(Organic and Biological Electrochemistry Division Manuel M. Baizer Award) Following the Lead of R. B. Woodward and M. M. Baizer: Using Concepts in Physical Organic Chemistry to Shape the Course of Electrochemical Reactions
Authors: Moeller Kevin D 
Published: February 2020

One of R. B. Woodward’s many contributions to organic chemistry was the way in which he used physical organic chemistry and an understanding of mechanism to shape the development of new synthetic methods. From the use of temporary, conformational constraints to dictate the stereochemistry of a complex target to the interception of a key intermediate to bring about a cis-hydroxylation reaction from the most hindered face of a molecule, the Woodward group beautifully demonstrated that the outcome of a reaction could be predetermined by considering and then controlling its mechanistic features.

     In a similar manner, Manuel M. Baizer taught us much about how to think about electrochemical reactions. His work helped take the “magic” out of electroorganic processes and demonstrated that electroorganic reactions were indeed organic reactions. They were triggered by electron-transfer processes and had additional parameters that needed to be considered, but to a great extent they could be understood and optimized as synthetic transformations by considering their chemical mechanism. This perspective served to make organic electrochemistry accessible to the larger synthetic community.

      The combination of lessons learned from these two pioneers laid the foundation for our own studies concerning electrochemical reactions and their use in synthesis. From the oxidation of amides used in the synthesis of peptidomimetics, to the use of oxidative cyclization reactions in synthesis, to the site-selective generation of chemical reagents for the functionalization of microelectrode array surfaces, we have continually relied on the fact that electroorganic reactions are simply organic reactions and can thus be optimized as such. The overall approach has fueled not only our own work, but also that of so many others, far too many to name here.

      In the talk to be presented, an overview of electrochemical synthetic methods will be presented against a backdrop of the mechanistic insights and findings that enabled and enhanced their development. An emphasis will be placed on the synthetic utility of reactions that take advantage of reactive radical cation intermediates,1 site-selective reactions on conducted on microelectrode arrays,2 and a look toward the future use of paired electrochemical reactions for the on-site generation of chemical reagents.3

References:

 1. See “Oxidative Cyclization Reactions: Controlling the Course of a Radical Cation-Derived Reaction with the Use of a Second Nucleophile.” Alison Redden, Robert J. Perkins, and Kevin D. Moeller. Angew. Chem. Int. Ed.
2013, 52, 12865 and references therein.

 2. “An Introduction to Microelectrode Arrays, The Site-Selective Functionalization of Electrode Surfaces, and the Real-Time Detection of Binding-Events.” Matthew D. Graaf and Kevin D. Moeller. Langmuir
2015, 31, 7697.

 3. “Solvolysis, Electrochemistry, and the Development of Synthetic Building Blocks from Sawdust.” Bichlien H. Nguyen, Robert J. Perkins, Jake A. Smith, and Kevin D. Moeller. J. Org. Chem.
2015, ASAP.