- Direct preparation of trifluoromethylindium reagents from trifluoromethyl iodide: Effective trifluoromethylation and perfluoroalkylation reagents
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The direct synthesis of trifluoromethylindium reagents prepared from trifluoromethyl iodide by using just one equivalent each of indium, lithium chloride or sodium iodide, and ferrocene is reported. The weak In···F interaction is suitable to prepare stable but nucleophilic perfluoroalkyl reagents, which were successfully employed in the perfluoroalkylation of aldehydes. Notably, the nucleophilic trifluoromethylation of various aldehydes took place with trifluoromethyl iodide by utilizing just one equivalent each of indium, lithium chloride, and ferrocene.
- Fujiu, Motohiro,Nakamura, Yuzo,Serizawa, Hiroki,Aikawa, Kohsuke,Ito, Shigekazu,Mikami, Koichi
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- One-Pot Successive Turbo Grignard Reactions for the Facile Synthesis of α-Aryl-α-Trifluoromethyl Alcohols
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A novel straightforward one-pot methodology for two successive turbo Grignard reagent (iPrMgCl·LiCl) reactions, was developed for a facile synthesis of α-aryl-α-trifluoromethyl alcohols, motifs of value in pharmaceutical chemistry. The method displayed broad functional group tolerance, including reducible groups. Dual roles of iPrMgCl·LiCl were exploited in the tandem reaction with commercially available iodoarenes or iodoheteroarenes and 2,2,2-trifluoroethyl trifluoroacetate. The process encompasses three successive reactions in a one-pot process: the iPrMgCl·LiCl-mediated iodine/magnesium-exchange reaction of iodoarenes or iodoheteroarenes; nucleophilic addition of various generated aryl or heteroarylmagnesium reagents to 2,2,2-trifluoroethyl trifluoroacetate; and the reduction of in-situ generated aryl trifluoromethyl ketones with iPrMgCl·LiCl, to produce the corresponding α-aryl or α-heteroaryl-α-trifluoromethyl alcohols bearing various substituents, including reducible functional groups in good to excellent yields.
- Kani, Ryunosuke,Inuzuka, Toshiyasu,Kubota, Yasuhiro,Funabiki, Kazumasa
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supporting information
p. 4487 - 4493
(2020/06/01)
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- One-Pot and Reducible-Functional-Group-Tolerant Synthesis of α-Aryl- and α-Heteroaryl-α-Trifluoromethyl Alcohols via Tandem Trifluoroacetylation and MPV Type Reduction
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We have developed a new one-pot synthesis of α-aryl- and α-heteroaryl-α-trifluoromethyl alcohols carrying not only arenes with electron-withdrawing groups but also electron-deficient nitrogen-containing heteroarenes, which are of increasing interest becau
- Funabiki, Kazumasa,Hayakawa, Ayaka,Kani, Ryunosuke,Inuzuka, Toshiyasu,Kubota, Yashuhiro
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p. 5978 - 5984
(2019/08/30)
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- Oxidation of α-trifluoromethyl and non-fluorinated alcohols: Via the merger of oxoammonium cations and photoredox catalysis
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We present an alcohol oxidation strategy to access α-trifluoromethyl ketones (TFMKs) merging catalytic oxoammonium cation oxidation with visible-light photoredox catalysis. This work uses 4-acetamido-(2,2,6,6-tetramethyl-piperidin-1-yl)oxyl as an organic oxidant capable of generating TFMKs in good yields. The methodology serves as an improvement over previous reports of an analogous oxidation strategy requiring superstoichiometric quantities of oxidant. Both primary and secondary non-fluorinated alcohols can also be oxidised in good yields.
- Pistritto, Vincent A.,Paolillo, Joshua M.,Bisset, Kathryn A.,Leadbeater, Nicholas E.
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supporting information
p. 4715 - 4719
(2018/07/06)
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- Palladium-Catalyzed Direct Approach to α-Trifluoromethyl Alcohols by Selective Hydroxylfluorination of gem-Difluoroalkenes
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A novel palladium-catalyzed selective hydroxylfluorination of gem-difluoroalkenes has been developed. By employing easily obtainable gem-difluoroalkenes and NFSI as the fluorine source, the scope, advantages, and limitations of this reaction were investigated. The reaction presents an efficient synthesis to afford a series of α-trifluoromethyl alcohols in good to excellent yields. Furthermore, this reaction probably proceeds via oxidation of Pd0 to PdII fluoride complex by NFSI, followed by fluoropalladation of gem-difluoroalkenes to generate an α-trifluoromethylbenzyl–Pd intermediate. And this strategy offers more possibilities for the construction of other bonds, such as C–C, C–N and C–S.
- Zhang, Bin,Zhang, Xiaofei,Hao, Jian,Yang, Chunhao
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p. 5007 - 5015
(2018/10/05)
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- NHC-Copper(I) Halide-Catalyzed Direct Alkynylation of Trifluoromethyl Ketones on Water
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An efficient and easily scalable NHC-copper(I) halide-catalyzed addition of terminal alkynes to 1,1,1-trifluoromethyl ketones, carried out on water for the first time, is reported. A series of addition reactions were performed with as little as 0.1-2.0?mo
- Czerwiński, Pawe?,Molga, Edyta,Cavallo, Luigi,Poater, Albert,Michalak, Micha?
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supporting information
p. 8089 - 8094
(2016/06/13)
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- Condensed-phase, halogen-bonded CF3I and C2F5I adducts for perfluoroalkylation reactions
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A family of practical, liquid trifluoromethylation and pentafluoroethylation reagents is described. We show how halogen bonding can be used to obtain easily handled liquid reagents from gaseous CF3I and CF3CF2I. The synthetic utility of the new reagents is exemplified by a novel direct arene trifluoromethylation reaction as well as adaptations of other perfluoroalkylation reactions. Its (no longer) a gas! A family of practical, liquid trifluoromethylation and pentafluoroethylation reagents enabled by halogen bonding is described. The synthetic utility of these reagents is exemplified by a novel direct arene trifluoromethylation reaction as well as adaptations of other perfluoroalkylation reactions.
- Sladojevich, Filippo,McNeill, Eric,B?rgel, Jonas,Zheng, Shao-Liang,Ritter, Tobias
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supporting information
p. 3712 - 3716
(2015/03/18)
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- FLUOROALKYLATION REAGENTS AND USES THEREOF
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Provided herein are halogen-bonded complexes of Formula (I), wherein is a halogen bond; R1 is unsubstituted C1-3 fluoroalkyl; D is N(R2)3, ((R2)2N)2C=NR2, 0=S(R2)2, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted heteroaryl, and wherein R2 and y are as defined herein. D----(I??R1)y (I) Further provided are methods of preparing compounds of Formula (I), compositions, reagents, and kits comprising a compound of Formula (I), and methods for fluoroalkylating an organic compound using a compound of Formula (I).
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Paragraph 00202
(2015/11/23)
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- Development of (Trifluoromethyl)zinc Reagent as Trifluoromethyl Anion and Difluorocarbene Sources
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The trifluoromethylation of carbonyl compounds is accomplished by the stable (trifluoromethyl)zinc reagent generated and then isolated from CF3I and ZnEt2, which can be utilized as a trifluoromethyl anion source (CF3-). The reaction proceeds smoothly with diamine as a ligand and ammonium salt as an initiator, providing the corresponding trifluoromethylated alcohol products. Moreover, the (trifluoromethyl)zinc reagent can also be employed as a difluorocarbene source (:CF2) not only for gem-difluoroolefination of carbonyl compounds with phosphine but also for gem-difluorocyclization of alkenes or alkynes via the thermal decomposition, respectively.
- Aikawa, Kohsuke,Toya, Wataru,Nakamura, Yuzo,Mikami, Koichi
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supporting information
p. 4996 - 4999
(2015/11/03)
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- Polyfluoroalkylation of carbonyl compounds by polyfluoroalkyl anions generated from polyfluorocarboxamides
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Polyfluoroalkyl anions, generated by reduction of (polyfluoroalkanoyl)piperidines with Et3BHK, were used for the polyfluoroalkylation of carbonyl compounds. Trifluoromethylation of aromatic aldehydes proceeded in good yields, and that of aliphatic aldehydes afforded a moderate yield. In contrast, the yield was low when the reaction involved benzophenone. Pentafluoroethylation and octafluorobutylation of aldehydes were also carried out by using the corresponding (polyfluoroalkanoyl)piperidines, which were prepared from commercially available polyfluorocompounds. The (polyfluoroalkanoyl)piperidines were also prepared through polyfluorination, and were used in the polyfluoroalkylation of aldehydes.
- Wakita, Natshumi,Hara, Shoji
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p. 1201 - 1212
(2016/11/07)
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- Highly efficient synthesis of aryl and heteroaryl trifluoromethyl ketones via o-iodobenzoic acid (IBX)
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A two-step process for the synthesis of aryl and heteroaryl trifluoromethyl ketones from the corresponding aldehydes is described. Trifluoromethyl alcohols were prepared from aryl and heteroaryl aldehydes in excellent yields using catalytic amount of K2CO3. The trifluoromethyl alcohols were then oxidized conveniently and efficiently by o-iodoxybenzoic acid (IBX) under mild conditions to get the desired functionalized aryl and heteroaryl trifluoromethyl ketones.
- Cheng, Huicheng,Pei, Yu,Leng, Faqiang,Li, Jingya,Liang, Apeng,Zou, Dapeng,Wu, Yangjie,Wu, Yusheng
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p. 4483 - 4486
(2013/07/26)
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- Asymmetric transfer hydrogenation of 1-naphthyl ketones by an ansa-Ru(II) complex of a DPEN-SO2N(Me)-(CH2)2(η 6-p-tol) combined ligand
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The first second-generation designer Ru(II) catalyst 1b featuring an enantiopure N,C-(N-ethylene-N-methyl-sulfamoyl)-tethered (DPEN- κ2N,N′)/η6-toluene hybrid ligand is introduced. Using an S/C = 1000 in HCO2H-Et3N 5:2 transfer hydrogenation medium, secondary 1-naphthyl alcohols are obtained in up to >99.9% ee under mild conditions. Mechanistic factors are discussed.
- Kisic, Andrea,Stephan, Michel,Mohar, Barbara
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supporting information
p. 1614 - 1617
(2013/06/26)
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- Solvent selection in synthesis of 4-(1-arylfluoroethoxy)quinazolines and thienopyrimidines
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The nucleophilic aromatic substitution of 4-chloroquinazoline and 6-bromo-4-chlorothieno[2,3-d]pyrimidine with 1-aryl-2-fluoroethanols as nucleophilies has been studied focusing on the use of carbonate bases in combination of environmental acceptable solvents. The conversion rate depended on the solvent properties, the acidity of the nucleophile and the nature of the base. By using acetonitrile as reaction medium and K2CO3 as base, 2,2,2-trifluoro-, 2,2-difluoro-, and 2-fluoro-1-phenylethanol could efficiently be coupled to 4-chloropyrimidines. Alternatively, employing Cs 2CO3, allowed for shorter reaction time for these substrates, and also couplings of the non-fluorinated alcohols proceeded well. tert-Butanol was also found to be a suitable reaction medium in transformation of the fluoro alcohols. Testing of hydrolytic stability of the 4-alkoxypyrimidines revealed that the fluorinated and nonfluorinated derivatives were labile under acidic conditions, whereas in basic media the fluoroalkoxy derivatives were more stable than their non-fluorinated counterparts.
- Han, Jin,Sundby, Eirik,Hoff, B?ge H.
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supporting information
p. 82 - 88
(2013/11/06)
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- Organocatalysis approach to trifluoromethylation with fluoroform
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The organic base methodology exploits an access to generate the "trifluoromethyl anion" for carbonyl, ester, acid halide, epoxide, deuterium donor, and carbon dioxide substrates to afford the trifluoromethylation products with good overall efficiency even in organocatalysis conditions. The NMR analysis of the mixture of fluoroform and P4-base shows no change thereof. However, on addition of electrophiles, the trifluoromethylation products were obtained efficiently.
- Zhang, Yuan,Fujiu, Motohiro,Serizawa, Hiroki,Mikami, Koichi
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supporting information
p. 367 - 371
(2014/01/06)
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- Nucleophilic trifluoromethylation with organoboron reagents
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Potassium trialkoxy(trifluoromethyl)borates are shown to behave as convenient reagents for nucleophilic trifluoromethylation of non-enolizable aldehydes and N-tosylimines to give CF3-substituted alcohols and N-tosylamines in good yields.
- Levin, Vitalij V.,Dilman, Alexander D.,Belyakov, Pavel A.,Struchkova, Marina I.,Tartakovsky, Vladimir A.
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supporting information; experimental part
p. 281 - 284
(2011/02/26)
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- Magnesium metal-mediated reductive trifluoromethylation of aldehydes with phenyl trifluoromethyl sulfone
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An unprecedented reductive nucleophilic trifluoromethylation of aldehydes by using phenyl trifluoromethyl sulfone is reported. Mercury(II) chloride efficiently activates magnesium metal to induce the desulfonylative trifluoromethylation process. The new r
- Zhao, Yanchuan,Zhu, Jieming,Ni, Chuanfa,Hu, Jinbo
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experimental part
p. 1899 - 1904
(2010/08/19)
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- Nonenzymatic kinetic resolution of racemic 2,2,2-trifluoro-1-aryl ethanol via enantioselective acylation
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Kinetic resolution of a series of 2,2,2-trifluoro-1-aryl ethanol with (R)-benzotetramisole as the catalyst has been investigated. The result showed that when the aryl group in the substrate was a phenyl (or a phenyl substituted by an electron-donating group) or a naphthyl (an extended phenyl) group, the system could give an s value higher than 20. Preparative KR examples demonstrated the applicability of this method in the preparation of some of enantiomerically pure 2,2,2-trifluoro-1-aryl ethanol or 2,2,2-trifluoro-1-aryl-ethyl iso-butyrate.
- Xu, Qing,Zhou, Hui,Geng, Xiaohong,Chen, Peiran
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supporting information; experimental part
p. 2232 - 2238
(2009/07/11)
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- Reduction of 2,2,2-trifluoro-1-arylethanones with alkyl phosphines
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In the presence of alkyl phosphines, reduction of 2,2,2-trifluoro-1-arylethanones proceeded smoothly to give the corresponding reduction products in moderate to high yields at room temperature. The possible mechanism was discussed on the basis of deuteriu
- Shi, Min,Liu, Xu-Guang,Guo, Ying-Wen,Zhang, Wen
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p. 12731 - 12734
(2008/03/15)
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- Nucleophilic trifluoromethylation using trifluoromethyl iodide. A new and simple alternative for the trifluoromethylation of aldehydes and ketones
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(Matrix Presented) A novel method for nucleophilic trifluoromethylation of aldehydes and ketones, based on photoinduced reduction of trifluoromethyl iodide by tetrakis(dimethylamino)ethylene (TDAE), is presented.
- Ait-Mohand, Samia,Takechi, Naoto,Medebielle, Maurice,Dolbier Jr., William R.
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p. 4271 - 4273
(2007/10/03)
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- A chiral triaminosulfonium salt: Design and application to catalytic asymmetric synthesis
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The first chiral triaminosulfonium salt, tris((S,S)-3,4-diphenylpyrrolidino)sulfonium difluorotriphenylstannate, catalyzes trifluoromethylation of benzaldehyde with (trifluoromethyl)trimethylsilane to give the corresponding optically active alcohol with 52% ee.
- Kuroki, Yoshichika,Iseki, Katsuhiko
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p. 8231 - 8234
(2007/10/03)
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- Lipase-catalysed Enantioselective Synthesis of Naphthyl Trifluoromethyl Carbinols and Their Corresponding Non-Fluorinated Counterparts
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Enantioselective synthesis of both enantiomers of β- and α-naphthyl trifluoromethyl carbinols (R)-1a, (S)-1a, (R)-2a, (S)-2a has been achieved through acylation of the corresponding racemic alcohols (RS)-1a and (RS)-2a with vinyl acetate in the presence of lipase PS.The effect of fluorine atoms on the extent and enantioselectivity of the process has been tested by carrying out the same biocatalytic transformation on their non-fluorinated counterparts (RS)-1b and (RS)-2b.The order of reactivity follows the trend (RS)-1b > (RS)-2b ca. (RS)-1a > (RS)-2a.Effect of thehydrophobicity of the solvent in the resolution of (RS)-1a is also presented.
- Gaspar, Jordi,Guerrero, Angel
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p. 231 - 238
(2007/10/02)
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