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Synthesis of α-fluorocarboxylic acids and derivatives

Recent Literature


A catalytic asymmetric coupling of aryl alkyl ketenes with commercially available N-fluorodibenzenesulfonimide (NFSI) and C6F5ONa furnishes tertiary α-fluoroesters. Mechanistic studies suggest that the addition of an external nucleophile (C6F5ONa) is critical for turnover, releasing the catalyst from an N-acylated intermediate.
S. Y. Lee, S. Neufeind, G. C. Fu, J. Am. Chem. Soc., 2014, 136, 8899-8902.


A Ag-catalyzed decarboxylative fluorination reaction provides an unprecedented route to either gem-difluoroalkanes or α-fluorocarboxylic acids from malonic acid derivatives by the judicious selection of base and solvent. This reaction features the use of readily available starting materials, tunable chemoselectivity and good functional group compatibility.
Z. Wang, C.-Y. Guo, C. Yang, J.-P. Chen, J. Am. Chem. Soc., 2019, 141, 5617-5622.


A copper-catalyzed H-F insertion into α-diazocarbonyl compounds provides complex α-fluorocarbonyl derivatives under mild conditions using potassium fluoride (KF) and hexafluoroisopropanol. The method is readily adapted to radiofluorination with [18F]KF.
E. E. Gray, M. K. Nielsen, K. A. Choquette, J. A. Kalow, T. J. A. Graham, A. G. Doyle, J. Am. Chem. Soc., 2016, 138, 10802-10805.


By altering the amount of Selectfluor, a highly selective mono- and difluorination of 1,3-dicarbonyl compounds provides various 2-fluoro- and 2,2-difluoro-1,3-dicarbonyl compounds in very good yields. This  practical and convenient fluorination can be performed in aqueous media without any catalyst and base.
L. Tang, Z. Yang, J. Jiao, Y. Cui, G. Zou, Q. Zhou, Y. Zhou, W. Rao, X. Ma, J. Org. Chem., 2019, 84, 10449-10458.


By altering the amount of Selectfluor, a highly selective mono- and difluorination of 1,3-dicarbonyl compounds provides various 2-fluoro- and 2,2-difluoro-1,3-dicarbonyl compounds in very good yields. This  practical and convenient fluorination can be performed in aqueous media without any catalyst and base.
L. Tang, Z. Yang, J. Jiao, Y. Cui, G. Zou, Q. Zhou, Y. Zhou, W. Rao, X. Ma, J. Org. Chem., 2019, 84, 10449-10458.