Premium
Catalytic Asymmetric Five‐Component Tandem Reaction: Diastereo‐ and Enantioselective Synthesis of Densely Functionalized Tetrahydropyridines with Biological Importance
Author(s) -
Shi Feng,
Tan Wei,
Zhu RenYi,
Xing GuiJuan,
Tu ShuJiang
Publication year - 2013
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.201300001
Subject(s) - chemistry , enantioselective synthesis , stereocenter , tandem , catalysis , cascade reaction , imine , combinatorial chemistry , organocatalysis , organic chemistry , component (thermodynamics) , materials science , physics , composite material , thermodynamics
The first catalytic asymmetric five‐component tandem reactions of β‐keto esters, aromatic aldehydes and anilines have been established in the presence of a chiral phosphoric acid, affording densely functionalized tetrahydropyridines with concomitant generation of five σ bonds and two stereogenic centers in high diastereo‐ and enantioselectivities (up to >99:1 dr , 95:5 er ). In addition, the first isolation and preparation of a diene species as the key intermediate of the reaction has been successfully realized, leading to the formation of the desired tetrahydropyridine via further condensation with in situ generated imine, which supported the proposed tandem [4+2] reaction pathway to some extent. This protocol not only represents the first enantioselective example of this five‐component tandem reaction, but also provides an unprecedented access to enantioenriched tetrahydropyridines with structural diversity, which holds great potential in medicinal chemistry.