TY - JOUR
T1 - Epimerization in intramolecular carbanilide cyclization to hydantoins
T2 - A computational study
AU - Gong, Young Dae
AU - Kim, Soo Kyung
AU - Yoo, Sung eun
AU - Kurth, Mark J.
PY - 2002
Y1 - 2002
N2 - 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.
AB - 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.
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U2 - 10.1246/bcsj.75.2477
DO - 10.1246/bcsj.75.2477
M3 - Article
AN - SCOPUS:0036906271
VL - 75
SP - 2477
EP - 2480
JO - Bulletin of the Chemical Society of Japan
JF - Bulletin of the Chemical Society of Japan
SN - 0009-2673
IS - 11
ER -