School of Pharmaceutical Sciences, MOE Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Tsinghua University, Beijing, 100084, China.
Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education and Beijing National Laboratory for Molecular Science (BNLMS), College of Chemistry, Peking University, Beijing, 100871, China.
Angew Chem Int Ed Engl. 2021 Feb 19;60(8):4221-4230. doi: 10.1002/anie.202013169. Epub 2020 Dec 21.
An unprecedented strain-driven dyotropic rearrangement of α-methylene-β-lactones has been realized, which enables the efficient access of a wide range of α-methylene-γ-butyrolactones displaying remarkable structural diversity. Several appealing features of the reaction, including excellent efficiency, high stereospecificity, predictable chemoselectivity and broad substrate scope, render it a powerful tool for the synthesis of MBL-containing molecules of either natural or synthetic origin. Both experimental and computational evidences suggest that the new variant of dyotropic rearrangements proceed in a dualistic pattern: while an asynchronous concerted mechanism most likely accounts for the reactions featuring hydrogen migration, a stepwise process involving a phenonium ion intermediate is favored in the cases of aryl migration. The great synthetic potential of the title reaction is exemplified by its application to the efficient construction of several natural products and relevant scaffolds.
实现了前所未有的应变驱动的α-亚甲基-β-内酰胺的双稠合重排，这使得广泛的α-亚甲基-γ-丁内酯能够高效地获得，同时展示出显著的结构多样性。该反应具有许多吸引人的特点，包括高效率、高立体选择性、可预测的化学选择性和广泛的底物范围，使其成为合成天然或合成来源的含 MBL 分子的有力工具。实验和计算证据表明，双稠合重排的新变体以二元模式进行：虽然异步协同机制很可能解释了具有氢迁移的反应，但在芳基迁移的情况下，涉及苯鎓离子中间体的分步过程更为有利。该标题反应的巨大合成潜力通过其在几种天然产物和相关支架的高效构建中的应用得到了例证。
