Copper-Catalyzed Enantioconvergent Radical <i>N</i>-Alkylation of Diverse (Hetero)aromatic Amines
Xuan‐Yi Du, Jia‐Heng Fang, Ji‐Jun Chen, Boming Shen, Weilong Liu, Jia‐Yong Zhang, Xue-Man Ye, Ning‐Yuan Yang, Qiang‐Shuai Gu, Zhong‐Liang Li, Peiyuan Yu, Xin‐Yuan Liu
Abstract
The 3d transition metal-catalyzed enantioconvergent radical cross-coupling provides a powerful tool for chiral molecule synthesis. In the classic mechanism, the bond formation relies on the interaction between nucleophile-sequestered metal complexes and radicals, limiting the nucleophile scope to sterically uncongested ones. The coupling of sterically congested nucleophiles poses a significant challenge due to difficulties in transmetalation, restricting the reaction generality. Here, we describe a probable outer-sphere nucleophilic attack mechanism that circumvents the challenging transmetalation associated with sterically congested nucleophiles. This strategy enables a general copper-catalyzed enantioconvergent radical N -alkylation of aromatic amines with secondary/tertiary alkyl halides and exhibits catalyst-controlled stereoselectivity. It accommodates diverse aromatic amines, especially bulky secondary and primary ones to deliver value-added chiral amines (>110 examples). It is expected to inspire the coupling of more nucleophiles, particularly challenging sterically congested ones, and accelerate reaction generality.