Alkyl fluorides cleavage

Reductive cleavage of alkyl fluorides.1 Potassium or Na/K and dicyclohexyl-18-crown-6 in toluene is the most effective of known systems for reductive cleavage of unactivated C—F bonds. Addition of a proton source is not necessary and actually is deleterious. 

Adamantyltetrafluorophosphorane (23) cannot be prepared from the phos-phonyl difluoride (77) by treatment with sulphur tetrafluoride. Instead, it has been prepared in good yield by Lewis-acid-induced cleavage of 1-fluoroadamantane the first time this has been achieved with an alkyl fluoride. ... 

Trimethylsilyl ethers are readily cleaved by fluoride ion, mild acids, and bases. If the TMS derivative is somewhat hindered, it also becomes less susceptible to cleavage. A phenolic TMS ether can be cleaved in the presence of an alkyl TMS ether [Dowex lX8(IfO ), EtOH, rt, 6 h, 78% yield]. ... 

In contrast to phosphorus esters, sulfur esters are usually cleaved at the carbon-oxygen bond with carbon-fluorine bond formation Cleavage of esteri nf methanesulfonic acid, p-toluenesidfonic acid, and especially trifluoromethane-sulfonic acid (tnflic acid) by fluoride ion is the most widely used method for the conversion of hydroxy compounds to fluoro derivatives Potassium fluoride, triethylamine trihydrofluoride, and tetrabutylammonium fluoride are common sources of the fluoride ion For the cleavage of a variety of alkyl mesylates and tosylates with potassium fluoride, polyethylene glycol 400 is a solvent of choice, the yields are limited by solvolysis of the leaving group by the solvent, but this phenomenon is controlled by bulky substituents, either in the sulfonic acid part or in the alcohol part of the ester [42] (equation 29)... 

In 1998, Harmata and co-workers <98T9995> published a new synthesis of 2-alkenyl anilines. The silylated 2,1-benzothiazines 187 could be deprotonated by n-BuLi and alkylated by different electrophiles. The corresponding products could be desilylated by fluoride with concomitant cleavage of the carbon-sulfur bond to give 2-alkenylsulfinanilides that can then be hydrolyzed by base to the anilines 195 in good yields (Scheme 55). 

Furthermore, the cleavage of organic sulfites and sulfates by hydrogen fluoride gives the corresponding alkyl or acyl fluorides in fair to good yield,287 e.g. formation of acetyl fluoride from the mixed anhydride287 or sulfonyl fluorides from sulfonic acid anhydrides.287... 

Bridgehead iodides, namely bicyclo[n.l.l]alkyl iodides, react with xenon difluoride in dichlo-romethane at ambient temperature to form the corresponding bridgehead fluorides in high yields.1617 The process apparently involves a cationic intermediate forming as a result of heterolytic cleavage of the appropriate difluoroiodoalkane and has been named "fluorode-iodination . 

Entries 6 and 7 in Table 3.3 are additional linkers based on intramolecular nucleophilic cleavage. In Entry 6, it is an imidazole that efficiently catalyzes the saponification of the ester linkage, whereas in Entry 7 a hydroquinone is O-alkylated intramole-cularly, with the carboxylate acting as a leaving group. Esters of resin-bound (2-hydro-xyethyl)silanes have also been used as linkers, which can be cleaved by treatment with either TFA or fluoride ions (TBAF in THF [76]). 

Benzhydrylamines are better suited than benzylamines as acid-labile linkers for amines. The MBHA linker ( methylbenzhydrylamine ), which is usually used to prepare peptide amides (see Section 3.3), can also be used as a linker for amines (Entry 1, Table 3.21). Hydrogen fluoride is, however, required as the cleavage reagent. Easier to cleave are alkoxy-substituted benzhydrylamines (Entries 2-5, Table 3.21), which can be prepared from the corresponding benzhydryl chlorides [263] or by reductive alkylation [410] or solvolysis [411] of the Rink amide linker. In the case of benzhydrylamines linked to polystyrene as benzyl ethers, treatment with TFA can lead to the release of the linker into solution (acidolysis of the benzylic C-O bond, see Figure 3.18). 

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