Gu Xing-Wei, Zhao Yan-Hua, Wu Xiao-Feng
Leibniz-Institut für Katalyse e.V., 18059, Rostock, Germany.
Dalian National Laboratory for Clean Energy, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 116023, Dalian, Liaoning, China.
Nat Commun. 2024 Oct 31;15(1):9412. doi: 10.1038/s41467-024-53571-0.
Four-membered carbocycles are among the most sought-after backbones which are commonly found in biologically active molecules. However, difficulties on their producing are existing due to its highly strained ring system. On the other hand, cyclobutanols can be straightforwardly prepared and can serves as precursors for synthesizing cyclobutane derivatives. Here we report an example of regioselective aminocarbonylation of cyclobutanols in which the cyclobutane core remained intact. The method exhibits good functional group compatibility, as well as high regio- and stereoselectivity, offering new pathways for synthesizing several pharmaceuticals. Furthermore, this strategy enables the rapid installation of cyclobutane as a conformational restricted skeleton, greatly facilitating direct access to valuable drug molecules that require conformational restriction.
四元碳环是生物活性分子中最受追捧的骨架之一。然而，由于其高度紧张的环系，它们的制备存在困难。另一方面，环丁醇可以直接制备，并可作为合成环丁烷衍生物的前体。在此，我们报道了一个环丁醇区域选择性氨甲酰化的例子，其中环丁烷核心保持完整。该方法具有良好的官能团兼容性，以及高区域和立体选择性，为几种药物的合成提供了新途径。此外，该策略能够快速引入环丁烷作为构象受限骨架，极大地促进了直接获得需要构象限制的有价值药物分子。
