Fu Xiang, Tang Jie, Hua Ruyu, Li Xiaoqian, Kang Zhenghui, Qiu Huang, Hu Wenhao
Guangdong Provincial Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
Org Lett. 2022 Mar 25;24(11):2208-2213. doi: 10.1021/acs.orglett.2c00516. Epub 2022 Mar 15.
To explore potential chemical space using DNA-encoded library (DEL) technology, the development of various types of robust DNA-compatible reactions is urgently needed. Diazo compounds, which serve as valuable building blocks and important synthons in synthetic chemistry, have been rarely applied in DEL synthesis, probably because of their potential modifications of the bases and phosphate backbone of DNA. Herein we report two cases of DNA-compatible reactions with alkenes and diazo compounds, providing corresponding hydroalkylation and cyclopropanation products in moderate to excellent yields. Notably, these transformations not only provide new access to C(sp)-C(sp) bond formation in DELs with excellent functional group tolerance but also represent practical ligation methods to introduce functionalized molecules into DNA.
为了利用DNA编码文库（DEL）技术探索潜在的化学空间，迫切需要开发各种类型的稳健的DNA兼容反应。重氮化合物在合成化学中是有价值的结构单元和重要的合成子，但很少应用于DEL合成，这可能是因为它们可能会修饰DNA的碱基和磷酸骨架。在此，我们报告了两例与烯烃和重氮化合物的DNA兼容反应，以中等至优异的产率提供了相应的氢烷基化和环丙烷化产物。值得注意的是，这些转化不仅为DELs中形成具有优异官能团耐受性的C(sp)-C(sp)键提供了新途径，而且代表了将功能化分子引入DNA的实用连接方法。
