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

Abstract

Abstract Trifluoromethyl arenes (Ar–CF3) are amongst the commonly encountered fluorinated substructures in pharmaceutical, agrochemical, and material sciences. However, predominant methods to access Ar–CF3 possess several limitations, including harsh conditions, lack of availability of substrates, and poor regioselectivity, which combined restrict access to desirable highly functionalized Ar–CF3-containing compounds. To expand the scope of accessible Ar–CF3-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 (TMSCF3) followed by aromatization to deliver highly functionalized Ar–CF3 compounds in a one/two-pot sequence. This general strategy enables access to highly substituted Ar–CF3-containing molecules that are difficult, expensive, and/or impossible to access by current synthetic methods.