- Fluoro-functionalization mediated by the reactive chalcogen reagents
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Two types of fluoro-functionalizations mediated by reactive chalcogen reagents have been summarized. The first is a generation of benzeneselenenyl fluoride and its electrophilic reactions with alkenes, electron-deficient alkenes, isonitriles and α-diazoca
- Uneyama, Kenji
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- Organocatalyzed Sulfa-Michael Addition of Thiophenols on Trisubstituted α-Fluoroacrylates, a Straightforward Access to Chiral Fluorinated Compounds
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In this manuscript, a simple and efficient sulfa-Michael addition reaction of aryl thiols to trisubstituted α-fluoro-α,β-unsaturated esters both in racemic and, for the first time, in enantioselective version is reported. The commercially available dimer of cinchona derivatives (DHQ)2PYR was used as a catalyst. This strategy showed a great tolerance for various substrates and substituents, providing fair to excellent yields, moderate to excellent diastereoselectivities (2:1 to >99:1), and low to good enantioselectivities (2 to 87%). The reaction has been applied to the synthesis of fluorinated analogues of diltiazem and tiazesim, both therapeutic agents.
- Huang, Xin,David, Emilie,Jubault, Philippe,Besset, Tatiana,Couve-Bonnaire, Samuel
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p. 14055 - 14067
(2020/11/20)
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- Stereospecific synthesis of tri- and tetrasubstituted α-fluoroacrylates by mizoroki-heck reaction
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Ligand-free, efficient, palladium-catalyzed Mizoroki-Heck reaction between methyl α-fluoroacrylate and arene or hetarene iodides is reported for the first time. The reaction is stereospecific and provides fair to quantitative yields of fluoroalkenes. The Mizoroki-Heck reaction starting from more hindered and usually reluctant trisubstituted acrylate, to access tetrasubstituted fluoroalkenes, is also reported. Finally, the use of a three-step synthesis sequence, including Mizoroki-Heck reaction, allows the synthesis of fluorinated analogues of therapeutic agents with high yield.
- Rousée, Kevin,Bouillon, Jean-Philippe,Couve-Bonnaire, Samuel,Pannecoucke, Xavier
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supporting information
p. 540 - 543
(2016/02/18)
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- A substrate-driven approach to determine reactivities of α,β-unsaturated carboxylic esters towards asymmetric bioreduction
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The degree of C=C bond activation in the asymmetric bioreduction of α,β-unsaturated carboxylic esters by ene-reductases was studied, and general recommendations to render these "borderline-substrates" more reactive towards enzymatic reduction are proposed. The concept of "supported substrate activation" was developed. In general, an additional α-halogenated substituent proved to be beneficial for enzymatic activity, whereas β-alkyl or β-aryl substituents were detrimental for the reactivity of nonhalogenated substrates, and α-cyano groups showed little effect. The alcohol moiety of the ester functionality was found to have a strong influence on the reaction rate. Overall, activities were determined by both steric and electronic effects. Biotransformation: The asymmetric bioreduction of α,β-unsaturated carboxylic esters by ene-reductases could be tuned by varying the degree of C=C bond activation (see scheme). An additional α-halogenated substituent proved to be beneficial for enzymatic activity, whereas β-alkyl or β-aryl substituents were detrimental for the reactivity of nonhalogenated substrates. Copyright
- Tasnádi, Gábor,Winkler, Christoph K.,Clay, Dorina,Sultana, Nargis,Fabian, Walter M. F.,Hall, Mélanie,Ditrich, Klaus,Faber, Kurt
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supporting information; experimental part
p. 10362 - 10367
(2012/10/08)
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- Synthetic utilization of 2-chloro-1,1,1,2-tetrafluoroethane
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β-Substituted α-fluoro-α,β-unsaturated carboxylic acids have been successfully synthesized, usually in a (Z)-stereospecific manner by way of a stepwise or a one-pot three-step procedure starting from 2-chloro-1,1,1,2-tetrafluoroethane (HCFC-124), one of the major byproducts of the industrial process for tetrafluoroethene formation from chlorofluoromethane (HCFC-22). Get some Z's! β-Substituted α-fluoro-α,β- unsaturated carboxylic acids have been successfully synthesized from 2-chloro-1,1,1,2-tetrafluoroethane, one of the major byproducts of tetrafluoroethene formation from chlorofluoromethane. The products are usually obtained with Z stereoselectivity, by either a stepwise or a one-pot three-step procedure (see scheme).
- Notsu, Keiji,Zushi, Yasuyuki,Ota, Shin,Kawasaki-Takasuka, Tomoko,Yamazaki, Takashi
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p. 9200 - 9208
(2011/09/19)
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- Highly efficient and stereoselective Julia-Kocienski protocol for the synthesis of α-fluoro-α,β-unsaturated Esters and Weinreb amides employing 3,5-bis(trifluoromethyl)phenyl (BTFP) sulfones
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: α-Fluoroacetates 3 and Weinreb amide 4, bearing a α-[3,5-bis(trifluoromethyl)phenyl]sulfonyl (BTFP-sulfonyl) group at the α-position, are employed in the highly stereoselective synthesis of α-fluoro-α,β-unsaturated alkenoates and Weinreb amides, respectively. Aromatic and aliphatic aldehydes are condensed under extremely mild and simple reaction conditions using potassium carbonate in dimethylformamide at room temperature under solid-liquid phase-transfer catalysis conditions in good yields and high Z-diastereoselectivities, specially in the case of the fluorinated Weinreb amides. A detailed computational mechanistic study suggests a final non-concerted elimination of sulfur dioxide and 3,5-bis(trifluoromethyl)phenoxide and explains the observed high stereoselectivities for the reaction on the basis of thermodynamic and kinetic considerations.
- Alonso, Diego A.,Fuensanta, Monica,Gomez-Bengoa, Enrique,Najera, Carmen
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experimental part
p. 1823 - 1829
(2009/07/11)
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- Toward (Z)-selective Horner-Wadsworth-Emmons reaction of aldehydes with 2-fluoro-2-diethylphosphonoacetic acid
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The stereoselective Horner-Wadsworth-Emmons reaction of aldehydes with 2-fluoro-2-diethylphosphonoacetic acid utilizing i-PrMgBr afforded (Z)-α-fluoro-α,β-unsaturated carboxylic acids as the major products.
- Sano, Shigeki,Teranishi, Rie,Nagao, Yoshimitsu
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p. 9183 - 9186
(2007/10/03)
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- tert-Butylsulfinyl-fluoroacetate: Versatile reagent for the preparation of fluoroethylidenoate derivatives
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The preparation of (Z)-α-fluoroalkenoates from readily available methyl-tert-butylsulfanyl- or tert-butylsulfinylfluoroacetate 1 or 5 is described. This short synthesis, based on a direct extrusion of SO2 from β-hydroxysulfoxides, presents a mo
- Chevrie, David,Lequeux, Thierry,Pommelet, Jean-Claude
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p. 4759 - 4767
(2007/10/03)
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- Chemistry of fluorinated enamines. Novel reaction of trifluoromethylated enamine with Grignard reagents
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Trifluoromethylated enamine, N-(2,3,3,3-tetrafluoro-1- propenyl)dimethylamine (1), readily reacted with a variety of Grignard reagents 2 at room temperature to afford the trifluorovinyl compounds 3 in good yields.
- Park, Hee Moon,Uegaki, Tomonori,Konno, Tsutomu,Ishihara, Takashi,Yamanaka, Hiroki
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p. 2985 - 2988
(2007/10/03)
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- Thia-Wittig-like reactions as a new route for the stereoselective synthesis of (Z)-fluoroalkenoates
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(matrix presented). Stereoselective syntheses of (Z)-fluoroalkenoates 3a-g have been developed in three steps from the readily available fluorosulfide 5 and aldehydes. This preparation, involving a Durst reaction, was highly stereoselective and led to flu
- Chevrie, David,Lequeux, Thierry,Pommelet, Jean-Claude
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p. 1539 - 1541
(2008/02/09)
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- Mechanistic and stereochemical study of phenylpyruvate tautomerase
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A variety of substrates and potential enol/enolate mimics for the product/transition state of the enzyme phenylpyruvate tautomerase (E.C. 5.3.2.1) have been prepared and studied. Their stereostructures have been secured by a combination of NMR spectroscopy based on vicinal H-F and H-C coupling constants and X-ray crystallography. On the basis of the inhibition by stereoisomeric substituted cinnamates, it has been concluded that the enzyme produces the thermodynamically less stable (E) enol via a syn tautomerization transition state. Free energy profiles for the reaction suggest that vinyl fluorides act as product analogues. Because amide and dicarboxylate enolate mimics are relatively poor inhibitors of the enzyme, it is believed that an enolate is not involved in the tautomerization process.
- Pirrung, Michael C.,Chen, Jrlung,Rowley, Elizabeth G.,McPhail, Andrew T.
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p. 7103 - 7110
(2007/10/02)
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- Zinc(0)-Copper(I) Chloride Promoted Reaction of Methyl Dichlorofluoroacetate with Carbonyl Compounds. A New Efficient Method for the Synthesis of Methyl (Z)-α-Fluoro-α,β-unsaturated Carboxylates
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Methyl dichlorofluoroacetate, easily prepared from methyl trichloroacetate and antimony(III) fluoride, underwent the reductive coupling-elimination raection with carbonyl compounds in the presence of zinc(0), a catalytic amount of copper(I) chloride, acetic anhydride, and molecular sieves to give the corresponding (Z)-α-fluoro-α,β-unsaturated carboxylic acid methyl esters in high yields.
- Ishihara, Takashi,Kuroboshi, Manabu
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p. 1145 - 1148
(2007/10/02)
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- Synthese stereoselective d'esters α,β-ethyleniques α-fluores E par reaction de Wittig-Horner a partir du diethyl phosphono α-fluoroacetate de methyle. Etude comparative avec le diphenyl phosphonoxy α-fluoroacetate de methyle
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The reaction of methyl diethylphosphono α-fluoroacetate with aliphatic,α,β-ethylenic or aromatic aldehydes in the presence of nBuLi in THF at -78 deg C gives E α-fluoro esters with a very high stereoselectivity and a good yield.At 20 deg C, the stereoselectivity is not so high.From the corresponding phosphine oxide, the reaction is less stereoselective favoring the E ester from aliphatic aldehydes and the Z one from α,β- unsaturated aldehydes or PhCHO. These results are in line with the previous interpretations taking into account the electron density and steric hindrance around the phosphorus atom.
- Etemad-Moghadam, Guita,Seyden-Penne, Jacqueline
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p. 448 - 454
(2007/10/02)
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