Copper-Catalyzed Asymmetric Three-Component Radical 1,2-Carboamination of Acrylamides with Arylamines: Access to Chiral α-Tertiary N-Arylamines

Abstract

The asymmetric radical carboamination of 1,1-disubstituted alkenes from readily available alkyl halides and arylamines provides expedient access to value-added chiral α-tertiary N-arylamines but has been less recognized. A challenge arises mainly from the difficult reaction initiation inherent in alkyl halides and the construction of fully substituted chiral C–N bonds from sterically congested tertiary alkyl radicals. Herein, we report a copper-catalyzed asymmetric three-component radical carboamination of acrylamides utilizing an anionic chiral N,N,N-ligand under mild conditions. This ligand was essential for the reaction initiation by enhancing the reducing capability of copper and enabling the enantiocontrol over tertiary alkyl radicals. The substrate scope was broad, covering an array of acrylamides, aryl- and heteroaryl-amines, as well as alkyl halides and sulfonyl chlorides, enabling good functional group tolerance. When combined with the follow-up transformation, this strategy provides a versatile platform for accessing structurally diverse chiral α-tertiary N-arylamine building blocks of interest in organic synthesis.