Schlosser Manfred
Institut de Chimie Moléculaire et Biologique Ecole Polytechnique Fédérale, BCh, 1015 Lausanne, Switzerland.
Angew Chem Int Ed Engl. 2006 Aug 18;45(33):5432-46. doi: 10.1002/anie.200600449.
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.
在生命科学领域,氟仍然是一个内行人才知道的窍门,因为它能实现生物特性的微调。然而,含氟取代目标化合物的合成并非总是轻而易举的。实际上,连接在有机主链上的任何氟原子最终都必须从无机来源引入。对于医药和农业研究中的整个合成规划而言,关键在于决定在哪个阶段以及如何引入卤素。标准技术工艺,特别是使用无水氟化氢或氟化钾取代氯的方法,在实验室规模上很难合理实施。因此,工业界和学术界研究人员都适用的通用方法具有很大吸引力。如果目标化合物是三氟甲基取代的芳烃或杂环,那么有两个出色的选择。可以通过将合适的底物与原位生成的(三氟甲基)铜偶联,以整装方式引入CF(3)基团。或者,也可以从CF(3)取代的芳烃或杂环作为核心开始,再用最终结构中缺失的部分将其完善。