F-based Small Group Decoration of Heteroarenes Via C-H Activation: Medicinal Chemistry Rationale and Late Stage Synthetic Methods

Author(s): Paolo Ronchi*, Sara Guariento, Daniele Pala, Daniela Pizzirani, Claudio Fiorelli, Paolo Bruno, Veronica Nigroni, Matteo Biagetti

Journal Name: Current Organic Chemistry

Volume 25 , Issue 18 , 2021

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Graphical Abstract:


The use of F-based decorations in drug discovery started from the development of fluorocorticoids and fluorochinolones (1950s and 1980s respectively) and it resulted in about 20% of approved drugs on the Market containing fluorine. From a medicinal chemistry perspective, the installation of F-based small groups (e.g. -CF3, -CF2H, -OCF3, -OCF2H, -SCF3, - SCF2H) necessarily impacts on physicochemical, pharmacokinetics, pharmacodynamics and toxicological properties of small molecules. Accordingly, a huge interest on this topic is constantly arising in the medicinal chemistry community. Focusing on heteroarenes, the synthetic access to these substitutions is guaranteed by a number of effective reactions, such as Miniscitype reaction, photochemistry or electrochemistry C-H activation. The aim of this work is to analyze the rational in using these groups in medicinal chemistry and to highlight the current available synthetic toolbox of C-H activation for their introduction on heteroarenes of pharmaceutical interest. A particular focus has been given to those procedures amenable at late-stage functionalisation process.

Keywords: Late stage functionalisation, LSF, fluoro-based small groups, C-H activation, OCF3, OCF2H, CF2H, SCF3, SCF2H.

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Article Details

Year: 2021
Published on: 06 July, 2021
Page: [2089 - 2115]
Pages: 27
DOI: 10.2174/1385272825666210706130210
Price: $65

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PDF: 138