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Synthesis of fluoroketones and fluoroaldehydes

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Catalytic enantioselective fluorination and chlorination reactions of carbonyl compounds were achieved with high enantioselectivity by the use of a dbfox-NiII complex.
N. Shibata, J. Kohno, K. Takai, T. Ishimaru, S. Nakamura, T. Toru, S. Kanemasa, Angew. Chem. Int. Ed., 2005, 44, 4204-4207.


The use of 1-fluoro-4-hydroxy-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) (Accufluor NFTh) as a fluorine transfer reagent and methanol as solvent enabled direct regiospecific fluorofunctionalization of the α-carbonyl position in ketones without prior activation of the target molecules.
S. Stavber, M. Jereb, M. Zupan, Synthesis, 2002, 2609-2615.


The direct fluorination reaction of acetophenone derivatives, acetonaphthones, benzyl phenyl ketone, propiophenone, butyrophenone, 1-indanone, and phenacyl chloride using iodosylarenes and TEA·5HF gives the corresponding α-fluoroketone derivatives in good yields under mild conditions except for use of a HF reagent.
T. Kitamura, K. Muta, K. Muta, J. Org. Chem., 2014, 79, 5842-5846.


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.


An efficient and mild fluorination of vinyl azides enables the synthesis of α-fluoroketones via a single-electron transfer (SET) and a subsequent fluorine atom transfer.
S.-W. Wu, F. Liu, Org. Lett., 2016, 18, 3642-3645.


Allylic alcohols are isomerized into enolates (enols) by [Cp*IrCl2]2. A subsequent reaction with Selectfluor present in the reaction media produces α-fluoro ketones as single constitutional isomers in good yields.
N. Ahlsten, A. Bartoszewicz, S. Agrawal, B. Martín-Matute, Synthesis, 2011, 2600-2608.


A micellar system was developed and applied for direct regioselective fluorination of various cyclic and acyclic ketones to α-fluoroketones in water as reaction medium with Selectfluor (F-TEDA-BF4) as fluorinating reagent. The inexpensive ionic amphiphile sodium dodecyl sulfate (SDS) was found to be an excellent promoter.
G. Stavber, M. Zupan, S. Stavber, Synlett, 2009, 589-594.


A metal-free and green catalytic system enables an oxyfluorination of olefins for the synthesis of α-fluoroketones which is an important building block for organic synthesis. Moreover, this reaction system exhibits great functional group tolerance.
Q. Yang, L.-L. Mao, B. Yang, S.-D. Yang, Org. Lett., 2014, 16, 3460-3463.


A decarboxylative fluorination of tertiary β-keto carboxylic acids using an electrophilic fluorinating reagent proceeded in the absence of a catalyst or base to yield the corresponding α-fluoroketones very good yields.
M. Katada, K. Kitahara, S. Iwasa, K. Shibatomi, Synlett, 2018, 29, 2408-2411.


A vanadium-catalyzed coupling of allenylic alcohols with electrophilic halide sources provides α-halo-α',β'-unsaturated ketones. Fluorine, chlorine, and bromine electrophiles can be utilized, and the resulting products can give rise to the introduction of nitrogen, oxygen, sulfur, and iodine nucleophiles α to the ketone through substitution chemistry.
B. M. Trost, J. S. Tracy, T. Yusoontorn, Org. Lett., 2019, 21, 1207-1211.


A β,β-diaryl serine catalyzes an enantioselective fluorination of α-substituted β-diketones to afford the corresponding fluorinated products in very good yields with excellent enantioselectivity. The CO2H group of the primary amine organocatalyst plays an important role in inducing the high enantioselectivity. Products could be converted into diols, aldols, and allylic fluorides without racemization.
S. Poorsadeghi, K. Endo, S. Arimitsu, Org. Lett., 2022, 24, 420-424.


A transition-metal-free coupling of esters with geminal bis(boron) compounds provides an α,α-bis(enolate) equivalent which can be trapped with electrophiles including alkyl halides and fluorinating agents. This presents an efficient, convergent synthetic strategy for the synthesis of α,α-difunctionalized ketones.
C. E. Iacono, T. C. Stephens, T. S. Rajan, G. Pattison, J. Am. Chem. Soc., 2018, 140, 2036-2040.


A desulfurizing difluorination reaction of benzyl sulfides having an electron-withdrawing group such as an ester, a ketone, a nitrile, or an amide in the presence of IF5 gave gem-difluoro compounds in good yield.
T. Fukuhara, S. Hara, Synlett, 2009, 198-200.


Reactions of enamines with Selectfluor under mild conditions easily led to the corresponding difluorinated carbonyl compounds in high yields.
W. Peng, J. M. Shreeve, J. Org. Chem., 2005, 70, 5760-5763.


W. Peng, J. M. Shreeve, J. Org. Chem., 2005, 70, 5760-5763.


W. Peng, J. M. Shreeve, J. Org. Chem., 2005, 70, 5760-5763.


Allenyl carbinol esters isomerize to an E,Z mixture of the corresponding dienes in the presence of a gold catalyst. In a subsequent reaction with Selectfluor, this mixture can be converted to monofluoroalkyl α,β-unsaturated ketones with exclusive E selectivity in high yields.
Z. Jin, R. S. Hidinger, B. Xu, G. B. Hammond, J. Org. Chem., 2012, 77, 7725-7726.


An organocatalytic system of L-proline and salicylic acid enables a highly stereoselective synthesis of α,α-difluoro-γ,γ-disubstituted butenals. The reaction offers a wide substrate scope and excellent E stereoselectivity in most cases.
S. Arimitsu, M. Nakasone, J. Org. Chem., 2016, 81, 6707-6713.


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.


A convenient reaction of isoxazoles with an electrophilic fluorinating agent (Selectfluor) provides tertiary fluorinated carbonyl compounds under mild reaction conditions and with good functional group tolerance. Diverse transformations of the resulting α-fluorocyanoketones furnish a broad range of fluorinated compounds.
M. Komatsuda, H. Ohki, H. Kondo Jr., A. Suto, J. Yamaguchi, Org. Lett., 2022, 24, 3270-3274.

Related


A method for the homologation of ketones with the CF2 fragment involves silylation, room-temperature difluorocyclopropanation of silyl enol ethers, and selective ring opening of cyclopropanes under acidic conditions. The whole three-step sequence is conveniently performed in one-pot.
M. D. Kosobokov, V. V. Levin, M. I. Struchkova, A. D. Dilman, Org. Lett., 2015, 17, 760-763.


A general site-selective difluoroalkylation of alkyl carboxylic redox esters with difluoroenoxysilanes through photoredox-catalyzed decarboxylation offers high efficiency, mild reaction conditions, and broad substrate scope. The reaction tolerates primary, secondary, and sterically hindered tertiaryl alkyl substrates and can also be extended to aliphatic amine derived pyridinium salts.
H. Song, R. Cheng, Q.-Q. Min, X. Zhang, Org. Lett., 2020, 22, 7747-7751.