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A DFT Study of the Molecular Mechanisms of the Nucleophilic Addition of Ester‐Derived Lithium Enolates and Silyl Ketene Acetals to Nitrones: Effects of the Lewis Acid Catalyst
Author(s) -
Domingo Luis R.,
Arnó Manuel,
Merino Pedro,
Tejero Tomás
Publication year - 2006
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.200600105
Subject(s) - ketene , chemistry , silylation , cycloaddition , nucleophile , electrophile , lewis acids and bases , regioselectivity , nitrone , nucleophilic addition , medicinal chemistry , lithium (medication) , catalysis , organic chemistry , medicine , endocrinology
The molecular mechanisms for the nucleophilic addition of lithium enolates and silyl ketene acetals to nitrones in the absence and in the presence of a Lewis acid (LA) catalyst to give isoxazolidin‐5‐ones or hydroxylamines have been investigated by DFT methods at the B3LYP/6‐31G* level. The addition of lithium enolates to nitrones gives the corresponding hydroxylamines, while the addition of silyl ketene acetals affords isoxazolidin‐5‐ones through a concerted 1,3‐dipolar cycloaddition. The addition of the silyl ketene acetals to LA‐coordinated nitrones yields isoxazolidin‐5‐ones by a polar concerted cycloaddition or a stepwise nucleophilic attack via zwitterionic intermediates. A silyl migration on the [3+2] cycloadduct yields the corresponding O ‐silylhydroxylamine. An analysis of the global electrophilicity of the reagents accounts for the strong electrophile activation of the LA‐coordinated nitrone, and the analysis of the local indices leads to an explanation for the experimentally observed regioselectivity. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)