Enantioselective
CuH-Catalyzed Anti-Markovnikov Hydroamination
of 1,1-Disubstituted Alkenes

Barker T. J.; Barrett A. G. M.; Beller M.; Berman A. M.; Brinkmann C.; Bronner S. M.; Corberán R.; Czekelius C.; Côté A.; Enders V. D.; Erdik E.; Gant T. G.; Gonzalez A. Z.; Guin J.; Hesp K. D.; Horrillo-Martínez P.; Kumar K.; Lipshutz B. H.; Lipshutz B. H.; Lipshutz B. H.; Lu Z.; Mampreian D. M.; Martin N. J. A.; McIntyre S.; Miki Y.; Munro-Leighton C.; Müller T. E.; Nguyen T. M.; Nobis M.; Nugent T. C.; Reznichenko A. L.; Roseblade S. J.; Rucker R. P.; Ryu J.-S.; Shaolin Zhu; Stephen L. Buchwald; Takaya J.; Thomas S. P.; Utsunomiya M.; Utsunomiya M.; Wang B.; Xia Q.-H.; Zhang X.; Zhang Z. B.; Zhu S.

Enantioselective CuH-Catalyzed Anti-Markovnikov Hydroamination of 1,1-Disubstituted Alkenes

Abstract

Enantioselective synthesis of β-chiral amines has been achieved via copper-catalyzed hydroamination of 1,1-disubstituted alkenes with hydroxylamine esters in the presence of a hydrosilane. This mild process affords a range of structurally diverse β-chiral amines, including β-deuterated amines, in excellent yields with high enantioselectivities. Furthermore, catalyst loading as low as 0.4 mol% could be employed to deliver product in undiminished yield and selectivity, demonstrating the practicality of this method for large-scale synthesis