Study on Transition Metal-Catalyzed Reactions of a Highly Strained Alkyne and Its Application to the Synthetic Organic Chemistry

该项目的重点是利用过渡金属催化剂开发芳烃和杂芳烃等高应变炔烃的新反应。提出了一种钯催化的联芳烃[2+2+2]共环合成联芳烃的新方法。通过这种方法，各种芳基萘衍生物，包括空间受阻的2，2‘-二取代-1，1’-联萘，可以通过二炔和芳烃前体的各种组合来构建。以该反应为关键步骤，实现了黄芩素C、E和脱氢鬼臼毒素的全合成。此外，还研究了二炔和杂芳烃的[2+2+2]共环化反应。因此，首次实现了镍催化的二炔和3，4-吡啶的[2+2+2]共环化反应，以较高的产率合成了异喹啉类化合物。在该反应中，3，4-吡啶前体的吡啶环上的给电子取代基被容忍，分别以较高的产率得到了各种取代的异喹啉。另一方面，发现前驱体吡啶环上的吸电子取代基阻碍了[2+2+2]的环化反应。

This project focused on the development of new reactions of highly strained alkynes such as arynes and heteroarynes using a transition metal catalyst. A novel method for construction of biaryls via palladium-catalyzed [2+2+2] cocyclization of diynes and arynes was developed. By this methodology, various arylnaphthalene derivatives, including a sterically hindered 2,2'-disubstituted-1,1'-binaphthyl, can be constructed by virtue of a variety of combinations of diynes and aryne precursors. Using this reaction as a key step, the total syntheses of taiwanins C, E, and dehydrodesoxypodophyllotoxin were achieved. Furthermore, a [2+2+2] cocyclization of diynes and heteroarynes was also investigated. As the result, a nickel-catalyzed [2+2+2] cocyclization of diynes and 3,4-pyridynes was developed for the first time, affording isoquinoline derivatives in good yields. In this reaction, an electron-donating substituent on the pyridine ring of the 3,4-pyridyne precursor was tolerated, giving various substituted isoquinolines in good yields, respectively. On the other hand, it was found that an electron-withdrawing substituent on the pyridine ring of the precursor retarded the [2+2+2] cocyclization.