Harnessing the Potential of Alkoxy Radicals

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This proposal will establish electrochemistry as the state-of-the-art method to access and utilize privileged alkoxy radical intermediates. This will be achieved by introducing the first broadly applicable approach for the electrochemical generation of alkoxy radicals from unprotected alcohols and applying this to the development of a diverse range of novel electrosynthetic transformations, accessing valuable products whilst addressing an important existing deficiency in the area.The research outlined in this proposal will significantly advance the fields of organic electrosynthesis and radical chemistry in several ways, including:i. The first broadly applicable approach for the electrochemical generation and utilization of alkoxy radicals will be introduced. This area is significantly underdeveloped and remains largely limited to the anodic generation of methoxy radicals from methoxide at high potentials, which precludes general use in synthesis.ii. Electrochemically driven intermolecular PCET processes will be used to access alkoxy radicals for the first time.iii. The utilization of various distinct strategies for the diverse functionalization of C-centered radical intermediates will be employed, including trapping with SOMOphiles, Ni-catalyzed C-C cross-coupling via convergent paired electrochemistry, and trapping with nucleophiles via radical-polar crossover.iv. The application of our new electrosynthetic methods to the late-stage functionalization of (derivatives of) natural products and pharmaceuticals, lignin depolymerization, the direct functionalization of commodity chemicals, and the formation of anisole bioisosteres (bicyclo[1.1.1]pentyl ethers).A comprehensive training programme has been constructed in addition to mechanisms to facilitate a two-way knowledge transfer between host and fellow. The proposed host organisation and primary supervisor are the University of Bath and Dr Louis Morrill, respectively, due to their expertise in this area.