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Highly Chemoselective Synthesis of Hindered Amides via Cobalt-Catalyzed Intermolecular Oxidative Hydroamidation
preprintsubmitted on 25.11.2020, 06:01 and posted on 25.11.2020, 13:07 by Yun-Nian Yin, Rui-Qi Ding, Dong-Chen Ouyang, Qing Zhang, Rong Zhu
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 orthogonal to 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.