Fluorinated alkenes reactions with nucleophiles

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). 

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). 

Fluorinated -alkenes and -cycloalkenes have a special relationship with their hydrocarbon analogues, usually exhibiting a chemistry that is complementary. For example, the fluorinated systems are frequently susceptible to nucleophilic attack, in some cases dramatically so, and therefore reactions of nucleophiles with fluorinated alkenes often reveal unique new chemistry. This chapter covers electrochemical reduction, principles governing orientation and reactivity of fluorinated alkenes towards nucleophiles, fluoride ion as a nucleophile and the mirror-image relationship of this chemistry with that of proton-induced reactions, reactions with nitrogen-, oxygen-, carbon- centred nucleophiles etc., and, finally, chemistry of some oligomers of fluorinated -alkenes and -cycloalkenes. 

The most obvious feature of the chemistry of highly fluorinated aromatic compounds and alkenes which can be exploited is their susceptibility to nucleophilic attack. Therefore, reactions with anionic species containing metals can be useful and the most significant examples of this type involve transition-metal carbonyl anions [6, 10] (Figure 10.5). 

Ammonia and other nitrogen-containing nucleophiles react readily with internally fluorinated alkenes (e. g 28) to form products via addition-elimination sequences. The product ratio (e. g of 29 and 30) depends strongly on the reaction conditions.22... 

Alkenes can be converted into fluorinated products electrophilically with CSOSO2OF, by incorporating solvents or external nucleophiles in the reaction (Scheme 2.17) [32]. 

Model compound studies reveal factors which influence free—radical additions of ethers, polyethers, and crown—polyethers, to fluorinated alkenes. Stereo-electronic effects significantly affect relative reactivities of cyclic amines. Novel dienes are obtained by reactions of some oligomers of fluorinated alkenes with sodium amalgam and some reactions of these systems with nucleophiles are described. 

This reaction demonstrates that fluorinated alkenes are especially reactive towards nucleophilic radicals. Throughout the text, examples of free—radical reactions initiated by -rays are interspersed with peroxide—initiated processes and it is worth emphasising that the o -ray technique is an extremely useful experimental probe because it is, in effect, a universal initiator, i.e. the method can be applied over a wide range of temperature. Furthermore, it leaves essentially no fragments in the product, as do chemical initiators, and the technique may be used with metal apparatus. 

Reactions of perfluorinated alkenes, such as hexafluoropropene, with fluoride ion give perfluoroalkylcarbanions which can act as nucleophiles in S Ar reactions with perfluoroheteroaromatic systems (Fig. 8.13). These reactions are another example of mirror-image chemistry and reflect well-known Friedel-Crafts reactions of hydrocarbon systems that proceed by reaction of the corresponding electrophile and carbocationic intermediates. Poly substitution processes are possible and, indeed, all five fluorine atoms may be replaced upon reaction with an excess of tetrafluoroethylene and fluoride ion. ... 

BayUflf AE, Bryce MR, Chambers RD (1987) PolyhalogenoheterocycUc compounds. Part 38 reactions of fluorinated alkenes and cycloalkenes with difunctional nucleophiles. J Chem Soc Perkin 1763-767. doi 10.1039/P19870000763... 

Unsaturated fluorinated compounds are fundamentally different from those of hydrocarbon chemistry. Whereas conventional alkenes are electron rich at the double bond, fluoroal-kenes suffer from a deficiency of electrons due to the negative inductive effect. Therefore, fluoroalkenes react smoothly in a very typical way with oxygen, sulfur, nitrogen and carbon nucleophiles.31 Usually, the reaction path of the addition or addition-elimination reaction goes through an intermediate carbanion. The reaction conditions decide whether the product is saturated or unsaturated and if vinylic or allylic substitution is required. Highly branched fluoroalkenes, obtained from the fluoride-initiated ionic oligomerization of tetrafluoroethene or hexafluoropropene, are different and more complex in their reactions and reactivities. 

Nucleophilic perfluorophenylation reactions of terminal and internal polyfluoroalkencs have been studied. As expected, terminal alkenes first undergo substitution of one fluorine atom in the 1-position to form perfluorinated 1-arylalkenes. In turn, these primary products may further react with substitution of one vinyl or aromatic fluorine atom. Actually, these reactions proceed concurrently resulting in an isomeric mixture. For example, pcrfluoro(2-methyl-propene) is tran.sformed into such a mixture (Table 3). ... 

Organic fluorine compounds and methods for their preparation are the central topic of the next four procedures. Much of the synthetic versatility of methyl phenyl sulfone is embodied in FLUOROMETHYL PHENYL SULFONE and the fluoro Pummerer reaction of methyl phenyl sulfoxide with DAST is a key step in its preparation. The utility of this fluoromethyl sulfone in the preparation of fluoroalkenes Is demonstrated in a companion procedure for Z-[2-(FLUOROMETHYLENE) CYCLOHEXYL]BENZENE, a procedure with several prominent stereoselective features. Geminal difluoroalkenes are featured in the following procedure. (3,3 DIFLUOROALLYL)TRIMETHYLSILANE is prepared by a method in which the radical addition of dibromodifluoromethane to alkenes and the selective reduction of a-bromoalkylsilanes are key steps. A procedure for nucleophilic introduction of the trifluoromethyl group completes this set. The key reagent, (TRIFLUOROMETHYL)-TRIMETHYLSILANE is obtained by reductive coupling of TMS chloride and bromotrifluoromethane. Liberation of a CF3- equivalent with fluoride ion in the presence of cyclohexanone affords 1-TRIFLUOROMETHYL-1-CYCLOHEXANOL. 

The fluorination of alkenes 41 and 43 and alkynes 45 with difluoroiodotoluene in the presence of iodine affords vt c-fluoroiodoalkanes 42 and 44 and fluoroiodoalkenes 46 in moderate to good yields (Scheme 3.16) [40]. This reaction proceeds in a Markovnikov fashion and with prevalent an//-stereoselectivity via initial addition of the electrophilic iodine species followed by nucleophilic attack of fluorine anion. The analogous reaction of alkenes and alkynes with difluoroiodotoluene in the presence of diphenyl diselenides affords the respective products of phenylselenofluorination in good yields [41],... 

We want to convince you that this chemistry is useful and also that it works in more complicated molecules so we are going to describe in part the preparation of the antibiotic ofloxacin. The sequence starts with an aromatic compound having four fluorine atoms. Three are replaced sequentially by nucleophiles and the last is present in the antibiotic itself. The first reaction is a conjugate substitution of the ethoxy group marked in orange. An amino alcohol is used as the nucleophile and it is the more nucleophilic amino group (rather than the hydroxyl group) that adds to the alkene. 

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