✍ Scribed by Manfred Schlosser
No coin nor oath required. For personal study only.
Fluorine remains an insiders' tip in the life sciences as it enables the fine‐tuning of biological properties. However, the synthesis of fluorine‐substituted target compounds is not always trivial. Virtually any fluorine atom attached to an organic backbone has ultimately to be imported from inorganic sources. Crucial for the entire synthetic planning in medicinal and agricultural research is the decision on at what stage and how the halogen will be introduced. Standard technical processes, in particular the displacement of chlorine using anhydrous hydrogen fluoride or potassium fluoride, can hardly be implemented rationally on the laboratory scale. Universal methods that are applicable by both industrial and academic researchers thus have great appeal. If a trifluoromethyl‐substituted arene or heterocycle is the target compound, two splendid options exist. The CF~3~ group can be delivered packagewise by coupling an appropriate substrate with in situ generated (trifluoromethyl)copper. Alternatively, one may start from a CF~3~‐substituted arene or heterocycle as a core and complete it with the missing parts of the ultimate structure.
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