(190g) Mechanistic Insights into the Influence of Rapid Alternating Polarity on the Selective Reduction of Arenes from First Principles Kinetic Simulations

The selective reduction of aromatic substrates is pivotal in organic synthesis for pharmaceutical intermediates and natural products. In this study, we explore the efficacy of rapid alternating polarity (rAP) electrochemical transformations in enhancing arene reduction selectivity while suppressing side reactions. Previous reported experiments show alternating the polarity at a frequency of 50 ms significantly enhanced the selective 1,4 reduction of thiophene, exhibiting an 83% yield, in stark contrast to the < 5% yield observed under direct current (DC) conditions. To unravel the underlying mechanisms, we employ a computational approach integrating Density Functional Theory (DFT) and ab initio molecular dynamics to simulate the complex reaction environment at the electrode interface. Through our investigations, we delineate potential-dependent activation energies for various proposed elementary steps involved in selective arene reduction and competing HER. Simulations unveil that at cathodic potentials the substrate reduction proceeds via an electrochemical-chemical-electrochemical-chemical (ECEC) type mechanism versus that of direct surface hydrogen attack and that the HER can readily occur on the graphene surface via Volmer and Heyrovský steps. The detailed DFT results were subsequently used to determine the kinetics for all of the proposed elementary steps and establish a database for kinetic Monte Carlo (kMC) simulations on the selective electrochemical reduction of thiophene. KMC elucidates the influence of rAP on selectivity and reaction kinetics. We find that under constant cathodic potential, the electrode surface is predominantly occupied by protonated ethanol, exacerbating HER and compromising selectivity. In contrast, rAP facilitates hydrogen species desorption and thiophene adsorption, effectively suppressing HER and promoting selective hydrogenation. Overall, the combination of DFT and kMC simulations allows us to rationalize the observed effects of rAP on reaction selectivity. The concerted approach provides valuable insights into the processes governing selective hydrogenation on the electrode surface and the framework for the design of rAP synthetic methodologies.