Direct Electrochemical Carboxylation of Benzylic C–N Bonds with Carbon Dioxide

Abstract

We report a direct and efficient electrochemical carboxylation of benzylic C-N bonds with CO2 at room temperature. The reaction has been successfully applied to both primary and secondary benzylic C-N bonds with compatibility of a variety of functional groups. This procedure does not require stoichiometric metals, external reducing agents, or sacrificial anodes, making column chromatography unnecessary for product purification. Differential 2 electrochemical mass spectrometry (DEMS) was used to elucidate key intermediates of the electrocarboxylation reaction.

Suppressing carboxylate nucleophilicity with inorganic salts enables selective electrocarboxylation without sacrificial anodes

“…48,51,60 DMF was chosen as the solvent, since it has also been commonly used in previous electrocarboxylation studies and can be readily separated into the aqueous phase during workup. 34,61 Based on condition optimization described below, silver and DMF turned out to be optimal choices for the cathode and solvent, respectively. Tetra-n-butylammonium tetrauoroborate (TBA-BF 4 ) was used as an inert supporting electrolyte, and TBA-Br was used to perform bromide oxidation.…”

“…[27][28][29][30] Given the sustainability and operability drawbacks of using sacricial anodes, numerous strategies have been developed to avoid their use. 17,31 All of these strategies rely on alternative oxidation chemistries including oxidation of oxalate, 32,33 trimethylamine, 34 acetonitrile (MeCN), 35 N,N-dimethylformamide (DMF), 36 halides, [37][38][39] water, 40,41 H 2 , 42 conjugated dienes, 43 and alcohols. 44 Several of these alternative oxidation chemistries have also been accompanied by improved cell designs to achieve better carboxylation selectivities.…”

Metal Free, Direct and Selective Deoxygenation of α‐Hydroxy Carbonyl Compounds: Access to α,α‐Diaryl Carbonyl Compounds

“…2,2‐Diphenylethanoic acid (2m) . A solution of α‐hydroxy acid 1m (500 mg, 2.19 mmol) in CH 2 Cl 2 (3 mL) and Et 3 SiH (1.5 equiv.)…”

Recent Advances in the Synthesis of Ibuprofen and Naproxen

“…The carboxylation of quaternary ammonium salt, achieved by a direct electrochemical reaction with CO 2 , is shown in Scheme 9 [ 39 ]. Although this conversion shows a similar reaction pathway, it features electrochemical coupling of quaternary ammonium bromide 23 from benzylic bromide 22 [ 40 ] with CO 2 without further metal catalysts, complex ligands, or external reducing agents.…”