The iron-catalyzed reaction enables high-yield enantioselective alkylation of α-imino esters with unactivated alkyl halides, suggesting broad applications.
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.
No takes yet. Share an insight, caveat, or question.
Bai et al. (2025) studied this question.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: