Radical trifluoromethylation of ketone Li enolates

It has generally been believed that highly basic Li enolates cannot be applied as substrates for radical trifluoromethylation due to defluorination of the α-CF₃ product. However, Li enolates can be in fact employed for radical trifluoromethylation. Moreover, the reaction is extremely fast and the minimum reaction time is only ∼1 s.     

Nucleophilic trifluoromethylation of arylidenemalononitriles

A method for the nucleophilic trifluoromethylation of arylidenemalononitriles using Me₃SiCF₃ is described. The reaction is carried out in dimethylformamide in the presence of AcONa as a Lewis base, and affords products of Michael addition in high yield.     

Mechanistical insight into ‘electrophilic’ trifluoromethylation with S-(trifluoromethyl)dibenzothiophenium salts

Trifluoromethyl sulfonium salts are widely used for the introduction of a trifluoromethyl group through reaction with a wide range of nucleophiles. Nevertheless, the reaction mechanism is far from obvious and has been the subject of various literature discussions. In this Letter, we show, through trapping experiments with a radical probe that, at least in the case of nucleophiles such as enol silyl ethers, the reaction proceeds by SET.     

Novel addition in trifluoromethylation of [70]fullerene

Pyrolytic trifluoromethylation of [70]fullerene with CF₃CO₂Ag at 300 °C results in the addition of up to 12 CF₃ groups to the fullerene cage. Forty-six C₇₀(CF₃)_n derivatives (numbers in parentheses) were separated by two-stage high pressure liquid chromatography (HPLC) as follows: n = 2(2), 4(16), 6(9), 8(14) 10(5), some being characterised by NMR. The range of derivatives is much greater than for other [70]fullerene reactions, and as with [60]fullerene trifluoromethylation, no single derivative is dominant, indicating that kinetic stability mainly controls product formation. NMR spectra show most derivatives to be unsymmetrical, with combinations of quartets and septets (overlapping quartets) due to contiguous (‘linear’) addend arrays, having significantly different coupling constants of the ‘terminal’ quartets of between 9.1 and 17.7 Hz. These differences, together with those observed previously in trifluoromethylation of [60]fullerene are consistent with addition across both 6:6- and 5:6-ring junctions. Of the two C₇₀(CF₃)₂ isomers, one has either C_s or C₂ symmetry, the other has C₁ symmetry, whilst the C₇₀(CF₃)₄ derivatives fall into four categories: (i) symmetrical compounds (one gives only two singlets in the NMR); (ii) unsymmetrical compounds that show a ‘linear’ coupling sequence; (iii) unsymmetrical compounds having a remote pairs of adjacent groups; (iv) compounds having a coupled array of three CF₃ groups, together with a remote group suggesting sterically-driven migration. The first evaluation of differential NMR couplings across 6:6- and 5:6-bonds in a fullerene has been made using C₆₀F₆ as a model.     

An efficient, transition-metal-free process for the synthesis of substituted dihydrofurans via a Michael/cyclization tandem reaction

An efficient green route for the synthesis of substituted dihydrofurans was developed through a simple base-catalyzed, tandem reaction of nitrostyrene with 1,3-dicarbonyl compounds. The desired products were prepared with a large substrate scope and in excellent yields (up to 95%).     

Manganese(III)-mediated oxidative annulation of vinylidenecyclopropanes with 1,3-dicarbonyl compounds

Manganese(III)-mediated oxidative annulation of vinylidenecyclopropanes with 1,3-dicarbonyl compounds in acetonitrile/acetic acid produces the corresponding functionalized dihydrofuran derivatives in moderate to good yields under mild conditions. The substrate scope has been examined and a plausible reaction mechanism has been also proposed on the basis of experimental results and previous literature.     

Nucleophilic trifluoromethylation of arylidene Meldrum’s acids

A method for the trifluoromethylation of arylidene Meldrum’s acids using Me₃SiCF₃ followed by transformation of the initial products to CF₃-substituted esters and alcohols is described. The sequence of reactions is performed without isolation of intermediate compounds furnishing the final products in good overall yields.     

Alkoxide-induced nucleophilic trifluoromethylation using diethyl trifluoromethylphosphonate

A novel alkoxide-induced nucleophilic trifluoromethylation of carbonyl compounds, disulfides, and diselenides using diethyl trifluoromethylphosphonate is presented. In these reactions diethyl trifluoromethylphosphonate acts as a synthon.     

Development of Electrophilic Radical Perfluoroalkylation of Electron-Deficient Olefins

Fluorinated organic compounds have attracted significant attention over the past few decades owing to their unique properties and versatility. An established method for the synthesis of fluorinated organic compounds involves radical perfluoroalkylation reactions towards double bonds. In this radical pathway, electrophilic perfluoroalkyl radicals exhibit excellent reactivity towards electron-rich olefins. Therefore, several splendid perfluoroalkylation reactions of electron-rich olefins have been reported. However, there are only a few examples of reaction involving electron-deficient olefins because of their poor electronic compatibility with perfluoroalkyl radicals. This review focuses on the reports that challenge this long-standing issue. Radical perfluoroalkylation/bifunctionalization reactions of electron-deficient olefins are described according to the radical generation methods.     

An efficient synthesis of a new class of spiroheterocycles: diastereoselective synthesis of dihydropyrrolo[2,1-a]isoquinolines

Isoquinoline reacts with diaroylacetylenes in the presence of 1,3-dicarbonyl compounds in a one-pot reaction to afford functionalized spiropyrroloisoquinolines in 90-96% yields.     

Halogenation of fluorinated cyclic 1,3-dicarbonyl compounds: new aspects of synthetic application

In order to elaborate on an approach towards 2-(fluoroacyl)phenols being the superior alternative to the conventional Fries-rearrangement based methodology, the behaviour of cyclic fluorinated 1,3-dicarbonyls in reactions with halogenating agents was examined. The synthetic relevance of the polyhalogenated compounds obtained was demonstrated by the synthesis of several new heterocycles. An aromatization via a halogenation-dehydrohalogenation sequence proved to be a rewarding synthetic route to 2-(fluoroacyl)phenols and previously unknown 3-(fluoroacyl)thiochromones. The structure of one of the synthesized compounds was confirmed by X-ray diffraction analysis.     

Cinchona alkaloid-derived quaternary ammonium salt combined with NaH: a facile catalyst system for the asymmetric trifluoromethylation of ketones

Enantioselective trifluoromethylation of aromatic ketones promoted by the cinchona alkaloid-derived ammonium bromide and sodium hydride was described. A series of trifluoromethyl-substituted aryl alcohols could be obtained in up to 82% ee with 98% yield under mild conditions. A possible catalytic cycle was also presented.     

Decarboxylative trifluoromethylation of aryl halides using well-defined copper-trifluoroacetate and -chlorodifluoroacetate precursors

New synthetic routes to (NHC)copper-trifluoroacetate and -chlorodifluoroacetate complexes were developed (NHC = N-heterocyclic carbenes) so baseline reactivity patterns could be established for the decarboxylative trifluoromethylation of organic halides. In the presence of aryl halides, loss of CO₂ from these new precursors occurred at 160 °C concurrent with the formation of aryl-CF₃.     

Microwave-assisted rapid electrophilic fluorination of 1,3-dicarbonyl derivatives with Selectfluor

A microwave-assisted fluorination method for 1,3-dicarbonyl compounds using Selectfluor^® has been developed. 2-Monofluorinated products can be obtained in high yield in neutral reaction conditions with addition of 1 eq. of Selectfluor^®. Treatment of 1,3-dicarbonyls with 3 eq. of Selectfluor^® in the presence of tetrabutylammonium hydroxide (TBAH) as the base results in the formation of 2,2-difluorinated derivatives only.     

One-pot synthesis of 3-trifluoromethylbenzofurans via tandem iodocyclization and trifluoromethylation of 2-alkynylanisoles

A two-step, one-pot tandem iodocyclization and trifluoromethylation have been developed. A variety of 3-trifluoromethylbenzofurans were prepared in moderate to good yields via the tandem reaction of 2-alkynylanisoles with elemental iodine and (trifluoromethyl)trimethylsilane.     

Copper-catalyzed α-aminoxylation of 1,3-dicarbonyl compounds with 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) via an aerobic oxidative sp C–H bond activation

A facile and direct synthetic method for the construction of alkoxyamine derivatives through copper-catalyzed aerobic oxidative activation of sp³ C–H bond was developed in good to excellent yields (75−95%), by treating the readily available 1,3-dicarbonyl compounds with 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) and its derivatives. This method was also successfully applied to the preparation of quaternary α-fluorinated α-hydroxyl acid derivatives.     

Regioselective electrophilic trifluoromethylation of indolines, oxindoles and indoles in superacid

Treatment of indolines and N-acylindoles with HF/SbF₅/CCl₄ yields 6-trifluoro derivatives (indole numbering) whereas indoles and oxindoles give the 5-trifluoro derivatives in good yield.     

Orthogonal synthesis of pyrroles and 1,2,3-triazoles from vinyl azides and 1,3-dicarbonyl compounds

Tri- and tetrasubstituted N-H pyrroles were prepared by the simple treatment of vinyl azides with 1,3-dicarbonyl compounds in toluene at 100 °C via 2H-azirine intermediates generated in situ. When the reactions of vinyl azides and 1,3-dicarbonyl compounds were performed in DMF in the presence of a catalytic amount of K₂CO₃, 1-vinyl-1,2,3-triazoles were obtained via 1,3-dipolar cycloaddition. These methodologies exploited orthogonal modes of chemical reactivity of vinyl azides, which could be achieved by slight modification of the reaction conditions.     

Synthesis of optically active michael adducts via chiral enamines

Chiral enamines, obtained bySchiff base condensation from 1,3-dicarbonyl compounds and (R)-(+)-1-phenylethylamine, were found to undergo diastereoselectiveMichael reactions with ,-unsaturated carbonyl compounds. After removal of the chiral auxiliary (R)-(+)-1-phenylethylamine by hydrolysis, theMichael adducts were isolated in 59–95% optical yield.

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Synthese von optisch aktiven Michaeladdukten via chirale Enamine

Zusammenfassung Chirale Enamine, durchSchiffbasenkondensation aus 1,3-Dicarbonylverbindungen und (R)-(+)-1-Phenylethylamin erhalten, gehen mit ,-ungesättigten Carbonylverbindungen diastereoselektiveMichaelreaktionen ein. Nach hydrolytischer Abspaltung des chiralen Hilfsstoffs (R)-(+)-1-Phenylethylamin werden dieMichaeladdukte in 59–95% optischer Ausbeute isoliert.

     

Catalytic fluorination of 1,3-dicarbonyl compounds using iodoarene catalysts

Catalytic fluorination of 1,3-dicarbonyl compounds with aqueous hydrofluoric acid proceeded efficiently with the aid of iodoarene catalysts in the presence of m-CPBA as a terminal oxidant. o-Iodotoluene, o-iodoanisole, and o-ethyliodobenzene showed a high catalytic efficiency to give 2-fluoro-1,3-dicarbonyl compounds in good yields.