Categories: C-F Bond Formation >
Synthesis of α-fluorocarboxylic acids and derivatives
Recent Literature
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.
The reaction of ketene acetals with AcOF made directly from fluorine provides
α-fluorocarboxylic esters and acids in good yields. This route circumvents the
problems associated with nucleophilic fluorinations such as eliminations and
rearrangements. Even α-fluoro derivatives of α- and β-branched carboxylic acid
derivatives can be isolated in good yield.
S. Rozen, A. Hagooly, R. Harduf, J. Org. Chem., 2001,
66, 7464-7468.
An unbalanced ion pair promoter consisting of a bulky and charge-delocalized cation and a small and
charge-localized anion, greatly accelerates nucleophilic fluorinations with KF.
An inexpensive and commercially
available ion-exchange resin can easily be converted into a recycable polymer-supported ion pair promoter, which
can also be used in continuous flow conditions.
W. Li, Z. Lu, G. B. Hammond, B. Xu, Org. Lett., 2021, 23,
9640-9644.
A divergent strategy for the fluorination of phenylacetic acid derivatives is
induced by a charge-transfer complex between Selectfluor and
4-(dimethylamino)pyridine. In the presence of water, decarboxylative
fluorination through a single-electron oxidation is dominant. Non-aqueous
conditions result in the clean formation of α-fluoro-α-arylcarboxylic acids.
A. Madani, L. Anghileri, M. Heydenreich, H. M. Möller, B. Pieber, Org. Lett.,
2022, 24, 5376-5380.
Planar chiral [2.2]paracyclophane-based isothiourea catalysts catalyze a
highly efficient enantioselective fluorination of carboxylic acids to provide a
broad range of optically active α-fluoroesters in high yield and excellent
enantioselectivity.
S. Yuan, C. Liao, W.-H. Zheng, Org. Lett., 2021, 23,
4142-4146.
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.
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.
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.
An isothiourea-catalyzed fluorination of alkynyl-substituted acetic acids
provides a broad range of optically active tertiary α-alkyl fluorides in high
enantioselectivity (up to 97% ee). Furthermore, this methodology can be scaled
up to a Gram scale without loss of enantioselectivity.
S. Yuan, W.-H. Zheng, J. Org. Chem., 2022, 87,
713-720.
Related
A efficient copper-catalyzed cross-coupling of allyl phosphate with
2-fluoro-2-(trimethylsilyl)acetate provides a series of monofluoroalkylation
products in high yields.
Y. Liu, R. Chen, L. Lu, D. Yin, F. Yan, X.-X. Li, H. Xiao, S. Fun, S. Fun,
Y.-S. Feng, J. Org. Chem., 2023, 88,
7469-7476.
A photochemically mediated defluorinative hydroalkylation of ethyl
trifluoroacetate with a diverse suite of alkenes in the presence of sodium
formate enables a concise synthetic approach to novel gem-difluoro
analogs of FDA-approved pharmaceutical compounds. Furthermore,
trifluoroacetamides can also be functionalized via synergistic Lewis acid/photochemical
activation.
M. W. Campbell, V. C. Polites, S. Patel, J. E. Lipson, J. Majhi, G. A.
Molander, J. Am. Chem. Soc.,
2021, 143, 19648-19654.
Under mild irradiation conditions using violet light-emitting diodes, a
catalytic amount of N-(4-mercaptophenyl)pivalamide promotes monoselective
defluoroalkylation of trifluoroacetates with a variety of aliphatic alkenes in
the presence of a formate salt to provide valuable α,α-difluoro substituted
aliphatic carboxylate esters.
C. Liu, N. Shen, R. Shang, Synthesis, 2023,
55,
1401-1409.