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.
Zhang et al. (Thu,) studied this question.