Electrochemistry as an enabling tool for reaction discovery

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Project Summary This proposal focuses on using electrochemistry as an unconventional tool to uncover new organic reactions and invent synthetic strategies with the goal of facilitating the preparation of bioactive compounds. Improving the organic synthesis of medicinally active compounds is crucial to modern biomedical research. In this context, oxidation and reduction reactions are among the most important and frequently used processes in organic synthesis. However, manipulating the oxidation states of functional groups in complex settings with high efficiency, precision, and minimal waste remains an important challenge in modern organic chemistry. Given its many distinct characteristics, electrochemistry represents an attractive approach to discovering new reactivities, enabling new synthetic strategies, and meeting the prevailing trends in organic synthesis. Therefore, there exists a clear impetus for the invention of new reaction strategies to improve the scope of synthetic electrochemistry and provide new platforms for reaction discovery and synthetic innovations. In the past funding period, we demonstrated a new catalytic approach that combines electrochemistry and redox-metal catalysis for the oxidative difunctionalization of alkenes to access a diverse array of highly functionalized structures. These promising results led us to envision that electrochemistry will ultimately emerge as a powerful tool for solving a wide range of longstanding synthetic problems. In the new funding cycle, we aim to build upon our previous success but move our research into new grounds. In each of the projects targeted herein, we aim to apply electrochemistry to address a prominent challenge in organic synthesis. The transformations targeted in this grant are either currently unknown or display salient limitations in reaction scope or selectivity. Among the specific reactions that we aim to develop in the context of this grant are: two- and three-component cross-electrophile couplings; asymmetric synthesis and late-stage functionalization of N-containing compounds; and regioselective C–H functionalization of pyridines. In addition, in-depth studies using canonical physical organic and electroanalytical techniques will provide insights into the reaction mechanisms. The development and mechanistic understanding of these proposed transformations will represent significant advances for the field of organic synthesis.