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We report a kinetic study of the water exchange on lanthanide ions in water/[1-ethyl-3-methylimidazolium][trifluoromethylsufate] (water/[EMIm][OTf]). The results from 17O-NMR measurements show that the water-exchange rates in water/[EMIm][OTf] increase with decreasing size of the lanthanide ions. This trend forwater-exchange is similar to the previously reported trend inwater/1-ethyl-3-methylimidazolium ethyl sulfate (water/[EMIm][EtSO4]) but opposite to that in water. To gain atomic-level insight into these water-exchange reactions, molecular dynamics simulations for lanthanide ions in water/[EMIm][OTf] have been performed using the atomic-multipole-optimizedenergetics-for-biomolecular-application polarizable force field. Our molecular dynamics simulations reproduce the experimental water-exchange rates in terms of the trend and provide possible explanations for the observed experimental behavior. The smaller lanthanide ions in water/[EMIm][OTf] undergo faster water exchange because the smaller lanthanide ions coordinate to the first shell [OTf] anions more tightly, resulting in a stronger screening effect for the second-shell water. The screening effect weakens the interaction of the lanthanide ions with the second-shell water molecules, facilitating the dissociation of water from the second-shell and subsequent association of water molecules from the outer solvation shells. [ABSTRACT FROM AUTHOR]

Currently, a great deal of research efforts are focused on C–C bond activation for development of novel synthetic methodology. In this paper, a detrifluoroacetylation of trifluoromethyl‐β‐diketones is described, which allows for the synthesis of succinimides and 1,4‐diketones through cascade Michael addition/retro‐Claisen reaction and nucleophilic substitution/retro‐Claisen reaction. The readily available trifluoromethyl‐β‐diketones, wide substrate scope, and mild conditions make this method very practical. [ABSTRACT FROM AUTHOR]

A new and efficient method for the synthesis of 2-trifluoromethyl-2-hydroxy-2 H -chromenes was developed via intermolecular cyclization of ( Z )-trifluoromethyl alkenyl triflates and salicylaldehydes. A series of 2-trifluoromethyl-2-hydroxy-2 H -chromenes with aryl or alkyl groups at 3-position have been obtained in moderate to excellent yields. And a key intermediate, 3-phenyl-4-(pyrrolidin-1-yl)-2-(trifluoromethyl)chroman-2-ol ( 6 ), was isolated and fully characterized, which suggests that the elimination of pyrrolidine from this intermediate is the last step during the formation of 2-trifluoromethyl-2-hydroxy-2 H -chromenes. [ABSTRACT FROM AUTHOR]

Synthesis of a new series of trifluoromethyl‐4,5‐dihydro‐1,2,4‐oxadiazoles and trifluoromethyl‐1,2,4‐oxadiazoles have been described by utilizing the reactions between amidoximes and trifluoroacetimidoyl chlorides. Trifluoromethyl‐4,5‐dihydro‐1,2,4‐oxadiazoles have been synthesized under mild conditions such as Na2CO3, THF‐H2O, and titanium dioxide nanoparticles as catalyst in good to excellent yields. Also, trifluoromethyl‐1,2,4‐oxadiazoles have been synthesized directly from reaction of amidoximes and trifluoroacetimidoyl chlorides in a one‐pot manner in present of NaH, THF, and titanium dioxide nanoparticle as catalyst. [ABSTRACT FROM AUTHOR]

Abstract: The first catalytic enantioselective γ‐boryl substitution of CF3‐substituted alkenes is reported. A series of CF3‐substituted alkenes was treated with a diboron reagent in the presence of a copper(I)/Josiphos catalyst to afford the corresponding optically active γ,γ‐gem‐difluoroallylboronates in high enantioselectivity. The thus obtained products could be readily converted into the corresponding difluoromethylene‐containing homoallylic alcohols using highly stereospecific allylation reactions. [ABSTRACT FROM AUTHOR]

A simplified effective synthetic process is described for the diastereoselective synthesis of the chiral C 2 -symmetric CF 3 -ureas ( R,R )- 15 and ( S,S )- 15 from ( S )-α-phenylethylamine, glyoxal and CF 3 I. [ABSTRACT FROM AUTHOR]

Abstract: A new protocol has been developed for the synthesis of α-trifluoromethyl ketones via organocatalyzed decarboxylative trifluoromethylation of β-ketoacids with Togni’s reagent. Among various simple amine catalysts, primary amines and secondary amines were identified to be more effective than tertiary amines, with piperazine being the most effective. Mechanistic investigations suggested that the primary or secondary amine-catalyzed reactions proceed mainly through trifluoromethylation of an enamine intermediate, which is more effective than the tertiary amine-catalyzed pathway that involves an enol intermediate. By using piperazine as the optimal organocatalyst, various β-ketoacids, including the sterically hindered α,α-disubstituted ones, were converted into the corresponding α-trifluoromethyl ketones in good yields. This research not only provides a useful strategy for the efficient synthesis of a wide range of α-trifluoromethyl ketones under mild conditions, but also constitutes one of the few studies on decarboxylative alkylation of β-ketoacids, which can intrigue further exploitation on organocatalyzed asymmetric decarboxylative alkylation reactions.Graphical Abstract: [ABSTRACT FROM AUTHOR]

The reaction of the divalent ruthenium complexes [CpFRuCl]n and [CpFRu(MeCN)3]PF6 with substituted pentafulvenes 1,2-(Me2NCH)(CO2Et)C5H3 and 1,3-(Me2NCH)(CO2Et)- C5H3 followed by hydrolysis affords new homoannular disubstituted ruthenocenes {1,2- (CO2Et)(CHO)C5H3}RuCpF and {1,3-(CO2Et)(CHO)C5H3}RuCpF (CpF = C5Me4CF3), re- spectively. [ABSTRACT FROM AUTHOR]

The copper $$\hbox {CF}_{3}$$ or $$\hbox {SCF}_{3}$$ complexes as the fluoride sources for the synthesis of trifluoromethylated or trifluoromethylthiolated compounds are reviewed. Compared with the ordinary fluoride reagents, the addition of reactant species in the reaction systems of copper trifluoromethyl or trifluoromethylthio complexes were less, so the reaction systems are relatively simple and easy to operate. In most cases, the trifluoromethylated or trifluoromethylthiolated products were obtained in moderate to excellent yields. GRAPHICAL ABSTRACT: SYNOPSISThis mini-review highlights recent developments in trifluoromethylation or trifluoromethylthiolation using copper $$\hbox {CF}_{3}$$ or $$\hbox {SCF}_{3}$$ complexes, such as (phen) $$\hbox {CuCF}_{3}$$ , (phen) $$\hbox {Cu}(\hbox {CF}_{3})_{3}$$ , (bpy) $$\hbox {Cu}(\hbox {CF}_{3})_{3}$$ , $$(\hbox {Ph}_{3}\hbox {P})_{3}\hbox {CuCF}_{3}$$ , and (bpy) $$\hbox {CuSCF}_{3}$$ . [ABSTRACT FROM AUTHOR]

Cross-coupling reactions of aryl groups with α-fluoro carbonyl compounds catalyzed by palladium complexes have been reported, but palladium fluoroenolate intermediates relevant to such reactions have not been isolated or even detected previously. We report the synthesis, structural characterization, and reactivity of a series of C-bound arylpalladium fluoroenolate complexes ligated by monophosphines and bisphosphines. DPPF-ligated arylpalladium fluoroenolate complexes (DPPF = 1,1-bis(diphenylphosphino)-ferrocene) derived from a monofluoroester, a difluoroester, difluoroamides, and difluoroacetonitrile underwent reductive elimination in high yields. Reductive elimination was faster from complexes containing less electron-withdrawing fluoroenolate groups and longer Pd-C(enolate) bonds than from complexes containing more electron-withdrawing fluoroenolate groups and shorter Pd-C(enolate) bonds. The rates of reductive elimination from these C-bound fluoroenolate complexes were significantly faster than those of the analogous trifluoromethyl complexes. [ABSTRACT FROM AUTHOR]

The enantioselective synthesis of tetralin derivatives bearing a trifluoromethylated all-carbon quaternary stereocenter has been accomplished through a synthetic sequence comprising an organocatalytic β-functionalization of ortho-1-trifluoromethylvinyl-(hetero)aromatic conjugated aldehydes followed by the intramolecular nitrone 1,3-cycloaddition reaction (INCR). Both nitromethane and N-Cbz-hydroxylamine were employed as nucleophiles in the initial organocatalytic conjugate addition step, which provided the chiral information required for the subsequent diastereoselective INCR. Although diastereoselectivity was moderate, good yields and enantioselectivities were, in general, obtained. Interestingly, an inversion of the selectivity in the intramolecular cycloaddition step was observed when either nitromethane or N-Cbz-hydroxylamine was employed. This outcome was studied by means of theoretical calculations, which were in agreement with the experimental results. In addition, the ring opening of the isoxazolidine moiety furnished the corresponding fluorinated diamino alcohols in a very efficient manner. [ABSTRACT FROM AUTHOR]

A new series of 7-trifluoromethyl-2-pyridylquinazolin-4(3H)-one-based acyl thiourea derivatives has been generated and tested for their cytotoxicity towards human ovarian cancer (SK-OV-3), cervical cancer (HeLa), renal cancer (Caki-2) cell lines, as well as noncancerous a human umbilical vein endothelial cell (HUVEC) line. The new thiourea derivatives were found to be promisingly cytotoxic towards the cancerous cell lines. Changing the substituent at the thiourea linkage led to variations in the cytotoxic potential of the resultant derivatives towards specific cell lines. Molecules with fluorine functionality and multiple pyridyl moieties showed encouraging anticancer effects and could be used as a platform for the design of further chemotherapeutic agents. The proposed structures of the products were ascertained through FTIR, mass, 1H NMR and 13C NMR spectra and elemental analyses. [ABSTRACT FROM AUTHOR]

Metal complexes display functional interfaces for association with and stimulation of certain enzymes, that are liable to transfer genetic information in DNA for synthesis of specific proteins. Biological activity of five organotin carboxylates based on the ligand, 4-oxo-4-[3-(trifluoromethyl)phenylamino]butanoic acid, such as [BuSnL] ( 1), [PhSnL] ( 2), [MeSnL] ( 3), [BuSnL] ( 4), and [PhSnL] ( 5) have been synthesized and their biological activity as a function of substitution on the ligand was tested. Structure of the complexes was evaluated by elemental analysis, FT-IR and H, and C NMR spectra. FT-IR data and theoretical calculations revieled that the ligand acted as bidentate in complexes 1- 5. NMR data revealed four and six coordinated geometry of tin in solutions. The HOMO-LUMO study indicated thermodynamic stability of the complexes. AFM confirmed catalytic potential of the synthesized complexes. Biological screening showed that, with few exceptions, all the complexes exhibited significant activity against various bacterial and fungal strains. UV-Vis study confirmed that the ligand and its complexes binded to DNA via intercalative interactions. [ABSTRACT FROM AUTHOR]

Two novel fluorinated diimide-diacid monomers, [2,2′-(4,4′-(4′-chloro-3′-(trifluoromethyl)biphenyl-2,5-diyl)bis(oxy)bis(3-(trifluoromethyl)-4,1-phenylene))bis(1,3-dioxoisoindoline-5-carboxylic acid)] (III) and [2,2′-(4,4′-(3′,5′-bis(trifluoromethyl)biphenyl-2,5-diyl)bis(oxy)bis(3-(trifluoromethyl)-4,1-phe-nylene))bis(1,3-dioxoisoindoline-5-carboxylic acid)] (IV), were respectively designed and synthesized viathe reactions between the diamine (I or II) and two molar equivalents of trimellitic anhydride. Based on these two diimide-diacids, two families of novel poly(amide-imide)s (PAIs) (IIIa–IIIe and IVa–IVe) bearing different trifluoromethyl groups were prepared by directly polymerizing diimide-diacids with a series of aromatic diamines (a–e). All of the PAIs exhibited high glass transition temperatures ( T g s, 236–268 °C), excellent thermal stability (only 5% weight loss at 493–542 °C under nitrogen) and good solubility in various organic solvents since the bulky pendant groups were introduced. The cast films of these PAIs (thickness = 80–90 μm) had excellent optical transparency (70–83% at 450 nm, 85–87% at 550 nm and 88–89% at 800 nm) and low dielectric constants (2.62–2.92 at 1 MHz). In addition, the spin-coated films of these PAIs presented very low birefringence values the minimum of which was 0.0073 at 650 nm. These spin-coated films also exhibited very weak absorption at the near-infrared communication wavelengths of 1310 and 1550 nm. [ABSTRACT FROM AUTHOR]

The discovery of nematic phase in 3-fluoro-4-trifluoromethyl-4ʹ-(4ʹ-alkyl [trans,trans-1,1ʹ-bicyclohexyl]-4-yl) 1,1ʹ-biphenyls (n = 2, 3, 4, 5) is an accidental affair. A convenient method was used for the synthesis of these target compounds. After the preparation of the intermediate with trifluomethyl group, the target compounds were synthesised by Suzuki cross-coupling reaction. Then, these phase transition temperatures were measured by polarising textural observation, which confirmed the existence of single nematic phase. These temperatures were also measured by differential scanning calorimetry, which showed that the clearing point of compound (n = 3) is 267℃. The possible mechanism of occurrence of unique nematic phase was discussed on the basis of the principles of fluorine chemistry. [ABSTRACT FROM PUBLISHER]

The biological properties of trifluoromethyl compounds have led to their ubiquity in pharmaceuticals, yet their chemical properties have made their preparation a substantial challenge, necessitating innovative chemical solutions. We report the serendipitous discovery of a borane-catalyzed formal C(sp3)-CF3 reductive elimination from Au(III) that accesses these compounds by a distinct mechanism proceeding via fluoride abstraction, migratory insertion, and C-F reductive elimination to achieve a net C-C bond construction. The parent bis(trifluoromethyl)Au(III) complexes tolerate a surprising breadth of synthetic protocols, enabling the synthesis of complex organic derivatives without cleavage of the Au-C bond. This feature, combined with the “fluoride-rebound” mechanism, was translated into a protocol for the synthesis of 18F-radiolabeled aliphatic CF3-containing compounds, enabling the preparation of potential tracers for use in positron emission tomography. [ABSTRACT FROM AUTHOR]

Hydroxytrifluoromethylation of alkenes using the fluoroform (CF3H)-derived [CuCF3] reagent is described. In the presence of additive B2Pin2 and air, this reagent effectively facilitates the addition of hydroxy and trifluoromethyl groups across an alkene double bond, a formal hydroxytrifluoromethylation process. Various β-trifluoromethyl alcohols can be synthesized from simple alkenes where the ultimate CF3 source is the industrial byproduct fluoroform. [ABSTRACT FROM AUTHOR]

This paper describes firstly an effective protocol for the synthesis of a new series of five examples of 3-(trifluoromethyl)-3,3a-dihydrospiro[chromeno[4,3- c ]isoxazole-4,1′-cycloalkan]-3-ols ( 4 ), in which the cycloalkanes — cyclopentane, cyclohexane, cycloheptane, and 4′-methyl- and 4′- t -butyl-cyclohexane — were isolated at yields of 65–84%. The dihydro-isoxazolinols 4 were obtained regioselectively from the reactions of 2,2,2-trifluoro-1-[4-methoxy-spiro(2 H -chromen-2,1′-cycloalkane)-3-yl]ethanones ( 3 ) with hydroxylamine hydrochloride, in the presence of sodium bicarbonate and methanol as solvent, for 24 h at 60 °C. The ethanone precursors 3 were synthesized by trifluoroacetylation reaction, employing trifluoroacetic anhydride and mixtures of enolethers and/or acetals derived from spiro[chroman-2,1′-cycloalkan]-4-ones ( 2 ) (Kabbe’s adducts), which were obtained beforehand from the reaction of cycloalkanones 1 with 2-hydroxyacetophenone and pyrrolidine. Subsequently, dehydration reactions of isoxazolinols 4 , employing thionyl chloride and pyridine, enabled the isolation of another series of five novel spiro-isoxazoles 5 (76–95% yield). The structural features of the two series of new spiro heterocycles ( 4 and 5) were unequivocally determined with the aid of: one-dimensional 1 H, 13 C, and 19 F NMR spectroscopy; two-dimensional 1 H and 13 C NMR spectroscopy (NOESY, gHMBC, and gHMQC); single crystal X-ray diffraction; and GC–MS. [ABSTRACT FROM AUTHOR]

The reaction of hexafluoropropene trimers with Ruppert-Prakash (CF 3 SiMe 3 ) reagent gave highly congested perfluoroolefins such as the mono-trifluoromethylation products F -2,4-dimethyl-3-isopropyl-2-pentene ( P1 ) and E - and Z -forms of F -4,4-dimethyl-3-isopropyl-2-pentene ( 2 E and 2 Z ), and the bis-trifluoromethylation product F -2,4,4-trimethyl-3-isopropyl-2-pentene ( 3 ). The E -form of 2 was also comprised of two rotamers. Various aprotic polar solvents were surveyed for this reaction, and it was found that the aprotic solvent DMI has a unique solvent effect to selectively give the mono-trifluoromethylated perfluoroolefin P1 , a precursor for the persistent perfluoroalkyl radical F -3-isopropyl-2,4-dimethyl-3-pentyl, in very high yield. [ABSTRACT FROM AUTHOR]

An iron-catalyzed thiocyclization of propynols with aryl disulfides has been developed for the synthesis of trifluoromethylated benzothiophenes. The one-pot tandem reaction involves Meyer-Schuster rearrangement of propynols and radical cyclization through C-H functionalization of aryl disulfides. A variety of 2-trifluoroacyl benzothiophenes were prepared in moderate to good yields with good functional-group tolerance. [ABSTRACT FROM AUTHOR]

New set of trifluromethyl, diethylamino and morpholino derived coumarin compounds were prepared by reacting various coumarin 3-carboxylic acids with various phenyl esters with peripheral alkyl, ester and polar cyano moieties in the presence of EDC.HCl/DMAP as esterification agent. The chemical structures of new coumarin derivatives were confirmed by standard spectroscopic techniques and mesomorphic behaviours were established by polarised optical microscopy (POM) and differential scanning calorimetry (DSC). Trifluoromethane and morpholino derivatives show SmA/Nematic phase, while diethylamino derivatives did not show liquid crystalline property. [ABSTRACT FROM AUTHOR]

reaction of l-proline with trifluoroacetimidoyl chlorides has been developed as an efficient strategy for the synthesis of trifluoromethyl oxazole derivatives by two methods: (a) in the presence of K2CO3 as a base in acetonitrile at room temperature and (b) in the presence of K2CO3 as a base in acetonitrile using , in one pot reaction. The has been found to be the most efficient method. High yields and short reaction times were obtained for both electron-releasing and electron-withdrawing substituted N-aryltrifluoroacetimidoyl chloride derivatives by . [ABSTRACT FROM AUTHOR]

The first ferrous chloride catalyzed boration/β-fluorine elimination of trifluoromethyl alkenes is described. Thus, a full range of gem-difluoroallylboronates were obtained in high yield under mild conditions. As an important fluorinated building block, gem-difluoroallylboronate can be readily converted into diverse difluoro-substituted species. [ABSTRACT FROM AUTHOR]

A novel method for the conversion of vinyl triflates into α-trifluoromethylated ketones in the absence of external trifluoromethyl sources is described. This process accomplishes an efficient migration of the trifluoromethyl group of the triflate to the α-position in the ketone through a radical process. The reaction proceeds by the addition of a trifluoromethyl radical to the vinyl triflate and subsequent fragmentation of the trifluoromethane sulfonyl radical. Based on this reaction, a one-pot two-step procedure for the trifluoromethylation of ketones was developed. The method presented herein also allows the transfer of perfluoroalkyl groups from vinyl perfluoroalkanesulfonates, which are readily accessible from alkynes and perfluoroalkanesulfonic acids. [ABSTRACT FROM AUTHOR]

An improved procedure was developed for the synthesis of 3,3,3-trifluoro-1-nitropropene, and a new representative of gem-bromonitroalkenes, 1-bromo-3,3,3-trifluoro-1-nitropropene, was synthesized therefrom. Its reaction with phenyl azide gave a mixture of two regioisomeric 1,2,3-triazoles, from which pure 5-nitro-1-phenyl-4-(trifluoromethyl)-1 H-1,2,3-triazole was isolated. [ABSTRACT FROM AUTHOR]

A convergent synthesis of a series of 16 new polysubstituted (5-hydroxy-5-(trifluoromethyl)-4,5-dihydro-1 H -pyrazol-1-yl)(quinolin-4-yl)methanones, starting from isatin and alky(aryl/heteroaryl) ketones, is described. The diheteroaryl methanones were achieved at yields of up to 95% by a [3 + 2] cyclocondensation reaction involving 4-alkyl(aryl/heteroaryl)-4-methoxy-1,1,1-trifluorobut-3-en-2-ones (by two-step reaction) and 2-alkyl(aryl/heteroaryl)-4-carbohydrazides (by three-step reaction). Subsequently, representative dehydrated heterocyclic derivatives were obtained from the respective 5-hydroxy-2-pyrazoline moieties by classical dehydration reactions, which resulted in the corresponding (5-(trifluoromethyl)-1 H -pyrazol-1-yl)(quinolin-4-yl)methanones (three examples) at yields of 69–82%. The subsequent cytotoxicity evaluation showed that compounds with aromatic groups at the 2-position of the quinoline and a methyl moiety at the 3-position of the pyrazole have significant cytotoxicity in human leukocytes at high concentrations (200 μM). [ABSTRACT FROM AUTHOR]

A method is proposed for the synthesis of 3-nitro-2-phenyl-2-(trifluoromethyl)-2 H-chromenes by tandem condensation of salicylic aldehydes with ( E)-3,3,3-trifluoro-1-nitro-2-phenylprop-1-ene in the presence of triethylamine. The example of 3-nitro-2-phenyl-2-(trifluoromethyl)-2 H-chromene was used to demonstrate conjugated addition reactions with enamines, nitromethane, and aniline, which are characteristic for this class of compounds. The structure of the obtained products was confirmed by X-ray structural analysis. [ABSTRACT FROM AUTHOR]

The reaction with β-trifluoromethyl acrylamide 3e and azomethine ylides generated from l -proline and several aldehydes provided the corresponding trifluoromethylated pyrrolizidines with excellent diastereoselectivity (>20/1) in all cases and moderate regioselectivity (up to 1/5.9). A DFT calculation was also examined to reveal the origin of these stereoselectivities. [ABSTRACT FROM AUTHOR]

A series of 5,5-bis(trifluoromethyl)-5,6-dihydropyrimido[4,5-d]pyrimidine-2,4(1 H ,3 H )-diones has been prepared by the cyclocondensation of N -acylimines of hexafluoroacetone and 6-aminouracils. The obtained compounds were screened for their activities against Gram-positive ( Staphylococcus aureus, Staphylococcus epidermidis and Bacillus anthracis ) and Gram-negative ( Escherichia coli ) bacteria, as well as fungus Candida albicans. A few of the title compounds showed promising antimicrobial activity. [ABSTRACT FROM AUTHOR]

Efficient preparation of synthetically important CF3-containing α,β-unsaturated esters is described using an NHC-catalyzed multicomponent reaction. This approach combines sequential NHC-mediated HOMO and LUMO activation to produce a C-C bond and C-O bond in a one-pot operation. [ABSTRACT FROM AUTHOR]

An efficient, scalable and operationally simple one-pot, 2-step strategy for the nucleophilic formylation of trifluoromethyl ketones is presented. The key step is an unprecedented diaza-carbonyl-ene reaction of formaldehyde tert-butyl hydrazone and trifluoromethyl ketones under solvent-free conditions. This reaction proved to be very fast, clean and high-yielding, affording densely functionalised α-hydroxy α-trifluoromethyl diazenes. The ensuing diazene-to-aldehyde transformation, avoiding protection/deprotection reactions and chromatographic purifications, and subsequent derivatizations in a one-pot fashion provide a direct entry to a variety of useful trifluoromethylated building blocks. [ABSTRACT FROM AUTHOR]

Here we report a facile, efficient, and catalyst-free method to realize C-C cross-coupling of aryl chlorides and inert arenes under UV light irradiation. The aryl radical upon homolytic cleavage of C-Cl bond initiated the nucleophilic substitution reaction with inert arenes to give biaryl products. This mild reaction mode can also be applied to other synthetic reactions, such as the construction of C-N bonds and trifluoromethylated compounds. [ABSTRACT FROM AUTHOR]

Considering the increasing importance of fluorinated peptides, the development of efficient and reliable synthetic methods for the incorporation of unnatural fluorinated amino acids into peptides is a current matter of interest. In this study, we report the convenient Boc/benzyl and Cbz/ tert-butyl protection of both enantiomers of the quaternarized amino acid α-trifluoromethylalanine [( R)- and ( S)-α-Tfm-Ala]. Because of the deactivation of the nitrogen atom of this synthetic amino acid by the strong electron withdrawing trifluoromethyl group, the peptide coupling on this position is a challenge. In order to provide a robust synthetic methodology for the incorporation of enantiopure ( R)- and ( S)-α-trifluoromethylalanines into peptides, we report herein the preparation of dipeptides ready to use for solid phase peptide synthesis. The difficult peptide coupling on the nitrogen atom of the α-trifluoromethylalanines was performed in solution phase by means of highly electrophilic amino acid chlorides or mixed anhydrides. The synthetic effectiveness of this fluorinated dipeptide building block strategy is illustrated by the solid phase peptide synthesis (SPPS) of the Ac-Ala-Phe-( R)-α-Tfm-Ala-Ala-NH tetrapeptide. [ABSTRACT FROM AUTHOR]

New derivatives of chrysin containing 2-mercaptopyridine ( 2a – 2e ) or 5-(trifluoromethyl)-2-mercaptopyridine ( 3a – 3e ) moieties were prepared from the reaction between bromides ( 1a – 1e ) and 2-mercaptopyridine or 5-(trifluoromethyl)-2-mercaptopyridine, respectively. Their structures were elucidated by NMR, IR and elemental analysis. The molecular structure of compounds 1a, 1c – 1e , 2b – 2e and 3a was determined by single-crystal X-ray diffraction studies. All rings in these structures are nearly coplanar and they showed an intramolecular hydrogen bond between the phenolic hydroxyl H atom and the carbonyl O atom that forms a six membered ring. The crystal packing also showed a wide variety of intermolecular contacts such as C–H⋯A, π–π, C–H⋯π and lone pair⋯π interactions which were supported by quantum theory of atoms in molecules (QTAIM), Hirshfeld surface, and fingerprint plot analyses. Biological activity of all compounds was tested in growth assays of the nematode Caenorhabiditis elegans . Compounds 2e , 3b and 3c inhibited larval development. [ABSTRACT FROM AUTHOR]

A series of 1-alkyl-3-methyl-1,2,3-triazolium bis(trifluoromethylsulfonyl)imide [NTf 2 ] ionic liquids were prepared synthetically using azide–alkyne ‘click’ cyclization chemistry and their physicochemical and thermal properties were determined. Increasing the alkyl chain length resulted in increased viscosities and higher thermal transitions ( T g or T m ) with depressed molar conductivities. Walden plot analysis indicated that the ionicity of 1-butyl-3-methyl-1,2,3-triazolium [NTf 2 ] was comparable to the analogous imidazolium system and higher than the 1,2,4-triazolium equivalent. [ABSTRACT FROM AUTHOR]

The syntheses of novel C-nucleoside phosphonic acids as potential antiviral agents are described. The sugar moiety that served as the nucleoside skeleton was produced starting from commercially available 1,3-dihydroxy cyclopentane. The key C-C bond formation from sugar to base precursor was performed using the Knoevenagel-type condensation. The synthesized compounds exhibited anti-HIV activity and cytotoxicity. Also, the synthesized compounds were screened in vitro for tumor growth inhibitory activity against mouse leukemia cell lines (L-1210, P-815). [ABSTRACT FROM PUBLISHER]

A highly enantioselective Diels–Alder reaction of 4,4,4-trifluorocrotonaldehyde and dienes was performed with a diarylprolinol silyl ether catalyst. The reaction with cyclopentadiene, 1,3-cyclohexadiene, and 2-substituted 1,3-butadienes yielded the corresponding cycloadducts bearing a trifluoromethylated chiral carbon center with up to 97% ee, whereas the reaction with furan yielded the corresponding Friedel–Crafts adduct with high enantioselectivity. [ABSTRACT FROM AUTHOR]

This paper describes an efficient approach for the synthesis of 2-(trifluoromethyl)-1,2,3,4,7,8-hexahydroquinolin-5(6 H)-one derivatives via a one-pot four-component reaction of aromatic aldehyde, 5,5-dimethylcyclohexane-1,3-dione, 4,4,4-trifluoro-1-(thien-2-yl)butane-1,3-dione, and NH4OAc with excellent yields at room temperature. In this synthesis, the trifluoromethyl was efficiently introduced in hexahydroquinoline structure, and they may be valuable the drug candidates. This approach also offered several other advantages, such as catalyst-free, mild conditions, and simple experimental operation. [ABSTRACT FROM AUTHOR]

A general visible light induced photoredox-catalyzedradical trifluoromethylation/cyclizationcascade of β-aryl-β,γ-unsaturated hydrazones andoximes is described. The protocol enables an efficient access to variousdensely functionalized and biologically important CF3-containingdihydropyrazoles and isoxazolines with generally high yields. [ABSTRACT FROM AUTHOR]

L-α-Amino esters were considered valuable chiral starting materials in the with trifluoroacetaldehyde (fluoral) ethyl hemiacetal to obtain new functionalized trifluoromethyl aldimines. Starting from these latter compounds, isovaleraldehyde was used in proline-catalyzed Mannich-type to give trifluoromethyl syn- or anti-γ-amino alcohols bearing the L-α-amino ester function, simply by changing the reaction temperature. Chirality 27:571- 575, 2015. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

An improved synthesis of 3-[3-(trifluoromethyl)-3 H -1,2-diazirin-3-yl]aniline, achieving an overall yield of 38% over seven steps is reported. Only three chromatographic separations were needed and the preparation of ∼0.7 g of the target compound was demonstrated. The stability of the diazirine in solution at room temperature while exposed to ambient light was studied. No significant degradation of the compound was observed over the course of five weeks in a 130 mM sample and only minor degradation was observed in weaker samples (10, 5, and 2.5 mM), as demonstrated by 1 H and 19 F NMR. [ABSTRACT FROM AUTHOR]

The α-trifluoromethylthiolation of carbonyl compounds in soft acidic conditions has been developed. With this method only mono-trifluoromethylthiolation was selectively observed. Base-sensitive ketones can then be trifluoromethylthiolated. More sensitive aldehydes are also trifluoromethylthiolated under these conditions with good yields. This work provides a new route towards the synthesis of various valuable trifluoromethylthiolated molecules. [ABSTRACT FROM AUTHOR]

A new series of indole–isoxazolone hybrids bearing substituted amide, substituted [(1,2,3-triazol-4-yl)methoxy]methyl group or substituted benzylic ether at position-2 of the indole nucleus was synthesised using a facile synthetic route and the molecules were characterised using spectroscopic techniques. The molecules were screened against three human cancer cell lines to evaluate their in vitro cytotoxic property. Most of the trifluoromethyl substituted derivatives exhibited better growth inhibition activity than their methyl substituted analogues. The SIRT1 inhibition activity of two potent molecules ( I17 and I18 ) was investigated and the SIRT1 IC 50 values are 35.25 and 37.36 μM, respectively for I17 and I18 . The molecular docking studies with SIRT1 enzyme revealed favourable interactions of the molecule I17 with the amino acids constituting the receptor enzyme. [ABSTRACT FROM AUTHOR]

A facile two-step synthesis of 2-methyl-1,5-dinitro-3- and 2-methyl-1,3-dinitro-5-(trifluoromethyl)benzenes is described. The first step is the nitration of otho- and para -methylbenzoic acids to furnish the corresponding dinitroacids. The dinitroacids then react with sulfur tetrafluoride to provide the corresponding trifluoromethylated products. The latter are easily transformed into 6-nitro-4-(trifluoromethyl)- and 4-nitro-6-(trifluoromethyl)-1 H -indoles by applying the Batcho–Leimgruber synthetic protocol. [ABSTRACT FROM AUTHOR]

Unlike the hydrocarbon analogs, this first report of enolboration–aldolization of 3,3,3-trifluoropropanoic acid provides essentially pure anti -diastereomers of α-trifluoromethyl-β-hydroxy carboxylic acids in 77–90% yields. [ABSTRACT FROM AUTHOR]

The title reaction proceeds with acetylenic triflones and isocyanides under mild conditions using copper as a catalyst. This transformation provides an efficient access to (E)-N-alkyl trifluoromethyl alkynyl ketoimines, which are useful building blocks for the synthesis of CF3-containing N-heterocycles, propargylamines, etc. [ABSTRACT FROM AUTHOR]

Herein is reported a study of asymmetric decarboxylative Mannich addition reactions between (Ss)-N-t-butylsulfinyl-3,3,3-trifluoroacetaldimine and Schiff bases derived from various aldehydes and lithium 2,2-diphenylglycinate. These reactions proceed with excellent diastereoselectivities and good chemical yields, providing a practical method for preparation of trifluoromethyl-containing vicinal diamines. The procedures can be conducted under convenient conditions, rendering this approach of high synthetic value. [ABSTRACT FROM AUTHOR]

The synthesis, characterisation, and crystal structure determination of the closely related compounds 3,3'-bi-(5-trifluoromethyl-1,2,4-oxadiazole) and 5,5'-bi-(2-trifluoromethyl-1,3,4-oxadiazole) are reported. These two compounds are known for their bioactivity; however, in this study they serve as model compounds to evaluate the suitability of the heterocyclic oxadiazole ring system for energetic materials when the fluorine atoms in the exocyclic CF3 groups are substituted successively by nitro groups. Quantum chemical calculations for the bi-1,3,4-oxadiazole derivatives with difluoronitromethyl, fluorodinitromethyl, and trinitromethyl groups have been carried out and predict promising energetic performances for both explosive and propulsive applications. [ABSTRACT FROM AUTHOR]

A convenient access to (2 S ,3 S )-β-(trifluoromethyl)-α,β-diamino acid is reported by using highly diastereoselective Mannich addition reactions of either chiral or achiral Ni(II) complexes derived from glycine Schiff bases to a chiral sulfinimine, N - tert -butylsulfinyl-3,3,3-trifluoroacetaldimine. Disassembly of the resultant Ni(II) complexes affords the target amino acid which was, for the first time, isolated in enantiomerically pure form and fully characterized. [ABSTRACT FROM AUTHOR]

Three new co-poly(arylene ether)s (PAE) containing cardo fluorene moiety in the main chain and pendent trifluoromethyl group have been synthesized by one pot high temperature polycondensation reaction using two kinds of bis-hydroxy compound, 9,9-bis(3,5-dimethoxy-4-hydroxyphenyl)fluorene (DMHF), bisphenol A (BPA) and three different bis-fluoro monomers. The structures of the resulting co-PAEs were investigated by FT-IR and NMR spectroscopy. All the polymers showed good solubility in common organic solvents and high weight average molecular weight up to 443,000 g/mol. Flexible, transparent and mechanically strong films were obtained after solution casting from N,N-dimethylacetamide (DMAc). The polymers exhibited reasonably high thermal stability (T d10 , in the range of 459–485 °C) and high glass transition temperature (215–228 °C). The PAE membranes also revealed good optical transparency (λ cut-off = 350–370 nm) along with very small water absorption (0.38–0.49%) after 72 h immersion in water. Furthermore, the PAE membranes showed low dielectric constants with the values in the range of 2.25–2.42 at room temperature and at 1 MHz frequency, measured from their capacitance. [ABSTRACT FROM AUTHOR]