From Molecules to Molecular Surfaces. Exploiting the Interplay Between Organic Synthesis and Electrochemistry

For many years, we have been looking at electrochemistry as a tool for exploring, developing, and implementing new synthetic methods for the construction of organic molecules. Those efforts examined electrochemical methods and mechanisms and then exploited them for synthetic gain. Chief among the tools utilized was the fact that in a constant current electrolysis the working potential at the electrodes automatically adjusted to the oxidation (anode) or reduction (cathode) potential of the substrates in solution. This allowed for a systematic examination of the radical cation intermediates that are involved in a host of oxidative cyclization reactions. The result has been a series of structure-activity studies that have led to far greater insight into the behavior of radical cation intermediates and in turn an expansion in our capabilities of using those intermediates to trigger interesting synthetic reactions. With that said, the relationship between synthetic organic chemistry and electrochemistry is not a "one-way" interaction. For example, we have been using modern synthetic methodology to construct complex addressable molecular surfaces on electroanalytical devices that in turn can be used to probe biological interactions between small molecules and biological receptors in "real-time". Synthetic chemistry can then be used to recover the molecules that give rise to positive signals so that they can be characterized. The result is an analytical method that both gives accurate data on the interactions and provides a unique level of quality control with respect to the molecules giving rise to that data. Synthetic organic chemistry is essential to this task because it is our ability to synthesize the surfaces that defines the nature of the biological problems that can be studied. But the relationship between the fields does not end there. Recently, we have begun to show that work to expand the scope of microelectrode arrays as bioanalytical devices is teaching us important lessons for preparative synthetic chemistry. These lessons come in two forms. First, the arrays have taught us about the on-site generation of chemical reagents, a lesson that is being used to expand the use of paired electrochemical strategies for synthesis. Second, the arrays have taught us that reagents can be generated and then confined to the surface of the electrode used for that generation. This has led to a new approach to taking advantage of molecular recognition events that occur on the surface of an electrode for controlling the selectivity of a preparative reaction. In short, the confinement strategy developed for the arrays is used to ensure that the chemistry in a preparative electrolysis happens at the electrode surface and not in the bulk solution. This Account details the interplay between synthetic chemistry and electrochemistry in our group through the years and highlights the opportunities that interplay has provided and will continue to provide in the future.