Electrochemical cobalt-catalyzed selective carboxylation of benzyl halides with CO2 enabled by low-coordinate cobalt electrocatalysts

The direct, transition metal-catalyzed carboxylation of organohalides with carbon dioxide is a highly desirable transformation in organic synthesis as it utilizes feedstock chemicals and delivers carboxylic acids –among the most utilized class of organic molecules. Phenyl acetic acids, in particular, are privileged motifs that appear in many pharmaceuticals and biologically active compounds. This article reports the development of a sustainable and selective cobalt-catalyzed electrochemical carboxylation of benzyl halides with CO2 to generate phenyl acetic acids. The success of this transformation is enabled by the development of low-coordinate cobalt/pyrox complexes as electrocatalysts to convert various benzyl chlorides and bromides to their corre-sponding phenyl/heteroaryl acetic acids with high selectivity over undesired homocoupling of the benzyl halides. The combina-tion of electroanalytical methods, simulation studies, control reactions, and first-principles density functional theory (DFT) calculations informed the mechanistic analysis of this reaction. An EC’C-type activation mechanism of benzyl halides, which is unique to Co(II)/pyrox electrocatalysts, provides the rationalization of the exceptional observed selectivity for carboxylation. Specifically, the Co(II)/pyrox catalyst undergoes reduction to Co(I) followed by halogen abstraction and a favorable radical rebound to Co(II)/pyrox to form alkyl–Co(III) intermediates. Although voltammetry only shows a single electron transfer step, bulk electrolysis shows a two electron process and using DFT calculations, the intermediates are proposed to undergo two-electron reduction to alkyl–Co(I) followed by a ZnCl2-assisted CO2 insertion to form the carboxylated adducts with regenera-tion of Co(I)/pyrox.