Science of Synthesis

DiRocco, D. A.; Schultz, D. M., Science of Synthesis: Photocatalysis in Organic Synthesis, (2018) 1, 633.

A key step in the synthesis of elbasvir, an HCV NS5A inhibitor, is the oxidation of indoline ‌41‌ to indole ‌42‌ without epimerization of the adjacent stereocenter. In a collaboration with Knowles and coworkers, researchers at MSD discovered a visible-light-mediated oxidation using peroxides as the terminal oxidant that proceeds with high stereoretention.[‌34‌] It was determined that oxidants that proceed via single-electron transfer, rapidly racemize the adjacent stereocenter through radical β-scission. The photoredox-mediated reaction proceeds through reductive quenching of iridium photocatalyst ‌17‌ which initiates the generation of a chain carrying the tert-butoxy radical after reduction of tert-butyl peroxybenzoate. The tert-butoxy radical is responsible for the selective hydrogen-atom transfer. This method is scalable in flow with a catalyst loading as low as 0.1 mol%, thus making it amenable to commercial-scale production (‌Scheme 13‌).

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References