Li Long, Zhu Xin-Qi, Zhang Ying-Qi, Bu Hao-Zhen, Yuan Peng, Chen Jinyu, Su Jingyi, Deng Xianming, Ye Long-Wu
State Key Laboratory of Physical Chemistry of Solid Surfaces , Key Laboratory for Chemical Biology of Fujian Province , College of Chemistry and Chemical Engineering , Xiamen University , Xiamen 361005 , China . Email:
State Key Laboratory of Cellular Stress Biology , School of Life Sciences , Xiamen University , Xiamen , Fujian 361102 , China.
Chem Sci. 2019 Jan 24;10(10):3123-3129. doi: 10.1039/c9sc00079h. eCollection 2019 Mar 14.
Alkene carbooxygenation has attracted considerable attention over the past few decades as this approach provides an efficient access to various oxygen-containing molecules, especially the valuable O-heterocycles. However, examples of catalytic alkene carbooxygenation a direct C-O cleavage are quite scarce, and the C-O cleavage in these cases is invariably initiated by transition metal-catalyzed oxidative addition. We report here a novel Brønsted acid-catalyzed intramolecular alkoxylation-initiated tandem sequence, which represents the first metal-free intramolecular alkoxylation/Claisen rearrangement. Significantly, an unprecedented Brønsted acid-catalyzed intramolecular alkene insertion into the C-O bond a carbocation pathway was discovered. This method allows the stereocontrolled synthesis of valuable indole-fused bridged [4.2.1] lactones, providing ready access to biologically relevant scaffolds in a single synthetic step from an acyclic precursor. Moreover, such an asymmetric cascade cyclization has also been realized by employing a traceless chiral directing group. Control experiments favor the feasibility of a carbocation pathway for the process. In addition, biological tests showed that some of these newly synthesized indole-fused lactones exhibited their bioactivity as antitumor agents against different breast cancer cells, melanoma cells, and esophageal cancer cells.
在过去几十年中，烯烃碳氧加成反应备受关注，因为这种方法能够有效合成各种含氧分子，尤其是有价值的氧杂环化合物。然而，催化烯烃碳氧加成反应中直接碳 - 氧键断裂的例子相当稀少，并且在这些情况下碳 - 氧键的断裂总是由过渡金属催化的氧化加成引发。我们在此报道一种新型的布朗斯特酸催化的分子内烷氧基化引发的串联反应序列，这是首例无金属的分子内烷氧基化/克莱森重排反应。值得注意的是，发现了一种前所未有的通过碳正离子途径实现的布朗斯特酸催化的分子内烯烃插入碳 - 氧键的反应。该方法能够立体选择性地合成有价值的吲哚稠合桥连[4.2.1]内酯，从无环前体通过一步合成即可方便地得到具有生物学相关性的骨架结构。此外，通过使用无痕手性导向基团也实现了这种不对称串联环化反应。对照实验支持了该过程中碳正离子途径的可行性。另外，生物学测试表明，这些新合成的一些吲哚稠合内酯作为抗肿瘤剂对不同的乳腺癌细胞、黑色素瘤细胞和食管癌细胞表现出生物活性。
