Electrocatalyzed direct arene alkenylations without directing groups for selective late-stage drug diversification
2023 | journal article. A publication with affiliation to the University of Göttingen.
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Electrocatalyzed direct arene alkenylations without directing groups for selective late-stage drug diversification
Lin, Z.; Dhawa, U.; Hou, X.; Surke, M.; Yuan, B.; Li, S.-W. & Liou, Y.-C. et al. (2023)
Nature Communications, 14(1). DOI: https://doi.org/10.1038/s41467-023-39747-0
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Details
- Authors
- Lin, Zhipeng; Dhawa, Uttam; Hou, Xiaoyan; Surke, Max; Yuan, Binbin; Li, Shu-Wen; Liou, Yan-Cheng; Johansson, Magnus J.; Xu, Li-Cheng; Chao, Chen-Hang; Ackermann, Lutz
- Abstract
- Electrooxidation has emerged as an increasingly viable platform in molecular syntheses that can avoid stoichiometric chemical redox agents. Despite major progress in electrochemical C−H activations, these arene functionalizations generally require directing groups to enable the C−H activation. The installation and removal of these directing groups call for additional synthesis steps, which jeopardizes the inherent efficacy of the electrochemical C−H activation approach, leading to undesired waste with reduced step and atom economy. In sharp contrast, herein we present palladium-electrochemical C−H olefinations of simple arenes devoid of exogenous directing groups. The robust electrocatalysis protocol proved amenable to a wide range of both electron-rich and electron-deficient arenes under exceedingly mild reaction conditions, avoiding chemical oxidants. This study points to an interesting approach of two electrochemical transformations for the success of outstanding levels of position-selectivities in direct olefinations of electron-rich anisoles. A physical organic parameter-based machine learning model was developed to predict position-selectivity in electrochemical C−H olefinations. Furthermore, late-stage functionalizations set the stage for the direct C−H olefinations of structurally complex pharmaceutically relevant compounds, thereby avoiding protection and directing group manipulations.
- Issue Date
- 2023
- Journal
- Nature Communications
- eISSN
- 2041-1723
- Language
- English
- Sponsor
- Open-Access-Publikationsfonds 2023