- Synthesis of (benzenesulfonyl)difluoromethyl thioethers from ((difluoromethyl)sulfonyl)benzene and organothiocyanates generatedin situ
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Easily available aryl and alkyl thiocyanates were converted into the corresponding (benzenesulfonyl)difluoromethyl thioethersviathe direct nucleophilic substitution of ((difluoromethyl)-sulfonyl)benzene under transition metal free conditions. Combined wit
- Dai, Jianjun,Shen, Xiao,Wu, Cheng,Xu, Huajian,Xu, Jun
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supporting information
p. 7607 - 7610
(2021/09/22)
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- Regio- and chemoselectivity in S- and O- difluoromethylation reactions using diethyl (bromodifluoromethyl)phosphonate
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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
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- Iron-Catalyzed, Site-Selective Difluoromethylthiolation (-SCF2H) and Difluoromethylselenation (-SeCF2H) of Unactivated C(sp3)-H Bonds in N-Fluoroamides
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The iron-catalyzed δ-C(sp3)-H bond difluoromethylthiolation and difluoromethylselenation of aliphatic amides with high site selectivity are reported. Essential to the success is the employment of an amide radical formed in situ to activate the inert C(sp3
- Zhang, Hongwei,Yu, Fei,Li, Chuang,Tian, Peiyuan,Zhou, Yulu,Cao, Zhong-Yan
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supporting information
p. 4721 - 4725
(2021/06/28)
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- Nickel-Catalyzed Decarbonylative Synthesis of Fluoroalkyl Thioethers
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This report describes the development of a nickel-catalyzed decarbonylative reaction for the synthesis of fluoroalkyl thioethers (RFSR) from the corresponding thioesters. Readily available, inexpensive, and stable fluoroalkyl carboxylic acids (RFCO2H) serve as the fluoroalkyl (RF) source in this transformation. Stoichiometric organometallic studies reveal that RF-S bond-forming reductive elimination is a challenging step in the catalytic cycle. This led to the identification of diphenylphosphinoferrocene as the optimal ligand for this transformation. Ultimately, this method was applied to the construction of diverse fluoroalkyl thioethers (RFSR), with R = both aryl and alkyl.
- Brigham, Conor E.,Malapit, Christian A.,Lalloo, Naish,Sanford, Melanie S.
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p. 8315 - 8320
(2020/08/28)
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- Asymmetric Difluoromethylthiolation of Carbon Nucleophiles with Optically Pure Difluoromethylthiolating Reagents Derived from Camphorsultam
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The invention of a family of optically pure electrophilic difluoromethylthiolating reagents 9a–c based on the camphorsultam skeleton was described. These reagents reacted with a variety of soft carbon nucleophiles such as oxazolone, oxindole, benzolactone and β-ketoester in good to excellent enantioselectivities.
- Zhang, He,Wan, Xiaolong,Shen, Qilong
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p. 1041 - 1050
(2019/11/05)
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- Preparation method for N-difluoromethylthiophthalimide compound
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The invention discloses a preparation method for a N-difluoromethylthiophthalimide compound. The preparation method comprises a step of subjecting difluoromethanesulfonyl chloride and a compound as show in a formula 1 which is described in the specification to difluoromethylthiolation in an organic solvent so as to obtain the N-difluoromethylthiophthalimide compound as show in a formula 3 which isdescribed in the specification. The preparation method of the invention has the advantages of simple operation, few steps, a wide scope of applicable substrates, mild reaction conditions, a high reaction conversion rate, high yield, low cost and suitability for industrial production.
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Paragraph 0070-0076
(2018/03/01)
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- Preparation method for difluoromethyl-substituted sulfoaryl sulfonate
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The invention discloses a preparation method for difluoromethyl-substituted sulfoaryl sulfonate. The preparation method comprises a step of subjecting a compound as show in a formula 2 which is described in the specification or a salt thereof and difluoro
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Paragraph 0054-0058
(2018/04/01)
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- Radical Difluoromethylation of Thiols with (Difluoromethyl)triphenylphosphonium Bromide
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A method for facile difluoromethylation of various thiols using (difluoromethyl)triphenylphosphonium bromide under mild reaction conditions is presented. The transformation proceeds in the absence of any transition metal using a bench-stable and readily accessible phosphonium salt. Deuterium labeling experiments and cyclic voltammetry measurements reveal that the difluoromethylation occurs via a SRN1-type mechanism. Substrate scope is broad, and various functional groups are tolerated (OH, NH2, amide, ester).
- Heine, Niklas B.,Studer, Armido
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supporting information
p. 4150 - 4153
(2017/08/14)
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- Radical Difluororomethylation of Thiols with Difluoromethylphosphonium Triflate under Photoredox Catalysis
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A convenient, visible light-induced radical difluoromethylation of aryl-, heteroaryl-, and alkylthiols with difluoromethyltriphenylphosphonium triflate was developed to afford various difluoromethyl thioethers in moderate to excellent yields. The key reaction features include the use of a readily available CF2H radical source, mild reaction conditions, and excellent chemoselective thiol-difluoromethylation.
- Ran, Yang,Lin, Qing-Yu,Xu, Xiu-Hua,Qing, Feng-Ling
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p. 7373 - 7378
(2017/07/26)
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- Efficient Difluoromethylation of Alcohols Using TMSCF2Br as a Unique and Practical Difluorocarbene Reagent under Mild Conditions
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A general method for the efficient difluoromethylation of alcohols using commercially available TMSCF2Br (TMS=trimethylsilyl) as a unique and practical difluorocarbene source is developed. This method allows primary, secondary, and even tertiary alkyl difluoromethyl ethers to be synthesized under weakly basic or acidic conditions. The reaction mainly proceeds through the direct interaction between a neutral alcohol and difluorocarbene, which is different from the difluoromethylation of phenols. Moreover, alcohols containing other moieties that are also reactive toward difluorocarbene can be transformed divergently by using TMSCF2Br. This research not only solves the synthetic problem of difluorocarbene-mediated difluoromethylation of alcohols, it also provides new insights into the different reaction mechanisms of alcohol difluoromethylation and phenol difluoromethylation with difluorocarbene species.
- Xie, Qiqiang,Ni, Chuanfa,Zhang, Rongyi,Li, Lingchun,Rong, Jian,Hu, Jinbo
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supporting information
p. 3206 - 3210
(2017/03/17)
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- Difluoro methylation reagent, preparation method and application thereof (by machine translation)
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The present invention discloses a two-trifluoromethylation of the reagent, preparation method and application thereof. The invention [...] methylation reagent preparation process is simple, high yield; and the reagent can be a more moderate, high-efficiently the sulfonic acid, alcohol, carbonyl and on the α carbon atom of the difluoromethyl. (by machine translation)
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Paragraph 0176; 0177; 0178
(2017/10/23)
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- A Two-Step, One-Pot, and Multigram-Scale Synthesis of N-Difluoromethylthiophthalimide
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A new method for the 100 g scale synthesis of N-difluoromethylthiophthalimide 1 from cheap commodity chemical benzyl mercaptan and HCF2Cl or other difluorocarbene precursors was described. Reagent 1 is an excellent electrophilic difluoromethylthiolating reagent as demonstrated by the gram-scale synthesis of five difluoromethylthiolated derivatives of structurally complicated drug-like molecules and natural products.
- Zhu, Dianhu,Hong, Xin,Li, Dezhi,Lu, Long,Shen, Qilong
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p. 1383 - 1387
(2017/09/22)
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- PhSO2SCF2H: A Shelf-Stable, Easily Scalable Reagent for Radical Difluoromethylthiolation
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A new shelf-stable and easily scalable difluoromethylthiolating reagent S-(difluoromethyl) benzenesulfonothioate (PhSO2SCF2H) was developed. PhSO2SCF2H is a powerful reagent for radical difluoromethylthiolation of aryl and alkyl boronic acids, decarboxylative difluoromethylthiolation of aliphatic acids, and a phenylsulfonyl-difluoromethylthio difunctionalization of alkenes under mild reaction conditions.
- Zhu, Dianhu,Shao, Xinxin,Hong, Xin,Lu, Long,Shen, Qilong
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supporting information
p. 15807 - 15811
(2016/12/16)
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- Preparation of difluoromethylthioethers through difluoromethylation of disulfides using TMS-CF2H
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We report an operationally simple, metal-free approach for the late-stage introduction of the important lipophilic hydrogen-bond donor motif, SCF2H. This reaction converts diaryl- and dialkyl-disulfides into the corresponding aryl/alkyl-SCF2H through the nucleophilic transfer of a difluoromethyl group with good functional group tolerance. This method is notable for its use of commercially available TMSCF2H, and does not rely on the need for handling of sensitive metal complexes.
- Howard, Joseph L.,Schotten, Christiane,Alston, Stephen T.,Browne, Duncan L.
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supporting information
p. 8448 - 8451
(2016/07/07)
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- Photoredox-Catalyzed Intramolecular Difluoromethylation of N-Benzylacrylamides Coupled with a Dearomatizing Spirocyclization: Access to CF2H-Containing 2-Azaspiro[4.5]deca-6,9-diene-3,8-diones
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A visible light-mediated difluoromethylation of N-benzylacrylamides with HCF2SO2Cl as the HCF2 radical precursor is described. The reaction incorporates a tandem cyclization/dearomatization process to afford various difluoromethylated 2-azaspiro[4.5]deca-6,9-diene-3,8-diones bearing adjacent quaternary stereocenters under mild conditions in moderate to excellent yields.
- Zhang, Zuxiao,Tang, Xiao-Jun,Dolbier, William R.
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supporting information
p. 1048 - 1051
(2016/03/15)
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- Difluoromethylation and gem-difluorocyclopropenation with difluorocarbene generated by decarboxylation
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Difluoromethylation of the activated X-H bond (X = N, O and S) and aliphatic thiols, and gem-difluorocyclopropenation of alkynes with difluorocarbene generated in situ from difluoromethylene phosphobetaine (Ph3P+CF2CO2-) by decarboxylation occurred smoothly without the presence of any base or other additives.
- Deng, Xiao-Yun,Lin, Jin-Hong,Zheng, Jian,Xiao, Ji-Chang
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supporting information
p. 8805 - 8808
(2015/05/20)
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- Efficient cu-catalyzed atom transfer radical addition reactions of fluoroalkylsulfonyl chlorides with electron-deficient alkenes induced by visible light
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Fluoroalkylsulfonyl chlorides, RfSO2Cl, in which Rf=CF3, C4F9, CF2H, CH2F, and CH2CF3, are used as a source of fluorinated radicals to add fluoroalkyl groups to electron-deficient, unsaturated carbonyl compounds. Photochemical conditions, using Cu mediation, are used to produce the respective α-chloro-β-fluoroalkylcarbonyl products in excellent yields through an atom transfer radical addition (ATRA) process. Facile nucleophilic replacement of the α-chloro substituent is shown to lead to further diverse functionalization of the products.
- Tang, Xiao-Jun,Dolbier, William R.
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supporting information
p. 4246 - 4249
(2015/04/14)
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- Photoredox-Catalyzed Tandem Insertion/Cyclization Reactions of Difluoromethyl and 1,1-Difluoroalkyl Radicals with Biphenyl Isocyanides
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Using visible-light photoredox conditions, difluoromethylation and 1,1-difluoroalkylation of biphenyl isocyanides have allowed the synthesis of a series of 6-(difluoromethyl)- and 6-(1,1-difluoroalkyl)phenanthridines via tandem addition/cyclization/oxidation processes. The reactions are carried out in wet dioxane at room temperature using fac-Ir(ppy)3 as catalyst to form a large variety of substituted phenanthridine products in good to excellent yield.
- Zhang, Zuxiao,Tang, Xiaojun,Dolbier, William R.
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supporting information
p. 4401 - 4403
(2015/09/28)
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- Direct Photoredox-Catalyzed Reductive Difluoromethylation of Electron-Deficient Alkenes
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Photoredox-catalyzed reductive difluoromethylation of electron-deficient alkenes was achieved in one step under tin-free, mild and neutral conditions. This protocol affords a facile method to introduce RCF2 (R=H, Ph, Me, and CH2N3) groups at sites β to electron-withdrawing groups. It was found that TTMS (tris(trimethylsilyl)silane) served nicely as both the H-atom donor and the electron donor in the catalytic cycle. Experimental and DFT computational results provided evidence that RCF2 (R=H, Ph, Me) radicals are nucleophilic in nature.
- Tang, Xiao-Jun,Zhang, Zuxiao,Dolbier, William R.
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supporting information
p. 18961 - 18965
(2016/01/26)
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- Direct S-difluoromethylation of thiols using the Ruppert-Prakash reagent Dedicated to Prof. Veronique Gouverneur on the occasion of receiving the ACS Award for Creative Work in Fluorine Chemistry.
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Direct S-difluoromethylation of aryl and aliphatic thiols using the Ruppert-Prakash reagent is demonstrated. The reaction produces trimethylsilyldifluoromethyl sulfides, which upon cleavage with fluoride produces the difluoromethyl sulfides. The key reaction features are the use of relatively inexpensive and commercially available starting materials, shorter reaction times, ambient temperatures, easy reaction procedure, and selective S-difluoromethylation in the presence of -OH, -NH2 and -CO2H functional groups. Furthermore, one-pot arylthiodifluoromethyl transfer to PhCHO is also demonstrated.
- Prakash, G.K. Surya,Krishnamoorthy, Sankarganesh,Kar, Sayan,Olah, George A.
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p. 186 - 191
(2015/10/28)
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- Synthesis of difluoromethyl thioethers from difluoromethyl trimethylsilane and organothiocyanates generated in situ
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A copper-CF2H complex generated in situ from copper thiocyanate and TMS-CF2H smoothly converts organothiocyanates into valuable difluoromethyl thioethers. This reaction step can be combined with several thiocyanation methods to one-pot protocols, allowing late-stage difluoromethylthiolations of widely available alkyl halides and arenediazonium salts. This strategy enables the introduction of difluoromethylthio groups - a largely unexplored substituent with highly promising properties - into drug-like molecules. A copper-CF2H complex generated in situ from copper thiocyanate and TMS-CF2H smoothly converts organothiocyanates into valuable difluoromethyl thioethers. This reaction step can be combined with several thiocyanation methods to one-pot protocols, allowing late-stage difluoromethylthiolations of widely available alkyl halides and arenediazonium salts.
- Bayarmagnai, Bilguun,Matheis, Christian,Jouvin, Kvin,Goossen, Lukas J.
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p. 5753 - 5756
(2015/06/10)
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- Deoxygenative gem-difluoroolefination of carbonyl compounds with (chlorodifluoromethyl)trimethylsilane and triphenylphosphine
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Background: 1,1-Difluoroalkenes cannot only be used as valuable precursors for organic synthesis, but also act as bioisosteres for enzyme inhibitors. Among various methods for their preparation, the carbonyl olefination with difluoromethylene phosphonium ylide represents one of the most straightforward methods. Results: The combination of (chlorodifluoromethyl)trimethylsilane (TMSCF2Cl) and triphenylphosphine (PPh3) can be used for the synthesis of gem-difluoroolefins from carbonyl compounds. Comparative experiments demonstrate that TMSCF2Cl is superior to (bromodifluoromethyl)trimethylsilane (TMSCF2Br) and (trifluoromethyl)trimethylsilane (TMSCF3) in this reaction. Conclusion: Similar to many other Wittig-type gem-difluoroolefination reactions in the presence of PPh3, the reaction of TMSCF2Cl with aldehydes and activated ketones is effective.
- Wang, Fei,Li, Lingchun,Ni, Chuanfa,Hu, Jinbo
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supporting information
p. 344 - 351
(2014/03/21)
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- Photoredox-catalyzed tandem radical cyclization of N-arylacrylamides: General methods to construct fluorinated 3,3-disubstituted 2-oxindoles using fluoroalkylsulfonyl chlorides
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Fluorinated radicals were generated from RfSO2Cl by photoredox catalysis under mild conditions, where Rf = n-C4F9, CF3, CF2H, CH2F, CH2CF3, and CF2CO2Me. This method provided a general way to construct fluorinated 2-oxindoles from reaction with N-arylacrylamides via a proposed tandem radical cyclization process.
- Tang, Xiao-Jun,Thomoson, Charles S.,Dolbier, William R.
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supporting information
p. 4594 - 4597
(2015/01/08)
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- Synthesis of gem-difluorocyclopropa(e)nes and O-, S-, N-, and P-difluoromethylated compounds with TMSCF2Br
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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
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supporting information
p. 12390 - 12394
(2013/12/04)
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- N-tosyl-S-difluoromethyl-S-phenylsulfoximine: A new difluoromethylation reagent for S-, N-, and C-nucleophiles
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The first α-difluoromethyl sulfoximine compound, 2, was successfully prepared by using the copper(ll)-catalyzed nitrene transfer reaction. Compound 2 was found to be a novel and efficient difluoromethylation reagent for transferring the CF2H gr
- Zhang, Wei,Wang, Fei,Hu, Jinbo
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supporting information; experimental part
p. 2109 - 2112
(2009/09/30)
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- Process for the synthesis of hydrogenofluoromethylenesulphonyl radical derivatives
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The invention concerns a method for synthesis of hydrogenofluoromethylenesulphonyl radical derivatives, comprising: a) a step which consists in condensing a thiolate (that is a monoalkyl sulphide salt) with a compound having a sp; 3hybridized carbon bearing a hydrogen, a fluorine, a heavy halogen selected among chlorine, bromine and iodine and an electron-attracting group selected among fluorine and those whereof the is not less than 0.2, advantageously than 0.4; b) a step which consists in oxidizing the compound obtained in step a). The invention is applicable to the synthesis of various compounds having a suphinyl or sulphonyl group.
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Page/Page column 4-5
(2008/06/13)
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