Perfluoroalkylation electrophilic

The reaction of various nucleophiles with A-trifluoromethyldibenzothiophenium triflate constitutes an excellent general method for the electrophilic perfluoroalkylation of nucleophilic substrates. This forms the subject matter of Section 3.10.5. 

Whereas haloalkanes are widely used for the electrophilic alkylation of a broad variety of nucleophiles, perfluoroalkyl bromides or iodides do not act analogously as electrophilic perfluoroalkylation reagents (Figure 2.7). For example, the reaction of perfluoroalkyl iodides with aliphatic alcoholates does not yield the expected alkyl perfluoroalkyl ether (analogous to the Williamson ether synthesis) but mostly the hydrofluorocarbon resulting from the reduction of the iodide [1]. In contrast, perfluoroalkyl iodides and bromides have been used as preparatively useful electrophilic iodination or bromination reagents [2]. 

As already discussed in Section 2.2.1, perfluoroalkyl halides do not act as effective electrophilic perfluoroalkylation reagents, as might be expected by analogy with the reactivity of alkyl halides. Even if some electrophilic perfluoroalkylation reactivity is mimicked with some especially suitable (i. e. easily oxidizable) substrates by an electron-transfer-induced radical mechanism, the practical usefulness of this reaction pathway is limited to very few examples. 

Scheme 2,146 Examples of the electrophilic perfluoroalkylation of olefins with FITS reagents [19].

Scheme 2.151 A Naflon-based polymeric version of FITS facilitates work-up of the reaction mixtures after electrophilic perfluoroalkylation. The effective concentrations of perfluoroalkyl groups of different chain lengths are approximately 0.4 mmol g [23].

Both addition to -ir-bond of alkenes and hydrogen abstraction reactions are involved in most of the common reactions of radicals. The reactivities are mostly governed by these factors combined with electronic, steric, and bond-strengthening effects [31]. The relative reactivities of the electrophilic perfluoroalkyl radicals such as CF3 and C3F7 radicals for addition to hydrogen abstraction in heptane are summarized in Table 1.37 [32]. The rate... 

They are powerful electrophilic perfluoroalkylating agents and react with a large variety of anions. The reactivity depends on the aromatic character of the dibenzochalcogenophene (S > Se > Te). 

Fluoroalkyl(aryl)iodonium salts are the most stable and practically important class of alkyl(aryl)iodonium derivatives. The application of such salts as electrophilic fiuoroalkylating reagents was reviewed in 1996 by Umemoto [1017]. Perfluoroalkyl(phenyl)iodonium trifiates (FITS reagents) 764 are efficient perfluoroalky-lating reagents toward various nucleophiUe substrates, sueh as arenes, carbanions, alkynes, alkenes, carbonyl compounds, amines, phosphines and sulfides [1017]. Scheme 3.300 shows several representative examples of electrophilic perfluoroalkylations using FITS reagents. 

Other systems for generation of electrophilic perfluoroalkyl radicals were also applied to the synthesis of perfluoroalkylfurans. Thus, trifluoromethylation of furan and benzofuran with trifluoromethyl iodide in DMSO afforded the 2-trifluoromethyl derivatives in 16 and 30 % yield correspondingly [51], Better results were reported for the photocatalytic Ru(bpy)3Cl2-TMEDA system. Trifluoromethylation of... 

Electrophilic perfluoroalkylation has been performed with the use of iodonium salts RfI(Ar)X, where the perfluoroalkyl group is bonded with a positively charged heteroatom. The trifluoromethylation of thiophene 1 with CgFi7l(Ph)0S02CF3 in dichloromethane at room temperature proceeds in 73 % yield in the presence of 2,6-di-terf-butyl-4-methylpyiidine as a base [46]. 

Additions of halogen fluorides to the more electrophilic perfluonnated olefins generally require different conditions Reactions of iodine fluoride, generated in situ from iodine and iodine pentafluoride [62 102 103, /05] or iodine, hydrogen fluoride, and parapeiiodic aud [104], with fluormated olefins (equations 8-10) are especially well studied because the perfluoroalkyl iodide products are useful precursors of surfactants and other fluorochemicals Somewhat higher temperatures are required compared with reactions with hydrocarbon olefins Additions of bromine fluoride, from bromine and bromine trifluonde, to perfluonnated olefins are also known [lOti]... 

Ketones and imines with adjacent perfluoroalkyl moieties show sharply reduced abilities to interact with electrophiles. Hexafluoroacetone is not protonated even in superacidic media... 

Silyl enol ethers have also been used as a trap for electrophilic radicals derived from a-haloesters [36] or perfluoroalkyl iodides [32]. They afford the a-alkylated ketones after acidic treatment of the intermediate silyl enol ethers (Scheme 19, Eq. 19a). Similarly, silyl ketene acetals are converted into o -pcriluoroalkyl esters upon treatment with per fluoro alkyl iodides [32, 47]. The Et3B/02-mediated diastereoselective trifluoromethylation [48,49] (Eq. 19b) and (ethoxycarbonyl)difluoromethylation [50,51] of lithium eno-lates derived from N-acyloxazolidinones have also been achieved. More recently, Mikami [52] succeeded in the trifluoromethylation of ketone enolates... 

The perfluoroalkyl Grignard reagents participate in a wide variety of functionalization reactions with electrophiles as illustrated in Scheme 9 [27-35]. 

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... 

Perfluoroalkyl)methyl-substituted electrophilic cyclopropanes are synthesized in excellent yields by a chromium (III) chloride/iron powder-promoted reaction of perfluoroalkyl iodides with allylamalonic ester and its analogues (equation 51)67. Oxidative coupling of... 

Peptidyl fluoromethyl ketones are widely used as fairly potent inhibitors for a variety of proteases, including serine, cysteine, and aspartyl proteases. Unlike other halomethyl ketones (Section 15.1.3), fluoromethyl ketones are reversible transition-state mimics. The electron-withdrawing fluorine(s) next to the carbonyl group enhances the electrophilicity of the a-fluoroalkyl ketone functionality, thereby making the carbonyl more susceptible to nucleophilic attack. a-Fluoroalkyl ketones are good mimics of peptide bonds due to the small size of the fluorine and the stability of C F bonds. There are three general classes of peptidyl fluoromethyl ketones fluoromethyl ketones (irreversible inhibitors of cysteine proteases), difluoromethyl ketones (reversible inhibitors of both serine and aspartyl proteases), and trifluoromethyl/perfluoroalkyl ketones, which typically exist in hydrated forms and are excellent inhibitors of both serine and cysteine proteasesJ1 ... 

The rates of bromine atom abstraction by tris(trimethylsilyl)silyl radicals from a range of /Jara-substitutcd benzyl bromides has indicated that the silyl radical is nucleophilic. In addition both the polar and spin-delocalization effects of the substituents play a role in the abstraction reaction with the latter effect greater than for H-atom abstractions.166 The perfluoroalkylation of aromatics and alkenes has been investigated using C4F9I as the source of C,. Measurement of rate constants indicated that perfluoroalkyl radicals were 2-3 orders of magnitude more reactive than the corresponding alkyl radicals. This was attributed primarily to the reaction enthalpy and far less to the electrophilic nature of the radicals.167... 

The selective oxidation of C—H bonds in alkanes under mild conditions continues to attract interest from researchers. A new procedure based upon mild generation of perfluoroalkyl radicals from their corresponding anhydrides with either H2O2, m-CPBA, AIBN, or PbEt4 has been described. Oxidation of ethane under the reported conditions furnishes propionic acid and other fluorinated products.79 While some previously reported methods have involved metal-mediated functionalization of alkanes using trifluoroacetic acid/anhydride as solvent, these latter results indicate that the solvent itself without metal catalysis can react as an oxidant. As a consequence, results of these metal-mediated reactions should be treated with caution. The absolute rate constants for H-abstraction from BU3 SnH by perfluorinated w-alkyl radicals have been measured and the trends were found to be qualitatively similar to that of their addition reactions to alkenes.80 a,a-Difluorinated radicals were found to have enhanced reactivities and this was explained as being due to their pyramidal nature while multifluorinated radicals were more reactive still, owing to their electrophilic nature.80... 

Calculated equilibrium geometries, bond lengths, and charge densities have been compared for halonium ions (1-5 X = Cl or Br) derived from the addition of halogen electrophiles to fluoro-substituted terminal alkenes (R = alkyl or perfluoroalkyl with... 

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