Directed Amination of Non‐Acidic Arene CH Bonds by a Copper–Silver Catalytic System

TLDR: The reaction is catalyzed by Cu(OAc)2 and a Ag2CO3 cocatalyst, and shows high generality and functional-group tolerance, as well as providing a straightforward means for the preparation of ortho-aminobenzoic acid derivatives.

Abstract: New methods for direct arylation, alkylation, and oxygenation of sp2 carbon-hydrogen bonds in directing-group containing benzenes have resulted in efficient synthetic routes to functionalized arenes.[1] In contrast, direct amination reactions that do not proceed via nitrenoid intermediates[2] are relatively rare. In most cases, palladium catalysis is used for aminations.[3a-p] Furthermore, majority of publications describe intramolecular C-N bond formation.[3a-i] Typically, protected amines or hydroxylamine derivatives are used to install nitrogen moiety. Simple amine coupling partners are employed only rarely. Several deprotonative, copper-catalyzed thiazole and oxazole aminations have been reported.[4b,c,e] Yu has reported a method for palladium-catalyzed benzamide amination by employing a removable auxiliary.[3k] We disclose here a method for an auxiliary-assisted amination of non-acidic benzamide β-C–H bonds and benzylamine derivative γ-C–H bonds that is catalyzed by copper(II) acetate.