- Metal-Free and User-Friendly Regioselective Hydroxyfluorination of Olefins
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A simple, user-friendly, metal-free protocol for the regioselective anti-Markovnikov hydrofluorination of olefins using readily available and inexpensive reagents has been developed. This new approach displays a broader scope than previously reported methodologies and has been applied to the late-stage fluorination of a complex molecule, giving rise to a fluorosteroid derivative. The stereochemistry of the process has also been studied in some detail.
- Sedgwick, Daniel M.,López, Inés,Román, Raquel,Kobayashi, Nanako,Okoromoba, Otome E.,Xu, Bo,Hammond, Gerald B.,Barrio, Pablo,Fustero, Santos
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supporting information
p. 2338 - 2341
(2018/04/30)
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- Influence of Alcohol β-Fluorination on Hydrogen-Bond Acidity of Conformationally Flexible Substrates
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Rational modulations of molecular interactions are of significant importance in compound properties optimization. We have previously shown that fluorination of conformationally rigid cyclohexanols leads to attenuation of their hydrogen-bond (H-bond) donat
- Graton, Jerome,Compain, Guillaume,Besseau, Francois,Bogdan, Elena,Watts, Joseph M.,Mtashobya, Lewis,Wang, Zhong,Weymouth-Wilson, Alex,Galland, Nicolas,Le Questel, Jean-Yves,Linclau, Bruno
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p. 2811 - 2819
(2017/03/05)
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- Enzymatic preparation of (1S,2R)- and (1R,2S)-stereoisomers of 2-halocycloalkanols
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The stereoisomers of cis-2-halocycloalkanols were resolved by a kinetically controlled transesterification with vinyl acetate in the presence of lipases in organic media. High enantioselectivities (ee >98%) and good isolated yields were obtained for all substrates using the appropriate lipase. Burkholderia cepacia lipase was the most efficient enzyme for the resolution of these substrates. The enantiomeric purities of the compounds were defined by derivatization with Mosher's acid and the absolute configurations were determined by chemical correlation.
- Kolodiazhna, Olga O.,Kolodiazhna, Anastasy O.,Kolodiazhnyi, Oleg I.
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- Fluorinated ε-caprolactone: Synthesis and ring-opening polymerization of new α-fluoro-ε-caprolactone monomer
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Fluorinated polyester was synthesized from a novel α-fluoro-ε- caprolactone monomer (α-FCL). The monomer was synthesized from commercially available cyclohexene oxide in three steps. Baeyer-Villiger reaction using 3-chloroperoxybenzoic acid of the corresp
- Al-Azemi, Talal F.,Mohamod, Abdirahman A.
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experimental part
p. 5431 - 5438
(2012/05/20)
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- Conformational analysis of cis-2-halocyclohexanols; Solvent effects by NMR and theoretical calculations
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Conformational problems often involve very small energy differences, even low as 0.5 kcal mol-1. This accuracy can be achieved by theoretical methods in the gas phase with the appropriate accounting of electron correlation. The solution behavio
- Basso, Ernani A.,Abiko, Layara A.,Gauze, Gisele F.,Pontes, Rodrigo M.
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experimental part
p. 145 - 153
(2011/03/19)
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- Asymmetric hydrogenation of racemic 2-fluorocyclohexanone over cinchona modified Pt/Al2O3 catalyst
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The first example of enantioselective heterogeneous catalytic hydrogenation of an α-fluoro ketone is reported. The hydrogenation of racemic 2-fluorocyclohexanone over cinchonidine- or methoxycinchonidine-modified Pt/Al2O3 resulted in
- Szori, Kornel,Szoellosi, Gyoergy,Bartok, Mihaly
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p. 255 - 259
(2007/10/03)
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- Trifluoromethylthiocopper catalyzed oxirane ring opening
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Trifluoromethylthiocopper has been found to catalyze the opening of the epoxide ring and to furnish not-so-easily accessible novel trifluoromethylthiolated α-hydroxy compounds. This communication presents the mechanism of the formation of the various comp
- Munavalli,Rohrbaugh,Durst
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p. 1657 - 1671
(2007/10/03)
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- Regioselective synthesis of fluorohydrines via SN2-type ring-opening of epoxides with TBABF-KHF2
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We found that the ring-opening fluorination of terminal epoxides using TBABF-KHF2 proceeds with high selectivity through the SN2 mechanism. As TBABF-KHF2 is easily obtainable, is stable, and can be used in glassware, it ca
- Akiyama, Yuriko,Fukuhara, Tsuyoshi,Hara, Shoji
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p. 1530 - 1532
(2007/10/03)
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- Selectivity of biohydroxylation with Beauveria bassiana of trans-2-fluorocycloalkyl N-phenylcarbamates
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Biohydroxylation with Beauveria bassiana of racemates and the pure enantiomers of trans-2- fluorocyclohexyl- 3 and trans-2-fluorocycloheptyl N-phenylcarbamates 6 were investigated and compared with results found for the corresponding nonfluorinated parent compounds. In all cases, mixtures of diastereomeric products hydroxylated in the 4-position were isolated, besides products of p-hydroxylation of the aromatic ring and succeeding compounds derived from these primary reaction products. The regioselectivity of hydroxylation by this fungus is not changed by a single fluorine substituent attached closely to the electron-rich anchoring group in the trans-2-position. There is a different influence on the diastereoselectivity of hydroxylation depending on the absolute configuration of the fluorinated substrates. While the transformation of the (S,S)-2-fluorocycloalkyl N-phenylcarbamates is not diastereoselective giving almost 1:1 mixtures of cis- and trans-4-hydroxyl compounds, the corresponding reactions of the (R,R)-isomers led preferentially to the products transhydroxylated in the 4-position. The transformation of the racemic fluorinated six-membered N-phenylcarbamate 3 led to products having a very small enantiomeric excess. The fluorine substituent slightly increased the enantioselectivity of transformation of the racemic seven-membered substrate 6 compared to the C8-symmetric nonfluorinated carbamate. Thus, the fluorine substituent in the trans-2-position in these examples did not change the regioselectivity but rather influenced the stereochemistry of biotransformation, depending on the absolute configuration of the substrate and ring size.
- Haufe, Guenter,Woelker, Doerthe,Froehlicht, Roland
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p. 3022 - 3028
(2007/10/03)
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- Synthesis of optically active vicinal fluorohydrins by lipase-catalyzed deracemization
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Three microbial lipases have been used to deracemize trans-2-fluorocycloalkanols 2 both by hydrolysis of the corresponding acetates 3 or chloroacetates 4 and by esterification of the fluorohydrins 2 using vinyl acetate and vinyl chloroacetate, respectivel
- Woelker, Doerthe,Haufe, Guenter
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p. 3015 - 3021
(2007/10/03)
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- (Salen)chromium Complex Mediated Asymmetric Ring Opening of meso- And Racemic Epoxides with Different Fluoride Sources
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The asymmetric ring opening of five meso-and three racemic epoxides with different fluorinating reagents in the presence of stoichiometric or slightly sub-stoichiometric amounts of Jacobsen's enantiopure (salen)chromium chloride complex A gave the corresponding optically active vicinal fluorohydrins. Silver fluoride was used as one of the fluoride sources either in the presence of Bu4N+H2F3- in diethyl ether or in acetonitrile. The latter reactions starting from cyclohexene oxide (1) showed maximum 72% ee in the formed fluorohydrin 2 isolated in 90% yield. From other meso-epoxides such as cyclopentene oxide and cycloheptene oxide the corresponding fluorohydrins were isolated in 80% and 82% yield with 65% and 62% ee, respectively. In case of ring opening under similar conditions of the racemic styrene oxide or phenyl glycidyl ether 83% and 75% of the fluorohydrins with fluorine in the primary position were isolated with 74% ee and 65% ee, respectively. Tetrahydronaphthalene oxide yielded a 2:1 mixture of trans- (23% ee) and cis-2-fluoro-3,4-benzocyclohexenol (2% ee) suggesting competing SN2 and SN1 type ring openings. Other epoxides such as cyclooctene oxide, cis-stilbene oxide and α-methylstyrene oxide did not react or gave the fluorohydrins with very small enantiomeric excess.
- Haufe, Guenter,Bruns, Stefan
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p. 165 - 171
(2007/10/03)
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- Enantioselective ring-opening of epoxides by HF-reagents: Asymmetric synthesis of fluoro lactones
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The asymmetric ring opening of meso- and racemic-epoxides with different HF-reagents mediated by enantiopure (salen)chromium chloride provides optically active fluorohydrins with maximum 90% e.e. This reaction as well as lipase-catalyzed deracemization of
- Haufe, Günter,Bruns, Stefan,Runge, Martina
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- Axial/equatorial proportions for 2-substituted cyclohexanones
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Axial-equatorial conformational proportions have been measured for 2- substituted cyclohexanones in chloroform by the Eliel method for F, Cl, Br, I, MeO, MeS, Me2N, MeSe, and Me. For the first seven of these, at least five experimentally independent measurables were used and the resulting conformational preferences appear to be accurate to within 10%. Systematic errors degraded the results for MeSe and Me. For Me2N, the conformational preference also was measured for the first time at slow exchange in the low- temperature 13C spectrum in several solvents. In chloroform, steric and polar effects contribute to the conformational preferences, with steric effects dominant for large groups such as I and MeS.
- Basso,Kaiser,Rittner,Lambert
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p. 7865 - 7869
(2007/10/02)
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- Hypofluorous acid and acetonitrile: the taming of a reagent
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The strong oxidant produced by the reaction of elemental fluorine with acetonitrile containing ca. 10percent water has been shown to be hypofluorous acid, HOF, which is stabilized by complexing to the solvent.The reaction represents a new and convenient method of preparing and handling HOF, a unique oxygenating reagent.The presence of acetonitrile results in subtle but significant changes in the chemical behavior of the HOF.Vibrational and NMR spectroscopic studies of the solutions resulting from this reaction, as well as of solutions prepared by dissolving neat HOF in dry acetonitrile, have shown that the complex as a 1:1 hydrogen-bridged entity, in which the HOF proton is most likely bonded to the nitrogen atom of the nitrile.The 19F NMR data indicate that the complexation reaction has an equilibrium constant of ca. 3 at room temperature, and that the enthalpy of formation of the complex is -14.3+/-0.5 kJ mol-1.The success of this method of synthesizing hypofluorous acid is a consequence of the very slow reaction between HOF and low concentrations of water in acetonitrile.This reaction accelarates drastically as the water content increases.As the solution composition approaches 100percent water, the rate constant appears to approach a limit of about 0.7 s-1 at 25 deg C, which may be the actual rate of reaction of HOF with the water.
- Appelman, Evan H.,Dunkelberg, Oliver,Kol, Moshe
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p. 199 - 213
(2007/10/02)
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- Synthesis, Regioselective Deprotonation, and Stereoselective Alkylation of Fluoro Ketimines
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Fluoroacetone imines of cyclohexylamine, valinol O-methyl ether, and phenylalaninol O-methyl ether and 2-fluorocyclohexanone imines of cyclohexylamine and phenylalaninol O-methyl ether were prepared.The temperature-dependent, regioselective deprotonation of these imines was employed in highly regioselective alkylation reactions.The deprotonation of fluoroacetone cyclohexylimine on the carbon bearing fluorine yielded only a single stereoisomer as determined by low temperature 19F NMR.In contrast, deprotonation of fluoroacetone O-benzyloximes was not regiospecific under any of the conditions examined.
- Welch, John T.,Seper, Karl W.
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p. 2991 - 2999
(2007/10/02)
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- Mechanistic aspects of the fluorination of cyclohexane and cyclohexene with acetyl hypofluorite in acetic acid
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The reaction of acetyl hypofluorite in acetic acid with both cyclohexane and cyclohexene has been investigated.Analysis by GCMS and radio-HPLC, using (18)F as a tracer, revealed that apart from typical products expected from a radical reaction, several compounds originating from carbocationic intermediates were formed.On the basis of the observed products, a single-electrontransfer (SET) mechanism leading to an intermediate radical-cation is proposed.
- Visser, G. W. M.,Bakker, C. N. M.,Halteren, R. W. v.,Herscheld, J. D. M.,Brinkman, G. A.,Hoekstra, A.
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p. 214 - 219
(2007/10/02)
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- Photoreduction of Cyclic α-Fluoroketones
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Irradiation of the α-fluoroketones 1a and 6a in i-PrOH selectively affords the parent ketone 1b and 6b, respectively.It is concluded that in this solvent heterolytic C-F bond cleavage of the radical -formed by electron transfer to the excited fluoroketone- is a faster process than the subsequent protonation by the cation radical of the solvent.In cyclohexane 1b and 6b are only formed a minor amounts, the fluorinated RH-reduction product 4 now being the major product from 1a.In non-reducing solvents as t-BuOH or benzene 2-fluorocyclohexanone (1a) exhibits a similar behavior as cyclohexanone (1b) on excitation.The quantum yields for α-cleavage are alike for both compounds, but oxetane formation with 2-methylpropene as olefinic component occurs much more readily with 1a than with 1b.
- Reinholdt, Karin,Margaretha, Paul
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p. 2534 - 2539
(2007/10/02)
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