Highly chemoselective synthesis of hindered amides via cobalt-catalyzed intermolecular oxidative hydroamidation

• Published in: Nature communications Vol. 12; no. 1; pp. 2552 - 10
• Main Authors: Yin, Yun-Nian, Ding, Rui-Qi, Ouyang, Dong-Chen, Zhang, Qing, Zhu, Rong
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 05.05.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 639/638/403/933; 639/638/77/888; Acids; Alcohols; Alkenes; Amides; Bonding strength; Carboxylic acids; Chemical synthesis; Cobalt; Humanities and Social Sciences; Hydration; Laboratories; multidisciplinary; Natural products; Nitriles; Pharmaceutical sciences; Pharmaceuticals; Reagents; Science; Science (multidisciplinary)
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-22373-z

α-Tertiary amides are of great importance for medicinal chemistry. However, they are often challenging to access through conventional methods due to reactivity and chemoselectivity issues. Here, we report a single-step approach towards such amides via cobalt-catalyzed intermolecular oxidative hydroamidation of unactivated alkenes, using nitriles of either solvent- or reagent-quantities. This protocol is selective for terminal alkenes over groups that rapidly react under known carbocation amidation conditions such as tertiary alcohols, electron-rich alkenes, ketals, weak C−H bonds, and carboxylic acids. Straightforward access to a diverse array of hindered amides is demonstrated, including a rapid synthesis of an aminoadamantane-derived pharmaceutical intermediate. α-Tertiary amides are common in bioactive natural products and pharmaceuticals, but challenging to access by conventional methods. Here, the authors report a single-step approach toward α-tertiary amides via cobalt-catalyzed intermolecular oxidative hydroamidation of unactivated alkenes.