Synthesis and Elaboration of All‐<i>cis</i>‐1,2,4,5‐Tetrafluoro‐3‐Phenylcyclohexane: A Polar Cyclohexane Motif

Durie, Alastair J.; Fujiwara, Tomoya; Cormanich, Rodrigo A.; Bühl, Michæl; Slawin, Alexandra M. Z.; O’Hagan, David

doi:10.1002/chem.201400354

Cited by 24 publications

(38 citation statements)

References 37 publications

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“…Treatment of dipoxide 14 with the more basic Et 3 N.3HF reagent, gave a more predictable outcome and this reaction furnished a mixture of inseparable difluoro diols 19 and 20 in 2.8:1 ratio as illustrated in Scheme 4 [4,5,21]. Under the latter conditions rearranged product 18 was not detected.…”

Section: Methodsmentioning

confidence: 97%

“…We have recently introduced all-cis phenyl-2,3,5,6-tetrafluorocyclohexane 1 as the starting point for the synthesis of a diversity of products 2 carrying a tetrafluorocyclohexyl motif with four fluorine up [1][2][3][4][5][6]. The diversity emerges as the aromatic ring of 1 can be modified by a range of standard electrophilic aromatic substitution reactions [4,6].…”

Section: Introductionmentioning

confidence: 99%

“…The diversity emerges as the aromatic ring of 1 can be modified by a range of standard electrophilic aromatic substitution reactions [4,6]. This gives rise to products 2 that contain a unique motif which has four fluorine atoms on one face of a cyclohexane and offers a facially polarized ring, the properties of which appear unique and remain to be fully explored in medicinal and agrochemical discovery programmes.…”

Section: Introductionmentioning

confidence: 99%

“…This gives rise to products 2 that contain a unique motif which has four fluorine atoms on one face of a cyclohexane and offers a facially polarized ring, the properties of which appear unique and remain to be fully explored in medicinal and agrochemical discovery programmes. Compound 1 was prepared in a synthesis protocol starting with a Birch reduction of biphenyl 3 to give diene 4 [7][8][9] followed by diepoxidation with mCPBA to generate diepoxide 5 [4,5]. This diepoxide was then treated with 3HF.NEt 3 and converted to inseparable diols 6 and 7.…”

Section: Introductionmentioning

confidence: 99%

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Synthesis of selectively fluorinated cyclohexanes: The observation of phenonium rearrangements during deoxyfluorination reactions on cyclohexane rings with a vicinal phenyl substituent

Bykova

Al‐Maharik

Slawin

et al. 2015

Journal of Fluorine Chemistry

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A study focused on the synthesis of a derivative of all-cis phenyl-2,3,5,6-tetrafluorocyclohexane, incorporating a methyl group at the benzylic position, found that the fluorination reactions of diepoxide and diol precursors, were susceptible to rearrangement and unexpected products. The origin of these rearranged products can be rationalised by aryl migrations occurring via phenonium ion intermediates, in adventitious pathways occurring during deoxofluorination reactions with hydrogen fluoride reagents.We dedicate this paper to Professor Veronique Gouverneur in recognition of her 2015 ACS Award for Creative work in Fluorine Chemistry.

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Section: Methodsmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Synthesis of selectively fluorinated cyclohexanes: The observation of phenonium rearrangements during deoxyfluorination reactions on cyclohexane rings with a vicinal phenyl substituent

Bykova

Al‐Maharik

Slawin

et al. 2015

Journal of Fluorine Chemistry

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“…2). These C-H···π interactions are a feature of the solid state packing found in phenyl derivatives of 2 [29]. …”

Section: Resultsmentioning

confidence: 99%

Organofluorine chemistry: Difluoromethylene motifs spaced 1,3 to each other imparts facial polarity to a cyclohexane ring

Jones¹,

Callejo²,

Slawin³

et al. 2016

Beilstein J. Org. Chem.

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2,2-Dimethyl-5-phenyl-1,1,3,3-tetrafluororocyclohexane has been prepared and characterised as an example of a facially polarised cyclohexane containing 1,3 related CF2 groups. The dipolar nature of the ring arises from the axial orientation of two of the C–F bonds pointing in the same direction, and set by the chair conformation of the cyclohexane. This electrostatic profile is revealed experimentally both in the solid-state (X-ray) packing of the rings and by solution (NMR) in different solvents. A computationally derived electrostatic profile of this compound is consistent with a more electronegative and a more electropositive face of the cyclohexane ring. This placing of CF2 groups 1,3 to each other in a cyclohexane ring is introduced as a new design strategy which could be applicable to the preparation of polar hydrophobic cyclohexane motifs.

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Influence of Fluorination on the Conformational Properties and Hydrogen‐Bond Acidity of Benzyl Alcohol Derivatives

Bogdan

Compain

Mtashobya

et al. 2015

Chemistry A European J

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The effect of fluorination on the conformational and hydrogen-bond (HB)-donating properties of a series of benzyl alcohols has been investigated experimentally by IR spectroscopy and theoretically with quantum chemical methods (ab initio (MP2) and DFT (MPWB1K)). It was found that o-fluorination generally resulted in an increase in the HB acidity of the hydroxyl group, whereas a decrease was observed upon o,o′-difluorination. Computational analysis showed that the conformational landscapes of the title compounds are strongly influenced by the presence of o-fluorine atoms. Intramolecular interaction descriptors based on AIM, NCI and NBO analyses reveal that, in addition to an intramolecular OH⋅⋅⋅F interaction, secondary CH⋅⋅⋅F and/or CH⋅⋅⋅O interactions also occur, contributing to the stabilisation of the various conformations, and influencing the overall HB properties of the alcohol group. The benzyl alcohol HB-donating capacity trends are properly described by an electrostatic potential based descriptor calculated at the MPWB1K/6-31+G(d,p) level of theory, provided solvation effects are taken into account for these flexible HB donors.

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Synthesis and Elaboration of All‐cis‐1,2,4,5‐Tetrafluoro‐3‐Phenylcyclohexane: A Polar Cyclohexane Motif

Cited by 24 publications

References 37 publications

Synthesis of selectively fluorinated cyclohexanes: The observation of phenonium rearrangements during deoxyfluorination reactions on cyclohexane rings with a vicinal phenyl substituent

Synthesis of selectively fluorinated cyclohexanes: The observation of phenonium rearrangements during deoxyfluorination reactions on cyclohexane rings with a vicinal phenyl substituent

Organofluorine chemistry: Difluoromethylene motifs spaced 1,3 to each other imparts facial polarity to a cyclohexane ring

Influence of Fluorination on the Conformational Properties and Hydrogen‐Bond Acidity of Benzyl Alcohol Derivatives

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