Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry and Molecular Engineering, Peking University, Beijing, China.
Nat Commun. 2021 May 5;12(1):2552. 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-叔酰胺在药物化学中具有重要意义。然而，由于反应性和化学选择性问题，它们通常难以通过传统方法获得。在这里，我们报告了一种通过钴催化的未活化烯烃的分子间氧化氢氨化反应来制备这些酰胺的单步方法，使用的腈的量可以是溶剂用量或试剂用量。与已知的碳正离子氨化条件下快速反应的基团（如叔醇、富电子烯烃、缩酮、弱 C-H 键和羧酸）相比，该方案对末端烯烃具有选择性。该方法还可以方便地制备多种位阻酰胺，包括一种快速合成金刚烷衍生的药物中间体。
