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the new kingpin of drug discovery


*Corresponding author
University of Southern California, Loker Hydrocarbon Research Institute, 837 Bloom Walk, Los Angeles, CA 90089, USA


The benefit of introducing fluorine into pharmaceuticals has been widely recognized. This thus leads to an urgent demand of capable protocols that enable fluorination and fluoroalkylations with high efficacy and selectivity. Although challenges remain, significant progress has been made over the past three decades, thereby allowing efficient incorporation of fluorine into complex organic molecules. Covering a brief history of fluorine chemistry and its association with pharmaceutical chemistry, this article reviews what the authors consider the state of the art in the field of synthetic organofluorine chemistry.



Although organofluorine compounds are very scarce in the biosphere, fluorine has become the kingpin of drug discovery (1). To date, 20-25 percent of drugs contain at least one fluorine atom. Due to its steric resemblance to hydrogen and extreme electronegativity (a small atom with a big ego), fluorine has been extensively employed to modulate the biological properties of drug molecules, such as acidity, basicity, protein binding affinity, and lipophilicity. The introduction of fluorine can enhance the metabolic stability (bioavailability) of organic molecules due to the unfavourable energetic cost of breaking a C-F bond to form a C-O bond. Owing to the large dipole moment of the C-F bond,