Electrochemical Fluorination of Organic Compounds Using a Hexafluorosilicate Salt as an Inexpensive and Widely...

The introduction of fluorine into organic molecules is of the utmost importance in the preparation of active pharmaceutical ingredients (APIs). While a wide range of fluorine sources for organic synthesis have been used over the past decades, the associated safety risks, cost, or environmental impact are still serious limitations. Hexafluorosilicate salts are one of the most inexpensive and readily available sources of nucleophilic fluorine, but they have so far not been used in organic synthesis. Herein we report the first example of the use of a hexafluorosilicate salt as a reagent for the formation of C-F bonds. We have selected as the model reaction an electrochemical decarboxylative fluorination procedure. The synthesis of bis(5-ethyl-2-methylpyridin-1-ium) hexafluorosilicate(IV) was key to obtaining a soluble and reactive hexafluorosilicate salt. This protocol enabled the synthesis of a wide range of primary, secondary, and tertiary aliphatic fluorides (22 examples) in up to 85% yield. The electrochemical method was also successfully transferred to a flow electrolysis cell, demonstrating its robustness and scalability. Finally, we extended the scope of the fluorine source by demonstrating its applicability to electrochemical benzylic C-H fluorination.