Epimerization in Intramolecular Carbanilide Cyclization to Hydantoins: A Computational Study

An efficient and diastereoselective route for the synthesis of 2,5,6,7-tetrasubstituted-1H-pyrrolo[1,2-c]imidazoles has been developed using intramolecular azomethine ylide cycloaddition and carbanilide cyclization. Ab initio calculations at the 6-31G (d,p) basis set reveal that the thermal stabilit...

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Bibliographic Details
Published in:Bulletin of the Chemical Society of Japan 2002-11, Vol.75 (11), p.2477-2480
Main Authors: Gong, Young-Dae, Kim, Soo-Kyung, Yoo, Sung-eun, Kurth, Mark J
Format: Article
Language:English
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Summary:An efficient and diastereoselective route for the synthesis of 2,5,6,7-tetrasubstituted-1H-pyrrolo[1,2-c]imidazoles has been developed using intramolecular azomethine ylide cycloaddition and carbanilide cyclization. Ab initio calculations at the 6-31G (d,p) basis set reveal that the thermal stability of diastereomers determine the epimerization during the intramolecular carbanilide cyclization (→ hydantoin). These stereochemical results are consistent with an endo-like cycloaddition of a trans,anti-azomethine ylide followed by base-mediated C7a-H epimerization (C7a-Hβ → C7a-Hα) to deliver the thermodynamically preferred trans,anti,trans-(Ha-Hb, Hb-Hc, Hc-Hd)-pyrrolidine stereochemistry (3) which is ca. 20.1 kJ/mol more stable than the trans,anti,cis-pyrrolidine stereochemistry. In the case of 2-hydroxy-1-naphthaldehyde, naphthalene ring steric effects result in a different stereochemical arrangement about each pyrrolidine ring.
ISSN:0009-2673
1348-0634
DOI:10.1246/bcsj.75.2477