repertoire of retrosynthetic strategies in the carbonyl α-aminations. − Indeed, the catalytic activity in this electrophilic amination has been improved to introduce various N-electrophiles, such as azodicarboxylates, , nitroso, , or sulfonyliminoiodinane reagents. − However, to achieve a satisfactory level of umpolung reactivity, a stoichiometric amount of pregenerated silyl enol ethers is generally utilized, − although in situ enolization procedures are also available under acidic conditions albeit with limited scope and low functional group compatibility. − In this context, the development of a multifaceted catalytic system that can readily utilize abundant feedstock starting materials with high functional group compatibility would be highly appealing.…”