Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Ling-Ling Road, Shanghai, 200032, China.
School of Physical Science and Technology, ShanghaiTech University, 100 Haike Road, Shanghai, 201210, China.
Angew Chem Int Ed Engl. 2017 Mar 13;56(12):3206-3210. doi: 10.1002/anie.201611823. Epub 2017 Feb 9.
A general method for the efficient difluoromethylation of alcohols using commercially available TMSCF Br (TMS=trimethylsilyl) as a unique and practical difluorocarbene source is developed. This method allows primary, secondary, and even tertiary alkyl difluoromethyl ethers to be synthesized under weakly basic or acidic conditions. The reaction mainly proceeds through the direct interaction between a neutral alcohol and difluorocarbene, which is different from the difluoromethylation of phenols. Moreover, alcohols containing other moieties that are also reactive toward difluorocarbene can be transformed divergently by using TMSCF Br. This research not only solves the synthetic problem of difluorocarbene-mediated difluoromethylation of alcohols, it also provides new insights into the different reaction mechanisms of alcohol difluoromethylation and phenol difluoromethylation with difluorocarbene species.
本文开发了一种使用商业可得的 TMSCFBr（TMS=三甲基硅基）作为独特且实用的二氟卡宾源高效地对醇进行二氟甲基化的通用方法。该方法允许在弱碱性或酸性条件下合成伯、仲甚至叔烷基二氟甲基醚。该反应主要通过中性醇与二氟卡宾的直接相互作用进行，这与酚的二氟甲基化反应不同。此外，通过使用 TMSCFBr，还可以使含有其他对二氟卡宾也具有反应性的部分的醇进行发散转化。这项研究不仅解决了二氟卡宾介导的醇的二氟甲基化的合成问题，还为二氟卡宾与醇和酚的不同反应机制提供了新的见解。
