Premium
A General Protocol for C−H Difluoromethylation of Carbon Acids with TMSCF 2 Br
Author(s) -
Xie Qiqiang,
Zhu Ziyue,
Li Lingchun,
Ni Chuanfa,
Hu Jinbo
Publication year - 2019
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.201900763
Subject(s) - protocol (science) , carbon fibers , chemistry , computer science , medicine , algorithm , composite number , alternative medicine , pathology
An efficient method for the selective C‐difluoromethylation of carbon acids with the reagent TMSCF 2 Br has been developed. A variety of structurally diverse sp 3 ‐ and sp‐hybridized carbon nucleophiles, including esters, amides, fluorenes, terminal alkynes, β‐ketoesters, malonates, and other activated C−H nucleophiles, could be efficiently and selectively transformed into the corresponding C‐difluoromethylated products under mild conditions. This protocol is also effective for the late‐stage difluoromethylation of pharmaceutically relevant molecules and can be readily scaled up. Moreover, ambident substrates with more than one reactive site towards difluorocarbene can be difluoromethylated orthogonally using TMSCF 2 Br.