Trifluoromethyl Compounds Research Articles

Phenyliodonium diacetate mediated carbotrifluoromethylation of N-acylhydrazones.

A concise, efficient and direct trifluoromethylation method of aldehyde-derived N-acylhydrazones has been firstly developed by using the combination of inexpensive, stable and commercially available TMSCF3 and PhI(OAc)2 as the CF3 source under mild reaction conditions. This method provides easy access to highly functionalized trifluoromethylated N-acylhydrazones, which could be used as trifluoromethyl synthetic building blocks to be further transformed into other valuable trifluoromethyl compounds.

ChemInform Abstract: Copper‐Catalyzed Enantioselective Conjugate Addition of Grignard Reagents to Methyl 4,4,4‐Trifluorocrotonate: Synthesis of Enantioenriched Trifluoromethylated Compounds.

Copper-catalyzed enantioselective 1,4-conjugate addition of methyl 4,4,4-trifluorocrotonate with aliphatic Grignard reagents to access an asymmetric tertiary carbon center attached with a trifluoromethyl group was achieved under mild reaction conditions. The desired products could be obtained in reasonable yields and good enantioselectivities.

Copper‐Catalyzed Enantioselective Conjugate Addition of Grignard Reagents to Methyl 4,4,4‐Trifluorocrotonate: Synthesis of Enantioenriched Trifluoromethylated Compounds

Copper-catalyzed enantioselective 1,4-conjugate addition of methyl 4,4,4-trifluorocrotonate with aliphatic Grignard reagents to access an asymmetric tertiary carbon center attached with a trifluoromethyl group was achieved under mild reaction conditions. The desired products could be obtained in reasonable yields and good enantioselectivities.

Quantum chemical calculation of 19F NMR chemical shifts of trifluoromethyl diazirine photoproducts and precursors

Irradiation of aryl(trifluoromethyl)diazirines may result in a multitude of products, which are difficult to assign in the 19F NMR spectrum. In this article, it is demonstrated that an average accuracy of 2.9ppm (standard deviation) can be achieved by quantum chemical calculations at the B3LYP 6-311G++(2d,2p) level of theory, followed by a Boltzmann weighting of the optimized conformers. A set of 30 compounds was investigated both experimentally and theoretically. 19F NMR chemical shifts of precursor Z-oximes and Z-tosyloximes ranged from δF −62.9 to −61.8ppm, whereas their E counterparts showed shifts between δF −67.2 and −66.2ppm. Stereochemical assignments were confirmed by two X-ray analyses. Quantum chemical calculation also allowed the assignment of the configuration of an (E,E) azine. Trifluoromethyl diazirines exhibited a δF between −66.1 and −65.6, diaziridines between −76.2 and −75.9ppm. The smallest δF values were observed for α-oxygenated trifluoromethyl compounds (δF −78.9 to −77.4ppm). The average deviation of the calculated from the experimental values corresponds to only about 1% of the standard 19F NMR chemical shift range.

Pushing and pulling electrons: the effect on the heat of formation of trifluoromethyl compounds

The effect on heats of formation, of conjoined or proximate functional groups which can interact via polar or resonance effects, is examined using the –CF3 group as a standard. Two metrics are applied: the difference in heat of formation of G–CF3 and G–CH3, where –G is a wide range of functional groups, and also the deviation of the heat of formation of G–CF3 from the average of the heats of formation of G–G and CF3–CF3. This latter metric reveals both stabilizing and destabilizing effects on the heat of formation, of up to 60 kcal/mol, depending on the polar and resonance nature of the –G structure. The possibility of using such metrics as a correction the group additivity values is examined.

Recent Advances in Catalytic Asymmetric Friedel-Crafts Reactions with Prochiral Trifluoromethylated Compounds

* E-mail: huangyy@whut.edu.cn Received January 16, 2013; published March 5, 2013. Project supported by the Sichuan Provincial Department of Education Scientific Research Fund Project (13ZA0034), the Fundamental Research Funds for the Central Universities (WUT: 2013-IV-077), the Chinese Hubei Government for a “Chutian Scholar” Honor, and the Chinese Central Government for an “Expert of the State” Position in the Program of “Thousand Talents”. 项目受四川省教育厅科研项目基金(13ZA0034), 中央高校基本科研业务费专项资金(项目编号: 2013-IV-077), 湖北省“楚天学者计划”和中组部“外 专千人计划”资助.

ChemInform Abstract: Nucleophilic (Phenylsulfonyl)difluoromethylation of Alkyl Halides Using PhSO2CF2SiMe3: Preparation of gem‐Difluoroalkenes and Trifluoromethyl Compounds.

AbstractNucleophilic substitution followed by base‐mediated 1,2‐elimination allows an improved synthesis of gem‐difluoroalkenes if the substrate bears an aryl substituent.

Nucleophilic (phenylsulfonyl)difluoromethylation of alkyl halides using PhSO 2CF 2SiMe 3: preparation of gem-difluoroalkenes and trifluoromethyl compounds

Nucleophilic (phenylsulfonyl)difluoromethylation of both alkyl iodides and bromides was successfully accomplished by using CsF/15-crown-5 as an initiating system in DME, and the amount of 15-crown-5 was found to be critical to the yield of the product. The prepared (phenylsulfonyl)difluoromethylated alkanes were converted into gem-difluoroalkenes by a base-mediated 1,2-elimination reaction, and the latter species could be further transformed into trifluoromethyl compounds in the presence of KF/18-crown-6 or TBAF.

ChemInform Abstract: Stereoselective Synthesis of Trifluoromethylated Compounds: Nucleophilic Addition of Formaldehyde N,N-Dialkylhydrazones to Trifluoromethyl Ketones.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Synthesis of Fluorine Compounds Based on Special Property of Fluorine Compounds

This review describes new syntheses of organofluorine compounds taking advantage of the special properties of fluorine compounds as synthones. The main reactions presented are as follows: 1) Trifluoromethylation of aryl or alkyl halides. Application of this reaction for the synthesis of fluorine analogues of nucleic acid bases is discussed. 2) Some syntheses of trifluoromethyl compounds using the Diels-Alder or the 1,3-dipolar reaction, trifluoromethylated carbene, and photoreaction. 3) The Friedel-Crafts reaction of 3,3,3-trifluoropropene, where linear alkylation occurs due to electronic effect of the trifluoromethyl group in good contrast with the Friedel-Crafts reaction of propene. 4) The ene reaction of trifluoromethylated carbonyl compounds, which work as good enophiles. Application of this reaction to the synthesis of trifluoro analogues of terpenes is discussed. 5) The ene reaction of trifluoromethylated imines. 6) Reaction of halothane, which has a highly acidic hydrogen and two halogens adjacent to the trifluoromethyl group and shows interesting reactivities with various bases and metals to give products with unexpected structures. 7) Reaction of 2-bromo-2,2-difluoroacetate with Cu, where the cross-coupling reaction, Michael-type reaction, and radical reaction for different types of difluoroacetates are presented. 8) Reaction of 2-bromo-2,2-difluoroacetate in the presence of Rh catalyst. This reaction provided a new methodology for the introduction of fluoroalkyl substituents to the alpha-position of alpha,beta-unsaturated ketones. The Rh catalyst solved some difficulties in the introduction of difluoroacetate to carbonyl compounds (Reformatsky reaction). Application of this reaction to imines provided easy access to beta,beta-difluoro-beta-lactams.

Quantitative evaluation of weak nonbonded Se...F interactions and their remarkable nature as orbital interactions.

To evaluate weak intramolecular nonbonded Se...F interactions recently characterized for a series of o-selenobenzyl fluoride derivatives (Iwaoka et al., Chem. Lett. 1998, 969-970), the temperature dependence of the nuclear spin coupling between Se and F (J(Se...F)) was investigated for 2-(fluoromethyl)phenylselenenyl cyanate (1a) and bis[2-(fluoromethyl)phenyl] diselenide (1e) in CD2Cl2 and CD3CN. A significant increase in the magnitude of J(Se...F) was observed for both 1a and 1e upon lowering temperature, whereas the values of J(Se...F) for the corresponding trifluoromethyl compounds slightly reduced or remained unchanged at low temperatures. Application of the rapid equilibrium model between two possible conformers revealed that conformer A with an intramolecular Se...F interaction is more stable in enthalpy (DeltaH) by 1.23 kcal/mol for 1a (in CD2Cl2) and by 0.85 and 0.83 kcal/mol for 1e (in CD2Cl2 and CD3CN, respectively) than conformer B, which does not have close Se...F contact. The negligible solvent effects for 1e suggested marginal electrostatic nature of the Se...F interactions. Instead, importance of the n(F) -->sigma*(Se-X) orbital interaction was suggested by quantum chemical (QC) calculations and the natural bond orbital (NBO) analysis.

Isolation and spectroscopic characterisation of C60F17CF2CF3 and isomers of C60F17CF3; insertion of :CF2 into fluorofullerene C–F bonds

The perfluoroalkylfluoro[60]fullerenes C60F17CF2CF3 (Cs) and three isomers of C60F17CF3 [Cs (major, 65%), enantiomeric C1 pair (minor, 35%)] have been separated by HPLC from the many products obtained by fluorination of [60]fullerene by K2PtF6 at ca. 465 °C. They have been characterised by 19F NMR spectroscopy, and for the trifluoromethyl compound, by single crystal X-ray structure determination. The trifluoromethyl compound shows either extremely weak or no resonances for the CF3 group in the 19F NMR spectrum, which led to an earlier misidentification of the major isomer in this compound as a CF2 derivative. Isolation of these compounds indicates that trifluoromethyl compounds are formed under these conditions by insertion of :CF2 groups (from fragmentation of other fluorinated fullerene cages) into C–F bonds.

Studies on organofluorine compounds: an overview of our 30 years

This review article covers our research activities over 30 years in organofluorine chemistry. The followings are briefly summarized researches in this memorandum: (1) Trifluoromethylation of organic halides with trifluoromethyl copper complex and its application to trifluoromethylated nucleosides, (2) a systematic study on reactivity of aromatic trifluoromethyl compounds, (3) valence bond isomers of aromatic compounds stabilized by the trifluoromethyl groups, and (4) synthesis of fluorinated bioactive compounds which involve vitamin D3, arachidonic acid and its metabolites, and retinal.

Electrophilic Substitution of 1,1,2,2,9,9,10,10-Octafluoro[2.2]paracyclophane

Nitration of octafluoro[2.2]paracyclophane (OFP) provides an entry into the synthesis of a series of 11 monosubstituted OFPs, including the nitro, amino, chloro, bromo, iodo, hydroxy, and trifluoromethyl compounds. The NMR, mass spectrometric, and UV spectral properties of all of these derivatives are presented and discussed, and they are compared with those of its hydrocarbon analogue, [2.2]paracyclophane.

ChemInform Abstract: Asymmetric α‐Alkylation of α,β‐Unsaturated Esters. Application to the Synthesis of (R)‐Lavandulol, (R)‐Sesquilavandulol and Related Trifluoromethyl Compounds.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Asymmetric α-Alkylation of α,β-Unsaturated Esters. Application to the Synthesis of (R)-Lavandulol, (R)-Sesquilavandulol and Related Trifluoromethyl Compounds

Diastereoselective α-alkylation/deconjugation of esters of diacetone D-glucose has been performed and applied to the syntheses of (R)-lavandulol, (R)-sesquilavandulol with de up to 74%. The same reaction performed with trifluoromethyl derivatives was also achieved but without significant diastereoselectivity.

ChemInform Abstract: Stereoselective Synthesis of Trifluoromethylated Compounds via Johnson—Claisen and Eshenmoser—Claisen Rearrangements.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

GR205171: A novel antagonist with high affinity for the tachykinin NK 1 receptor, and potent broad-spectrum anti-emetic activity

It has been demonstrated recently that antagonists of the tachykinin NK 1 receptor, specifically CP-99,994 and GR203040, possess anti-emetic activity in a range of species. To optimise this activity, a series of analogues based around the structure of GR203040 have been synthesised and their affinity at the human tachykinin NK 1 receptor determined. In addition, the potency of these analogues to inhibit emesis induced in the ferret by whole-body X-irradiation has been examined. A range of substitutions at the C-1 position of the tetrazole moiety in GR203040 were explored in vitro and in vivo. The trifluoromethyl compound, GR205171, was the most potent antagonist with regard to the ability to inhibit emesis induced by X-irradiation. This compound was demonstrated to have a broad spectrum of anti-emetic activity, inhibiting emesis in the ferret induced by cisplatin, cyclophosphamide, morphine, ipecacuanha and copper sulphate. Furthermore, emesis was also inhibited in the house-musk shrew, Suncus murinus, when induced by either motion or cisplatin, and in the dog when induced by ipecacuanha. GR205171 has the most potent anti-emetic activity of any tachykinin NK 1 receptor antagonist described to date. The compound is orally active in the ferret and dog, long-lasting, and warrants further investigation as a potential broad-spectrum anti-emetic agent.

ChemInform Abstract: Stereoselective Synthesis of Trifluoromethylated Compounds with Controlled Adjacent Tertiary Carbons by Michael Addition to (E)‐3‐( Trifluoromethyl)acrylates.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: Ab initio Investigation of the Heats of Formation of Several Trifluoromethyl Compounds

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.