186297-56-3Relevant academic research and scientific papers
Decarboxylative fluorination of β-Ketoacids with N-fluorobenzenesulfonimide (NFSI) for the synthesis of α-fluoroketones: Substrate scope and mechanistic investigation
Zhang, Rui,Ni, Chuanfa,He, Zhengbiao,Hu, Jinbo
, p. 166 - 172 (2017)
Cesium carbonate (Cs2CO3)-mediated decarboxylative fluorination of β-ketoacids using NFSI in the MeCN/H2O mixed solvent system affords α-fluoroketones with a broad scope. Both electron-rich and electron-deficient α-non-substituted β-ketoacids are amenable to this protocol. The mechanistic study indicates that the reaction proceeds through electrophilic fluorination followed by decarboxylation, which is different from the decarboxylative fluorination of normal carboxylic acids.
Fluoro-Substituted Methyllithium Chemistry: External Quenching Method Using Flow Microreactors
Colella, Marco,Degennaro, Leonardo,Higuma, Ryosuke,Ishikawa, Susumu,Luisi, Renzo,Nagaki, Aiichiro,Takahashi, Yusuke,Tota, Arianna
, p. 10924 - 10928 (2020/05/08)
The external quenching method based on flow microreactors allows the generation and use of short-lived fluoro-substituted methyllithium reagents, such as fluoromethyllithium, fluoroiodomethyllithium, and fluoroiodostannylmethyllithium. Highly chemoselective reactions have been developed, opening new opportunities in the synthesis of fluorinated molecules using fluorinated organometallics.
Ruthenium-catalysed asymmetric transfer hydrogenation of para-substituted α-fluoroacetophenones
Fuglseth, Erik,Sundby, Eirik,Hoff, B?rd H.
experimental part, p. 600 - 603 (2009/11/30)
The first examples of asymmetric transfer hydrogenation of α-fluoroacetophenones are reported. Eight para-substituted α-fluoroacetophenones have been reduced using four catalytic systems constructed of [RuCl2(p-cymene)2]2 or [RuCl2(mesitylene)2]2 in combinations with each of the ligands (1R,2R)-N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine ((R,R)-TsDPEN) and (1R,2R)-N-(p-toluenesulfonyl)-1,2-cyclohexanediamine ((R,R)-TsCYDN). All reactions were performed in both water and formic acid/triethylamine. The highest enantioselectivity was obtained using the (R,R)-TsDPEN ligand in a formic acid/triethylamine mixture, giving the (S)-1-aryl-2-fluoroethanols in high to moderate enantiomeric excess (97.5-84.5%). For this solvent system the presence of electron withdrawing groups in the para position reduced the enantioselectivity. Reactions performed in water generally gave lower enantioselectivity and reaction rate, although RuCl(mesitylene)-(R,R)-TsDPEN yielded the product alcohols with enantiomeric excess in the range of 95.5-76.5%.
Microwave assisted fluorination: an improved method for side chain fluorination of substituted 1-arylethanones
Krane Thvedt, Thor H?kon,Fuglseth, Erik,Sundby, Eirik,Hoff, B?rd Helge
experimental part, p. 9550 - 9556 (2010/02/27)
A two-step, one-pot microwave (MW) assisted fluorination of 1-arylethanones to their corresponding 1-aryl-2-fluoroethanones has been developed. The first step utilises Selectfluor as a fluorinating agent in methanol forming 1-aryl-2-fluoroethanones and their corresponding dimethyl acetals. In the second step, water is added and Selectfluor acts as a Lewis acid in the hydrolytic cleavage of the dimethyl acetals. Compared to the thermal synthesis, the MW assisted method leads to a reduction in reaction time both in the fluorination and for the dimethyl acetal cleavage. Moreover, the one-pot procedure reduces reagent and solvent consumption. The method is best suited for the preparation of 1-aryl-2-fluoroethanones containing substituents that deactivates electrophilic aromatic substitution, however highly electron deficient ketones such as 1-(3,5-dinitrophenyl)ethanone reacts more slowly. Reactions using electron rich aromatic ketones had a low regioselectivity, and also produced fluoroaromatic products.
Electrophilic and nucleophilic side chain fluorination of para-substituted acetophenones
Fuglseth, Erik,Thvedt, Thor H?kon Krane,M?ll, Maria F?rde,Hoff, B?rd Helge
, p. 7318 - 7323 (2008/12/21)
para-Substituted α-fluoroacetophenones have been synthesised by three different routes. Electrophilic fluorination of trimethylsilyl enol ethers of acetophenones using Selectfluor (F-TEDA-BF4, 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis-(tetrafluoroborate)) gave high to moderate yield depending on the electronic properties of the substituents. F-TEDA-BF4 mediated fluorination of acetophenones in methanol resulted in a mixture of α-fluoroacetophenones and the corresponding 2-fluoro-1,1-dimethyl acetals. The dimethyl acetals were hydrolysed using trifluoroacetic acid in water to maximise the yield of the product. Nucleophilic fluorination of α-bromoacetophenones using tetrabutylammonium hydrogen bifluoride (TBABF) led to moderate yield when having electron-donating substituents, whereas low yields were experienced when more electron-withdrawing substituents were introduced.
Use of kinetic isotope effects in mechanism studies. Isotope effects and element effects associated with Hydron-Transfer steps during alkoxide-promoted dehydrohalogenations
Koch, Heinz F.,Lodder, Gerrit,Koch, Judith G.,Bogdan, David J.,Brown, Geoffrey H.,Carlson, Carrie A.,Dean, Amy B.,Hage, Ronald,Han, Patrick,Hopman, Johan C. P.,James, Lisa A.,Knape, Petra M.,Roos, Eric C.,Sardina, Melissa L.,Sawyer, Rachael A.,Scott, Barbara O.,Testa III, Charles A.,Wickham, Steven D.
, p. 9965 - 9974 (2007/10/03)
The Arrhenius behavior of the primary kinetic isotope effect, (k(H)/k(D))(Obs) and (k(H)/k(T))(Obs), associated with the methanolic sodium methoxide-promoted dehydrohalogenations of m-ClC6H4C(i)HClCH2Cl (I), m-CF3C6H4C(i)-HClCH2Cl (II) and p-CF3C6H4C(i)HClCH2F (III) has been used to calculate the internal-return parameters, a = k(-1)/K(Elim)(X), in a two-step mechanism featuring a hydrogen-bonded carbanion. This carbanion partitions between returning the hydron to carbon, k(-1), and the loss of halide, K(Elm)(X). Isotope effects at 25°C for I, (k(H)/k(D))(Obs) = 3.40 and (k(H)/ k(T))(Obs) = 6.20, and II, (k(H)/k(D))(Obs) = 3.49 and (k(H)/k(T))(Obs) = 6.55, result in similar values for a: a(H) = 0.59, a(D) = 0.13-0.14 and a(T) = 0.07. Smaller values of (k(H)/k(D))(Obs) = 2.19 and (k(H)/k(T))(Obs) = 3.56 for III are due to more internal return [a(H) = 1.9, a(D) = 0.50, and a(T) = 0.28] associated with the dehydrofluorination reaction. Calculation of k1 ( k(Obs) [a + 1]) results in similar isotope effects for hydron transfer in these reactions: k1(H)/k1(D) = 4.74 and k1(H)/K1(T) = 9.20; II, k1(H)/k1(D) = 4.91 and k1(H)/k1(T) = 9.75; III, k1(H)/k1(D) = 4.75 and k1(H)/k1(T) = 9.17. Reactions of m-ClC6H4C(i)HBrCH2Br and m-ClC6H4C(i)HClCH2Br have very small amounts of internal return, a(H) = 0.05 and a(D) = 0.01, and (k(H)/k(D))(Obs) = 4.95 results in k1(H)/k1(D) = 5.11 The measured isotope effects are therefore due to differences in the amount of internal return and not in the symmetry of transition state structures for the hydron transfer, and the element effect, (k(HBr)/ k(HCl)) = 29, for m-ClC6H4CHClCH2X is mainly due to the hydron-transfer step, k1(HBr)/k1(HCl) = 19, and not the breaking of the C-X bend. The kinetic solvent isotope effects, k(MeOD)/k(MeOH) ~ 2.5, are consistent with three methanols of solvation lost prior to the hydron-transfer step. The energetics associated with desolvation of methoxide ion are part of the measured reaction energetics of these systems.
