Aryl reaction with diaryliodonium salt

The arylation of nucleophiles by reaction with diaryliodonium salts can be greatly facilitated by copper catalysis. This effect was observed by Beringer et al in the thermal decomposition of diaryliodonium halides as well as by Caserio et al in the hydrolysis of diaryliodonium salts. 2 jhe thermal decomposition of diphenyliodonium chloride shows a reduced activation energy upon copper catalysis Ea = 19 kcal/mole in Methylene glycol in the presence of CuCl instead of 31 kcal/mole in the absence of catalyst.From the synthetic point of view, the copper-catalysed arylation with diaryliodonium salts has been particularly useful in the case of a number of reactions involving heteroatomic nucleophiles, in particular for 5-, 5e-, O- and N-arylation reactions. 

The reaction of alkyl aryl sulfides with diaryliodonium salts generated unsymmetrical diaryl sulfides in moderate to excellent yields through cleavage of the sulfur-carbon(sp ) bond and formation of a new sulfur-carbon(sp ) bond (Scheme 5.38) [60]. The synthesis was transition metal free and tolerated a host of different electron-withdrawing and donating groups. Another noteworthy aspect of the chemistry was that it was successful in an acidic environment. This renders the work complementary to the transition metal-catalyzed routes that are typically carried out under basic conditions. In related work, the... 

As mentioned above, condensed 1,2,3-triazine derivatives can be arylated by treatment with nitro-activated aryl halides. The only other report of direct arylation of the 1,2,3-triazine system is due to McKillop and Kobylecki, who studied the reaction of l,2,3-benzotriazin-4-one (10, R = H) with diaryliodonium salts in the presence of base. Treatment of 10, R = H, with diphenyl- and di-p-bromophenyliodonium chloride results in exclusive arylation at N2 and gives the corresponding triazinium betaines (77, R = Ph, p-BrCjH4) in good yield. When di-p-tolyliodonium chloride is used, a mixture of the Nj-, Nj-, and 0-arylated... 

Compounds containing an active methylene group, or the respective carbanions formed in situ, react smoothly with diaryliodonium salts to yield a-arylated products [1]. A recent example of arylation of carbanions under polar, non-cat-alytic conditions is represented by the reaction of diaryliodonium salts with malonates 90 (Scheme 41) [69]. 

Recent progress on the use of hypervalent iodine reagents for the construction of heteroatom-heteroatom bonds is reviewed. Reactions of aryl-A3-iodanes with heteroatom substrates derived from third-row elements and beyond are considered first, and an unusual example of heteroatom-heteroatom bond formation with diaryliodonium salts is then discussed. Finally, the use of sulfonylimino(aryl)iodanes for imidations of phosphorus, sulfur, selenium, and arsenic compounds, including enantioselective transformations (S,Se), and alternate hypervalent iodine approaches to N-sulfonylsulfilimines and N-sulfonylarsinimines are summarized. 

An early report of the beneficial influence of 1,1-diphenylethylene (DPE) on the yields of alkylaryl ether obtained in the reaction of diaryliodonium salts with sodium alkoxides showed that radical chain reactions compete efficiently with the 0-arylation reaction. By contrast, addition of diphenylpicrylhydrazyl, a stable free radical species, had no significant influence on the yields of products obtained in e absence of additives. In this case, the 0-arylation reaction was considered to be a direct nucleophilic aromatic substitution reaction, without the involvement of any transient covalent intermediate. (Table 2.11)... 

A similar beneficial effect of 1,1-diphenylethylene on the yields of arylation products was later observed in the synthesis of benzonitrile derivatives by reaction of diaryliodonium salts with potassium cyanide and in the reaction of diaryliodonium salts with the sodium salt of nitroalkanes. 7 In the latter case, the reaction was therefore considered to result from intermediate inner-sphere radicals. Some years later. Barton et al. showed that 1,1-diphenylethylene acts as an efficient inhibitor of the radical chain process in the reaction of enolates with diaryliodonium salts. They concluded that the arylation products arose from a non-radical process. 

In the case of P-diketones, a mixture of C- and O-arylated products were obtained in the reaction of l,3"diketones with diaryliodonium salts, the 0-aryl product being obtained generally in low yields. This ambident reactivity of 1,3-diketone derivatives was observed in different cases sterically hindered reactants,2 88 polybenzoylmethane derivatives and dimedone. ... 

The reaction of cyclohexanone enamines (26) with diaryliodonium salts gave only poor yields of the a-aryl ketones (27) after hydrolysis. ... 

The reaction of phenols with diaryliodonium salts leads to the diaryl ethers in modest to good yields, depending on the substrate and the reaction conditions.31 0>5l-i03 number of studies have dealt with this reaction as it was involved in the synthetic sequence towards diaryl ethers of biological importance, such as bisbenzylisoquinoline alkaloidsl04 or thyronine and tyrosine derivatives.105 The reaction requires relatively harsh conditions, as it is performed under reflux of the solvent. In the case of unsymmetrical diaryliodonium salts, the less electron-rich aryl group of the iodonium salt is preferentially transferred. 

Hydroxamic acids react with diaryliodonium salts to afford the O-phenyl derivatives. number of heterocyclic compounds containing A -hydroxyamino groups were selectively arylated on the oxygen atom. 0 (Table 5.4) In the case of oximate anions, ambident behaviour was observed, with predominant 0-arylation. With heterocyclic oximes, the 0-aryl ethers were mainly formed and served as precursors to prepare unstable aryl fulminates, 19 (Table 5.5) In the reaction of quinolone derivatives with diaryliodonium salts, the products of O- or C-arylation were obtained.(Table 5.6)... 

The outcome of the reaction of pyridine with diaryliodonium salts was dependent upon the nature of the counterion. With a non nucleophilic counterion as the tetrafluoroborate, the iV-phenylpyridinium salt (31) was obtained in high yield. 23 with bromide, no reaction occurred and with chloride, ring arylation was observed as a result of the formation of phenyl free radicals. 25... 

Although the reaction of hydroxamic acids with diaryliodonium salts affords the 0-phenyl derivatives, (see Section 5.1.1.3.3) the reaction of the closely related iV-hydroxycarbamates led exclusively to the N-aryl derivatives. 127... 

Reactions of diaryliodonium salts with various organochalcogen anions led to the arylchalcogen derivatives. (Table 5.7) The anions of sulfur compounds afford generally the 5-aryl derivatives. Sometimes the intermediate iodanes can be isolated. Examples are the reaction of dithiocarbamate and xanthate salts with diaryliodonium. Upon heating, the dithiocarbamate derived iodane afforded the aryldithiocarbamates.133 Thermal decomposition of the xanthate derived iodanes gave mixtures of arylxanthates and diaryldisulfides. ... 

The 5-arylation of sulfides is greatly improved by copper catalysis. The uncatalysed reaction requires heating under reflux to afford modest to moderate yields of the 5-aryl sulfonium derivatives. By contrast, upon copper catalysis, the reaction proceeds at room temperature to afford good to high yields of the 5-aryl sulfonium derivatives. 2-146,151 Moreover, the reaction was extended to the double arylation of the more readily available aiylthiols.l Similarly, the reaction of areneselenolates with diaryliodonium salts led to diarylselenides and triarylselenonium salts were easily obtained by copper catalysed arylation of diarylselenides. 2... 

Diaryliodonium salts have found synthetic application as arylating reagents in reactions with various organic substrates under polar, catalytic, or photochemical conditions. Typical examples of arylations of nucleophiles under polar, non-catalytic conditions are shown in Scheme 3.271 and include the reactions of diaryliodonium salts with thiosulfonate anions 675 [861], fluoride anion [862,863], malonates 676 [864] and silyl enol ethers 677 [865]. 

Additional examples include the electrophilic arylations of sodium arenesulflnates [866], potassium car-bonotrithioates [867] and benzazoles [868] using diaryliodonium salts in ionic liquids and the arylations of anilines [869], sodium tetraphenylborate [870] and vinyUndiums [871]. Particularly important are the reactions of diaryliodonium salts with fluoride anion as nucleophile. This reaction is widely applied for introduction of the radioactive F isotope into different organic substrates to obtain labeled agents for positron emission tomography. This topic is covered separately in Chapter 7 due to its importance and wide usage. 

Olofsson and coworkers have developed a general and high-yielding synthesis of various diaryl ethers 681 using the reaction of diaryliodonium salts with phenols under basic conditions (Scheme 3.273) [874]. The scope of products includes bulky orf/io-substituted diaryl ethers, which are difficult to obtain by metal-catalyzed protocols. A similar procedure has been used for the metal-free synthesis of aryl esters from carboxylic acids and diaryliodonium salts [875]. 

Several mechanistic studies on the reactions of diaryliodonium salts with nucleophiles have been published. Ochiai and coworkers performed a mechanistic study on the phenylation of 3-keto ester enolates with diaryliodonium salts. An aryl radical trap was added to the reaction without affecting the outcome, which indicates that radical pathways are unlikely and the reaction occurs by direct coupling of the ligands on the hypervalent iodine center [889]. 

The mechanism of solvolysis of methoxy-substituted diaryliodonium tetrafluoroborates, Arl+Ph Bp4, in methanoi and 2,2,2-trifluoroethanol has been investigated [893]. The solvolysis products include alkox-ide substitution products (ArOR and PhOR) as well as iodoarenes (Phi and Arl). The ratios of products, ArOR/PhOR, range from 8 2 to 4 6. The results of this study provide experimental evidence against the formation of aryl cation under these conditions and support the pathways via ligand coupling or 5nAt2 mechanisms involving a solvent molecule as a nucleophile in the transition state [893]. If the reaction is performed in inert (not nucleophilic) solvent, various nucleophiles may be involved in the reaction with iodonium salt. 

Further valuable electrophilic reactants in the Kharasch reaction are diaryliodonium salts. They smoothly react with aryl Grignard reagents in the Pd(PPh3)4-catalysed reactions in the presence of zinc chloride to give biaryls in excellent yields [31]. Although access to some diaryliodonium salts is somewhat difficult, they could be... 

Table 1. The yields in the cross-coupling reactions of diaryliodonium salts with aryl Grignard reagents [31]...

The drawback with diaryliodonium salts is the formation of a stoichiometric amount of iodoarene in the reaction. Arylations with unsymmetric diaryliodonium salts (Ar Ar ) are often desired, both because these salts are more easily synthesized and because an inexpensive dummy aryl moiety is wasted as Arl. The chemoselectivity of the reaction, i.e., the preference to transfer Ar over Ar, must be high to ascertain high yields and avoid purification problems (Scheme 2a). 

Kang and coworkers developed a number of metal-catalyzed arylations with diaryliodonium salts under mUd reaction conditions at the turn of the century, including the Pd-catalyzed arylation of secondary amines at room temperature and the Cu-catalyzed arylation of amines, anilines, amides, imidazoles, and triazoles at room temperature to 50 °C [98, 99]. The copper-catalyzed N-arylation of indoles, on the other hand, required heating to 150 °C in DMF [100], and makes an interesting comparison with the recently developed C-arylation of the same substrates (see Sect. 4.2.2). 

The arylation of fluoride with diaryliodonium salts has been extensively investigated because of the need for fluorine-18 labeled (hetero)aromatics in positron emission tomography (PET). [ F]Fluoroarenes with a wide range of substitution patterns can be prepared from advanced diaryliodonium salts at high temperatures in short reaction times, which is important because of the short half-life of F (110 min). Fluorination and radiofluoiination of diaryliodonimn salts have been reviewed several times in recent years [138—140], as have other strategies towards... 

This section describes selected arylations of phosphorus, sulfur, and halide nucleophiles under metal-free and metal-catalyzed conditions. Arylations of other nucleophiles, e.g., selenium and tellurium, have been reviewed previously [4]. Aryl phosphonates [ArPO(OR)2] can be synthesized by arylation of phosphite anions with diaryliodonium salts and NaH in DMF at 70-80 °C [158]. A copper-catalyzed arylation of various phosphorous nucleophiles, e.g., diarylphosphine oxides and //-phosphonates, was recently reported to proceed at room temperature. The observed chemoselectivity with unsymmetric salts was opposite to the general trend in metal-catalyzed reactions (see Sect. 2.1), which was explained by a radical mechanism [159]. 

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