IODINATION of arenes

Additional publications from Sanford et al. describe the full exploration of palladium-catalyzed chelate-directed chlorination, bromination, and iodination of arenes using N-halosuccinimides as the terminal oxidant <06T11483>. Moreover, an electrophilic fluorination of dihalopyridine-4-carboxaldehydes was reported by Shin et al. <06JFC755>. This was accomplished via transmetalation of the bromo derivative, followed by treatment with A-fluorobenzenesulfinimide as the source of electrophilic fluorine. 

The combination of 1 and iodine (2 1.2-1.5) effects iodination of arenes and trimethylsilyl enol ethers. 

Iodination of arenes.1 These two reagents generate nitryl iodide, which can iodinate arenes, particularly methylarenes, at 28°. The yield increases with the number of methyl substituents, being 90-95% with tri- and tetramethylbenzenes.1... 

Iodination of arenes2 Iodination of arenes can be effected by reaction with HgO HBF4 in the presence of iodine. The orientation conforms to that observed in electrophilic aromatic substitution except that ortho-attack is favored over para-attack in activated arenes. The method is particularly useful for meta-iodination of deactivated arenes (99% selectivity). 

Kitamura and Hossain have found that potassium peroxodisulfate can be used as an efficient oxidant for the preparation of (diacetoxyiodo)arenes and [bis(trifluoroacetoxy)iodo]arenes from iodoarenes [159,160]. A convenient modification of this approach employs the interaction of arenes with iodine and potassium peroxodisulfate in acetic acid (Scheme 2.16) [171]. The mechanism of this reaction probably includes the oxidative iodination of arenes, followed by oxidative diacetoxylation of Arl in situ leading to (diacetoxyiodo)-arenes 36. 

Iodine in combination with [bis(acyloxy)iodo]arenes is a classical reagent combination for the oxidative iodination of aromatic and heteroaromatic compounds [99], A typical iodination procedure involves the treatment of electron-rich arenes with the PhI(OAc)2-iodine system in a mixture of acetic acid and acetic anhydride in the presence of catalytic amounts of concentrated sulfuric acid at room temperature for 15 min [100,101]. A solvent-free, solid state oxidative halogenation of arenes using PhI(OAc)2 as the oxidant has been reported [102]. Alkanes can be directly iodinated by the reaction with the PhI(OAc)2-iodine system in the presence of f-butanol under photochemical or thermal conditions [103]. Several other iodine(in) oxidants, including recyclable hypervalent iodine reagents (Chapter 5), have been used as reagents for oxidative iodination of arenes [104-107]. For example, a mixture of iodine and [bis(trifluoroacetoxy)iodo]benzene in acetonitrile or methanol iodinates the aromatic ring of methoxy substituted alkyl aryl ketones to afford the products of electrophilic mono-iodination in 68-86% yield [107]. 

The reactivity pattern of compounds 90 and 91 is similar to common hypervalent iodine reagents, as illustrated by their use for the oxidation of sulfides, oxidative iodination of arenes and a-tosyloxylation of ketones (Scheme 5.32) [89]. The products of all these reactions can be conveniently separated from the by-product, 3-iodobenzoic acid, by simple treatment with ion-exchange resin IRA-900 according to... 

Chlorination is carried out in a manner similar to bromination and follows a similar mechanism to give aryl chlorides. Fluorination and iodination of arenes are rarely performed. Fluorine is so reactive that its reaction with benzene is difficult to control. Iodination is very slow and has an unfavorable equilibrium constant. However, iodine, in the presence of a powerful oxidizing agent can be used for electrophilic aromatic iodination. In the following example, the oxidant peroxyacetic acid reacts with iodine to... 

The iodination of cross-linked polystyrene has been achieved using iodine under strongly acidic reaction conditions [55] or in the presence of thallium(III) acetate [61], but this reaction does not proceed as smoothly as the bromination. More electron-rich arenes, such as thiophenes [45,62-64], furans [46], purines [65], indoles [66], or phenols [67,68] are readily halogenated, even in the presence of oxidant-labile linkers (Figure 6.2). Polystyrene-bound thiophenes have also been iodinated by lithiation with LDA followed by treatment with iodine [64],... 

Diaryliodonium salts (diaryl-A3-iodanes) are widely used as arylating agents. There are a number of methods available for their synthesis typically involving two or three steps.378,379 A recent one-pot approach, however, offers a simple and high-yielding access to unsymmetrical diaryliodonium triflates using meto-chloroperbenzoic acid (mCPBA) as the oxidant380 [Eq. (4.111)]. Moreover, symmetrical diaryliodonium salts can directly be prepared from iodine and arenes without the use of expensive aryl iodides [Eq. (4.112)]. 

Barluenga et al.565 have reported the selective monoiodination of arenes with bis (pyridine)iodonium(I) tetrafluoroborate [I(py2)BF4] in excess superacids (2 equiv.) [Eq. (5.210)]. Comparable results were found for activated compounds with both HBF4 and triflic acid, whereas triflic acid was more effective in the iodination of deactivated aromatics. For example, nitrobenzene and methyl benzoate are unreactive in HBF4 but give the corresponding iodo derivatives in triflic acid (83% and 84% yields, respectively, in 14 h). Iodination of phenol required low temperature (-60°C). 

One of the most important reactions in arene synthesis is the halogenation of arenes. Conventionally, these reactions are performed directly by bromine or chlorine [7]. However, on the laboratory scale chlorine is not easily manageable and is a toxic gas. Therefore, it is not often used in academic research. For iodinations normally a strong oxidizing agent is required. In halogenations, often unintentional side-chain... 

Irradiation of the / -(aryl)ethanesulfonamides 190 in the presence of DAIB-I2 provides access to the dihydrobenzothiazine dioxides 191 and 192 (Scheme 55) (OOJOC926). In these reactions, formation of the thiazine ring by the radical cyclization pathway to give 191 is followed by electrophilic iodination of the arene nucleus to give 192. 

Fig. 5. Typical dependence of the formation constants of arene complexes with different acceptors on the oxidation potential of the arene. Data from refs. [23, 28]. I2 = iodine, TCNE — tetracyamethylene PA — picric acid.

Decomplexation of ArCr CO)3. The chromium carbonyl complexes of arenes are useful for activation of the aryl group to nucleophilic attack (6, 28, 125-126 7, 71-72). Decomplexation has been effected with iodine or by photochemical oxidation with destruction of the expensive Cr(CO)3 unit. A more recent method involves reflux with pyridine to form Py3-Cr(CO)3 in yields of 70-100%. The pyridine complex in the presence of BF3 can be reused for preparation of ArCr(CO)3. Isomerization of 1,3-dienes. Ergosteryl acetate (1) is isomerized by chromium carbonyl to ergosteryl 83 acetate (2) in 81% yield. Under the same conditions ergosteryl 83 acetate (3) is isomerized to ergosteryl 81 acetate (4). 80th reactions involve isomerization of a cisoid diene to a transpid diene. In contrast iron carbonyl isomerizes steroidal transoid 3,5- and 4,6-dienes to 2,4-dienes. ... 

However, the substituents shown in the lefthand column hinder the oxidation of the toluene derivatives completely. Phenols, thiophenols, anilines, o-phenoxy-, and iodine-substituted arenes cannot be oxidized to the aromatic acids, for these substituents act as strong radical scavengers and thus as catalyst and autoxidation poisons. In contrast to m- and p-nitrotoluene, which can be smoothly oxidized to the nitro-substituted benzoic acids, o-nitrotoluene and its derivatives turned out be almost inert. This is due to the high reactivity of the benzylic radical, which ob-... 

Similarly, chelation-assisted palladium-catalyzed oxidative functionalizations of C—H bonds with, for example, hypervalent iodine(III) reagents turned out to be particularly valuable. These protocols allowed for, inter alia, regioselective acetoxyla-tion or etherification of aromatic and aliphatic C— H bonds [17-19], and also halogenations of arenes (Scheme 9.3) [20, 21]. 

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