Cobalt-Catalyzed Hydrogen-Atom Transfer Induces Bicyclizations that Tolerate Electron-Rich and Electron-Deficient Intermediate Alkenes
Cobalt-Catalyzed Hydrogen-Atom Transfer Induces Bicyclizations that Tolerate Electron-Rich and Electron-Deficient Intermediate Alkenes
复制标题
DOI：
10.1002/anie.202000252
复制
发表时间：
2020-02-25
影响因子：
16.6
通讯作者：
Vanderwal, Christopher D.
中科院分区：
文献类型：
--
作者：
Vrubliauskas, Darius;Vanderwal, Christopher D.
开发了一种新型的co - ii催化多烯环化反应，当以六氟异丙醇为溶剂时，该反应具有独特的效果。该过程可能是由金属催化的氢原子转移（MHAT）到1,1-二取代或单取代的烯烃引发的，并且该反应对含有富电子甲基或缺电子腈取代基的内烯烃具有显著的耐受性。在这两种情况下都需要富电子芳香终止体。获得了具有不同取代模式的萜类支架，具有良好的非对映选择性，并制备了具有生物活性的c20氧化枞烷二萜肉杂醛，以展示其含腈产品的实用性。还提供了几个机制实验的结果，表明该过程具有mhat诱导的自由基双环化和后期氧化以再生芳香终止物的特点。
A novel Co-II-catalyzed polyene cyclization was developed that is uniquely effective when performed in hexafluoroisopropanol as the solvent. The process is presumably initiated by metal-catalyzed hydrogen-atom transfer (MHAT) to 1,1-disubstituted or monosubstituted alkenes, and the reaction is remarkable for its tolerance of internal alkenes bearing either electron-rich methyl or electron-deficient nitrile substituents. Electron-rich aromatic terminators are required in both cases. Terpenoid scaffolds with different substitution patterns are obtained with excellent diastereoselectivities, and the bioactive C20-oxidized abietane diterpenoid carnosaldehyde was made to showcase the utility of the nitrile-bearing products. Also provided are the results of several mechanistic experiments that suggest the process features an MHAT-induced radical bicyclization with late-stage oxidation to regenerate the aromatic terminator.