Perfluoroalkylation of arenes

Fenton conditions, which result in eventual abstraction of I from RFI by methyl radicals (see Sect. 4.1.5), can be used effectively to provide perfluoroalkylation of arenes [61]. 

Perfluoroalkylation of arenes makes the aromatic ring electron deficient and thus it interacts with electron-rich arenes and Lewis bases. Figure 1.9 shows the TT-electron distribution on the hexafluorobenzene and benzene ring. Most of the TT-electrons in hexafluorobenzene are withdrawn from the aromatic ring by fluorine atoms to make the aromatic ring highly electron deficient, while the —-electrons in benzene are localized inside the ring. Thus both the benzenes interact attractively in a face-to-face manner [1]. 

More recently, Baciocchi [26a] and Byers [26b] showed that a-iodo esters, a-iodo malonates and a-iodo carbonitriles can be used as radical precursors in the aromatic substitution of various heteroarenes. The perfluoroalkylation of arenes is also possible using the same method [27]. 

In addition to the perfluoroalkylation of arenes Pd(dba)2 competently facilities the ortho-C-H amination of A-aryl benzamides with electrophilic 0-benzoyl hydroxylamines. Pd(dba)2 showed equal reactivity to other precatalysts, such as Pd(OAc)2. Although mechanistically unclear, the addition of AgOAc signiflcantly improved conversion, while the addition of external phosphine ligands was detrimental. Finally, the 4-CF3(C6p4) directing group was optimal because acidic N-H bonds are essential for this transformation (eq 36). ... 

The sonochemical conditions minimize p-elimination.274 Perfluoroalkylation of arene tricarbonyl-chromium aldehydes occurs without decomposition of the transition metal group used to induce stereoselectivity in the addition.275 l,l/l-Trifluoro-2-bromo-2-propene adds to an aldehyde function in the presence of zinc and copper chloride (Eq. 62).276 The adduct was used for the s3mthesis of steroid precursors via a ring opening of the benzocyclobutene to an ortho quino-dimethane, followed by an intramolecular Diels-Alder reaction. 

Finally, Sanford and Loy [45] reported the palladium(0)-catalyzed nondirected perfluoroalkylation of arenes (Scheme 19.28). By using BINAP as the ligand, good yields and regioselectivities were obtained with electron-rich arenes and N-methylpyrrole, whereas electron-deficient arenes were less reactive. Long perfluoroalkyl chains were introduced to facilitate isolation of the products, but the trifluoromethylation of benzene with CFj I could also be performed in modest yields. C(sp )-H activation is likely to occur via the CMD pathway in this case as well. 

The electronic effect of perfluoroalkyl substituents on the absorption spectra of arenes is relatively small (e.g., Xmax 3-perfluorooctylthiophe-ne = 229 nm 3-octylthiophene = 235 nm). Thus, the anomalously low absorption maximum of 504 is the effect of twisting around the backbone. It is apparent that the difference in size of the side chains is sufficiently large to cause twisting of the conjugated backbone of 504 due to steric interactions between the perfluoroalkyl substituents and the adjacent repeat unit. 504 exhibits green fluorescence (Xmax = 512 nm) in solution with a maximum blue shifted by 58 nm relative to POT (570 nm). Accordingly, 504 shows a Stokes shift of ca. 1.4 eV (186 nm) compared to only 0.6 eV (126 nm) for POT. 

Numerous perfluoroalkyl-substituted arenes have been prepared by the coupling of aryl iodides or bromides with perfluoroalkyl iodides in the presence of copper bronze in a dipolar aprotic solvent at elevated temperatures. Perfluoroalkyl bromides and chlorides can be utilized in similar reactions provided a bidentate ligand such as 2,2 -bipyridyl or 1,10-phenanthroline is added 199, 278). Perfluoroalkylcopper reagents are believed to be intermediates in the couplings 200, 201). 

Much of the research on the SbCls-catalyzed halogenation of arenes has focused on the chlorination and bromination of perfluoroalkyl-substituted aromatics [14]. The reaction of organic disulfides with electron-rich aromatic compounds under catalysis with SbCls and AgSbFg affords unsymmetrical aryl sulfides in modest yields [15a]. Electrophilic sulfinylation and sulfonation can be similarly effected by SbCls [15a-c]. Alkyl- and halobenzenes give thiocyano derivatives when treated with a mixture of SbCls and Pb(SCN)2 in CCI4 [16],... 

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). 

The reaction of perfluoroalkyl iodides with electron donor nucleophiles such as sodium arene and alkane sulfinates in aprotic solvents results in radical addition to alkenes initiated by an electron-transfer process The additions can be carried out at room temperature, with high yields obtained for strained olefins [4 (equations 3-5)... 

Perfluoroalkyl-substituted BINAPHOS ligand 29c was also developed for the asymmetric hydroformylation of vinyl arenes in SCCO2. With this ligand regio-and enantio-selectivity (ee s up to 93.6%) were high without the need for hazardous organic solvents [63,64],... 

Asymmetric induction of between 30 and 66% has been reported for the addition of perfluoroalkyl iodides to chiral arene/chromiumtricarbonyl complexes using ultraso-nically dispersed zinc at room temperature (Scheme 3.19) [101], Photochemical decomposition of the organometallic intermediate affords a chiral alcohol product. The reaction is carried out in DMF as solvent and high overall yields are reported e.g.80 % (R = Et). Only a small excess of the perfluoroalkyl iodide is required and the conversion is complete in under 1 h. 

Aryl-A3-iodanes bearing an electron-deficient alkyl ligand such as aryl(sul-fonylmethyl)-A3-iodanes (Section 3.2.7) and aryl(perfluoroalkyl)-A3-iodanes are relatively stable. A series of (perfluoroalkyl)phenyl-A3-iodanes 96 were synthesized in good yields by treating bis(trifluoroacetoxy)-A3-iodanes with benzene in the presence of triflic acid [47]. The AModanes 96 transfer the perfluoroalkyl groups to a variety of nucleophiles with reductive elimination of iodobenzene. The nucleophiles involve Grignard reagents, alkyllithiums, enolate anions, alkenes, alkynes, trimethylsilyl enol ethers, arenes, phenols, and thiols. In these reactions, the AModane 96 serves as a source of the perfluoroalkyl cation and, in... 

A variety of perfluoroalkyl(phenyl)iodonium salts were obtained from precursors such as RFI(OH)OTf, RfI(OOCCF3)2 and others when coupled with benzene or arenes, as reported in a recent review article [143]. Similarly, a trifluo-roethyl group attached to iodine(III) can also be coupled to the phenyl ring upon reaction with PhSiMe3 as outlined in Scheme 47 [144]. 

In a series of papers in the early 1980s, Sokolov s group reported relative rate studies which were similar in nature to those of the early Szwarc studies. Sokolov generated various perfluoroalkyl radicals via thermal decomposition of the respective perfluoro diacyl peroxides in heptane containing various olefins [89] or arenes [90]. Determination of the ratio of olefin addition products to hydrogen abstraction products provided the relative rate data given in Table 4 [89]. 

The fluorination of perfluoroacyloxy arenes with sulfur tetrafluoride to the corresponding perfluoroalkoxy arenes affords access to a larger structural variety [18]. For less sensitive structures, this method can also be extended to the synthesis of alkyl perfluoroalkyl ethers [19] (Scheme 2.173). 

The reaction of trifluoromethyl iodide with arene thiolates provides trifluoromethyl aryl sulfides via a single electron transfer (SET) reaction rather than the SN2 reaction, which is the only formal mechanism (Scheme 2.31). In general, perfluoroalkyl (Rf—X), ferf-alkyl, and vinyl and aromatic halides are strongly deactivated for the replacement of halogens with... 

The chain reaction was firstly proposed for the reaction of perfluoroalkyl iodides with arene thiolatesby Wakselman Wakselman, C., and Tordeux, M. (1984) /. Chem. Soc., Chem. Commun., 793-794. 

A convenient newer procedure for preparing various [bis(trifluoroacetoxy)iodo]perfluoroalkanes 37 and also [bis(trifluoroacetoxy)iodo]arenes 38 involves the oxidation of the corresponding aryl and perfluoroalkyl iodides with the commercially available and inexpensive oxidant Oxone (2KHS05-3KHS04-3K2S04) in trifluoroacetic acid at room temperature (Scheme 2.18) [135]. 

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. 

Full details (see Vol. 1, p. 185) of the Japanese work on the preparation of trifluoromethylarenes from trifluoroiodomethane and iodoarenes in the presence of copper powder and a dipolar aprotic solvent have become available, and it appears that the best solvent in some cases is pyridine. This method (but with DMF as solvent) has also been used to prepare the compounds PhR [R = Me03C (CF3)3, CF3 0 (CF2)2, or perfluoro-2-tetra-hydrofurfuryl] in good yields from iodobenzene and the corresponding polyfluoroiodo-compounds. Perfluoroalkyl-copper compounds are very probably involved in such reactions, and the reactions of preformed n-perfluoroheptylcopper in dimethyl sulphoxide with the aromatic carbon-hydrogen bonds of benzene, toluene, p-xylene, nitrobenzene, and chlorobenzene also lead to (perfluoroalkyl)arenes (some replacement of chlorine occurs in the case of chlorobenzene). Homolytic substitution by perfluoro-heptyl radicals, perhaps within the co-ordination sphere of the copper atom,... 

ONSH is an efficient tool for introduction of perfluoroalkyl groups into electron-deficient arenes. Due to moderate nucleophilicity and stability of perfluoroalkyl carbanions, the reaction proceeds only with highly electrophilic arenes such as azinium salts (Scheme 11.10) [20, 21]. 

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