Deoxytrifluoromethylation/aromatization of cyclohexan(en)ones to access highly substituted trifluoromethyl arenes

Trifluoromethyl arenes (Ar–CF 3 ) are amongst the commonly encountered fluorinated substructures in pharmaceutical, agrochemical, and material sciences. However, predominant methods to access Ar–CF 3 possess several limitations, including harsh conditions, lack of availability of substrates, and poo...

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Veröffentlicht in:Nature communications 2024-09, Vol.15 (1), p.7882-9, Article 7882
Hauptverfasser: Bhattarai, Pankaj, Abd El-Gaber, Mohammed K., Koley, Suvajit, Altman, Ryan A.
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Sprache:eng
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Zusammenfassung:Trifluoromethyl arenes (Ar–CF 3 ) are amongst the commonly encountered fluorinated substructures in pharmaceutical, agrochemical, and material sciences. However, predominant methods to access Ar–CF 3 possess several limitations, including harsh conditions, lack of availability of substrates, and poor regioselectivity, which combined restrict access to desirable highly functionalized Ar–CF 3 -containing compounds. To expand the scope of accessible Ar–CF 3 -based molecules, we present an orthogonal deoxyfluoroalkylation/aromatization approach that exploits readily accessible and programable cyclohexan(en)one substrates, which undergo a reliable 1,2-addition reaction with the Ruppert-Prakash reagent (TMSCF 3 ) followed by aromatization to deliver highly functionalized Ar–CF 3 compounds in a one/two-pot sequence. This general strategy enables access to highly substituted Ar–CF 3 -containing molecules that are difficult, expensive, and/or impossible to access by current synthetic methods. Trifluoromethyl arenes are amongst the commonly encountered fluorinated substructures in pharmaceutical, agrochemical, and material sciences. Herein, the authors report a deoxytrifluoromethylation/aromatization strategy that converts readily available cyclohexan(en)one substrate into highly substituted trifluoromethyl arenes.
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-024-52035-9