The electrophilic fluorination of enol esters using SelectFluor: a polar two-electron process

Susanna H. Wood, Stephen Etridge, Alan R. Kennedy, Jonathan M. Percy, David J. Nelson

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

The reaction of enol esters with SelectFluor is facile and leads to the corresponding α-fluoroketones under mild conditions and, as a result, this route is commonly employed for the synthesis of medicinally important compounds such as fluorinated steroids. However, despite the use of this methodology in synthesis, the mechanism of this reaction and the influence of structure on reactivity are unclear. We present a rigorous mechanistic study of the fluorination of these substrates, informed primarily by detailed and robust kinetic experiments. The results of this study implicate a polar two-electron process via an oxygen-stabilised carbenium species, rather than a single-electron process involving radical intermediates. The structure/reactivity relationships revealed here will assist synthetic chemists in deploying this type of methodology in the syntheses of α-fluoroketones
LanguageEnglish
Pages5574-5585
Number of pages12
JournalChemistry - A European Journal
Volume25
Issue number21
Early online date6 Feb 2019
DOIs
Publication statusPublished - 11 Apr 2019

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Fluorination
Esters
Fluorinated Steroids
Electrons
Oxygen
Kinetics
Substrates
selectfluor
Experiments

Keywords

  • SelectFluor
  • electrophilic fluorination
  • enol esters
  • kinetic experiments
  • oxygen-stabilised carbenium species

Cite this

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abstract = "The reaction of enol esters with SelectFluor is facile and leads to the corresponding α-fluoroketones under mild conditions and, as a result, this route is commonly employed for the synthesis of medicinally important compounds such as fluorinated steroids. However, despite the use of this methodology in synthesis, the mechanism of this reaction and the influence of structure on reactivity are unclear. We present a rigorous mechanistic study of the fluorination of these substrates, informed primarily by detailed and robust kinetic experiments. The results of this study implicate a polar two-electron process via an oxygen-stabilised carbenium species, rather than a single-electron process involving radical intermediates. The structure/reactivity relationships revealed here will assist synthetic chemists in deploying this type of methodology in the syntheses of α-fluoroketones",
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The electrophilic fluorination of enol esters using SelectFluor : a polar two-electron process. / Wood, Susanna H.; Etridge, Stephen; Kennedy, Alan R.; Percy, Jonathan M.; Nelson, David J.

In: Chemistry - A European Journal, Vol. 25, No. 21, 11.04.2019, p. 5574-5585.

Research output: Contribution to journalArticle

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T1 - The electrophilic fluorination of enol esters using SelectFluor

T2 - Chemistry - A European Journal

AU - Wood, Susanna H.

AU - Etridge, Stephen

AU - Kennedy, Alan R.

AU - Percy, Jonathan M.

AU - Nelson, David J.

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AB - The reaction of enol esters with SelectFluor is facile and leads to the corresponding α-fluoroketones under mild conditions and, as a result, this route is commonly employed for the synthesis of medicinally important compounds such as fluorinated steroids. However, despite the use of this methodology in synthesis, the mechanism of this reaction and the influence of structure on reactivity are unclear. We present a rigorous mechanistic study of the fluorination of these substrates, informed primarily by detailed and robust kinetic experiments. The results of this study implicate a polar two-electron process via an oxygen-stabilised carbenium species, rather than a single-electron process involving radical intermediates. The structure/reactivity relationships revealed here will assist synthetic chemists in deploying this type of methodology in the syntheses of α-fluoroketones

KW - SelectFluor

KW - electrophilic fluorination

KW - enol esters

KW - kinetic experiments

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