Trifluoromethylation‐Induced Lactonization: A Novel Transformation of Unsaturated Carboxylic Acids

Fluorinated drugs are highly important, and one of their common structural motifs is the trifluoromethyl group. As a result, there is an increasing demand for new or improved synthetic pathways toward trifluoromethylated compounds. One such route, developed less than one and a half decades ago, is trifluoromethylation‐induced lactonization of unsaturated carboxylic acids. Initial successes (including the only known enantioselective protocol for this reaction) were achieved using Togni's reagent II in the presence of a Cu(I) catalyst (mechanism: radical trifluoromethylation, then Cu‐assisted lactonization), then the focus shifted to photocatalytic methods (mechanism: radical trifluoromethylation, single‐electron oxidation, then lactonization). Later, electrocatalytic methods were developed too (mechanism: radical trifluoromethylation, single‐electron oxidation, then lactonization). Recently, the first CF 3 + transfer‐induced lactonization was finally realized as well. The purpose of this review is to provide a comprehensive overview of the current state of this field of research. First, the importance of trifluoromethylation, CF 3 ‐containing drugs, and lactonizations is explained briefly. Then, possible reaction mechanisms of trifluoromethylation‐induced lactonizations are discussed. Finally, I will present known trifluoromethylative lactonizations, grouped according to their mechanisms and the type of chemistry involved.