Efficient Difluoromethylation of Alcohols Using TMSCF2Br as a Unique and Practical Difluorocarbene Reagent under Mild Conditions.
A general method for the efficient difluoromethylation of alcohols using commercially available TMSCF2Br (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 TMSCF2Br. 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.
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.
Qiqiang
Q
Xie
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.
Chuanfa
0000-0002-2296-8835
C
Ni
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.
Rongyi
R
Zhang
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.
Lingchun
L
Li
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.
Jian
J
Rong
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.
Jinbo
0000-0003-3537-0207
J
Hu
alcohols; difluorocarbene; difluoromethyl ethers; fluorine; synthetic methods