Stereochemistry of Nucleophilic Substitution Reactions Depending upon Substituent

Evidence for Electrostatic Stabilization of Pseudoaxial Conformers of Oxocarbenium Ions by Heteroatom Substituents

Leticia Ayala, Claudia G. Lucero, Jan Antoinette, C. Romero, Sarah A. Tabacco, Keith Woerpel

Research output: Contribution to journalArticle

Abstract

Lewis acid-mediated nucleophilic substitution reactions of substituted tetrahydropyran acetates reveal that the conformational preferences of six-membered-ring cations depend significantly upon the electronic nature of the substituent. Nucleophilic substitutions of C-3 and C-4 alkyl-substituted tetrahydropyran acetates proceeded via pseudoequatorially substituted oxocarbenium ions, as would be expected by consideration of steric effects. Substitutions of C-3 and C-4 alkoxy-substituted tetrahydropyran acetates, however, proceeded via pseudoaxially oriented oxocarbenium ions. The unusual selectivities controlled by the alkoxy groups were demonstrated for a range of other heteroatom substituents, including nitrogen, fluorine, chlorine, and bromine. It is believed that the pseudoaxial conformation is preferred in the ground state of the cation because of an electrostatic attraction between the cationic carbon center of the oxocarbenium ion and the heteroatom substituent. This analysis is supported by the observation that selectivity diminishes down the halogen series, which is inconsistent with electron donation as might be expected during anchimeric assistance. The C-2 heteroatom-substituted systems gave moderately high 1,2-cis selectivity, while small alkyl substituents showed no selectivity. Only in the case of the tert-butyl group at C-2 was high 1,2-trans selectivity observed. These studies reinforce the idea that ground-state conformational effects need to be considered along with steric approach considerations.

Original languageEnglish (US)
Pages (from-to)15521-15528
Number of pages8
JournalJournal of the American Chemical Society
Volume125
Issue number50
DOIs
StatePublished - Dec 17 2003

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Stereochemistry
Static Electricity
Electrostatics
Acetates
Substitution reactions
Stabilization
Ions
Ground state
Cations
Positive ions
Bromine
Lewis Acids
Halogens
Fluorine
Chlorine
Conformations
Nitrogen
Carbon
Electrons
Acids

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Stereochemistry of Nucleophilic Substitution Reactions Depending upon Substituent : Evidence for Electrostatic Stabilization of Pseudoaxial Conformers of Oxocarbenium Ions by Heteroatom Substituents. / Ayala, Leticia; Lucero, Claudia G.; Antoinette, Jan; Romero, C.; Tabacco, Sarah A.; Woerpel, Keith.

In: Journal of the American Chemical Society, Vol. 125, No. 50, 17.12.2003, p. 15521-15528.

Research output: Contribution to journalArticle

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abstract = "Lewis acid-mediated nucleophilic substitution reactions of substituted tetrahydropyran acetates reveal that the conformational preferences of six-membered-ring cations depend significantly upon the electronic nature of the substituent. Nucleophilic substitutions of C-3 and C-4 alkyl-substituted tetrahydropyran acetates proceeded via pseudoequatorially substituted oxocarbenium ions, as would be expected by consideration of steric effects. Substitutions of C-3 and C-4 alkoxy-substituted tetrahydropyran acetates, however, proceeded via pseudoaxially oriented oxocarbenium ions. The unusual selectivities controlled by the alkoxy groups were demonstrated for a range of other heteroatom substituents, including nitrogen, fluorine, chlorine, and bromine. It is believed that the pseudoaxial conformation is preferred in the ground state of the cation because of an electrostatic attraction between the cationic carbon center of the oxocarbenium ion and the heteroatom substituent. This analysis is supported by the observation that selectivity diminishes down the halogen series, which is inconsistent with electron donation as might be expected during anchimeric assistance. The C-2 heteroatom-substituted systems gave moderately high 1,2-cis selectivity, while small alkyl substituents showed no selectivity. Only in the case of the tert-butyl group at C-2 was high 1,2-trans selectivity observed. These studies reinforce the idea that ground-state conformational effects need to be considered along with steric approach considerations.",
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