Arnold Marlene, Hammes Jasmin, Ong Mike, Mück-Lichtenfeld Christian, Wahl Johannes M
Department Chemie, Johannes Gutenberg-Universität, Duesbergweg 10-14, 55128, Mainz, Germany.
Organisch-Chemisches Institut, Universität Münster, Corrensstraße 36, 48149, Münster, Germany.
Angew Chem Int Ed Engl. 2025 Jun 10;64(24):e202503056. doi: 10.1002/anie.202503056. Epub 2025 Apr 14.
The condensation of prochiral cyclobutanones and diphenylphosphinyl hydroxylamine is achieved under Brønsted acid catalysis. Interestingly, the competing aza-Baeyer-Villiger reaction is completely suppressed and the axially chiral oxime esters can be isolated in excellent yield and selectivity (up to 96% yield, up to 97:3 er). Computational analysis highlights the crucial role of the Brønsted acid in facilitating a successful condensation. Building on the inherent reactivity of the corresponding oxime esters, a one-pot protocol toward cyanocyclopropanes was discovered, which establishes two consecutive stereocenters. This unusual ring contraction is triggered by strong base and permits an axial-to-point chirality transfer with good enantiospecificity (up to 98% es). Fine-tuning the reaction parameters enables stereodivergent access to both diastereomers of the cyanocyclopropanes, and the utility of this method is demonstrated through the formal synthesis of the drug tasimelteon.
在手性布朗斯特酸催化下实现了前手性环丁酮与二苯基磷酰羟胺的缩合反应。有趣的是，竞争性的氮杂拜耳 - 维利格反应被完全抑制，轴向手性肟酯能够以优异的产率和选择性分离得到（产率高达96%，对映体过量比高达97:3）。计算分析突出了布朗斯特酸在促进成功缩合反应中的关键作用。基于相应肟酯的固有反应性，发现了一种用于合成氰基环丙烷的一锅法，该方法构建了两个连续的立体中心。这种不寻常的环收缩由强碱引发，并允许以良好的对映体特异性实现轴向到点手性的转移（对映体过量高达98%）。微调反应参数能够立体发散地获得氰基环丙烷的两种非对映异构体，并且通过药物他司美琼的形式合成证明了该方法的实用性。
