Categories: C-F Bond Formation >
Synthesis of fluoroketones and fluoroaldehydes
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 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 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.
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.
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.