Fluorination reactions with alkenes

The synthesis of 2-chloro-2,3,3-trifluorocyclobutyl acetate illustrates a general method of preparing cyclobutanes by heating chlorotrifluoroethylene, tetrafluoroethylene, and other highly fluorinated ethylenes with alkenes. The reaction has recently been reviewed.11 Chlorotrifluoroethylene has been shown to form cyclobutanes in this way with acrylonitrile,6 vinylidene chloride,3 phenylacetylene,7 and methyl propiolate.3 A far greater number of cyclobutanes have been prepared from tetrafluoroethylene and alkenes 4,11 when tetrafluoroethylene is used, care must be exercised because of the danger of explosion. The fluorinated cyclobutanes can be converted to a variety of cyclobutanes, cyclobutenes, and butadienes. 

The overall reactivities of these radicals in their ummolecular 5-hexenyl cyclization processes reflects those same factors which affect the reactivity of partially-fluorinated radicals in their bimolecular addition reactions with alkenes, such as styrene. Table 17 indicates this clearly, and it also reflects the general leveling effect which would be expected for the more facile unimolecular cyclization processes which have log A s about 1-2 units larger than those for the bimolecular additions. 

Fluorinated cyclobutenes synthesized from the cycloaddition of fluoroalkenes with non-fluorinated alkynes (vide supra) undergo pyrolysis to give fluorinated butadienes, e.g. the pyrolysis of 3,3.4,4-tetrafluorocyclobut-l-ene gives l,1,4,4-tctrafluorobuta-l,3-diene (15) almost quantitatively. Tetrafluorodienes of this type undergo [2-F 2]-cycloaddition reactions with alkenes to give fluorinated cyclobutancs. ... 

What about diatomic fluorine, F-F For many years, elemental fluorine was thought to be too reactive and too dangerous for reaction with alkenes. To void such problems, fluorine is typically mixed with an inert gas such as nitrogen or argon. Diluted in this manner, fluorine does react with alkenes, but the yields are often poor and, in some cases, solvents for the alkene, such as methanol, participate in the reaction. 1-Phenylpropene (PhCH=CH2), for example, reacted with fluorine in methanol to give 51% of the corresponding difluoride, along with 49% of 2-fluoro-l-methoxy-l-phenylpropane. The problems associated with fluorine lead to a simpliflcation. In this chapter, alkene reactions are reported only for chlorine, bromine, or iodine but not fluorine. 

A convenient two-step access to valuable ethyl a-fluorocyclopropanecarboxylates that involves a Michael-initiated ring closure reaction between ethyl dichloroacetate and various terminal electron-deficient alkenes has been developed. In the second reaction step, fluorination reaction with potassium bifluoride takes place through a 1,2-elimination/addition pathway. 

Unlike their C-2 and C-4-substituted counterparts, pyrimidines with fluorinated alkyl at C-5 were rarely prepared using reaction of NCN binucleophiles and CCC bis-electrophiles. Several examples of such transformations were already mentioned in previous section (reactions with 710 leading to 4,5-bis-perfluoroalkylpyrimidines, see Table 40, Entries 6,7). Analogous reactions with alkene 817, as well as its precursor 816 (a stable adduct of methanol and 2-(trifluoromethyl)-l,l,3,3,3-pentafluoropropene), led to the formation of 5-trifluo-romethylpyrimidines 818 (Scheme 163) [505, 506], Pyrimidines 822 and 825 were also prepared from 816. Reaction of 816 with triethylamine resulted in formation of enolate 819 (Schane 163) [507]. When in situ generated 819 was treated with HCl, acyl fluoride 820 was formed. Reaction of 820 with AdV -dimethyl(thio)urea resulted in the formation of adduct 821, which underwent cyclization to 822 upon... 

The reaction of perfluoroalkyl iodides with alkenes affords the perfluoro-alkylated alkyl iodides 931. Q.a-Difluoro-functionalized phosphonates are prepared by the addition of the iododifluoromethylphosphonate (932) at room temperature[778], A one-electron transfer-initiated radical mechanism has been proposed for the addition reaction. Addition to alkynes affords 1-perfluoro-alkyl-2-iodoalkenes (933)[779-781]. The fluorine-containing oxirane 934 is obtained by the reaction of allyl aicohol[782]. Under a CO atmosphere, the carbocarbonylation of the alkenol 935 and the alkynol 937 takes place with perfluoroalkyl iodides to give the fluorine-containing lactones 936 and 938[783]. 

Mixtures of anhydrous hydrogen fluoride and tetrahydrofuran are successfully used as fluorinating agents to convert 1,1,2-trifluoro-l-allcen-3-ols, easily prepared from bromotrifluoroethene via lithiation followed by the reaction with aldehydes or ketones, to 1,1,1,2-tetrafluoro-2-alkenes The yields are optimal with a 5 1 ratio of hydrogen fluoride to tetrahydrofuran The fluorination reaction involves a fluonde lon-induced rearrangement (Sf,j2 mechanism) of allylic alcohols [65] (equation 40)... 

Fluorinated alkenes and alkynes are highly activated toward nucleophilic attack and reaction with bifunctional nucleophiles is a fruitful area for the synthesis of heterocycles. A review on perfluoroalkyl(aryl)acety-lenes contains many examples (91RCR501). 

Table 1 Results of the alkene epoxidation reactions with fluorinated (salen)Mn complexes under biphasic conditions ...

This element can never be controlled. Fluorine reacts violently with solid methane at -190°C. With liquid hydrocarbons at -210°C, the reaction is dangerous. All hydrocarbons react dangerously, from the first homologues to anthracene as well as lubricants. In the gaseous state, there is ignition with small quantities, and detonation with large quantities and when the mixture is made quickly. There is immediate detonation with alkenes and alkynes. With benzene, when fluorine is incorporated bubble by bubble and at a low temperature, this causes ignition on the surface. If the flow rate is substantial, there is immediate detonation. 

It is not normally possible to add fluorine directly to alkenes as the reaction is so exothermic that bond fission occurs. Many alkenes will not add iodine directly either, and when the reaction does occur it is usually readily reversible. Alkynes are also found to undergo preferential, though not exclusive, ANTI addition of halogens, e.g. with butyne-l,2-dioic acid (17) ... 

Related to the nitrile oxide cycloadditions presented in Scheme 6.206 are 1,3-dipolar cycloaddition reactions of nitrones with alkenes leading to isoxazolidines. The group of Comes-Franchini has described cycloadditions of (Z)-a-phenyl-N-methylnitrone with allylic fluorides leading to enantiopure fluorine-containing isoxazolidines, and ultimately to amino polyols (Scheme 6.207) [374]. The reactions were carried out under solvent-free conditions in the presence of 5 mol% of either scandium(III) or indium(III) triflate. In the racemic series, an optimized 74% yield of an exo/endo mixture of cycloadducts was obtained within 15 min at 100 °C. In the case of the enantiopure allyl fluoride, a similar product distribution was achieved after 25 min at 100 °C. Reduction of the isoxazolidine cycloadducts with lithium aluminum hydride provided fluorinated enantiopure polyols of pharmaceutical interest possessing four stereocenters. 

Various other biphasic solutions to the separation problem are considered in other chapters of this book, but an especially attractive alternative was introduced by Horvath and co-workers in 1994.[1] He coined the term catalysis in the fluorous biphase and the process uses the temperature dependent miscibility of fluorinated solvents (organic solvents in which most or all of the hydrogen atoms have been replaced by fluorine atoms) with normal organic solvents, to provide a possible answer to the biphasic hydroformylation of long-chain alkenes. At temperatures close to the operating temperature of many catalytic reactions (60-120°C), the fluorous and organic solvents mix, but at temperatures near ambient they phase separate cleanly. Since that time, many other reactions have been demonstrated under fluorous biphasic conditions and these form the basis of this chapter. The subject has been comprehensively reviewed, [2-6] so this chapter gives an overview and finishes with some process considerations. 

Hypofluorites, fluorinated, 26 119-137, see also individual compounds bisfluoroxy compounds, 26 134-137 of carbon, 26 134-136 of selenium, 26 137 monofluoroxy compounds, 26 123-133 of carbon, 26 123-127 inorganic, 26 128-133 Hypofluorus acid, 26 121-123 MO calculations, 26 122 reactions, 26 122-123 with alkenes, 26 123... 

Other nitrones (21-23) having the chiral moiety located at the carbon atom have been applied in reactions with various alkenes (Scheme 12.10) (33-35). Nitrone 21 offered poor discrimination in 1,3-dipolar cycloadditions with benzyl crotonate, as all four diastereomers were obtained in both reactions (33). The fluorinated nitrone... 

The reaction with ethylene is visualized as an alkene exchange to give the unstable parent /3-sultone, which undergoes ring opening and concomitant proton shift to give ethylenesul-fonic acid. The latter reacts with the fluorinated /3-sultone with ultimate formation of ethylenebis-sulfonic acid (Scheme 53) (70BAU574). 

The only stable 1,3,2-dioxathietanes known are fluorinated sulfate derivatives formed by addition of sulfur trioxide to bis(trifluoromethyl)ketene. These structures are fairly well characterized from spectral data and from reactions with nucleophiles. Hexafluoroisopropy-lidene-l,3,2-dioxathietane 2,2-dioxide acts as a sulfur trioxide transfer agent to alkenes and is in equilibrium with a dimeric form as indicated by 19F NMR (Scheme 138) (71KGS1645, 72KGS306, 73KGS178, 132l). 

The related 5-trifluoromethyl-l,3-dioxin-4-ones underwent high pressure Diels-Alder reactions with Danishefsky s diene (Eq. 114), and [2 + 2] photocycloadditions with alkenes [305]. The former reaction failed entirely when attempted in the absence of the fluorine atoms. 

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