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

ABSTRACT: 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.

SUBMITTER: Fujihira Y

PROVIDER: S-EPMC7884878 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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

Fujihira Yamato Y Liang Yumeng Y Ono Makoto M Hirano Kazuki K Kagawa Takumi T Shibata Norio N

Beilstein journal of organic chemistry 20210212

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 ...[more]

PMID: 33633811

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