Hypervalent iodine oxidant

Hypervalent aryl iodine reagents have also been used as the electrophile in direct ary-lation reactions. In these examples, the strongly oxidizing hypervalent iodine reagents are proposed to react with the intermediate Pd(II) species to generate a Pd(IV) intermediate. Subsequent reductive elimination of biaryl from this Pd(IV) intermediate is then believed to regenerate the active Pd(II) species (Equation 19.141). ... 

The Dess-Martin reagent can be shock sensitive under some conditions and explode > 200°C. Other hypervalent iodine oxidizing reagents are known, including PhI(OAc)2/TEMPO and PhI(OAc)2 supported on alumina with microwave irradiation. 

The hypervalent iodine oxidation of (pyridylalkyl)trimethylsilanes to the corresponding alcohols and esters has been reported <96H(43)1151>. Oxidation of 2-(phenylethynyl)p5nidine with HjOj/AcOH followed by ROH/NajCOj provides 6-alkoxy-2-phenacylpyridines 42 via an intermediate iV-oxide <96H(43)1179>. 

Finally, phthalocyanine iron catalysts were also used for the oxidation of alcohols to yield corresponding carbonyl compounds with nonbenign hypervalent iodine oxidants [147]. 

Oxidation by the Dess-Martin Reagent. Another reagent that has become important for laboratory synthesis is known as the Dess-Martin reagent,28 which is a hypervalent iodine(V) compound.29 The reagent is used in inert solvents such as chloroform or acetonitrile and gives rapid oxidation of primary and secondary alcohols. The by-product, o-iodosobenzoic acid, can be extracted with base and recycled. 

Scott was able to leverage the same type of methodology in an impressive display in which /V-methyltryptamine was dimerized directly to afford chimonanthine (7) (Scheme 9.2b) [9c]. Deprotonation of the indole 1H proton with methyl Grignard followed by treatment with FeCl3 accomplished the singleelectron oxidation and dimerization of the indole moiety. The racemic and meso stereoisomeric products were obtained as a mixture in 19 % and 7 % yields, respectively. Takayama later found hypervalent iodine to be a superior oxidant, affording yields of 17 % and 30 %, respectively [9j]. In both cases, however, as in the case of Hendrickson s example, stereocontrol could not be achieved. 

A Sml2-induced reductive cyclization of (V-(alkylketo)pyrroles provided an entry into medium ring 1,2-annelated pyrroles <06EJO4989>. An oxidative radical alkylation of pyrroles with xanthates promoted by triethylborane provided access to a-(pyrrol-2-yl)carboxylic acid derivatives <06TL2517>. An oxidative coupling of pyrroles promoted by a hypervalent iodine(III) reagent provided bipyrroles directly <060L2007>. 

Varma and coworkers have explored the use of hypervalent iodine compounds on solid support for the first time and developed a facile oxidative procedure that rapidly converts alcohols to the corresponding carbonyl compounds using alumina-sup-ported IBD under solvent-free conditions and MW irradiation in almost quantitative yields [108]. The use of alumina as a support improved the yields markedly as compared to neat IBD (Scheme 6.33). 1,2-Benzenedimethanol, under these conditions, undergoes cyclization to afford l(3H)-isobenzofuranone. 

Diimide from hydrazine hydrate Diimide can be generated from hydrazine hydrate by oxidation with this hypervalent iodine compound in CH2C12. 

Scheme 2.4 Polymer-supported oxidations using a hypervalent iodine reagent. 

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 oxidative method using C6H5l(OAc)2 3uelded the desired quadricyclyl azide and the process is being scaled up. In another approach (Fig. 2.17), the hypervalent iodine Hoffmann rearrangement was carried out on quadricyclyl carboxamides. 

Thieno benzazepine 109 was synthesized in moderate yield by oxidative biaryl-coupling using the hypervalent iodine reagent phenyliodine(lll)bis (trifluoroacetate) (FIFA) and BF3 OEt2 as the activating agent in methylene chloride (Equation (16) (2002X8581)). 

While the silver and zinc salts were effective Lewis acids for these cyclizations, Kikugawa and coworkers reported that the alkoxynitrenium ions could be generated directly from hydroxamic esters (4) using hypervalent iodine oxidants such as hydroxy(tosyloxy) iodobenzene (HUB) and phenyliodine(lll)bis(trifluoroacetate) (PIFA) . Presumably, with such reagents the reactions proceed through A-(oxoiodobenzene) intermediates (54), which can themselves be regarded as anomeric hydroxamic esters and sources of alkoxynitrenium ions (55) (Scheme 11). 

Common alcohol oxidation methods employ stoichiometric amounts of toxic and reactive oxidants like Cr03, hypervalent iodine reagents (Dess-Martin) and peracids that pose severe safety and environmental hazards in large-scale industrial reactions. Therefore, a variety of catalytic methods for the oxidation of alcohols to aldehydes, ketones or carboxylic acids have been developed employing hydrogen peroxide or alkyl hydroperoxides as stoichiometric oxygen sources in the presence of catalytic amounts of a metal catalyst. The commonly used catalysts for alcohol oxidation are different MoAV(VI), Mn(II), Cr(VI), Re(Vn), Fe(II) and Ru complexes . A selection of published known alcohol oxidations with different catalysts will be presented here. 

Oxidative C-H amination has been an area of intensive research since the publication of CHEC-II(1996). This methodology has been applied to the synthesis of a variety of 1,2-thiazine 1,1-dioxides. In the simple cases, substrates containing an aromatic C-H can be cyclized in the presence of hypervalent iodine. For instance, the reaction of A-methoxy(2-arylethane)sulfonamide 202 with [hydroxyl(tosyloxy)iodo]benzene rapidly affords benzenesulfon-amide 203 in excellent yield (Equation 30) <20030BC1342> see also <2000JOC926> and <2000JOC8391>. 

Collections of fundamental and thermodynamic data can be found in an earlier review [158] and in standard resources [13, 14]. However, due to the reactivity of iodine there are many less common or more reactive forms of iodine that have been less well characterized. For example, a blue 12 cation, a brown I3+, or a green I5+ cation are formed in concentrated sulfuric acid and 1+ is stabilized in donor environments such as pyridine [159]. So-called hypervalent iodine reagents have been developed as a versatile oxidation tool in organic synthesis and often iodine derivatives are employed as electron transfer catalysts. Some fundamental thermodynamic data and typical applications of iodine are summarized in Scheme 5. 

Oxathiane 2-oxides aie fonned by the oxidative ring expansion of 2-alkylthio-2-benzylthiolane 1-oxides brought about by [bis(trifluoroacetoxy)iodo]benzene. That the reaction is only successful with the (lR )-diastereoisomeis is attributed to chelation between the nucleophilic S and O atoms and the hypervalent iodine <99EJ0943>. A diazo-mediated thiolane ring expansion is the key step in a synthesis of the acenaphtho-[U-b][l,4]oxathiine system <99JCS(P2)755>. 

The above examples report perhaps the most well used routes to imidazo[4,5-3]pyridines however, there are many other less well known methods. For example, treatment of 2,3-diaminopyridines with aryl aldehydes and subsequent oxidation with sulfur affords the corresponding imidazo[4,5-/ ]pyridines in good yield <1996CHEC-II(7)283>. A catalytic Fe(iii)/Fe(ll) redox cycle approach to imidazopyridines has been reported (Equation 33) <2000S1380>. A hypervalent iodine oxidative rearangement of 2-aminopyridinecarboxamides has also been reported <2001S541>. Treatment of 2-amino-4,6-diphenyl-3-pyridinecarboxamide 123 with iodobenzene diacetate (IBD) in KOH/MeOH afforded the pyridin-2-one 124 (Equation 34). 

Note-. IBX, Uke other hypervalent iodine oxidants, can explode upon impact or heating. Plum, J. B. and Harper, D. J. Chem. Eng. News 1990, 68, 3. 

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... 

Other Hypervalent Iodine Compounds Used for Oxidation... 

The fluorine-containing hypervalent iodine compound 47, first described by Dess and Martin,5 finds occasional use in the oxidation of alcohols and is described in some substrates as superior than Dess-Martin periodinane.111... 

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