Dikošová Lívia, Laceková Júlia, Záborský Ondrej, Fischer Róbert
Institute of Organic Chemistry, Catalysis and Petrochemistry, Slovak University of Technology in Bratislava, Radlinského 9, 81237 Bratislava, Slovak Republic.
Beilstein J Org Chem. 2020 Jun 16;16:1313-1319. doi: 10.3762/bjoc.16.112. eCollection 2020.
Isoxazolidines represent a very important class of N/O-containing heterocycles used as the key intermediates in the synthesis of more complex cyclic and acyclic compounds, including various biologically active molecules. Here, we present a fast and highly stereoselective approach towards both C-3/4- and C-3/4- isomers of 3-substituted isoxazolidin-4-ols. The strategy relies on a highly regio- and -stereoselective hydroboration-oxidation reaction of the 4,5-unsubstituted 2,3-dihydroisoxazoles with basic hydrogen peroxide. The consecutive oxidation/reduction route, sequentially employing Dess-Martin periodinane and ʟ-selectride, is used for the inversion of the C-3/4- relative configuration of the isoxazolidine ring. The significance of the method lies in its variability and applicability to a concise synthesis of various 4-hydroxyisoxazolidines, starting from the readily available -alkyl/aryl-nitrones. The resemblance to 3-hydroxypyrrolidines certainly makes the 4-hydroxyisoxazolidines important and valuable structural fragments in drug discovery.
异恶唑烷是一类非常重要的含氮/氧杂环化合物，用作合成更复杂的环状和非环状化合物（包括各种生物活性分子）的关键中间体。在此，我们展示了一种快速且高度立体选择性的方法来合成3-取代异恶唑烷-4-醇的C-3/4-异构体和C-3/4-异构体。该策略依赖于4,5-未取代的2,3-二氢异恶唑与碱性过氧化氢的高度区域和立体选择性硼氢化氧化反应。连续的氧化/还原路线，依次使用戴斯-马丁高碘烷和L-选择氢化物，用于反转异恶唑烷环的C-3/4-相对构型。该方法的重要性在于其可变性以及适用于从容易获得的α-烷基/芳基硝酮简洁合成各种4-羟基异恶唑烷。与3-羟基吡咯烷的相似性无疑使4-羟基异恶唑烷成为药物发现中重要且有价值的结构片段。
