Ma Xingxing, Su Jianke, Zhang Xingang, Song Qiuling
The Institute of Next Generation Matter Transformation, College of Material Sciences Engineering at Huaqiao University, 668 Jimei Boulevard, Xiamen, Fujian 361021, China.
Key Laboratory of Organofluorine Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, CAS, Shanghai 200032, China.
iScience. 2019 Sep 27;19:1-13. doi: 10.1016/j.isci.2019.07.005. Epub 2019 Jul 8.
The development of C1 synthons to afford the products that add one extra carbon has become an important research theme in the past decade, and significant progress has been achieved with CO, CO, HCOOH, and others as C1 units. Despite the great advance, the search for new C1 synthons that display unique reactivity, complement to the current C1 sources, and add more value to C1 chemistry is still desirable. Herein, we report a quadruple cleavage of chlorodifluoromethane to yield a C1 source, which was successfully employed in the construction of various N-containing compounds especially with pharmaceutical molecules under mild conditions. This strategy provides a useful method for late-stage modification of pharmaceutical compounds. Four bonds in ClCFH were orderly cleaved under basic conditions in the absence of transition metals. Preliminary mechanistic studies revealed that (E)-N-phenylformimidoyl fluoride intermediate is involved in this process by in situH NMR studies and control experiments.
在过去十年中，开发能提供额外添加一个碳原子产物的C1合成子已成为一个重要的研究主题，并且以CO、CO₂、HCOOH等作为C1单元已取得了显著进展。尽管取得了巨大进步，但寻找具有独特反应性、补充现有C1源并为C1化学增添更多价值的新型C1合成子仍然是很有必要的。在此，我们报道了二氟一氯甲烷的四重裂解以产生一种C1源，该C1源在温和条件下成功用于构建各种含氮化合物，尤其是含药物分子的化合物。该策略为药物化合物的后期修饰提供了一种有用的方法。在无过渡金属的碱性条件下，ClCF₂H中的四个键被有序裂解。初步机理研究表明，通过原位¹H NMR研究和对照实验，(E)-N-苯基甲脒基氟中间体参与了这一过程。
