Synthesis of fluoroalkanes

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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.

Perfluoroalkyl ether carboxylic acids (PFECAs) are alternatives for perfluoroalkyl substances with the goal of protecting the environment. PFECAs decompose to carbonic difluoride (COF₂), which can be used for deoxyfluorination reactions of alcohols to provide alkyl fluorides in very good yields.
S. Zhao, Y. Guo, Z. Su, W. Cao, C. Wu, Q.-Y. Chen, Org. Lett., 2020, 22, 8634-8637.

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 method for deoxyfluorination of aliphatic alcohols employes a nontrigonal phosphorus triamide for base-free alcohol activation in conjunction with an organic soluble fluoride donor and a triarylborane fluoride shuttling catalyst. The substrate scope complements existing deoxyfluorination methods and enables the preparation of stereoinverted products.
H. W. Moon, M. N. Lavagnino, S. Lim, M. D. Palkowitz, M. D. Mandler, G. L. Beutner, M. J. Drance, J. M. Lipshultz, P. M. Scola, A. T. Radosevich, J. Am. Chem. Soc., 2023, 145, 22735-22744.

In situ generation of highly active CF₃SO₂F enables a deoxyfluorination of alcohols with KF as the fluorine source. This mild and fast reaction tolerates diverse functionalities, including halogen, nitro, ketone, ester, alkene, and alkyne.
J. Xu, C. Peng, B. Yao, H.-J. Xu, Q. Xie, J. Org. Chem., 2022, 87, 6471-6478.

The combination of methanesulfonic acid and potassium bifluoride enables a deoxyfluorination of tertiary alcohols. Using readily available, cheap, and easy-to-handle reagents, a range of tertiary alcohols could be converted into the corresponding fluorides in excellent yields. The application of these conditions for the fluorination of ethers and esters is also demonstrated.
X. Bertrand, M. Pucheault, L. Chabaud, J.-F. Paquin, J. Org. Chem., 2023, 88, 14527-14539.

The combination of silyl radical-mediated halogen-atom abstraction and benzophenone photosensitization enables a fluorination of alkyl bromides. Selectivity for halogen-atom abstraction over Si-F bond formation is observed in the presence of an electrophilic fluorinating reagent containing a weak N-F bond.
G. H. Lovett, S. Chen, X.-S. Xue, K. N. Houk, D. W. C. MacMillan, J. Am. Chem. Soc., 2019, 141, 20031-20036.

Inexpensive PPh₃ catalyzes a mild fluorination of unactivated tertiary alkyl chlorides (and bromides). This straightforward process is compatible with a range of hindered electrophiles and a variety of functional groups.
Z.-Y. Wang, D. J. Freas, G. C. Fu, J. Am. Chem. Soc., 2023, 145, 25093-25097.

Activation of a hydroxyl group by a Ph₂PCH₂CH₂PPh₂/ICH₂CH₂I system enables an efficient dehydroxylative fluorination of tertiary alcohols with Selectfluor. The reaction occurs rapidly to give the desired products in good yields.
W. Zhang, Y.-C. Gu, J.-H. Lin, J.-C. Xiao, Org. Lett., 2020, 22, 6642-6646.

KHSO₄-13HF (HF 68 wt/wt-%) as is an easily handled and inexpensive nucleophilic fluorination reagent, that is capable of hydrofluorinating diverse, highly functionalized alkenes, including natural products. The high efficiency of this reaction is caused by the activation of HF with a highly "acidic" hydrogen bond acceptor.
Z. Lu, X. Zeng, G. B. Hammon, B. Xu, J. Am. Chem. Soc., 2017, 139, 18202-18205.

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 combination of methanesulfonic acid and triethylamine trihydrofluoride enables a direct hydrofluorination of methallyl-containing substrates under those metal-free conditions that use readily available, cheap, and easy to handle reagents. A range of methallyl alkenes could be converted to their corresponding tertiary fluorides in good yield.
X. Bertrand, J.-F. Paquin, Org. Lett., 2019, 21, 9759-9762.

A β-boron effect accounts for high regioselectivity in electrophilic addition reactions to allylic MIDA (N-methyliminodiacetic acid) boronates. The boryl moiety is retained in the product when B(MIDA) is used as the nucleophilic stabilizer.
Y. Li, W.-X. Fan, S. Luo, A. Tofimova, Y. Liu, J.-H. Xue, L. Yang, Q. Li, H. Wang, A. K. Yudin, J. Am. Chem. Soc., 2023, 145, 7548-7558.

Iron salts catalyze an efficient and inexpensive protocol for the direct decarboxylative fluorination of aliphatic carboxylic acids under visible light irradition. This method allows the facile fluorination of a diverse array of carboxylic acids even on gram scale using a Schlenk flask without loss of efficiency.
Y. Zhang, J. Qian, M. Wang, Y. Huang, P. Hu, Org. Lett., 2022, 24, 5972-5976.

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.

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.

A bis-triethylene glycolic crown-5-calix[4]arene (BTC5A) is a multifunctional promoter for nucleophilic fluorination using KF. The synergetic effect of the calix-crown moiety and ethylene glycols of BTC5A enabled KF to be easily dissolved in organic solvents and activated the fluoride in even nonpolar aprotic media.
S. M. Kang, C. H. Kim, K. C. Lee, D. W. Kim, Org. Lett., 2019, 21, 3062-3066.

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.

Iodofluorination of aliphatic and aromatic alkenes with iodine and HF·pyridine complex (pyr·9HF) was performed under mild conditions in the presence of K₂S₂O₈ or Na₂S₂O₈ as oxidants. Substitution reactions of the iodofluorinated products by nitrogen, sulfur, and oxygen nucleophiles enable further applications as a building blocks for synthesis of 2-fluoroalkyl-substituted compounds.
T. Kitamura, R. Komoto, J. Oyamada, M. Higashi, Y. Kishikawa, J. Org. Chem., 2021, 86, 18300-18303.

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.

The reaction of unactivated alkenes with dibromofluoromethane under photoredox catalysis provides 1-bromo-1-fluoroalkanes in THF as solvent. 1,3-Dibromo-1-fluoroalkanes were chemoselectively formed using DMF/H₂O as solvent.
F. Chen, X.-H. Xu, F.-L. Qing, Org. Lett., 2021, 23, 2364-2369.

A general strategy for the 1,3-oxidation of cyclopropanes using aryl iodine(I-III) catalysis enables the synthesis of 1,3-difluorides, 1,3-fluoroacetoxylated products, 1,3-diols, 1,3-amino alcohols, and 1,3-diamines. These reactions make use of practical, commercially available reagents and can engage a variety of substituted cyclopropane substrates.
S. M. Banik, K. M. Mennie, E. N. Jacobsen, J. Am. Chem. Soc., 2017, 139, 9152-9155.

Azetidinium triflates are suitable substrates for enantioselective ring opening with CsF and a chiral bis-urea catalyst. The ability of hydrogen bonding phase-transfer catalysts to couple two ionic reactants, affords enantioenriched γ-fluoroamines in high yields.
G. Roagna, D. M. H. Ascough, F. Ibba, A. C. Vicini, A. Fontana, K. E. Christensen, A. Peschiulli, D. Oehrich, A. Misale, A. A. Tranco, R. S. Paton, G. Pupo, V. Gouverneur, J. Am. Chem. Soc., 2020, 142, 14045-14051.