Fujihira Yamato, Liang Yumeng, Ono Makoto, Hirano Kazuki, Kagawa Takumi, Shibata Norio
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.
Beilstein J Org Chem. 2021 Feb 12;17:431-438. doi: 10.3762/bjoc.17.39. eCollection 2021.
A straightforward method that enables the formation of biologically attractive trifluoromethyl ketones from readily available methyl esters using the potent greenhouse gas fluoroform (HCF, 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.
开发了一种直接的方法,该方法能够使用强效温室气体氟仿(HCF,HFC-23)从容易获得的甲酯形成具有生物吸引力的三氟甲基酮。在-40°C下,氟仿和KHMDS在三甘醇二甲醚中的组合对这种转化有效,产率高达92%。对芳香族、脂肪族和共轭甲酯的三氟甲基化反应的底物范围进行了探索。这项研究提出了一种直接的三氟甲基化过程,可将各种甲酯良好地转化为相应的三氟甲基酮。还探索了各种药效基团在反应条件下的耐受性。