Aryl (β,β′,β″-Trifluoro)-tert-butyl: A Candidate Motif for the Discovery of Bioactives
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...
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| Veröffentlicht in: | Organic letters 2023-09, Vol.25 (37), p.6802-6807 |
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| creator | Dobson, Luca S. Zhang, Qingzhi McKay, Benjamin A. Oke, Oluwayinka Isanbor, Chukwuemeka Khan, Mohd Faheem Piscelli, Bruno A. Cordes, David B. Cormanich, Rodrigo A. Murphy, Cormac D. O’Hagan, David |
| description | 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. |
| doi_str_mv | 10.1021/acs.orglett.3c02236 |
| format | Article |
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Lett</addtitle><date>2023-09-22</date><risdate>2023</risdate><volume>25</volume><issue>37</issue><spage>6802</spage><epage>6807</epage><pages>6802-6807</pages><issn>1523-7060</issn><eissn>1523-7052</eissn><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. 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| subjects | Letter |
| title | Aryl (β,β′,β″-Trifluoro)-tert-butyl: A Candidate Motif for the Discovery of Bioactives |
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