Copper(II)-Mediated Intermolecular C(sp²)–H Amination of Benzamides with Electron-Rich Anilines

Abstract

Despite significant progress, copper-catalyzed/mediated C-H amination reactions with electron-rich anilines remain an unsolved problem due to catalyst deactivation and deleterious side reactions. Herein, we report a copper(II)-mediated C(sp(2))-H amination of benzamides with electronically neutral or electron-rich anilines. A dramatic influence of silver(I) and tetrabutylammonium bromide was observed on the reaction outcome. The present protocol also demonstrates the synthesis of a number of nonsteroidal anti-inflammatory drugs.

A comprehensive overview of directing groups applied in metal-catalysed C–H functionalisation chemistry

“…A broad range of substrates with different substitution patterns was functionalised and the synthetic utility of this transformation was further demonstrated by the gram scale synthesis of a bioactive compound, namely mefenamic acid. 446 Worth to mention that an extension to heteroaryls as coupling partners was reported by Punniyamurthy also relying on a Cu-mediated transformation. 447 …”

Ligand‐Promoted Rhodium(III)‐Catalyzed ortho‐C−H Amination with Free Amines

“…The successful use of N ‐alkyl anilines prompted us to examine the compatibility of this reaction with free anilines. Transition‐metal‐catalyzed aminations of arenes with primary amines have been developed using several systems . However, only few examples with electron‐rich anilines have been reported.…”

“…However, only few examples with electron‐rich anilines have been reported. The groups of Daugulis and Jana recently disclosed copper‐mediated, bidentate‐auxiliary‐directed aminations with electron‐rich anilines. We were pleased to observe that the present amination conditions were compatible with a wide range of anilines in the reaction of 1 a (Table ).…”

Recent Advances in Transition-Metal-Catalyzed, Directed Aryl C–H/N–H Cross-Coupling Reactions

“…Other directing groups, such as the 8-aminoquinoline auxiliary, have been investigated for copper-mediated cross-dehydrogenative couplings, which have improved both the catalyst loading and the reaction conditions. [32][33][34] The most general procedure was reported by Daugulis and co-workers, who showed that a wide range of secondary amines could be coupled with 8-aminoquinoline-derived benzamides with catalyst loadings as low as 10 mol% and at reaction temperatures of typically 110 °C (Scheme 14). 32 Milder conditions have been achieved by further modification of both the aryl substituent and directing group.…”