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Synthesis of Chromen[4,3‐ b ]pyrrolidines by Intramolecular 1,3‐Dipolar Cycloadditions of Azomethine Ylides: An Experimental and Computational Assessment of the Origin of Stereocontrol
Author(s) -
Costa Paulo R. R.,
Sansano José M.,
Cossío Unai,
Barcellos Julio C. F.,
Dias Ayres G.,
Nájera Carmen,
Arrieta Ana,
de Cózar Abel,
Cossío Fernando P.
Publication year - 2015
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.201500434
Subject(s) - chemistry , pyrrolidine , intramolecular force , cycloaddition , ring (chemistry) , imine , epimer , stereoselectivity , 1,3 dipolar cycloaddition , stereochemistry , nitrogen atom , computational chemistry , organic chemistry , catalysis
Azomethine ylides, generated from imine‐derived O ‐cinnamyl or O ‐crotonyl salicylaldeyde and α‐amino acids, undergo intramolecular 1,3‐dipolar cycloaddition, leading to chromene[4,3‐ b ]pyrrolidines. Two reaction conditions are used: (a) microwave‐assisted heating (200 W, 185 °C) of a neat mixture of reagents, and (b) conventional heating (170 °C) in PEG‐400 as solvent. In both cases, a mixture of two epimers at the α‐position of the nitrogen atom in the pyrrolidine nucleus was formed through the less energetic endo ‐approach (B/C ring fusion). In many cases, the formation of the stereoisomer bearing a trans ‐arrangement into the B/C ring fusion was observed in high proportions. Comprehensive computational and kinetic simulation studies are detailed. An analysis of the stability of transient 1,3‐dipoles, followed by an assessment of the intramolecular pathways and kinetics are also reported.