Iron-Catalyzed Asymmetric Cross-Electrophile Alkylation of Imines
Jiahao Bai, Qinglin Wang, Wenyu Zhao, Yiwen Shen, Yuquan Xin, Xianqing Wu, Jingping Qü, Yifeng Chen
Abstract
Transition metal-catalyzed asymmetric cross-electrophile coupling has emerged as a synthetically useful strategy for the stereoselective construction of a carbon–carbon bond. Herein, we report an iron-catalyzed enantioselective cross-electrophile alkylation of α-imino esters with unactivated alkyl halides by employing a chiral NPN ligand. This method delivers α-tetrasubstituted amino esters in high yields (up to 93%) and enantioselectivity (up to 97:3 er), accommodating diverse substrates, including primary, secondary, and tertiary alkyl iodides, with broad functional group tolerance. The system is extended to asymmetric benzylation using benzyl chlorides, yielding chiral phenylalanine derivatives bearing quaternary stereocenters (up to 97.5:2.5 er), including bioactive motifs. Mechanistic studies suggest alkyl radical intermediates and a low-valent iron catalytic cycle initiated by a single-electron transfer.