- α-(Difluoromethyl)styrene: Improved approach to grams scale synthesis
-
Improved, efficient, grams scale synthesis of α-(difluoromethyl)styrene (DFMST) based on nucleophilic difluoromethylation process using difluoromethylphenyl sulfone, is presented. Difluoromethylating agent (PhSO2CF2H) was obtained in two-step synthetic sequence with 69% overall yield. Three-step DFMST synthetic route was easily implemented for the preparation of gram quantities of the monomer, allowing for polymerization studies. The syntheses were based on the use of commercially available and reasonable in price starting materials and reagents.
- Walkowiak-Kulikowska, Justyna,Kanigowska, Joanna,Koroniak, Henryk
-
-
Read Online
- C-H Electrophilic (phenylsulfonyl)difluoromethylation of (hetero)arenes with a newly designed reagent
-
The synthesis of an original electrophilic difluoromethylating reagent was successfully achieved upon a straightforward protocol (3 steps). Like a Swiss army knife, this bench-stable reagent allowed the functionalization of various classes of compounds under mild and transition metal-free conditions. Hence, an efficient and operationally simple tool for the construction of C(sp2)-, C(sp3)- and S-CF2SO2Ph bonds was provided, expanding the chemical space of PhSO2CF2-containing molecules. Late-stage functionalization of bioactive molecules and the synthesis of PhSO2CF2- and HCF2-analogs of Lidocaine were also successfully achieved.
- Nobile, Enzo,Castanheiro, Thomas,Besset, Tatiana
-
supporting information
p. 12337 - 12340
(2021/12/07)
-
- Regio- and chemoselectivity in S- and O- difluoromethylation reactions using diethyl (bromodifluoromethyl)phosphonate
-
The effective difluoromethylations of various S- and O- based- nucleophiles, presenting a wide range of pKa values, using diethyl(bromodifluoromethyl) phosphonate (1) under basic conditions is described. These reactions, which rely on the quantitative generation of difluorocarbene formed through the hydrolysis of 1, were found to be effective only once the starting materials had pKa values of less than ca. 11. Importantly, in cases in which the substrates held two or three nucleophilic centers this feature was successfully implemented to achieve a high chemo- or regioselective difluoromethylation of the center exhibiting the lowest pKa value and the highest polarizability.
- Amir, Dafna,Binyamin, Iris,Drug, Eyal,Fridkin, Gil,Gershonov, Eytan,Marciano, Daniele,Redy-Keisar, Orit,Yehezkel, Lea,Zafrani, Yossi
-
-
- Method for constructing fluorine-containing methyl sulfone compound through multi-component coupling
-
The invention discloses a fluorine-containing methyl sulfone compound as shown in a formula (1) and a synthesis method thereof. Aromatic iodide (aryl iodide or heteroaryl iodide), an inorganic sulfur reagent and a fluorine-containing building block are used as reaction raw materials and react in a solvent under the action of alkali, a catalyst and an additive to obtain a series of fluorine-containing methyl sulfone compounds. According to the invention, the fluorine-containing sulfone compound is constructed by a one-pot two-step method by taking an inorganic sulfur reagent as a sulfur source under a catalytic condition, so that the defects of the traditional synthesis of a fluorine-containing sulfone compound by thioether oxidation are avoided. According to the synthesis strategy developed by the invention, some clinical methyl sulfone drugs can be modified, and monofluoro, difluoro and trifluoromethyl sulfone compounds can be successfully obtained, which have huge potential in the field of drug development in the future.
- -
-
Paragraph 0109-0112
(2021/10/27)
-
- Preparation method of difluoromethyl sulfone compound
-
The invention discloses a preparation method of a difluoromethyl sulfone compound. The invention provides a preparation method of a difluoromethyl sulfone compound, which comprises the following step:in a solvent, in the presence of alkali and a phase transfer catalyst, carrying out difluoromethylation reaction shown in the specification on sulfinic acid and/or salt thereof and CHClF2 to obtain the difluoromethyl sulfone compound. The solvent is a mixed solvent of water and an organic solvent; The sulfinic acid and/or salt thereof comprises positive ions and negative ions, and the negative ions contain structural fragments shown as a formula I; and the difluoromethyl sulfone compound contains a structural fragment as shown in a formula II which is described in the specification. The preparation method provided by the invention has the advantages of accessible raw materials, wide substrate range, mild reaction conditions and simple operation, can implement separation without column chromatography, and is suitable for industrial production. The difluoromethyl sulfone compound can be obtained at a high yield.
- -
-
Paragraph 0088-0113; 0119-0121
(2021/03/31)
-
- Nucleophilic (Phenylsulfonyl/arylthio)difluoromethylation of Aldehydes with TMSCF2Br: A Three-Component Strategy
-
An efficient method for nucleophilic (phenylsulfonyl/arylthio)difluoromethylation of aldehydes with TMSCF2Br was developed. The reaction proceeds through in situ generation of difluorocarbene, which is captured by PhSO2Na or ArSNa to
- Xie, Qiqiang,Zhu, Ziyue,Ni, Chuanfa,Hu, Jinbo
-
p. 9138 - 9141
(2019/11/14)
-
- Decarboxylative difluoromethylation of aldehydes with PhSO2CF2COOK: A facile and efficient access to difluoromethylated carbinols
-
A novel decarboxylative difluoromethylation reaction of PhSO2CF2COOK with aldehydes under metal- and ligand-free conditions has been developed. The reaction is very mild and tolerates a wide range of aldehydes (both enolizable and non-enolizable aldehydes), providing a facile and efficient method for the synthesis of structurally diverse difluoromethylated carbinols in moderate to excellent yields.
- Zhu, Yu-Jun,Lei, Zhong-Liang,Huang, Da-Kang,Lian, Bo,Liu, Zhen-Jiang,Hu, Xiao-Jun,Liu, Jin-Tao
-
p. 3184 - 3187
(2018/07/13)
-
- Copper-Mediated Di- and Monofluoromethanesulfonylation of Arenediazonium Tetrafluoroborates: Probing the Fluorine Effect
-
A copper-mediated di- and monofluoromethanesulfonylation of arenediazonium tetrafluoroborates using di- and monofluoromethanesulfinate reagents provides aryl difluoromethyl (or monofluoromethyl) sulfones in good yields. It was found that the relative reactivity of these sodium fluoroalkanesulfinates in the present reactions decreases in the following order: CH2FSO2Na > CF2HSO2Na > CF3SO2Na.
- Xing, Bo,Ni, Chuanfa,Hu, Jinbo
-
p. 206 - 212
(2018/02/06)
-
- Conversion of methyl ketones and methyl sulfones into α-deutero-α,α-difluoromethyl ketones and α-deutero-α,α-difluoromethyl sulfones in three synthetic steps
-
Deuterodifluoromethyl ketones and sulfones were assembled in three synthetic steps from methyl ketones and sulfones, respectively. The key synthetic transformation is the deuteration of the difluorocarbanion generated by the release of trifluoroacetate from highly α-fluorinated gem-diols. High levels of deuterium on the “CF2D” group were routinely observed. This strategy is mild and versatile and it can be applied to both ketones and sulfones without additional concerns of over- or under-fluorination. Additional examples address issues of over-deuteration when compounds with other acidic protons are subjected to the reaction conditions. This process not only demonstrates a new method to install a “CF2D” group but also extends the scope of trifluoroacetate release to sulfones.
- Sowaileh, Munia F.,Han, Changho,Hazlitt, Robert A.,Kim, Eun Hoo,John, Jinu P.,Colby, David A.
-
p. 396 - 400
(2017/01/10)
-
- Radical (Phenylsulfonyl)difluoromethylation of Isocyanides with PhSO2CF2H under Transition-Metal-Free Conditions
-
An atom-economical method for radical (phenylsulfonyl)difluoromethylation of isocyanides with PhSO2CF2H under transition-metal-free conditions has been developed. A PhSO2CF2 radical is generated through the oxidation of PhSO2CF2- after the deprotonation of PhSO2CF2H in one pot. The reaction exhibits excellent functional-group tolerance and the resulting products can be further modified with the removal of a PhSO2 group to give other CF2-containing compounds.
- Xiao, Pan,Rong, Jian,Ni, Chuanfa,Guo, Junkai,Li, Xinjin,Chen, Dingben,Hu, Jinbo
-
supporting information
p. 5912 - 5915
(2016/11/29)
-
- Difluoromethylation of: N -arylsulfonyl hydrazones with difluorocarbene leading to difluoromethyl aryl sulfones
-
The difluoromethylation of N-arylsulfonyl hydrazones with difluorocarbene generated from difluoromethylene phosphobetaine (Ph3P+CF2CO2-) to give various difluoromethyl aryl sulfones is described.
- Zheng, Qu-Tong,Wei, Yun,Zheng, Jian,Duan, Ya-Ya,Zhao, Gang,Wang, Zong-Bao,Lin, Jin-Hong,Zheng, Xing,Xiao, Ji-Chang
-
p. 82298 - 82300
(2016/09/09)
-
- S-((Phenylsulfonyl)difluoromethyl)thiophenium salts: Carbon-selective electrophilic difluoromethylation of β-ketoesters, β-diketones, and dicyanoalkylidenes
-
S-((Phenylsulfonyl)difluoromethyl)thiophenium salts were designed and prepared by a triflic acid catalyzed intramolecular cyclization of ortho-ethynyl aryldifluoromethyl sulfanes. The thiophenium salts were found to be efficient as electrophilic difluoromehtylating reagents for introduction of a CF 2H group to sp3-hybridized carbon nucleophiles such as of β-ketoesters and dicyanoalkylidenes. The (phenylsulfonyl)difluoromethyl group can be readily transformed into CF2H under mild reaction conditions. Enantioselective electrophilic difluoromethylation was also achieved in the presence of bis(cinchona) alkaloids. S and F join forces: The title salts were designed and prepared by a triflic acid catalyzed intramolecular cyclization of ortho-ethynyl aryldifluoromethyl sulfanes. The salts 1 were efficient as electrophilic difluoromethylating reagents for introducing a CF2H group to sp3-hybridized carbon nucleophiles. Enantioselective electrophilic difluoromethylation was also investigated. DBU=1,8-diazabicyclo[5.4.0]undec-7-ene, Tf=trifluoromethanesulfonyl. Copyright
- Wang, Xin,Liu, Guokai,Xu, Xiu-Hua,Shibeta, Naoyuki,Tokunaga, Etsuko,Shibata, Norio
-
supporting information
p. 1827 - 1831
(2014/03/21)
-
- Synthesis of gem-difluorocyclopropa(e)nes and O-, S-, N-, and P-difluoromethylated compounds with TMSCF2Br
-
Two-in-one: Me3SiCF2Br is an efficient difluorocarbene source and is compatible with both neutral and aqueous basic conditions. Bromide-ion-initiated [2+1] cycloaddition with alkenes/alkynes and hydroxide ion promoted α-addition with (thio)phenols, (thio)alcohols, sulfinates, heterocyclic amines, and H-phosphine oxides give the corresponding gem-difluorinated compounds with broad functional-group tolerance. Copyright
- Li, Lingchun,Wang, Fei,Ni, Chuanfa,Hu, Jinbo
-
supporting information
p. 12390 - 12394
(2013/12/04)
-
- Nucleophilic fluoroalkylation of α,β-unsaturated carbonyl compounds with α-fluorinated sulfones: Investigation of the reversibility of 1,2-additions and the formation of 1,4-adducts
-
A detailed investigation of the reactions of PhSO2CF 2H and PhSO2CH2F with (E)-chalcone (=(E)-1,3-diphenylprop-2-en-1-one) at low temperatures revealed that these two reactions were kinetically controlled, and the ratios of 1,2- vs. 1,4-adducts, which did not change much over time at these temperatures, reflect the relative rates of the two reaction pathways. The controlled experiments of converting the PhSO2CF2- and PhSO2CHF-substituted 1,2-adducts to 1,4-adducts showed that these isomerizations are not favored due to the low stability and hard-soft nature of PhSO2CF2- and PhSO2CHF- anions. Moreover, taking advantage of the remarkable stability and softness of (PhSO2)2CF - anion, an efficient thermodynamically controlled isomerization of (PhSO2)2CF-substituted 1,2-adduct to 1,4-adduct was achieved for the first time. Copyright
- Shen, Xiao,Ni, Chuanfa,Hu, Jinbo
-
p. 2043 - 2051
(2013/01/15)
-
- Palladium-mediated heck-type reactions of [(Bromodifluoromethyl)sulfonyl] benzene: Synthesis of α-alkenyl- and α-heteroaryl-substituted α,α-difluoromethyl phenyl sulfones
-
Palladium-catalyzed Heck-type reactions of [(bromodifluoromethyl)sulfonyl] benzene (1) with styrene derivatives and heteroaromatic compounds successfully gave α-alkenyl- and α-heteroaryl-substituted α,α- difluoromethyl phenyl sulfones, respectively. Palladium-catalyzed Heck-type reactions of [(bromodifluoromethyl)sulfonyl]benzene (1) are reported. Both styrene derivatives and heteroaromatic compounds gave PhSO2CF 2-substituted products in moderate to good yields.
- Surapanich, Nakin,Kuhakarn, Chutima,Pohmakotr, Manat,Reutrakul, Vichai
-
p. 5943 - 5952,10
(2020/09/02)
-
- Syntheses of mono-, di-, and trifluorinated styrenic monomers
-
Concise syntheses of gram quantities of three fluorinated -methylstyrenic monomers suitable for polymerisation studies are disclosed, all based on the use of reasonably priced commercially available starting materials and reagents. Georg Thieme Verlag Stuttgart New York.
- Walkowiak, Justyna,Del Campo, Teresa Martinez,Ameduri, Bruno,Gouverneur, Veronique
-
experimental part
p. 1883 - 1890
(2010/08/20)
-
- Synthesis of 1,1-difluoroethylsilanes and their application for the introduction of the 1,1-difluoroethyl group
-
1,1-Difluoroethysilanes (R3SiCF2CH3, R = Me or Et) were synthesized from 1,1-difluoroethyl phenyl sulfone and chlorosilanes using magnesium metal via reductive 1,1-difluoroethylation. It was confirmed that 1,1-difluoroethylsilanes were effective 1,1-difluoroethylating reagents for carbonyl compounds.
- Mogi, Ryo,Morisaki, Kazuo,Hu, Jinbo,Prakash, G.K. Surya,Olah, George A.
-
p. 1098 - 1103
(2008/02/09)
-
- An efficient preparation of new sulfonyl fluorides and lithium sulfonates
-
(Formula Presented) An efficient preparation of several polyfluoroalkanesulfonyl fluorides is reported. This method, based on the synthesis of polyfluoroalkyl trimethyl silanes (precursors of polyfluoroalkylsulfinates) as intermediates, allows the successive transformations to be carried out in one pot. Moreover, these sulfonyl fluorides can be obtained from the corresponding sulfinates by electrophilic fluorination. This original approach avoids isolation and purification of some thermally or hydrolytically unstable intermediates. A series of new sulfonyl fluorides have been thus prepared from halogenodifluoromethylated precursors RCF2X (X = F, Br; R = ArC(O), ArS(O)n(CF2) m; n = 0, 1, 2; m = 1, 2) and have been transformed into the corresponding lithium sulfonates, which have potential applications as electrolytes for lithium batteries.
- Toulgoat, Fabien,Langlois, Bernard R.,Medebielle, Maurice,Sanchez, Jean-Yves
-
p. 9046 - 9052
(2008/03/27)
-
- Nucleophilic difluoromethylation of carbonyl compounds using TMSCF 2SO2Ph and Mg0-mediated desulfonylation
-
A new nucleophilic difluoromethylation chemistry using fluoride-induced (phenylsulfonyl)difluoromethylation with TMSCF2SO2Ph followed by the magnesium-metal-mediated desulfonylation has been achieved. This methodology is compatible w
- Ni, Chuanfa,Hu, Jinbo
-
p. 8273 - 8277
(2007/10/03)
-
- α-Fluorination of methyl phenyl sulfoxide and related compounds by molecular fluorine: A novel method for the introduction of fluorine into sulfoxides bearing α-H atoms
-
Direct formation of α-fluorosulfones from sulfoxides bearing α-H atoms merely by reaction with molecular fluorine (5% F2/N2) is reported, and a novel non-Pummerer-type mechanism is proposed for this α-fluorination reaction.
- Toyota, Akemi,Ono, Yoshinori,Chiba, Jun,Sugihara, Takumichi,Kaneko, Chikara
-
p. 703 - 708
(2007/10/03)
-
- α-Fluorination of Sulfoxides Bearing α-Hydrogens by Molecular Fluorine. A Novel Method for the Synthesis of α-Fluorosulfones
-
Direct formation of α-fluorosulfones from sulfoxides bearing α-hydrogens merely by reacting molecular fluorine (5percent F2/N2) is reported and a possible mechanism for this novel α-fluorination reaction is proposed.
- Chiba, Jun,Sugihara, Takumichi,Kaneko, Chikara
-
p. 581 - 582
(2007/10/03)
-
- NUCLEOPHILIC ADDITION OF DIFLUOROMETHYL PHENYL SULFONE TO ALDEHYDES AND VARIOUS TRANSFORMATIONS OF THE RESULTING ALCOHOLS
-
Nucleophilic addition of difluoromethyl phenyl sulfone (1) to various aldehydes occured in a two phase system ( 50 percent aqueous sodium hydroxide, dichloromathane, Aliquat 336 ) to give difluoro(phenylsulfonyl)methyl substituted alcohols (2-8).The product alcohol derived from para-tolualdehyde was converted to the difluoromethylated alcohol by desulfonylation and to the α, β, β-trifluorostyrene by a fluorination-elimination sequence.In the absence of aldehydes, 1 reacted in two phase system to give difluoro(phenylsulfonyl)methyl phenyl sulfide (9).The pathway of the latter conversion was studied.
- Stahly, G. Patrick
-
-
- Process for nucleophilic fluoroalkylation of aldehydes
-
Aryl difluoromethyl sulfone adds to alkehydes under phase transfer conditions to give novel substituted alcohols of the general formula wherein R is an aryl, cycloaliphatic, sec- or tert-aliphatic, or heterocyclic group and Ar is an aryl group. The substituted alcohols of formula I are of particular utility as intermediates in the synthesis of a variety of useful end products. For example, the products of formula I may be utilized in desulfonylation reactions, oxidation reactions and fluorination reactions.
- -
-
-
- Perfluoro- and Polyfluorosulfonic Acids. 21. Synthesis of Difluoromethyl Esters Using Fluorosulfonyldifluoroacetic Acid as a Difluorocarbene Precursor
-
Difluoromethyl alkanoates 5 and fluorinated and nonfluorinated alkanesulfonates 9 were synthesized in moderate yields by the reaction of alkali metal salts of acids with fluorosulfonyldifluoroacetic acid (3) in acetonitrile under mild conditions.The presumed intermediate anion FO2SCF2CO2- generates CF2: by elimination of SO2, CO2, and F-.The esters are formed by insertion of CF2: into the O-H of the acid, whereas HCF3 is formed by the competing capture of F-.Organic acids can be used indirectly in the reaction in the presence of inorganic salts such as Na2SO4 and KCl, with comparable yields of difluoromethyl esters.
- Chen, Qing-Yun,Wu, Sheng-Wen
-
p. 3023 - 3027
(2007/10/02)
-
