Oxidative functionalization, hypervalent

The first hypervalent iodine compound, (dichloroiodo)benzene 1, was prepared in 1886 by Willgerodt [9]. Since that time, several new reagents of iodine (III) and iodine (v) have been developed and are now frequently used in oxidative functionalizations. Scheme 1 shows a selection of the most frequently used... 

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]. 

Hypervalent iodine reagents have successfully been employed in the oxidative functionalization of enolizable carbonyl compounds over the years [6]. This methodology has allowed the construction of diverse C-C bonds in the context of heterocychc synthesis and has enriched the otherwise rare repertoire of such chemistry. Zhao, Du, and coworkers [37] have recendy realized a metal-free PIFA-mediated synthesis of 3-hydroxy-2-oxindoles 34 and spirooxindoles 35 starting from anilide derivatives 33 (Scheme 8 (1)). These processes showcase an oxidative cross coupling between an aromatic carbon and a pendant aliphatic carbon, followed by further oxidative hydroxylation or spirocycUzation. Later, the authors extended the same concept to achieve C(sp )-C(sp ) bond formation, where anilide derivatives possessing terminal enol functionality underwent PIDA-... 

Carbonyl oxidation with hypervalent iodine reagents involves the functionalization of the a-position of carbonyl compounds through the intermediacy of a hypervalent iodine enolate species. This electrophilic intermediate may be attacked by a variety of nucleophiles or undergo rearrangement or elimination [13]. Enantiomerically pure, a-substituted carbonyl compounds represent a family of derivatives important in nearly all fields of organic chemistry [14],... 

Singh FV, Wirth T. Hypervalent iodine-catalyzed oxidative functionalizations including stereoselective reactions. Chem Asian J. 2014 9 950-971. 

Following a similar strategy, an ingenious mixed resin bed quench and purification strategy was devised for the Dess-Martin periodinane mediated conversion of alcohols to carbonyls. This hypervalent iodine oxidant was viewed as containing an inherent masked carboxylic acid functionality that was revealed at the end of the reaction (Species (11) Scheme 2.30). Therefore purification was easily achieved by treatment of the reaction mixture with a mixed-resin bed containing both a thiosulfate resin and a polymeric base. The thiosulfate polymer was used to reduce excess hypervalent iodine lodine(V) and (III) oxidation states species to 2-iodoben-zoic acid (11), which was in turn scavenged by the polymeric base [51]. 

The oxidation of carbonyl compounds can be achieved with hypervalent iodine reagents quite easily. A general feature of these reactions is the electrophilic attack of the hypervalent iodine reagent at the a-carbon atom of a carbonyl group and a review on this chemistry has been published recently [6]. This leads to hypervalent iodine intermediates of type 55. These phenyliodinated intermediates are quite unstable and a variety of subsequent reactions are possible. Intermediates 55, Scheme 24, can be considered as umpoled substrates regarding the reactivity of the a-position of the initial carbonyl compounds. Major processes are the substitution by a nucleophile (see Sect. 3.5.1 Functionalization in the a-Position) or the introduction of a carbon-carbon double bond (see Sect. 3.5.2 Introduction of an a,/ -Unsaturation). 

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]. 

Generally, hypervalent iodine reagents are often better than traditional reagents of similar reactivity, with respect to efficiency and chemoselectivity - sometimes even stereoselectivity. Unusual reactivity is another interesting feature which has often resulted in unexpected transformation. Examples of such reactions may be found in the oxidation of nitrogen-containing compounds, the Hofmann rearrangement in acidic conditions, the acetalization of carbonyl compounds in alkali, the remote functionalization of steroids, etc. Some unique transformations were effected in the... 

As already mentioned, hypervalent iodine reagents are useful for the oxidatively assisted nucleophilic substitution of iodine in iodoalkanes (Section 5.4.2). In this way HTI was used for the preparation of some tosylates. A rearrangement occurred with neopentyl iodide, Me3CCH2I, which was converted into the ester Me2C(OTs)CH2Me (85%) [53]. The most successful application of such reactions for preparative purposes was the functionalization of some iodocubanes and iodohomocubanes, and especially the preparation of their triflates and mesylates from iodosylbenzene-trimethylsilyl triflate and [hydroxy(mesyloxy)iodo]benzene, respectively [54,55]. 

Aldehyde and ketone functions, and thione and thials, if suitably placed, can strongly interact with the ring sulfur by hypervalent or possibly polar effects <94SR3i7>. The exocyclic thione function is readily oxidized by, for example, peracetic acid. Thione-S -oxides (110) have been isolated. The reaction with more oxidizing agent under acidic conditions is a valuable synthesis of... 

The oxidation of alcohols is not limited to chromium derivatives, DMSO derivatives, or hypervalent iodine compounds. There are several metal-based reagents that can be very effective, particularly with sensitive functionality. This section will examine several of the more important regents. 

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