Aryl (β, β', β''-trifluoro)-tert-butyl: a candidate motif for the discovery of bioactives

David O'Hagan; David Bradford Cordes; Luca Dobson; Oluwayinka Omobolanle Oke; Qingzhi Zhang; Rodrigo Cormanich; Chukwuemeka  Isanbor; Benjamin McKay; Mohd Faheem Khan; Bruno Piscelli; Cormac Murphy

doi:10.1021/acs.orglett.3c02236

Aryl (β, β', β''-trifluoro)-tert-butyl: a candidate motif for the discovery of bioactives

David O'Hagan^*, David Bradford Cordes, Luca Dobson, Oluwayinka Omobolanle Oke, Qingzhi Zhang, Rodrigo Cormanich, Chukwuemeka Isanbor, Benjamin McKay, Mohd Faheem Khan, Bruno Piscelli, Cormac Murphy

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

The (β,β′,β″-trifluoro)-tert-butyl (TFTB) group has received very little attention in the literature. This work presents a direct synthesis of this group and explores its properties. The TFTB group arises when the methyl groups of a tert-butyl moiety are exchanged for fluoromethyl groups. Sequential fluoromethylations result in a decrease of Log P (increasing hydrophilicity), ultimately by 1.7 Log P units in the TFTB group relative to that of tert-butyl benzene itself. A focus is placed on synthetic transformations, conformational analysis, and metabolism of the TFTB group in the context of presenting a favorable profile as a motif for the discovery of bioactives.

Original language	English
Number of pages	6802
Journal	Organic Letters
Volume	25
Issue number	37
Early online date	8 Sept 2023
DOIs	https://doi.org/10.1021/acs.orglett.3c02236
Publication status	Published - 22 Sept 2023

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10.1021/acs.orglett.3c02236Licence: CC BY

Dobson_2023_OL_Aryl-BBB_CC
Copyright © 2022 The Authors. Published by American Chemical Society. This publication is licensed under CC-BY 4.0.
Final published version, 1.98 MBLicence: CC BY

Janus faced fluorocyclohexanes: Properties and applications of Janus faced fluorocyclohexanes
O'Hagan, D. (PI)
1/12/19 → 14/03/23
Project: Standard

CCDC 2270745: Experimental Crystal Structure Determination
Dobson, L. S. (Creator), Zhang, Q. (Creator), McKay, B. A. (Creator), Oke, O. (Creator), Isanbor, C. (Creator), Khan, M. F. (Creator), Piscelli, B. A. (Creator), Cordes, D. B. (Creator), Cormanich, R. A. (Creator), Murphy, C. D. (Creator) & O’Hagan, D. (Creator), Cambridge Crystallographic Data Centre, 2023
DOI: 10.5517/ccdc.csd.cc2g6wvf
Dataset

Cite this

@article{58809b3737ca4b01b5e3bfff7f4a0910,

title = "Aryl (β, β', β''-trifluoro)-tert-butyl: a candidate motif for the discovery of bioactives ",

abstract = "The (β,β′,β″-trifluoro)-tert-butyl (TFTB) group has received very little attention in the literature. This work presents a direct synthesis of this group and explores its properties. The TFTB group arises when the methyl groups of a tert-butyl moiety are exchanged for fluoromethyl groups. Sequential fluoromethylations result in a decrease of Log P (increasing hydrophilicity), ultimately by 1.7 Log P units in the TFTB group relative to that of tert-butyl benzene itself. A focus is placed on synthetic transformations, conformational analysis, and metabolism of the TFTB group in the context of presenting a favorable profile as a motif for the discovery of bioactives.",

author = "David O'Hagan and Cordes, {David Bradford} and Luca Dobson and Oke, {Oluwayinka Omobolanle} and Qingzhi Zhang and Rodrigo Cormanich and Chukwuemeka Isanbor and Benjamin McKay and Khan, {Mohd Faheem} and Bruno Piscelli and Cormac Murphy",

note = "Funding: UK Engineering and Physical Sciences Research Council - EP/S030506/1; Commonwealth Scholarship Commission.",

year = "2023",

month = sep,

day = "22",

doi = "10.1021/acs.orglett.3c02236",

language = "English",

volume = "25",

journal = "Organic Letters",

issn = "1523-7060",

publisher = "American Chemical Society (ACS)",

number = "37",

}

TY - JOUR

T1 - Aryl (β, β', β''-trifluoro)-tert-butyl

T2 - a candidate motif for the discovery of bioactives

AU - O'Hagan, David

AU - Cordes, David Bradford

AU - Dobson, Luca

AU - Oke, Oluwayinka Omobolanle

AU - Zhang, Qingzhi

AU - Cormanich, Rodrigo

AU - Isanbor, Chukwuemeka

AU - McKay, Benjamin

AU - Khan, Mohd Faheem

AU - Piscelli, Bruno

AU - Murphy, Cormac

N1 - Funding: UK Engineering and Physical Sciences Research Council - EP/S030506/1; Commonwealth Scholarship Commission.

PY - 2023/9/22

Y1 - 2023/9/22

N2 - The (β,β′,β″-trifluoro)-tert-butyl (TFTB) group has received very little attention in the literature. This work presents a direct synthesis of this group and explores its properties. The TFTB group arises when the methyl groups of a tert-butyl moiety are exchanged for fluoromethyl groups. Sequential fluoromethylations result in a decrease of Log P (increasing hydrophilicity), ultimately by 1.7 Log P units in the TFTB group relative to that of tert-butyl benzene itself. A focus is placed on synthetic transformations, conformational analysis, and metabolism of the TFTB group in the context of presenting a favorable profile as a motif for the discovery of bioactives.

AB - The (β,β′,β″-trifluoro)-tert-butyl (TFTB) group has received very little attention in the literature. This work presents a direct synthesis of this group and explores its properties. The TFTB group arises when the methyl groups of a tert-butyl moiety are exchanged for fluoromethyl groups. Sequential fluoromethylations result in a decrease of Log P (increasing hydrophilicity), ultimately by 1.7 Log P units in the TFTB group relative to that of tert-butyl benzene itself. A focus is placed on synthetic transformations, conformational analysis, and metabolism of the TFTB group in the context of presenting a favorable profile as a motif for the discovery of bioactives.

U2 - 10.1021/acs.orglett.3c02236

DO - 10.1021/acs.orglett.3c02236

M3 - Article

SN - 1523-7060

VL - 25

JO - Organic Letters

JF - Organic Letters

IS - 37

ER -

Aryl (β, β', β''-trifluoro)-tert-butyl: a candidate motif for the discovery of bioactives

Abstract

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Projects

Janus faced fluorocyclohexanes: Properties and applications of Janus faced fluorocyclohexanes

Datasets

CCDC 2270745: Experimental Crystal Structure Determination

Cite this