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Anodic olefin coupling reactions generate new bonds and ring skeletons through a net two electron process that reverses the polarity of a known, electron‐rich functional group. While much of the early work on the mechanism of these reactions focused on the initial oxidation and cyclization steps of the process, the second oxidation step also plays a central role in determining the success of the reaction. Evidence supporting this observation is presented, along with evidence that optimization of this second oxidation step is not enough to pull a poor cyclization to the desired product. Successful cyclization reactions require optimization of both processes.

 

Paired electrochemical reactions allow the optimization of both atom and energy economy of oxidation and reduction reactions. While many paired electrochemical reactions take advantage of perfectly matched reactions at the anode and cathode, this matching of substrates is not necessary. In constant current electrolysis, the potential at both electrodes adjusts to the substrates in solution. In principle, any oxidation reaction can be paired with any reduction reaction. Various oxidation reactions conducted on the anodic side of the electrolysis were paired with the generation and use of hydrogen gas at the cathode, showing the generality of the anodic process in a paired electrolysis and how the auxiliary reaction required for the oxidation could be used to generate a substrate for a non‐electrolysis reaction. This is combined with variations on the cathodic side of the electrolysis to complete the picture and illustrate how oxidation and reduction reactions can be combined.

 

Radical cation initiated cyclization reactions can be triggered by the one electron oxidation of an electron-rich olefin using either electrochemistry or visible light and a photoredox catalyst. In principle, the two methods can be used to give complimentary products with the electrolysis leading to products derived from a net two electron oxidation and the photoelectron transfer method being compatible with the formation of products from a redox neutral process. However, we are finding an increasing number of oxidative cyclization reactions that require the rapid removal of a second electron in order to form high yields of the desired product. In those cases, the electrochemical method can provide a superior approach to accessing the necessary two electron oxidation pathway. With that said, it is a combination of the two methods that provides the mechanistic insight needed to understand when a reaction has this requirement, and we are finding that the use of photoredox catalysis in combination with electrochemical methods is changing our understanding of even the most successful anodic cyclization reactions run to date.

 

For many years, we looked 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" as the interactions happen. 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 insure 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.