Department of Chemistry, Temple University, 1901 North 13th Street, Philadelphia, Pennsylvania 19122, United States.
J Am Chem Soc. 2023 May 31;145(21):11530-11536. doi: 10.1021/jacs.3c04294. Epub 2023 May 16.
Because of its impressive ability to promote pharmaceutical activity, the introduction of trifluoromethylacyl (CFCO) functionality into organic compounds has become an important and growing research area. Although various protocols have been developed to access trifluoroketones, the use of trifluoroacetyl radicals remains virtually undeveloped. Herein, we disclose a novel method for trifluoroacetylation through an umpolung reagent, thereby transforming an electrophilic radical into a nucleophilic radical. The applicability of this transformation is highlighted by large-scale, late-stage reactions of complex bioactive molecules sclareolide and loratadine. Furthermore, the direct transformation of trifluoromethyl ketones into various fluorinated analogues illustrates the potential synthetic application of our developed method.
由于其令人印象深刻的促进药物活性的能力，将三氟甲酰基（CFCO）官能团引入有机化合物已成为一个重要且不断发展的研究领域。尽管已经开发了各种方法来获得三氟酮，但三氟乙酰基自由基的应用实际上尚未得到开发。在此，我们通过反转试剂披露了一种新的三氟乙酰化方法，从而将亲电自由基转化为亲核自由基。这种转化的适用性通过复杂生物活性分子 sc 萜醇和氯雷他定的大规模、后期反应得到了强调。此外，三氟甲基酮直接转化为各种氟化类似物说明了我们开发的方法的潜在合成应用。
