Aryl (β,β',β″-Trifluoro)- tert -butyl: A Candidate Motif for the Discovery of Bioactives.

Autor: Dobson LS; School of Chemistry, University of St Andrews, North Haugh, St Andrews KY16 9ST, U.K., Zhang Q; School of Chemistry, University of St Andrews, North Haugh, St Andrews KY16 9ST, U.K., McKay BA; School of Chemistry, University of St Andrews, North Haugh, St Andrews KY16 9ST, U.K., Oke O; School of Chemistry, University of St Andrews, North Haugh, St Andrews KY16 9ST, U.K.; Chemistry Department, University of Lagos, Akoka, Lagos 101245, Nigeria., Isanbor C; Chemistry Department, University of Lagos, Akoka, Lagos 101245, Nigeria., Khan MF; School of Biomolecular and Biomedical Science, University College Dublin, Belfield, Dublin 4, Ireland., Piscelli BA; Chemistry Institute, University of Campinas, Monteiro Lobato Street, Campinas, Sao Paulo 13083-862, Brazil., Cordes DB; School of Chemistry, University of St Andrews, North Haugh, St Andrews KY16 9ST, U.K., Cormanich RA; Chemistry Institute, University of Campinas, Monteiro Lobato Street, Campinas, Sao Paulo 13083-862, Brazil., Murphy CD; School of Biomolecular and Biomedical Science, University College Dublin, Belfield, Dublin 4, Ireland., O'Hagan D; School of Chemistry, University of St Andrews, North Haugh, St Andrews KY16 9ST, U.K.
Jazyk: angličtina
Zdroj: Organic letters [Org Lett] 2023 Sep 22; Vol. 25 (37), pp. 6802-6807. Date of Electronic Publication: 2023 Sep 08.
DOI: 10.1021/acs.orglett.3c02236
Abstrakt: 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.
Databáze: MEDLINE
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