Radical additions to fluorinated alkenes

Radical Addition to Fluorinated Alkenes with Hydrogen Transfer... 

Diols may also be used in free-radical additions to fluorinated alkenes [154] (Figure 8.45). 

Table 17. Absolute rate constants for 5-hexenyl radical cyclizations involving fluorinated radical addition to hydrocarbon alkens, at 30 °C in C6D6 [140,162] ...

Surprise 62 addressed nucleophilic additions to fluorinated alkenes. Here, a free-radical addition is presented. What is the product of a reaction of methanol and 1-perfluorobutene in the presence of dibenzoyl peroxide ... 

Oxidative additions to iodoperfluoroalkanes proceed readily, whilst the additions to fluorinated alkenes shown in Figure 10.65 may well be radical processes. 

A variety of other factors affect reactivity of ethers in additions to fluorinated alkenes and we will gradually explore these. First, a process that was outlined by Muramatsu y), many years ago a 1,5—intramolecular hydrogen transfer occurs from the intermediate radical [1] and ultimately leads to a di—addition product [2]. 

The same principles that were outlined for ethers, apply to amines but we have a possible competing opportunity for nucleophilic attack (7). Nevertheless, the results given below indicate that the free-radical process competes very effectively, i.e. free-radical additions may compete successfully with nucleophilic attack, depending on the system. Other workers have also observed free—radical additions of fluorinated alkenes to amines 8,9). 

Fluorinated radicals play a significant role in synthetic organo-fluorine chemistry, for example, in electrophilic radical addition to alkenes, single-electron transfer reactions (SET), telomerization of fluoroalkenes with perfluoroalkyl iodides, polymerization to fluoropolymers and copolymers, and thermal, photochemical and radiation destruction of fluorocarbons. Furthermore, such free radicals are of interest for studying structures, reaction kinetics and ESR spectroscopic parameters.38... 

Borate esters of fluorinated alcohols, simply prepared by the free-radical addition of trialkyl borates to fluorinated alkenes, are cleaved by chlorine to yield fluorinated acid chlorides (equation 141)949. 

In contrast to nucleophilic additions of alcohols to fluorinated alkenes, where the reagent is alkoxide anion, in free-radical addition of alcohols the reacting species is a free radical generated by homolysis of the bond between hydrogen and the alkyl group. 

This intermediate free radical abstracts hydrogen from the methyl group of methanol, and thus propagates a chain process leading to the hydroxymethyl derivative, 1H, 1H, 3H-perfluoropentanol I [89]. Similar addition of alcohols to fluorinated alkenes occurs under y-irradiation. 

It is increasingly apparent that polar characteristics of radicals are important in organic synthesis [122] and the effect of fluorine on the polarity of radicals is very significant. Reactions of perfluoroalkyl radicals with a series of substituted p-styrenes [123] (Figure 4.51) shows that the rate constant for radical addition to alkenes increases as the alkene becomes more electron-rich (Table 4.16) and, in similar additions, perfluoroalkyl radicals reacted 40000 times faster with 1-hexene than the corresponding alkyl radicals. 

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. 

Stereodectronic Effects. The conformation of a ring effects the reactivity of cyclic ethers and we have already described the evidence for such processes in the literature 10). Here, however, we demonstrate that stereoelectronic effects may influence the reactivity of amines in free radical processes. Using a series of cyclic amines [15], radical addition to a fluorinated alkene may occur but then a choice is possible (a) the intermediate radical could react with amine to give the 1 1 adduct [16] (ki) or (b), a 1,5-shift of hydrogen can occur (k2) which ultimately leads to the 2 1 adduct [171. We anticipate that k2 would vary little with the amine but, of course, ki will vary with the ease of hydrogen—atom abstraction from the amine. Correspondingly, we find that the ratio of the 2 1 adduct [17] increases substantially in the series... 

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]. 

Radical addition of dibromodifluoromethane to alkenes followed by sodium borohydride reduction is a convenient two-step method for the introduction of the difluoromethyl group.5 Either one or both carbon-bromine bonds in the intermediate dibromides may be reduced, depending on the reaction conditions. In the case of acyclic dibromodifluoromethane-alkene adducts, the reduction occurs regioselectively to yield the relatively inaccessible bromodifluoromethyl-substituted alkanes. The latter are potential building blocks for other fluorinated compounds. For example, they may be dehydrohalogenated to 1,1-difluoroalkenes an example of this methodology is illustrated in this synthesis of (3,3-difluoroallyl)trimethylsilane. 

Additions of elemental halogens to unsaturated compounds are among the most common preparations of halogenated fluoroorganics. The transformations are usually fairly clean and proceed in good yields. Besides the numerous examples of halogen addition tofluoroalkenes and fluoroalkyl-substituted alkenes, additions to perfluoropropyl vinyl ether [2] and fluorinated styrenes [5, 4] have been reported. Both ionic and free-radical processes occur (equations 1 and 2)... 

Owing to the high electronegativity of fluorine atoms, perfluoroalkyl radicals show an electrophilic character moreover, these radicals are usually much more reactive than the nucleophilic alkyl radicals in the addition to alkenes, aromatic rings, and quinones for enthalpic reasons (Scheme 14.5b). 

Electron transfer from copper or copper salts to alkyl halides has been used to initiate atom transfer radical additions. One modification of this process involves catalytic amounts of copper powder and fluorinated alkyl iodides the radicals so generated may react in either inter- or intramolecular fashion with alkenes (equation 13)19. Alternatively, a-chloroesters with remote alkene functions undergo cyclization in the presence of cat-... 

The second problem in the addition of 1,1-dichlorodifluoroethylene to 1,3-butadiene is regiospecificity. Carbon 1 of 1,3-butadiene may become attached either to the carbon holding two chlorines or to the carbon with two fluorines. The cycloaddition of fluorinated alkenes is usually not a concerted four-center reaction in which the bonds are formed simultaneously or nearly so. Instead, the reaction is a stepwise biradical process in which the first step is formation of a free-radical intermediate with a single electron at that end of the double bond that can better accomodate it. That happens at the carbon linked to two chlorine atoms. Thus, a biradical is formed that cyclizes to form 2,2-dichloro-l,l-difluoro-3-vinylcyclobutane M [118, 119, 720]. 

Fluorinated adducts can be obtained either by addition of polyfluoroalkyl halides to various alkenes or by condensation of halides, such as bromotrichloromethane or carbon tetrachloride, with fluorinated alkenes. Factors which control the regiospecificity and relative rate of these free-radical addition reactions have been studied. 

Radicals with nucleophilic character add to electrophilic alkenes more rapidly than to nucleophilic alkenes whilst, conversely, the rate of addition of electrophilic radicals to electron-rich alkenes is greater than addition to electron-deficient alkenes. To be more sophisticated, we should refer to a high-SOMO (singly occupied molecular orbital nucleophilic) radical interacting favourably with a low-LUMO (lowest unoccupied molecular orbital electrophilic) alkene but, for simplicity and brevity, we will continue to use these short-hand terms [177]. For instance, compare rates of addition of perfluor-oalkyl radicals to ethene and various fluorinated derivatives with their rates of H-atom abstraction from heptane (Table 7.9) [186]. Broadly, reactivity of the alkene decreases with fluorine content, with trifluoromethyl having a large effect. 

Earlier in this chapter we noted that nucleophiles attack the CF2 = site in a fluorinated alkene exclusively and, in parallel with these observations, nucleophilic radicals, such as CH3S and carbon-centred radicals, give products arising predominantly from attack at this site (Path 1). Electrophilic radicals such as trifluoromethyl, on the other hand, are less selective and give a mixture of products (Paths 1 and 2) (Eigure 7.58). Examples of the regiochemistry of addition of trifluoromethyl to a variety of fluorinated alkenes are given in Table 7.10. 

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