Categories: C-F Bond Formation >
Synthesis of fluoroalkanes
Aminodifluorosulfinium tetrafluoroborate salts act as efficient deoxofluorinating reagents when promoted by an exogenous fluoride source and, in most cases, exhibited greater selectivity by providing less elimination byproduct as compared to DAST and Deoxo-Fluor. Aminodifluorosulfinium tetrafluoroborates are storage-stable, and unlike DAST and Deoxo-Fluor do not react violently with water.
F. Beaulieu, L.-P. Beauregard, G. Courchesne, M. Couturier, F. LaFlamme, A. L'Heureux, Org. Lett., 2009, 11, 5050-5053.
PyFluor is an inexpensive and thermally stable deoxyfluorination reagent that fluorinates a broad range of alcohols with only minor formation of elimination side products. The reagents combines selectivity, safety, and economic viability.
M. K. Nielsen, C. R. Ugaz, W. Li, A. G. Doyle, J. Am. Chem. Soc., 2015, 137, 9571-9574.
AlkylFluor, a salt analogue of PhenoFluor, enables a practical, high-yielding deoxyfluorination of various primary and secondary alcohols. AlkylFluor is readily prepared on multigram scale and is stable to long-term storage in air and exposure to water.
N. W. Goldberg, X. Shen, J. Li, T. Ritter, Org. Lett., 2016, 18, 6102-6104.
An attractive catalytic hydrofluorination of olefins using a cobalt catalyst offers exclusive Markovnikov selectivity, functional group tolerance, and scalability. A preliminary mechanistic experiment showed the involvement of a radical intermediate.
H. Shigehisa, E. Nishi, M. Fujisawa, K. Hiroya, Org. Lett., 2013, 15, 5158-5161.
A powerful free radical Markovnikov hydrofluorination of unactivated alkenes is mediated by Fe(III)/NaBH4 using Selectfluor reagent as a source of fluorine. In contrast to the traditional radical hydrofluorination of alkenes, the Fe(III)/NaBH4-mediated reaction is conducted under exceptionally mild reaction conditions, tolerates various functional groups, and even runs open to the air and with water as a cosolvent.
T. J. Barker, D. L. Borger, J. Am. Chem. Soc., 2012, 134, 13588-13591.
A catalytic amount of AgNO3 enables an efficient decarboxylative fluorination of aliphatic carboxylic acids with Selectfluor in aqueous solution to yield the corresponding alkyl fluorides in good yields under mild conditions. This radical fluorination method is not only efficient and general but also chemoselective and functional-group-compatible, thus making it highly practical in the synthesis of fluorinated molecules.
F. Yin, Z. Wang, Z. Li, C. Li, J. Am. Chem. Soc., 2012, 134, 10401-10404.
Visible light-promoted photoredox catalysis enables a direct conversion of aliphatic carboxylic acids to the corresponding alkyl fluorides. This operationally simple, redox-neutral fluorination method allows the conversion of a broad range of carboxylic acids.
S. Ventre, F. R. Petronijevic, D. W. C. MacMillan, J. Am. Chem. Soc., 2015, 137, 5654-5657.
Direct fluorination of primary and secondary alcohols by a combination of perfluoro-1-butanesulfonyl fluoride (PBSF) and tetrabutylammonium triphenyldifluorosilicate (TBAT) under mild conditions provides the corresponding fluorides in high yields with inversion at the reaction center and suppressed elimination side reactions.
X. Zhao, W. Zhuang, D. Fang, X. Xue, J. Zhou, Synlett, 2009, 779-782.
A nucleophilic fluorination of triflates by weakly basic tetrabutylammonium bifluoride provides excellent yields with minimal formation of elimination-derived side products. Most primary and secondary hydroxyl groups are excellent substrates, but benzylic and aldol-type secondary hydroxyl groups give poor yields as a result of the instability of their triflates.
K.-Y. Kim, B. C. Kim, H. B. Lee, H. Shin, J. Org. Chem., 2008, 73, 8106-8108.
Bis(2-methoxyethyl)aminosulfur trifluoride (Deoxo-Fluor reagent) is a new deoxofluorinating agent that is much more thermally stable than DAST (C2H5)2NSF3. It is effective for the conversion of alcohols to alkyl fluorides, aldehydes and ketones to the corresponding gem-difluorides, and carboxylic acids to the trifluoromethyl derivatives with, in some cases, superior performance compared to DAST.
G. S. Lal, G. P. Pez, R. J. Pesaresi, F. M. Prozonic, H. Cheng, J. Org. Chem., 1999, 7048-7054.
A synergistic effect in nucleophilic fluorination has been demonstrated for the molecular combination of an ionic liquid and a tert-alcohol. Consequently, these functionalized ILs not only increase the nucleophilic reactivities of the fluoride anion but also remarkably reduce the olefin byproduct.
S. S. Shinde, B. S. Lee, D. Y. Chi, Org. Lett., 2008, 10, 733-735.
Nucleophilic fluorination using CsF or alkali metal fluorides was completed in short reaction time in the presence of [bmim][BF4] affording the desired products without any byproducts. Facile nucleophilic substitutions such as halogenations, acetoxylation, nitrilation, and alkoxylations in the presence of ionic liquids provided the desired products in good yields.
D. W. Kim, C. E. Song, D. Y. Chi, J. Org. Chem., 2003, 68, 4281-4285.
Fluorinations of epoxides and alkyl mesylates can be effectively achieved by reaction with Et3N • 3 HF under microwave irradiation. The reactions were completed in a few minutes and the use of large excess of reagents could be avoided.
T. Inagaki, T. Fukuhara, S. Hara, Synthesis, 2003, 1157-1159.
Halofluorination of alkenes in the presence of trihaloisocyanuric acids and HF•pyridine results in the formation of vicinal halofluoroalkanes in good yields. The reaction is regioselective leading to Markovnikov-oriented products and the halofluorinated adducts follow anti-addition in the case of cyclohexene and 1-methylcyclohexene.
L. T. C. Crespo, R. da S. Ribeiro, M. S. S. de Mattos, P. M. Esteves, Synthesis, 2010, 2379-2382.