Chiral Isourea-Catalyzed Enantioselective Carbene Insertion into an N–H Bond through a Double Proton-Transfer Process
Abstract
The development of novel chiral catalysts and the discovery of new mechanisms remain central to the advancement of asymmetric catalysis. Chiral hydrogen-bond-donor (HBD) catalysts have proven to be effective for mediating asymmetric proton-transfer reactions and are therefore widely applied in enantioselective N-H bond insertions. Herein, inspired by biological processes, we report a class of chiral isourea catalysts that enable highly enantioselective amide N-H insertion with α-alkyl diazo esters. Mechanistic and computational studies uncovered an unprecedented double proton-transfer mechanism, which is brought about by the unique properties of the isourea catalyst and forms the basis for the catalyst's exceptional reactivity and enantioselectivity.
Fields of Study & Subjects
Cyclopropane Reaction Mechanisms
Synthesis and Catalytic Reactions
Asymmetric Synthesis and Catalysis
Publication details
- Journal / source
- Journal of the American Chemical Society
- Publisher
- American Chemical Society (ACS)
- Volume
- 148
- Issue
- 13
- Pages
- 13513–13519
- Publication date
- 27 March 2026
- Language
- EN