Catalytic Decarboxylative C−N Formation to Generate Alkyl, Alkenyl, and Aryl Amines

Abstract

Transition-metal-catalyzed sp² C-N bond formation is a reliable method for the synthesis of aryl amines. Catalytic sp³ C-N formation reactions have been reported occasionally, and methods that can realize both sp² and sp³ C-N formation are relatively unexplored. Herein, we address this challenge with a method of catalytic decarboxylative C-N formation that proceeds through a cascade carboxylic acid activation, acyl azide formation, Curtius rearrangement and nucleophilic addition reaction. The reaction uses naturally abundant organic carboxylic acids as carbon sources, readily prepared azidoformates as the nitrogen sources, and 4-dimethylaminopyridine (DMAP) and Cu(OAc)₂ as catalysts with as low as 0.1 mol % loading, providing protected alkyl, alkenyl and aryl amines in high yields with gaseous N₂ and CO₂ as the only byproducts. Examples are demonstrated of the late-stage functionalization of natural products and drug molecules, stereospecific synthesis of useful α-chiral alkyl amines, and rapid construction of different ureas and primary amines.