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.

三氟甲基芳烃 (Ar–CF ₃ ) 是制药、农业化学和材料科学中常见的氟化子结构之一。然而，获取Ar-CF ₃的主要方法具有一些局限性，包括苛刻的条件、缺乏可用的底物以及较差的区域选择性，这些限制了获得所需的高功能化的含Ar-CF ₃化合物。为了扩大可接近的Ar-CF ₃基分子的范围，我们提出了一种正交脱氧氟烷基化/芳构化方法，该方法利用易于接近和可编程的环己酮底物，该底物与Ruppert-Prakash进行可靠的1,2加成反应试剂（TMSCF ₃ ），然后进行芳构化，以一锅/两锅顺序提供高度功能化的 Ar-CF ₃化合物。这种通用策略使得能够获得高度取代的含Ar-CF ₃分子，而通过当前的合成方法很难、昂贵和/或不可能获得这些分子。