Synthesis of Quaternary Carbon-Centered Benzoindolizidinones via Novel Photoredox-Catalyzed Alkene Aminoarylation: Facile Access to Tylophorine and Analogues

Photoredox-catalyzed aminoarylation and thioamination of unactivated alkenes have been developed, providing novel synthetic routes to access synthetically challenging quaternary carbon-centered benzoindolizidinones and trifluoromethylthiolated piperidines using readily available starting materials. Notably, these transformations were enabled by merging amidyl radical generation from N-alkyl benzamides with oxidant incorporation. Density functional theory calculations were performed to understand the reaction mechanism and to rationalize the regioselectivities. Moreover, the newly developed catalytic aminoarylation provided a convenient synthetic route for natural product tylophorine and its gem-dimethyl analogues with greatly improved drug-like properties such as enhanced solubility and stability. [GRAPHICS] .