Phenols, oxidation with hypervalent iodine

The oxidation of phenols with hypervalent iodine compounds has been used frequently and nucleophilic additions can be performed as well as cyclization reactions using this technique. The resulting quinone derivatives show high reactivity and they have been used in a various subsequent reactions. Substituted phenols like 32 [78] or 34 [79] have been oxidized by hypervalent iodine reagents and, depending on the substitution pattern, cyclizations have taken place as shown in Scheme 16. Product 33 is unstable and undergoes subsequent... 

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]. 

The other key step in the synthetic approaches to FR901483 is the elaboration of the quaternary spirocenter at C(l) (Scheme 4). Sorensen, Ciufolini, and Wardrop all use an oxidative spirocyclization of nitrogen tethered phenol derivatives, employing hypervalent iodine reagents, to generate the spirocenter at C(l). In contrast, in the other approaches the formation of the quaternary stereocenter does not coincide with the... 

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... 

The transformation from arenes into phenol acetates can be achieved with hypervalent iodine compounds (such as phenyliodonium acetate, PhI(OAc)2), with chromates, or under aerobic conditions. Ligands, like picolinic acids, stabilize the intermediate palladium(IV) salts. In the presence of Lewis acids or silver salts, biaryl formation takes place. The influence of different directing groups has recently been reviewed. For example, diaryl sulfones or sulfoxides having at least one heteroaryl attached can be oxidized to the corresponding aryl acetates (Scheme 5-194, Experimental Procedure below). ... 

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. 

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. 

A more recent attempt<34) to improve yields at the phenolic oxidation stage of the Barton synthesis rested on the argument that species such as hypervalent iodine(35) offered milder reaction conditions because the iodine (III <= I) redox is closer to the potential required for the reticuline-salutaridine transformation. A range of aryliodosobistrifluoracetates was used, with the... 

The synthesis of ( )-oxomaritidine (192) and a formal synthesis of (+)-maritidine (178) were achieved by intramolecular oxidative coupling of phenol derivatives using a hypervalent iodine reagent as a key step 143). 2-[(4-Hydroxy)phenyl]-A/ -[(3,4-dimethoxy)phenyl]-A -trifluoroacetyl-ethylamine was treated with phenyliodonium bis(trifluoroacetate) in... 

There were hints in the literature that certain silylated phenols were more efficient substrates than free phenols in hypervalent iodine-mediated oxidative dearomatization reactions." The mechanistic underpinnings for this observation are still murky. Nevertheless, when phenol 40 was first converted into the corresponding trimethylsilyl ether and then treated with PhI(OAc)2 in acetonitrile-water, the desired quinol (42) was formed with improved yields (77-95%) and on larger scale (>1 g) (Scheme 16B). The conditions used to... 

Yakura et al. have shown that Oxone in combination with a catalytic quantity of 4-iodophenoxy acetic acid is an effective system for the hypervalent iodine oxidation of phenols and aryl ethers (eq 112). ... 

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],... 

The oxidative dearomatization of ort/io-substituted phenols 225 leads to 6,6-disubstituted cyclohexa-2,4-dienones 226 (Scheme 3.92), which can be conveniently utilized in situ as dienes in the Diels-Alder cycloaddition reaction. When the oxidation of phenols is performed in the absence of an external dienophile, a dimerization via [4-f2] cycloaddition often occurs spontaneously at ambient temperature to afford the corresponding dimers with an extraordinary level of regio-, site- and stereoselectivity [348-350]. A detailed experimental and theoretical investigation of such hypervalent iodine induced Diels-Alder cyclodimerizations... 

If the oxidation is performed in the presence of an external dienophile, the respective products of [4+2] cycloaddition are formed [351-356]. Typical examples are illustrated by a one-pot synthesis of several silyl bicyclic alkenes 283 by intermolecular Diels-Alder reactions of 4-trimethylsilyl substituted masked o-benzoquinones 282 generated by oxidation of the corresponding 2-methoxyphenols 281 [351] and by the hypervalent iodine-mediated oxidative dearomatization/Diels-Alder cascade reaction of phenols 284 with allyl alcohol affording polycyclic acetals 285 (Scheme 3.118) [352]. This hypervalent iodine-promoted tandem phenolic oxidation/Diels-Alder reaction has been utilized in the stereoselective synthesis of the bacchopetiolone carbocyclic core [353]. 

The oxidation of phenols or o- and p-hydroquinones with stoichiometric [bis(acyloxy)iodo]arenes to the corresponding benzoquinones is one of the most typical synthetic applications of hypervalent iodine reagents (Section 3.1.11). The catalytic version of this reaction was first reported by Yakuraand Konishi in 2007 [52], The reaction of p-alkoxyphenols 50 with a catalytic amount of 4-iodophenoxyacetic acid in the presence of Oxone as the terminal oxidant in aqueous acetonitrile at room temperature affords p-quinones 51 in high yields (Scheme 4.26) [52]. 4-Iodophenoxyacetic acid is a readily available and water-soluble aromatic iodide that has a particularly high catalytic activity in this reaction. 

Oxidative isomerization of vinylidenecyclopropanes gives dimethylenecyclopropane aldehydes using tetrapropylammonium perruthenate (TPAP)/4-methylmorpholine A-oxide (NMO) as a catalytic system. A Witkop-Winterfeldt oxidation with ozone has been reported to convert tetrahydropyridoindoles into pyrroloquinolones and cinnolines. Activation of phenol derivatives with a hypervalent iodine reagent has been reported to promote the formation of bicycUc and tricyclic products via a cationic cyclization process (Scheme 64). ... 

In the area of oxidation catalysis, several interesting reactions have been developed by Waser using a Koser-type hypervalent iodine 71 with an incorporated acetylene ligand (Scheme 16.17). Under catalysis with palladium hexafluoroacetylacetonate, nucleopalladation with both a phenol (e.g., 70) and an acid (e.g., 73) followed by oxidative C(sp )-C(sp) coupling led to new products 72 and 74. Initially, this reaction was developed for cyclization of alcohols or acids, respectively. Both five-and six-membered ring cyclization were successfully employed, and a total of 20 examples with 34-82% yield demonstrate the broad scope of this approach [58]. 

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