Premium
Efficient Difluoromethylation of Alcohols Using TMSCF 2 Br as a Unique and Practical Difluorocarbene Reagent under Mild Conditions
Author(s) -
Xie Qiqiang,
Ni Chuanfa,
Zhang Rongyi,
Li Lingchun,
Rong Jian,
Hu Jinbo
Publication year - 2017
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201611823
Subject(s) - difluorocarbene , reagent , alcohol , phosphonate , chemistry , organic chemistry , trimethylsilyl , primary (astronomy) , combinatorial chemistry , physics , astrophysics
A general method for the efficient difluoromethylation of alcohols using commercially available TMSCF 2 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 2 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.