Facile Synthesis of 2,3-Dihydrobenzofuran-3-ylacetic Acids by Novel Electrochemical Sequential Aryl Radical Cyclization-Carboxylation of 2-Allyloxybromobenzenes Using Methyl 4-tert-Butylbenzoate as an Electron-Transfer Mediator

Abstract

Facile synthesis of 2,3-dihydrobenzofuran-3-ylacetic acids and related analogues was successfully carried out by a novel electrochemical aryl radical generation and its 5-exo cyclization followed by a carboxylation sequence of 2-allyloxybromobenzenes by using methyl 4-tert-butylbenzoate as an electron-transfer mediator.

Aryl radical cyclization with alkyne followed by tandem carboxylation in methyl 4-tert-butylbenzoate-mediated electrochemical reduction of 2-(2-propynyloxy)bromobenzenes in the presence of carbon dioxide

“…19 These results clearly indicate that methyl 4-tert-butylbenzoate works as an electron transfer mediator in the present electroreductive generation of aryl radicals from aryl bromides. Based on these results, a probable reaction mechanism in the present aryl radical cyclization followed by tandem carboxylation is shown in Scheme 2.…”

“…Thus-generated aryl radicals were also found to undergo radical cyclization with alkene, and after further one-electron reduction of the resulting cyclized radical, the generated anion species efficiently reacted with carbon dioxide to give 2,3-dihydrobenzofuran-3-ylacetic acids as sequential aryl radical cyclization-anionic carbon-carbon bond-forming reaction products in high selectivities and good yields. 19 In the course of our efforts to apply electrochemistry to organic synthesis, 20 we recently found a unique electrochemical reaction in aryl radical cyclization using a carbon-carbon triple bond as an aryl radical acceptor. When 2-(2-propynyloxy)bromobenzene was similarly electrolyzed using methyl 4-tert-butylbenzoate as an electron transfer mediator in the presence of carbon dioxide, aryl radical cyclization followed by fixation of two molecules of carbon dioxide took place efficiently to give a cyclized dicarboxylic acid, 3-carboxy-2,3-dihydrobenzofuran-3-ylacetic acid.…”

“…Constant current electrolysis (current density of 20 mA/cm 2 ) of a DMF solution of 1a containing 0.1 M Bu 4 NBF 4 was carried out at 0 °C by using a one-compartment cell equipped with a platinum plate cathode (2 x 2 cm 2 ) and a magnesium rod anode (3 mmφ) in the presence of 0.5 equiv. of methyl 4-tert-butylbenzoate as an electron transfer mediator 19 with bubbling of carbon dioxide through the solution. After supplying 4 F/mol of electricity, conversion of 1 reached 79% by 1 H NMR, and 3-carboxy-2,3-dihydro-3-benzofuranacetic acid (2a) was obtained in 45% 1 H NMR yield (Entry 1).…”

“…19 In the absence of an electron transfer mediator, methyl 4-tert-butylbenzoate, two-electron reduction of aryl bromide 1 competitively occurs at the cathode to generate the corresponding aryl anion species, directly producing carboxylated benzoic acid (Entry 10 in Table 1). Intramolecular 5-exo cyclization of aryl radical A with a carbon-carbon triple bond takes place efficiently to generate the corresponding cyclized vinyl radical B.…”

Electrochemical Fixation of Carbon Dioxide

“…Consequently, selective synthesis of each carboxylic acid 15, 16, 17, and 18 from terminal alkyne 14 and carbon dioxide can be accomplished even by selecting appropriate ligands on nickel(II) complexes in the electrochemical carboxylation (Scheme 10.7). As a similar manner, control Carboxylation can take place with other electrochemically induced chemical reactions such as cyclization [75][76][77]. For example, electrochemical carboxylation of 2-allyloxybromobenzene (23) [51,71] followed by enantioselective hydrogenation.…”