(186a) First Principle Insights into Molecular Transformations That Control Electrochemical Organic Synthesis in the Production of Pharmaceutical and Chemical Intermediates.

The selective oxidation and reduction paths used to produce most pharmaceuticals and natural product proceed via organic synthetic methods and batch-type chemical processes. This is often very expensive, and requires non-green and hazardous chemical processes. There is a strong and growing interest in using electrochemistry and electrochemical cells to carry out such transformations. Herein we discuss the use of electrochemistry to selectively drive the Birch reduction reaction. Potential-dependent ab initio molecular dynamics simulations were used to examine the solution phase electrocatalytic reduction of model aromatics including phenyl ethanol and naphthalene in polar aprotic solvents like THF in the presence of LiBr and proton-donating reagents. Detailed theoretical simulations along with electrochemical analyses show that the classic Birch reaction which is controlled by Li metal ions in solution cannot take place at the potentials of interest. The reaction instead proceeds at the Zn electrode in a manner that is very similar to electrocatalytic O₂ as well as CO₂ reduction over metal cathodes. Phenyl ethanol can readily adsorb onto the Zn surface at reducing conditions and thus readily allow electron transfer. The Li+ cations aid and proton-donating source aid in stabilizing electron as well as proton transfer events and enhancing surface transformations. The insights from theory and electroanalytical analyses guided the development of electrochemical routes that resulted in > 70 % yield for a broad range of organic substrates, natural products and pharmaceutical intermediates. These transformations were ultimately carried out in very safe, small laboratory electrochemical cells.