The University of Southampton
University of Southampton Institutional Repository

Influence of alcohol beta-fluorination on hydrogen-bond acidity of conformationally flexible substrates

Influence of alcohol beta-fluorination on hydrogen-bond acidity of conformationally flexible substrates
Influence of alcohol beta-fluorination on hydrogen-bond acidity of conformationally flexible substrates
Rational modulations of molecular interactions are of significant importance in compound properties optimization. We have previously shown that fluorination of conformationally rigid cyclohexanols leads to attenuation of their hydrogen-bond (H-bond) donating capacity (designated by pKAHY) when OH⋅⋅⋅F intramolecular hydrogen-bond (IMHB) interactions occur, as opposed to an increase in pKAHY due to the fluorine electronegativity. This work has now been extended to a wider range of aliphatic β-fluorohydrins with increasing degrees of conformational flexibility. We show that the observed differences in pKAHY between closely related diastereomers can be fully rationalized by subtle variations in populations of conformers able to engage in OH⋅⋅⋅F IMHB, as well as by the strength of these IMHBs. We also show that the Kenny theoretical Vα(r) descriptor of H-bond acidity accurately reflects the observed variations and a calibration equation extended to fluorohydrins is proposed. This work clearly underlines the importance of the weak OH⋅⋅⋅F IMHB in the modulation of alcohol H-bond donating capacity.
0947-6539
2811-2819
Graton, Jerome
a9189e35-d606-4adb-85b2-ad337a826dfb
Compain, Guillaume
f88510bf-ad1a-4a67-8855-43303979f2d0
Besseau, François
436e47fa-e4a7-4a44-b5e4-476eb04184d9
Bogdan, Elena
bd2b4c26-9ae0-42eb-8397-3c8d95f48060
Watts, Joe
5dd231c2-7940-4372-97d3-964491b48614
Mtashobya, Lewis
f0f16ba6-808d-4b55-9c10-3982c374685b
Wang, Zhong
ef9f8b13-c3f0-48d7-b8e2-95b0f757c30a
Weymouth-Wilson, Alex
a25a6ccc-864f-45be-bbd3-016286c5f563
Galland, Nicolas
631c189a-ea3e-4149-9f23-abec8e26e47b
Le Questel, Jean-Yves
38aea4ae-64a3-43b7-8049-ea2f351459f2
Linclau, Bruno
19b9cacd-b8e8-4c65-af36-6352cade84ba
Graton, Jerome
a9189e35-d606-4adb-85b2-ad337a826dfb
Compain, Guillaume
f88510bf-ad1a-4a67-8855-43303979f2d0
Besseau, François
436e47fa-e4a7-4a44-b5e4-476eb04184d9
Bogdan, Elena
bd2b4c26-9ae0-42eb-8397-3c8d95f48060
Watts, Joe
5dd231c2-7940-4372-97d3-964491b48614
Mtashobya, Lewis
f0f16ba6-808d-4b55-9c10-3982c374685b
Wang, Zhong
ef9f8b13-c3f0-48d7-b8e2-95b0f757c30a
Weymouth-Wilson, Alex
a25a6ccc-864f-45be-bbd3-016286c5f563
Galland, Nicolas
631c189a-ea3e-4149-9f23-abec8e26e47b
Le Questel, Jean-Yves
38aea4ae-64a3-43b7-8049-ea2f351459f2
Linclau, Bruno
19b9cacd-b8e8-4c65-af36-6352cade84ba

Graton, Jerome, Compain, Guillaume, Besseau, François, Bogdan, Elena, Watts, Joe, Mtashobya, Lewis, Wang, Zhong, Weymouth-Wilson, Alex, Galland, Nicolas, Le Questel, Jean-Yves and Linclau, Bruno (2017) Influence of alcohol beta-fluorination on hydrogen-bond acidity of conformationally flexible substrates. Chemistry - A European Journal, 23, 2811-2819. (doi:10.1002/chem.201604940).

Record type: Article

Abstract

Rational modulations of molecular interactions are of significant importance in compound properties optimization. We have previously shown that fluorination of conformationally rigid cyclohexanols leads to attenuation of their hydrogen-bond (H-bond) donating capacity (designated by pKAHY) when OH⋅⋅⋅F intramolecular hydrogen-bond (IMHB) interactions occur, as opposed to an increase in pKAHY due to the fluorine electronegativity. This work has now been extended to a wider range of aliphatic β-fluorohydrins with increasing degrees of conformational flexibility. We show that the observed differences in pKAHY between closely related diastereomers can be fully rationalized by subtle variations in populations of conformers able to engage in OH⋅⋅⋅F IMHB, as well as by the strength of these IMHBs. We also show that the Kenny theoretical Vα(r) descriptor of H-bond acidity accurately reflects the observed variations and a calibration equation extended to fluorohydrins is proposed. This work clearly underlines the importance of the weak OH⋅⋅⋅F IMHB in the modulation of alcohol H-bond donating capacity.

Text
Linclau accepted manuscript.pdf - Accepted Manuscript
Download (1MB)

More information

Accepted/In Press date: 30 November 2016
e-pub ahead of print date: 27 December 2016
Published date: 24 February 2017
Organisations: Organic Chemistry: Synthesis, Catalysis and Flow

Identifiers

Local EPrints ID: 403795
URI: https://eprints.soton.ac.uk/id/eprint/403795
ISSN: 0947-6539
PURE UUID: 0e1488bf-0572-473f-a2c9-cb32db65dc69
ORCID for Bruno Linclau: ORCID iD orcid.org/0000-0001-8762-0170

Catalogue record

Date deposited: 12 Dec 2016 12:40
Last modified: 10 Sep 2019 05:11

Export record

Altmetrics

Contributors

Author: Jerome Graton
Author: Guillaume Compain
Author: François Besseau
Author: Elena Bogdan
Author: Joe Watts
Author: Lewis Mtashobya
Author: Zhong Wang
Author: Alex Weymouth-Wilson
Author: Nicolas Galland
Author: Jean-Yves Le Questel
Author: Bruno Linclau ORCID iD

University divisions

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of https://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×