Reactions Involving Hypervalent Iodines

The mechanism of the reaction was supposed to be similar to that of the allylation process. Deprotonation of benzyl cyanides requires very strong bases (pfC = 21.9) [44]. However, coordination of the CN group to the palladium atom of la allows easy deprotonation even with very weak bases, such as NaHCOj. The next step is a nucleophilic attack of the carbon atom of the imine group, which leads to C-C bond formation. This step determines the stereoselectivity of the process [43]. 

Arylation ofAlkenes Using Pincer Complex Catalysis 

Heck coupling is probably the most established catalytic method for the coupling of aryl compounds with alkenes [1, 54]. However, Heck coupling reactions are based 

Density functional theory (DFT) modebng studies [56] pointed out the relatively high activation energy of the oxidative addition. Since carbopaUadation of 24 is probably fast, complex 24 could not be detected. However, in the acetoxylation and the C-H borylation studies, the more strongly oxidizing iodine was used instead of 21, and detection of the Pd(IV) intermediate could be reabzed (Sections 4.4.2 and 4.4.3). 

Palladium-catalyzed aUyUc C-H acetoxylation (acyloxylation) of alkenes is one of the synthetically most established C-H functionabzation methods [57-62]. These reactions are conducted under oxidative reaction conditions. In the most commonly used approach, the reaction proceeds via a Pd(II)/Pd(0) catalytic cycle and benzoquinone (BQ) is used for reoxidation of Pd(0) and activation of the nudeophihc (acetate) attack [61, 62], 

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Dinitro-6-phenyliodonium phenolate (146) is a stable iodonium zwitterion484. It reacts under photolytic conditions with various alkenes, alkynes and aromatic compounds to afford 2,3-dihydrobenzo[ ]furans, benzo[6]furans and 6-aryl-2,4-dinitrophenols. The mechanism involves hypervalent iodine compounds (iodinanes, 147) and is illustrated for the reaction with an aromatic compound (equation 127). Compounds 148 are the major products when ArH = PhH, PhOCH3 or 1,4-dimethoxybenzene. With furan and thiophene, 149 is the principal product. The reaction does not proceed with chlorobenzene and nitrobenzene. 

The use of sources of positive halogen to bring about oxidations Is well known. While the molecular halogen Itself Is often sufficient to bring about the desired reaction, a less nucleophilic counterion Is often quite useful. If this counterion becomes bound to a polymer, then reaction workup Is substantially simplified. Below are discussed the major polymer-bound halogenatlng agents. Those involving hypervalent iodine are discussed later. 

In addition, the reaction between hypervalent iodine reagents such as iodosyl-benzene or its diacetate derivative with molecular iodine has been employed frequently in aliphatic amination reactions. These processes start from an initial formation of an alkyl hypoiodite derivative, which can promote subsequent radical amination pathways. An excellent use of this concept is the Suarez methodology for the generation of diversified aminated carbohydrate structures [80-86]. Although the hypervalent iodine reagent is not directly involved in the amination reaction, the efficiency of the method deserves mentioning within the present chapter. It was recently extended to catalytic transformations [87],... 

Hypervalent iodine has been thoroughly investigated as a catalytic, non-metal oxi-dant.25.26 Reagents involving hypervalent iodine are typically safe, green, and then-reactions simple to employ. Its utility will be explored throughout the rest of this chapter. 

H347). The reaction of Gilman s reagent, R2CuLi, also involves ligand coupling. There are many examples of hypervalent iodine compounds. 

The first reaction step involves a method developed by Stork use of the hypervalent-iodine species bis(tnfluoroacetoxy)iodobenzene (26), which effects oxidative removal of the dithiane.11 Methylace-lal 25 a is formed in methanol solution in the presence of traces of acid. Subsequent silylalion of the secondary alcohol is accomplished using TBS-lrifiate with lutidine as base. The third reaction... 

Once formed, hypervalent iodine compounds, i.e. A3- and A5-iodanes, can exchange readily their ligands with nucleophiles, sometimes with assistance from electrophiles. When only nucleophiles are involved, reactions follow an associative pathway, in which an iodate(III) or (V) species is formed. The mixed iodane initially formed is sometimes isolable but usually this procedure takes place with both ligands so that eventually the new species has two... 

The use of hypervalent iodine reagents in carbon-carbon bond forming reactions is summarized with particular emphasis on applications in organic synthesis. The most important recent methods involve the radical decarboxylative alkylation of organic substrates with [bis(acyloxy)iodo]arenes, spirocyclization of para- and ortho-substituted phenols, the intramolecular oxidative coupling of phenol ethers, and the reactions of iodonium salts and ylides. A significant recent research activity is centered in the area of the transition metal-mediated coupling reactions of the alkenyl-, aryl-, and alkynyliodonium salts. 

Recently, the reaction of masked ortho-benzoquinone [92] with C60 was tested [93]. The [4+2] cycloaddition reaction of such electron-deficient dienes with fullerenes resulted in the formation of highly functionalized bicyclo [2.2.2] octenone-fused fullerenes. The reactants were generated in situ by the oxidation of the readily available 2-methoxy phenols with hypervalent iodine agents. For the several different masked ortho-benzoquinones that were tested, it was found that the yield of the cycloadducts depends on the nature of the starting materials and the reaction conditions. Other Diels-Alder reactions of such electron-deficient dienes with electron-poor fullerenes involved tropones [94], 1,3-butadienes substituted with electron-withdrawing groups [95], and 2-pyrone [96]. 

Acetoxylation. Transformations of Carbonyl Compounds. Phenolic Oxidation. Oxidation of Nitrogen Compounds. Hypervalent iodine Reagents in Combination with Azido Compounds. DIB and Sodium Azide in Combination with Other Reagents. Transformations of Alkynes Involving Thiophenols and Diphenyl Diselenide. Miscellaneous Reactions. 

More involved studies of the oxidation of plant phenols [27], as well as the introduction of thallium and hypervalent iodine complexes and the use of electrochemical methods, have emphasized the importance of another intermediate involved in oxidative coupling reactions, namely the phenoxonium ion 8 [28-30]. Due to its ionic nature, reaction through an oxo-nium ion can improve the regioselectivity of bond formation and lead to fewer unwanted products (for example, no coupling via the oxygen atom). The coupling reaction can then be viewed as an electrophilic aromatic substitution between 17 and a nucleophilic aromatic unit 15 (Scheme 5). 

The question as to whether the reactive intermediate is the phenol-metal/leaving group complex 21/22 or the free phenoxonium ion 17 has been studied in the particular case of hypervalent iodine. Pelter and co-workers presented permissive evidence in support of a mechanism involving the free oxonium species 17 (Scheme 7) Phl(OAc) is an extremely good nucleofuge, no transfer of chirality is observed when homochiral hypervalent iodine compounds are used, and calculations made on the cation species correctly predict the re-gioselectivity of the substitution reaction [32, 33]. 

The oxidative protocol simply involves grinding of the two solid substrates using a pestle and mortar a mildly exothermic reaction results in the formation of a yellowish eutectic melt and the reaction gets completed in a few minutes. The work has now been extended to the synthesis of p-ketosulfones from ketones employing another hypervalent iodine reagent. 

The reaction involves first the electrophilic addition of a hypervalent iodine reagent to the enol tautomer of the ketone to give an a-phenyliodonioketone (144). The second step is generally assumed to be a classical Sn2 displacement yielding the final product.(Scheme 5.20)... 

A radical cation is involved in the direct synthesis of chromans by an intramolecular oxidative cyclisation of 3-arylpropanols 32 brought about by a hypervalent iodine(III) reagent <04TL2293> and iodonium species catalyse the intramolecular arylation of alkenes which yields iodo-substituted chromans 33 <04JA3416>. 3-Allenylchroman-4-ols result from a one-pot reaction between salicylaldehydes and 1,4-dibromobut-2-yne in which the intramolecular cyclisation of the intermediate ether is mediated by In metal <04SL45>... 

Processes involving a single-electron transfer (SET) step and cation-radical intermediates can occur in the reactions of X - or X -iodanes with electron-rich organic substrates in polar, non-nucleophilic solvents. Kita and coworkers first found that the reactions of p-substituted phenol ethers 29 with [bis(trifluoroacetoxy)iodo]benzene in the presence of some nucleophiles in fluoroalcohol solvents afford products of nucleophilic aromatic substitution 31 via a SET mechanism (Scheme 1.5) [212,213]. On the basis of detailed UV and ESR spectroscopic measurements, it was confirmed that this process involves the generation of cation-radicals 30 produced by SET oxidation through the charge-transfer complex of phenyl ethers with the hypervalent iodine reagent [213,214],... 

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 direct nucleophilic substitution of electron-rich phenol ethers using hypervalent iodine oxidants in the presence of Lewis acid or fluorinated alcohols and involving aromatic cation-radical intermediates was originally developed by Kita and coworkers in 1994 [362], Since then this procedure with some variations has been extensively applied by Kita and other researchers for various oxidative transformations. In the intermolecular mode, this reaction (Scheme 3.122) has been utilized for the preparation of the products 298 from N3, AcO , ArS, SCN , 3-dicarbony 1 compounds and other external nucleophiles [320]. The oxidative coupling reaction in the intramolecular mode provides a powerful synthetic tool for the preparation of various... 

Cationic cyclizations, induced by hypervalent iodine reagents, are particularly useful in the synthesis of het-erocycles. Tellitu and Dominguez have developed a series of [bis(trifluoroacetoxy)iodo]benzene-promoted intramolecular amidation reactions, generalized in Scheme 3.134, leading to various five, six and seven-membered heterocycles 335 [388,389]. Experimental evidence supports the ionic mechanism of these reactions, involving A -acylnitrenium intermediates 334 generated in the initial reaction of the amide 333 with the hypervalent iodine reagent [390]. 

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