Oxidative C-F Bonds Activation Using Electrochemical Techniques
Authors: Akiba Ikumi , Shida Naoki , Atobe Mahito 
Published: February 2024

Fluorinated organic compounds are widely used in diverse areas such as pharmaceuticals, agrochemicals, and materials science, and occupy an important position in modern chemistry.[1] Consequently, there has been a large library of fluorine-containing chemicals. Thus, the evolution of defluorination reactions using abundant fluorinated organic compounds as starting materials is expected to lead to further development in various fields. For example, it is expected to be applied to the synthesis of medical and agrochemical products with new functions using defluorination reactions, as well as to the defluorination process of polyfluorinated organic compounds that are highly persistent in the environment.

The inherent challenge of C-F functionalization is the highly stable and strong nature of C-F bond. To tackle this problem, various methods have been proposed to activate C-F bonds using transition metal complexes, and Lewis acids. However, these methods have some issues that using expensive heavy metals and toxic reagents. Recent years have seen a focus on the development of economical and environmentally friendly defluorination reactions, especially C-F bonds activation based on efficient energy input using electrochemical or photochemical methods. As for photochemical methods, Gouverneur and co-workers developed photocatalytic methods for the selective hydrodefluorination and defluoroalkylation of trifluoromethyl(hetero)arenes using 2,4,5,6-tetrakis(diphenylamino)isophthalonitrile as an organophotocatalyst.[2] As for electrochemical methods, Cheng and co-workers reported a defluorinative method to convert α,α,α-trifluoromethyl cinnamates to gem-difluorostyrenes using electrochemical reduction.[3] These methods of defluorination still have limitations in terms of the versatility of the substrates where only substrates with π-system or have electron acceptors like carbonyl groups are suitable for cleaving C-F bonds presumably for the facile single electron reduction. Thus, the activation and functionalization of C-F bonds in the aliphatic backbone by electrochemical or photochemical means still remain a challenge.

In this work, we have developed an electrochemical C-F bond activation and functionalization under oxidative conditions. After exploring the reaction conditions, the electrochemical defluorination reaction of 1-fluoroadamantane was found to proceed in weakly coordinating electrolyte composed of 0.1 M Bu4NB(C6F5)4/CH2Cl2. Nucleophiles such as allyltrimethylsilane and 4,4,5,5-tetramethyl-2-(p-tolyl)-1,3,2-dioxaborolane were applicable to affording 1-allyladamantane (72% yield) and p-(1-adamantyl)toluene (52% yield), respectively. In this reaction, the use of a divided cell was found to be necessary, evidencing that the defluorination reaction proceeds oxidatively at the anode.

In conclusion, we have successfully developed the first electrochemical defluorinative functionalization system under oxidative conditions, which potentially become a complementary strategy of electro-reductive counterpart of the defluorinative transformation of organic molecules. In the presentation, an exploration of the substrate scope, electrochemical studies, and the mechanistic proposal of the reaction will also be discussed.

[1] Y. Ogawa, E. Tokunaga, O. Kobayashi, K. Hirai, N. Shibata, iScience., 2020, 23, 101467–101467.

[2] J. B. I. Sap, N. J. W. Straathof, T. Knauber, C. F. Meyer, M. Médebielle, L. Buglioni, C. Genicot, A. A. Trabanco, T. Noël, C. W. am Ende, V. Gouverneur, J. Am. Chem. Soc.,
2020, 142, 20, 9181–9187.

[3] J. Sheng, N. Wu, X. Liu, F. Liu, S. Liu, W. Ding, C. Liu and X. Cheng, Chin. J. Org. Chem., 2020, 40, 11, 3873–3880.

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