N-C Axially Chiral Compounds with an ortho-Fluoro Substituent and Steric Discrimination between Hydrogen and Fluorine Atoms Based on a Diastereoselective Model Reaction

Asumi Iida, Mizuki Matsuoka, Hiroshi Hasegawa, Nicolas Vanthuyne, Daniel Farran, Christian Roussel, Osamu Kitagawa

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

The fluorine atom is the second smallest atom; nevertheless, the ortho-fluoro group may lead to stable N-aryl atropisomers when the steric demand of the flanking substituents is large enough. 2-Alkyl-3-(2-fluorophenyl)quinazolin-4-ones and 3-(2-fluorophenyl)-4-methylthiazoline-2-thione were found to be the first N-aryl axially chiral compounds bearing an ortho-fluoro group whose enantiomers were isolated at ambient temperature. The reaction of alkyl halides with the anionic species prepared from 2-ethyl-3-(2-fluorophenyl)quinazolin-4-one presenting an N-C axial chirality provided a model reaction for quantitative evaluation of the steric discrimination (slight difference of steric factor) between hydrogen and fluorine atoms. In the case of low steric demand (allylation reaction) no diastereoselectivity was detected, while in the case of high steric demand (isopropylation reaction) the diastereoselectivity became significant.

Original languageEnglish
Pages (from-to)3169-3175
Number of pages7
JournalJournal of Organic Chemistry
Volume84
Issue number6
DOIs
Publication statusPublished - 2019 Mar 15

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Fluorine
Hydrogen
Atoms
Bearings (structural)
Allylation
Thiones
Enantiomers
Chirality
Temperature
4-hydroxyquinazoline

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

N-C Axially Chiral Compounds with an ortho-Fluoro Substituent and Steric Discrimination between Hydrogen and Fluorine Atoms Based on a Diastereoselective Model Reaction. / Iida, Asumi; Matsuoka, Mizuki; Hasegawa, Hiroshi; Vanthuyne, Nicolas; Farran, Daniel; Roussel, Christian; Kitagawa, Osamu.

In: Journal of Organic Chemistry, Vol. 84, No. 6, 15.03.2019, p. 3169-3175.

Research output: Contribution to journalArticle

Iida, Asumi ; Matsuoka, Mizuki ; Hasegawa, Hiroshi ; Vanthuyne, Nicolas ; Farran, Daniel ; Roussel, Christian ; Kitagawa, Osamu. / N-C Axially Chiral Compounds with an ortho-Fluoro Substituent and Steric Discrimination between Hydrogen and Fluorine Atoms Based on a Diastereoselective Model Reaction. In: Journal of Organic Chemistry. 2019 ; Vol. 84, No. 6. pp. 3169-3175.
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abstract = "The fluorine atom is the second smallest atom; nevertheless, the ortho-fluoro group may lead to stable N-aryl atropisomers when the steric demand of the flanking substituents is large enough. 2-Alkyl-3-(2-fluorophenyl)quinazolin-4-ones and 3-(2-fluorophenyl)-4-methylthiazoline-2-thione were found to be the first N-aryl axially chiral compounds bearing an ortho-fluoro group whose enantiomers were isolated at ambient temperature. The reaction of alkyl halides with the anionic species prepared from 2-ethyl-3-(2-fluorophenyl)quinazolin-4-one presenting an N-C axial chirality provided a model reaction for quantitative evaluation of the steric discrimination (slight difference of steric factor) between hydrogen and fluorine atoms. In the case of low steric demand (allylation reaction) no diastereoselectivity was detected, while in the case of high steric demand (isopropylation reaction) the diastereoselectivity became significant.",
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AU - Hasegawa, Hiroshi

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AU - Roussel, Christian

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AB - The fluorine atom is the second smallest atom; nevertheless, the ortho-fluoro group may lead to stable N-aryl atropisomers when the steric demand of the flanking substituents is large enough. 2-Alkyl-3-(2-fluorophenyl)quinazolin-4-ones and 3-(2-fluorophenyl)-4-methylthiazoline-2-thione were found to be the first N-aryl axially chiral compounds bearing an ortho-fluoro group whose enantiomers were isolated at ambient temperature. The reaction of alkyl halides with the anionic species prepared from 2-ethyl-3-(2-fluorophenyl)quinazolin-4-one presenting an N-C axial chirality provided a model reaction for quantitative evaluation of the steric discrimination (slight difference of steric factor) between hydrogen and fluorine atoms. In the case of low steric demand (allylation reaction) no diastereoselectivity was detected, while in the case of high steric demand (isopropylation reaction) the diastereoselectivity became significant.

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