FITS reagents

FITS reagents), has undergone considerable development recently [141,142,143, 144, 14S. These compounds, available fromperfluoroalkyhodides (equation 76), are very effective electrophilicperfluoroalkylating agents They react with carban-lons, aromatic compounds, alkenes, alkynes, silyl enol ethers, and other nucleophiles under mild conditions to introduce the perfluoroalkyl moiety mto organic substrates (equation 77) (see the section on alkylation, page 446). 

An interesting development of this research is the preparation of polymer-supported FITS reagent from bis(trifluoroacetoxy)iodoperfluoroalkanes and Nafion-H [145]. FITS-Nafion reacts with organic substrates that react to usual FITS reagents, but the products of the perfluoroalkylation reaction can be separated easily from the insoluble resin by filtration [145]... 

T. Umemoto Perfluoroalkylation with (perfluoroalkyl)phenyliodonium trifluoromethanesulfonate (FITS) reagents [7]... 

Perfluoroalkyl(phenyl)iodonium sulfonates 42 (also known as FITS reagents), as well as lFf,lff-perfluoroalkyl(aryl)iodonium triflates 44, have found practical application as electrophilic fluoro alkylating reagents toward a... 

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

In addition to the arenes, enolates, and other nucleophiles depicted in Scheme 2.142, FITS reagents are also reactive in the perfluoroalkylation of unactivated alkenes, alkadienes [19], and acetylenes [20] (Scheme 2.146). In contrast with olefin perfluoroalkylation by means of perfluoroalkyl bromides or iodides (Section 2.2.1), this reaction does not follow a free radical mechanism but proceeds via cationic intermediates which can be either trapped by addition of nucleophiles or nucleophilic solvents or quenched by -deprotonation with a base (Scheme 2.147). 

Of spedal importance for introduction of perfluoroalkyl groups into pharmaceuticals and for synthesis of perfluoroalkylated analogs of natural products is the reaction of FITS reagents with silyl enol ethers, leading to a-perfluoroalkyl carbonyl compounds [21] (Scheme 2.149). 

Scheme 2.149 Perfluoroalkylation of silyl enol ethers with different FITS reagents [21].

Scheme 2.150 Synthesis and preparative use of perfluoroalkylene FITS reagents [22].

The synthesis of FITS reagents poses two principal difficulties (1) isolation of the FITS reagent from the reaction mixture often requires repeated yield-reducing recrystallization steps and (2) recovery of the expensive triflic acid obtained during the synthesis is difficult. A solution to these problems was found in the immobilization of the reagents [23] by means of a solid analog of triflic acid - Nafion-H resin [24] (Scheme 2.151). 

In the same way as for the FITS reagents, the basic concept for the dibenzothio-penium reagents has been successfully extended to the electrophilic transfer of longer perfluoroalkyl chains [29]. 

Enolate Umemoto s reagent, FITS reagent Perfluoroolefm + F + RX generation of perfluor-oalkyl anion and subsequent nucleophilic replace- 129, 132 ff... 

FITS reagents reacted with various carbanions to afford under mild conditions the corresponding fluoroalkylated derivatives. The yields are quite dependent upon the nature of the carbanion and of the counterion. (Table 5.9)... 

FITS reagents reacted very easily with thiols in the presence of pyridine to give the perfluoroalkyl sulfides in good to high yields. S-perfluoroalkylation was selective in the case of polyfiinctional substrates. In the presence of groups such as hydroxy, carboxy, alkoxycarbonyl or dialkylamino, the sulfur atom was always selectively substituted.216 (Table 5.10)... 

Table 5.10 Perfluoroalkylation of thiols with FITS reagents l ...

The reaction of phenol with FITS reagents led to a mixture of ortho-, meta- and para-perfluoroalkylphenols, formed by electrophilic aromatic substitution. In the case of the relatively hindered electron-rich phenols, a different outcome was observed 0-perfluoroalkylation was observed together with the C-perfluoroalkylation products. At high temperature, the amount of the 0-substituted product became predominant. ... 

FITS reagents are synthesized in high yields from oxidation of perfluoroalkyl iodides by trifluoroperacetic acid [60% H202 + (CF3C0)20] or by elementary fluorine followed by treatment with benzene or fluorobenzene in the presence of triflic acid in 1,1,2-trichlorotrifluoroethane or CF3COOH at 0°C to room temperature148 (equation 133). 

The FITS reagent, (perfluoroalkyl)aryllodoniuffl trlfluoro-Bulfonates, can also be Inmoblllzed on NAFION (65) In particular, bisCtrifIuoroacetoxy)lodoperfluoroalkanes react with PFIEP[SO H] as in equation 26. The iomobilized reagent. 

Several stabilized alkyliodine(ni) dicarboxylates have been reported in the literature. [Bis-(trifluoroacetoxy)iodo]perfluoroalkanes, RfI(C02CF3)2, were originally prepared by Yagupolskii and coworkers in almost quantitative yield by the oxidation of 1-iodoperfluoroalkanes with peroxytrifluoroacetic acid [173]. These relatively stable compounds have found practical application for the preparation of perflu-oroalkyl(phenyl)iodonium salts, which are used as electrophilic lluoroalkylating reagents (FITS reagents) (Section 2.1.9.5) [174]. 

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. 

Dihydroperfluoroalkyl)phenyliodonium trifiates, RfCH2l(Ph)OTf, are electrophilic fiuoroalkylating reagents with a reactivity pattern similar to FITS reagents 764 [1017]. The fiuoroalkylation of amines is a particularly important reaction. For example, trifiuoroethyl(phenyl)iodonium trifiate 765 has been used for the N-trifiuoroethylation of aminoalcohols (Scheme 3.301) [1018]. 

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