Fluoromethyl radical

Table 1.7 Values of for the Cross-Reaction between Fluoromethyl and Ethyl Radicals (25 °C) 172174...

Phenylseleno derivatives 71 are found to be good precursors of phosphonodi-fluoromethyl and phosphonothiodifluoromethyl radicals (Scheme 11). Moreover, when generated by the (TMS)3Si attack on 71 and in the presence of alkenes or... 

A type iii-d reaction leads to the formation of (69). Trifluoromethyl radicals generated electrochemically from triflu-oroacetate can attack electron-deficient olefins leading to trifluoromethylated carbon radicals whose chemical and electrochemical follow-up reactions can be controlled by current density, reaction temperature, and substituents of the olefins. With fumaronitrile (86) at 50 °C the monotri-fluoromethylated compound (87) was obtained in 65% yield (Scheme 31) [110]. 

Hi. Lysine. Gamma radiolysis of aerated aqueous solution of lysine (94) has been shown, as inferred from iodometric measurements, to give rise to hydroperoxides in a similar yield to that observed for valine and leucine. However, attempts to isolate by HPLC the peroxidic derivatives using the post-column derivatization chemiluminescence detection approach were unsuccessful. This was assumed to be due to the instability of the lysine hydroperoxides under the conditions of HPLC analysis. Indirect evidence for the OH-mediated formation of hydroperoxides was provided by the isolation of four hydroxylated derivatives of lysine as 9-fluoromethyl chloroformate (FMOC) derivatives . Interestingly, NaBILj reduction of the irradiated lysine solutions before FMOC derivatization is accompanied by a notable increase in the yields of hydroxylysine isomers. Among the latter oxidized compounds, 3-hydroxy lysine was characterized by extensive H NMR and ESI-MS measurements whereas one diastereomer of 4-hydroxylysine and the two isomeric forms of 5-hydroxylysine were identified by comparison of their HPLC features as FMOC derivatives with those of authentic samples prepared by chemical synthesis. A reasonable mechanism for the formation of the four different hydroxylysines and, therefore, of related hydroperoxides 98-100, involves initial OH-mediated hydrogen abstraction followed by O2 addition to the carbon-centered radicals 95-97 thus formed and subsequent reduction of the resulting peroxyl radicals (equation 55). 

Table 1.18 Inversion barrier of methyl and fluoromethyl radicals and dissociation energy of C—H bond of fluoromethanes ...

According to a recent Organic Syntheses procedure, fluoromethyl phenyl sul-fone, which can be prepared on a large scale [90] (Eq. 23), undergoes a number of useful reactions. A Wadsworth-Emmons-type procedure affords a-fluoro-vinylsulfones [91], which undergo tin-sulfur exchange under free radical conditions (Eq. 24). The products maybe protodestannylated [92],fluorinated [93],or coupled under palladium catalysis [94]. The difluoromethyl phenyl sulfone also shows some useful chemistry. 

Table 9.4 Isotropic hyperfine splittings (G) in the methyl and fluoromethyl radicals...

Cramer, C. J. 1991. Dependence of Isotropic Hyperfine Coupling in the Fluoromethyl Radical Series on Inversion Angle J. Org. Chem., 56, 5229. 

The irradiation of bis(nonafluoro-tert-butyl)peroxide in octafluorocyclopen-tene or decafluorocyclohexene yields the corresponding vicinal bis(nonafluoro-tert-butyl) diethers in 55 and 63%, respectively [30] Negligible amounts of dimeric or oligomeric products are obtained. Conversely, the similar reaction with bis(tn-fluoromethyl)peroxide yields primarily 2,2 -bis(tnfluoromethoxy)dicycloalkanes (equation 12). The dissimilar behavior is believed to be due to the reduced stability of the trifluoromethyloxy radical and thus its reduced population, which favors oligomerization [30]. 

Fluorine substituents have a dramatic impact upon the structure of alkyl radicals. The methyl radical itself is planar UV, IR, PES and ESR spectroscopy, as well as the highest level of theoretical analysis, all indicate that its conformational properties are best defined as deriving from a single minimum [2], Fluoromethyl radicals, on the other hand, are increasingly pyramidal [3], with the trifluoromethyl radical being essentially tetrahedral [3 - 7], with a significant barrier to inversion [8,9]. 

ESR spectroscopy is perhaps the best method for the unequivocal detection and observation of free radicals, and ESR 13C hyperfine splitting (hfs) constants are considered to be a very useful indicator of a radical s geometry because non-planarity introduces s character into the orbital that contains the unpaired electron. The methyl radical s 13Ca value of 38 G is consistent with a planar structure. Fluoromethyl radicals exhibit increased 13Ca values, as shown in Table 1, thus indicating increasing non-planarity, with trifluoromethyl radical s value of 272 G lying close to that expected for its sp3 hybridization [4]. 

Experimental support for the given order of stability in the fluoromethyl series has been provided in a study by Jiang et al. of the radical fragmentation of the respective series of fluorinated ferf-butoxy radicals [32] ... 

The ratio of the rate constants for the addition of fluoromethyl radicals to ethylene and tetrafluoroethylene at 437 K ... 

In Table 5 (p. 55) we compared the relative rates of addition of methyl, fluoromethyl, difluoromethyl and trifluoromethyl radicals to ethylene and tetra-fluoroethylene. Figure 3 shows the Arrnehius plots for these competitive reactions. These indicate in a very graphic way the fact that this systematic variation in relative rate can be entirely attributed to variation in the activation energy differences. 

Fig. 3 Arrhenius plot for the relative rates of addition of methyl and fluoromethyl radicals to ethylene and tetrafluoroethylene (Low et al., 1976a)...

In the fluoromethyl radical, FCH2, the C—F bond [133.4(5) pm] is shorter than in all monofluorinated methane derivatives and the molecule is almost flat with a nearly sp2-hybridized carbon. The barrier to inversion is very low. The structures of fluorocarbene FCH and difluorocarbene (see Table 6) in the lowest singlet state were derived from UV spectra. These diradicals possess very short C—F bonds ca 130 pm) and are strongly bent with Z FCH = 104.1(13)° and Z FCF = 104.94°. 

Xenon difluoride reacted with various carboxylic acids, and the type of transformation depends on the structure of the organic molecules35-39. The reaction with primary carboxylic acids involves free-radical intermediates. 6-Hexenoic acid was used as a free-radical clock device in which a A abs of 1.1 x 106 M-1s-1 at 25 °C was determined, while the alkyl radical was also spin-trapped to give an ESR signal37. The primary free radical was trapped by internal cyclization, and (fluoromethyl) cyclopentane in 25% yield was formed, while 6-fluoro-l-hexene could be formed from a radical or ionic intermediate, but 1-fluo-rocycloclohexane was not observed as a product (Scheme 42). 

G. Loss of a fluoromethyl radical from metastable ions ... 

Bell and co-workers 24, 25) have investigated the generation of tri-fluoromethyl radicals from photolysis of HFA in the presence of silanes. Abstraction of the proton is observed in the case of trichlorosilane (24), while methyl(fluoro)silanes lead to the formation of CFjH, CjF, and CF CH 2(25). 

The Consequences of Different Stability Definitions How Stable Are Ethyl and Fluoromethyl Radicals ... 

The differences in RSE values obtained from Equations 5.3, 5.6 and 5.8 will be illustrated here using the ethyl radical (CH3CH2, 8) and the fluoromethyl radical (FCH2, 9) as examples. Both systems are not burdened by steric effects and the RSE values can thus be interpreted as the consequences of electronic substituent effects. Also, experimentally measured C-H and C-C bond dissociation energies are available for both systems, allowing for a side-by-side evaluation of experimental and theoretical results (Table 5.1). 

C). While H3CS1H3 decomposes under these conditions primarily by geminal elimination of molecular H2 from the silicon moiety and secondarily by a slow surface-catalysed reaction yielding H-and CH3SiH2 radicals [27], the significantly lower decomposition temperatures of (fluoromethyl)silanes require different low energy decomposition pathways. 

Stabilities of methyl and fluoromethyl radicals have been calculated [114] to be in the order CFj < CHj < CF2H < CFH2 and the relative rates of formation of such radicals, measured in (S-scission reactions of a series of t-butoxy radical derivatives, as shown in Figure 4.45, lend support to this conclusion [115]. 

Methyl radicals are essentially planar but ESR measurements [116], supported by theoretical calculations [114], show that fluoromethyl radicals deviate from planarity to increasingly pyramidal structures upon further fluorination, with CF3 measured to be 49.1° from planarity. The barriers to inversion of fluoromethyl radicals increase in the order CFH2 < CF2H < CF, while fluorocyclopropyl radicals (Figure 4.46) adopt a fixed pyramidal conformation at the radical centre [117], as determined by ESR at — 108°C. The tendency for fluorine to induce pyrimidalisation of radical centres has also been used to account for the stereochemistry of products [118]. 

Fuchs and Gong reported an acyl radical transfer reaction from aldehydes to acetylenic trifluoromethylsulfones to give acetylenic ketones [43J. In this case, tri-fluoromethyl radical, arising from the a-scission of trifluoromethylsulfonyl radical, abstracts the hydrogen of an aldehyde to form an acyl radical, which then propagates the chain. 

---