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Five‐Membered Nitrogen Heterocycles Synthesis through 1,3‐Dipolar Cycloaddition of Non‐Stabilized Azomethine Ylides with 2‐Pyridone Heteroaromatic Systems as Dipolarophiles
Author(s) -
Ben Salah Sami,
Sanselme Morgane,
Champavier Yves,
Othman Mohamed,
Daïch Adam,
Chataigner Isabelle,
Martin Lawson Ata
Publication year - 2021
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.202001404
Subject(s) - cycloaddition , chemistry , regioselectivity , pyrrolidine , azomethine ylide , adduct , 1,3 dipolar cycloaddition , catalysis , ring (chemistry) , stereochemistry , combinatorial chemistry , medicinal chemistry , organic chemistry
We report an efficient 1,3‐dipolar cycloaddition involving non‐stabilized electron‐rich azomethine ylides and diversely substituted 2‐pyridones bearing two potential C=C dipolarophilic sites. The 1,3‐dipoles were prepared in situ under TFA catalysis and cycloadditions were studied according to the nature of the pyridones and position of the various substituents. These reactions occur under mild conditions, and lead to the expected cycloadducts in good yields and full control of the regioselectivity. Furthermore, mono‐ or biscycloadditions were performed, leading to the formation of polycyclic scaffolds bearing biologically relevant pyrrolidine rings, prevalent in natural products. The diastereoselectivity of the second cycloaddition was fully controlled by the first addition, leading to heterocycles with a trans relative stereochemistry of the two generated rings in the final tricyclo‐adduct.