The synthesis of phenylacetic acids and α-aryl carbonyls has high utility as they serve as motifs for pharmaceuticals and biologically active compounds. Electrochemistry provides new and more sustainable routes for the selective functionalization of organohalides with electrophilic reagents, where reactions can be carried out under milder conditions removing the use of unstable and toxic reagents. Various recent efforts have examined replacing expensive palladium and toxic nickel catalysts used in homogeneous catalytic processes with cheaper and less-toxic transition metals such as cobalt to enable electrocatalytic transformations. Herein, we examine the mechanisms and kinetics for the selective functionalization of secondary benzyl chloride with electrophiles including CO<sub>2</sub>, acetic anhydride, acyl chloride, etc., using the Cobalt-pyrox electrocatalyst using first-principles density functional theory (DFT) calculations. The low-coordinate Cobalt-pyrox electrocatalyst is selective towards the corresponding cross-coupling reactions compared to the high-coordinate Cobalt-salen electrocatalyst, which predominantly results in homocoupling products. We first examine the mechanism of oxidative addition of benzyl halides with these cobalt electrocatalysts. We subsequently examine the plausible elementary reaction steps, the active species for each step, and the effect of zinc- and magnesium-based sacrificial anodes for the selective functionalization of benzyl halides. Simulations support the experimental observations that salts derived from the sacrificial anodes are essential to enable these transformations and the yields are low in the absence of any sacrificial anode. Simulations are combined with electroanalytical results to answer various critical mechanistic questions concerning the reactive transformations, including the role of each cobalt species in the mechanism and the nature of cross-coupling steps to establish a mechanism consistent with recent experimental studies. Different electrophiles are screened using steric and electronic descriptors obtained from the mechanistic investigations to further predict suitable reagents for the selective functionalization of benzyl halides.

Understanding selective electrocatalytic functionalization of benzyl halides with electrophilic reagents over cobalt catalysts

ACS Spring 2022

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