Synthesis of Polyfluorobenzoic Acids By Regioselective Electrochemical Carboxylation of Polyfluoroarenes
First, we screened reaction conditions for electrochemical carboxylation of hexafluorobenzene (1a) as a substrate. When constant current electrolysis of 1a was carried out in DMF using a one-compartment cell equipped with a Pt cathode and an Mg anode with 3 F/mol of electricity in the presence of carbon dioxide, reductive cleavage of a C-F bond on the phenyl ring followed by reaction with carbon dioxide took place to give pentafluorobenzoic acid (2a). After reaction conditions screening, 2a could be obtained in 73% 19F NMR yield by electrolysis of 1a at –40°C with 5 mA/cm2 of current density. After recrystallization with hexane and acetone, pentafluorobenzoic acid (2a) was obtained in 65% isolated yield as a pure product.
We next investigated similar electrochemical carboxylations of several polyfluoroarenes, and the results are shown in Scheme. When pentafluorobenzene (1b) was subjected to the present electrochemical carboxylation under the same conditions for the reaction of 1a, C-F bond cleavage followed by carboxylation also took place efficiently to give 2,3,5,6-tetrafluorobenzoic acid (2b) in 78% 19F NMR yield and 66% isolated yield after recrystallization. It is noteworthy that C-F bond cleavage followed by carboxylation of 1b occurred at the C3 position of 1b predominantly to give 2b as a major product. Similar regioselective electrochemical carboxylation was also achieved when pentafluoroarenes 1c-f were used as substrates. Under the same conditions except for 1d, electrochemical carboxylation of 1c-f gave 4-substituted-2,3,5,6-tetrafluorobenzoic acids 2c-f in 61-84% 19F NMR yields and 49-76% isolated yields after recrystallization. It is also to note that C-F bond cleavage occurred at the para position of the substituents of Me-, AcO-, Me(RO)2C-, and MeS- in pentafluoroethylarenes 1c-f predominantly in all cases to give 4-substituted-2,3,5,6-tetrafluorobenzoic acids 2c-f as major products.
Other results of electrochemical carboxylation of polyfluoroarenes and proposed reaction mechanism including regioselectivity of the carboxylation will be presented.
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