A Modular and Diastereoselective 5+1 Cyclization Approach to N-(Hetero)Aryl Piperidines

Matthew A. Larsen, Elisabeth T. Hennessy, Madeleine C. Deem, Yu-hong Lam, Josep Sauri, Aaron C. Sather

Producció científica: Article en revista indexadaArticleAvaluat per experts

22 Cites (Scopus)

Resum

A new general de novo synthesis of pharmaceutically important N-(hetero)aryl piperidines is reported. This protocol uses a robustly diastereoselective reductive amination/aza-Michael reaction sequence to achieve rapid construction of complex polysubstituted ring systems starting from widely available heterocyclic amine nucleophiles and carbonyl electrophiles. Notably, the diastereoselectivity of this process is enhanced by the presence of water, and DFT calculations support a stereochemical model involving a facially selective protonation of a water-coordinated enol intermediate.
Idioma originalAnglès
Pàgines (de-a)726-732
Nombre de pàgines7
RevistaJournal of the American Chemical Society
Volum142
Número2
DOIs
Estat de la publicacióPublicada - 15 de gen. 2020
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