Fluoroarenes, synthesis

The trilluoromethyl group behaves in a similar way , but it is now clear that deprotonation of sites ortho to such acidifying but non-coordinating and non-electrophilic substituents is best carried out with BuLi-KOBu-t superbases (see Section VI). A combination of BuLi metallation and superbase metallation of fluoroarenes has been used in the synthesis of components 163 and 164 for fluorinated liquid crystals (Scheme 82). ... 

A. Shah, V.W. Pike, D.A. Widdowson, The synthesis of [F-18]fluoroarenes from the reaction of cyclotron-produced [F-18]fluoride ion with diaryliodonium salts, J. Chem. Soc. Perkin Trans. I Organic and Bio-Organic Chemistry 13 (1998) 2043-2046. 

The decomposition of arenediazonium tetrafluoroborates in the resulting fluoroarene as solvent has also been utilized.179 This method is very fruitful in the synthesis of fluorobenzene (96% yield) or fluorotoluenes (85-88% yield for the three isomers) but fails with substrates such as anisolediazonium tetrafluoroborates which probably arylate the reactive fluoroaromatic solvent. In contrast, perfluorinated tertiary amines (EF-L 174, F-C 40), perfluorinated alkyl tetrahydropyran (EF-L 102), perfluorodecahydronaphthalene (Flutec PP7) or other per-fluorocycloalkanes (Flutec s) are claimed to be the best media for fluorodediazoniation of all types of diazonium tetrafluoroborates.224 These media seem to be more efficient, at least in the synthesis of 1,2-difluorobenzene, than silicone oil which has also been claimed to improve fluorodediazoniation.225... 

Fluoroarene-Cr(CO)2L complexes 33p [L = CO, PPh3, P(OPh)3, P(pyrrolyl)3, P(pyrolyl)2 (NMeBn)], where L is a potential linker ligand for solid-phase synthesis, have been evaluated with regard to the rates of nucleophilic substitution by amines [35]. The preparative and kinetic results indicate that SNAr reactions on tris(pyrrolyl)phosphine-modified fluoroar-enechromium complexes proceed rapidly and with high efficiency, and are thus appropriate for the development of solid-phase versions for use in combinatorial synthesis (Scheme 18). 

The addition of two nucleophiles to a coordinated //6-arene is a synthetically important goal. A one-pot synthesis of 1,3-disubstituted cyclohexadienes involving an initial ipso addition to fluoroarene complexes is possible. Indeed, p-fluorotoluenetricarbonylchromium complex 22c reacts with isobutyronitrile carbanion (2 equiv.) in THF to give, after 5 days at —30 °C and acidic treatment under CO atmosphere, the cyclohexadiene 66 in 47 % yield (Scheme 31) [53] the yield can reach 75 % after several weeks Carbon monoxide was used in order to decoordinate the // -cyclohexadiene intermediate and to recover Cr(CO)6 needed for the preparation of the starting material [54]. 

Table 10. Synthesis of Fluoroarenes from Anilines via Thermally Induced Decomposition of Complex Diazonium Fluoride Salts ...

An industrially important application of the lipophilic tetrakis(dimethylamino) phosphonium fluoride is as a phase-transfer catalyst in the Halex process for technical synthesis of fluoroarenes. 

A comprehensive review of the synthesis and general chemistry of silylphos-phines has appeared. Routes to diorgano(trichlorosilyl)phosphines have been developed. A route to perfluoroarylphosphines, e.g., (172), is afforded by the reactions of fluoroarenes with either dimethyl(trimethylsilyl)- or dimethyl(trimethylstannyl)-phosphine. In a similar manner, primary, secondary, and tertiary phosphines, and their trimethylsilyl analogues, have been shown to react with pentafluoropyridine to give a range of tetrafluoropyridyl-phosphines The synthesis, coordination chemistry, and catalytic applications... 

Kantam et al. (2007) studied the synthesis of A -arylheterocycles via the nanocrystalline CuO-catalyzed N-arylation of heterocycles with activated chloro- and fluoroarenes (Scheme 4.25). Various V-aryl/V-heteroaryl imidazoles, benzimidazoles, indoles, pyrroles, and pyrazoles were synthesized in moderate to excellent yields (76%-94% yield in 23 h). Much higher reactivity was observed when fluoroarenes were used (81%-94% yield in 3 h). The Cu catalyst could be recovered by centrifugation and reused for five runs without obvious loss of activity. Transmission electron microscopy (TEM) studies of both fresh and used catalysts revealed that the shape and size of the particles remained unchanged, supporting the assumption that the morphology of the Cu catalyst remained the same after recycling. However, one of the major shortcomings of the above methods developed by Hyeon and Kantam... 

Besides electrophilic sulfonation, sulfonated phosphines can be produced by nucleophilic substitution reactions using PH3, primary or secondary phosphines, and fluoroarenes in superbasic media. This method has been applied for the synthesis of pura-isomer of TPPTS (p-TPPTS) (Scheme 10) as well as dozens of other interesting ligands including chelating, chiral, and amphiphilic phosphines (a selection is in Scheme 11). ... 

Laeva A, Nosova E, Lipunova G, Charushin V (2008) Fluoroarenes in the synthesis of ben-zoannulated nitrogen-containing heteiocycles. Russ Chem Bull 57 947-984... 

Therefore, Chun et al. described the application of a commerdaDy available microfluidic setup (NanoTek , Advion) (www.advion.com/products/nanotek/) for the synthesis of ortho- [14] and meto-substituted [13] [ F] fluoroarenes 26 from diaryHodonium salts 25 as a possibility to introduce [ F] fluoride ions in electron-poor and electron-rich arenes (Figure 6.14). The authors mainly focused on substituent influence, reaction rates, ener tics, product selectivity, and radiochemical yields. 

In 2008, the synthesis of fluoroarenes from unactivated haloarenes upon treatment with tetramethylammonium fluoride was reported by Grushin (Scheme 15.51). Fluorobenzene could be accessed in 65% yield from bro-mobenzene. However, fluorination of 2-bromonaphthalene results in a 3 2 mixture of 2-fluoronaphthalene and 1-fluoronaphthalene indicating the formation of an aryne intermediate. Elimination to form such an intermediate indicates the high basicity of the fluoride anion in anhydrous solvents. 

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