Synthesis of trifluoromethyl ketones by nucleophilic trifluoromethylation of esters under a fluoroform/KHMDS/triglyme system

Beilstein Journal of Organic Chemistry

Yamato Fujihira¹  Makoto Ono¹  Norio Shibata¹  Yumeng Liang²  Kazuki Hirano²  Takumi Kagawa³ 

[1] Department of Life Science and Applied Chemistry, Nagoya Institute of Technology, Gokiso, Showa-ku, Nagoya 466-5888, Japan;Department of Nanopharmaceutical Sciences, Nagoya Institute of Technology, Gokiso, Showa-ku, Nagoya 466-5888, Japan;Tosoh Finechem Corporation, 4988, Kaiseicho, Shunan, 746-0006, Japan;

关键词: fluoroform;    greenhouse gas;    hfc-23;    trifluoromethyl ketones;    trifluoromethylation;   

DOI  :  10.3762/bjoc.17.39

来源: DOAJ

【 摘 要 】

A straightforward method that enables the formation of biologically attractive trifluoromethyl ketones from readily available methyl esters using the potent greenhouse gas fluoroform (HCF3, HFC-23) was developed. The combination of fluoroform and KHMDS in triglyme at −40 °C was effective for this transformation, with good yields as high as 92%. Substrate scope of the trifluoromethylation procedure was explored for aromatic, aliphatic, and conjugated methyl esters. This study presents a straightforward trifluoromethylation process of various methyl esters that convert well to the corresponding trifluoromethyl ketones. The tolerance of various pharmacophores under the reaction conditions was also explored.

【 授权许可】

Unknown