Exploring the Synergistic Relationship between Organic Synthesis and Electrochemistry

Abstract

Electrochemistry has long held potential as a tool for constructing organic molecules, and the organic chemistry community is both recognizing and impressively exploiting that potential with increasing regularity. Those efforts have taught us a great deal about how to think about electrochemical reactions, how to use the technique to accomplish new transformations that enrich the synthetic enterprise, and when to employ those methods. Interestingly, the relationship between organic synthesis and electrochemistry can also be viewed in the opposite direction with the new synthetic chemistry being developed serving as a tool to facilitate and dramatically expand the scope of electrochemical methods. For example, new synthetic chemistry that allows for the site-selective generation of chemical reagents on an array have enabled the construction of complex, addressable molecular surfaces that can in turn be used to probe small molecule interactions with a variety of biological targets. The efforts set the stage for using microelectrode arrays as analytical devices for rapidly screening small molecule libraries in "real-time". The methods allow for the construction of libraries with tunable surfaces, careful control of surface concentrations, and previously unknown levels of quality control over the molecular library. The development of an even greater arsenal of synthetic tools for use on the arrays is underway, an effort that aims to expand the nature and size of the addressable libraries that can be used to probe the world around us. Not surprisingly, the exploration of these new electrochemical tools is beginning to “give back” to the synthetic arena. A number of preparative scale synthetic applications have now arisen based on the concept of site-selective reagent generation. Chief among these is the use of paired electrochemical reactions for more sustainable reagent generation and the recent discovery that chemical reagents can be confined to specific regions within a preparative reaction; a development that potentially offers a new strategy for controlling the selectivity of a chemical reaction. In the talk to be given, the interplay between organic synthesis and electrochemistry will be highlighted with an emphasis on how key concepts in physical organic chemistry are used to guide the development of new advances in both areas, and how we think those new developments will shape future efforts to expand the use of electroorganic synthesis.