Direct Asymmetric Aza-Vinylogous-Type Michael Additions of Nitrones from Isatins to Nitroalkenes.
Nitrones commonly act as 1,3-dipoles and electrophiles to furnish valuable isoxazolidine and N-hydroxyl products, respectively. They also can be converted to nitrone ylide species and undergo [3+2] formal cycloadditions to access N-hydroxyl pyrrolidines. Here, asymmetric direct aza-vinylogous-type additions of nitrones from isatins to nitroalkenes are presented, catalyzed by a bifunctional thiourea-tertiary amine, affording highly functionalized nitrones with extended carbon skeletons in excellent stereoselectivity. Notably, the nitrone moiety can be easily removed, thus furnishing the formal asymmetric α-functionalization of alkylamine-type substances. Moreover, the remaining electrophilic nitrone motif enables the subsequent annulations to construct spirocyclic products in high molecular complexity and diversity, which might have potential applications for drug discovery.
Department of Medicinal Chemistry, West China School of Pharmacy, Sichuan University, Chengdu, 610041, P. R. China.
Gu
G
Zhan
Department of Medicinal Chemistry, West China School of Pharmacy, Sichuan University, Chengdu, 610041, P. R. China.
Ming-Lin
ML
Shi
Department of Medicinal Chemistry, West China School of Pharmacy, Sichuan University, Chengdu, 610041, P. R. China.
Wei-Jia
WJ
Lin
College of Pharmacy, Third Military Medical University, Chongqing, 400038, P. R. China.
Qin
Q
Ouyang
Department of Medicinal Chemistry, West China School of Pharmacy, Sichuan University, Chengdu, 610041, P. R. China.
Wei
W
Du
Department of Medicinal Chemistry, West China School of Pharmacy, Sichuan University, Chengdu, 610041, P. R. China.|College of Pharmacy, Third Military Medical University, Chongqing, 400038, P. R. China.
Ying-Chun
http://orcid.org/0000-0003-1902-0979
YC
Chen
nitrones; organocatalysis; umpolung; vinylogous addition; α-functionalization of alkylamines