Hypervalent iodine-mediated oxidation

Scheme 38. Polymer-supported hypervalent iodine-mediated oxidative cyclization of a maritidine precursor.

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... 

This is a synthetically valuable process, as illustrated by the hypervalent iodine-mediated oxidative nucleophilic substitution of 269 with the silyl enol ether 271, leading to the highly functionalized naphthoid cyclohexa-2,4-dienone 272 (Scheme 3.113), which is an important intermediate product in the synthesis of aquayamycin-type angucyclinones [343,344],... 

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]. 

Additional examples of synthetic applications of hypervalent iodine-induced heterocyclizations include the following the metal-free one-pot synthesis of 2-acylbenzothiazoles by oxidative cyclization of multiform substrates [434], iodine(III)-mediated tandem oxidative cyclization for construction of 2-nitrobenzo[ ]furans [435], hypervalent iodine mediated oxidative cyclization of o-hydroxystilbenes into benzo- and naphthofu-rans [436], PhI(OCOCF3)2-mediated synthesis of 3-hydroxy-2-oxindoles and spirooxindoles from anilides [437], synthesis of isoxazoles by hypervalent iodine-induced cycloaddition of nitrile oxides to alkynes [438],... 

Oxycarboxylation of alkenes, unlike carbocarboxylation, yields two new C—O bonds in a single step. The Dong group also reported the first example of alkene dioxygenation as a route to lactone synthesis via Pd catalysis (Scheme 2.37). The proposed mechanism for this transformation involves a novel Pd(II)/Pd(IV) pathway made possible by the hypervalent iodine-mediated oxidation that occurs... 

F.V. Singh, T. Wirth, Hypervalent iodine mediated oxidative cyclization of o-hydroxystilbenes into benzo- and naphthofurans. Synthesis 44 (2012) 1171-1177. 

Ishihaia K. Hypervalent iodine-mediated oxidation of alcohok. Chem Commun. 2009 2086—2099. (d) Zhdankin W. Org3noiodine(V) reagents in organic synthesis. J Org Chem. 2011 76 1185-1197. 

Hypervalent iodine-mediated oxidation of the phenol component of 141, and the following sequential implementations of oxidation of the benzylic alcohol functionality and reduction of the quinone moiety in the same pot, gave palmarumycin C3 142. Methoxyacetylation of hydroxy groups of the hydroquinone was carried out, and subsequent acetoxylation using lead tetraacetate afforded 143 as an equimolar mixture of diastereomers. Further two-step operations including the oxidative cyclization completed the synthesis of 137. 

Scheme 8. Hypervalent iodine-mediated phenyl methyl ether oxidative coupling.

Quideau and coworkers have developed a hypervalent iodine-mediated regioselective protocol for the oxidative dearomatization of 2-alkoxyarenols in the presence of external carbon-based nucleophiles, such as allylsilanes or silyl enol ethers [342-345]. For example, the oxidation of 2-alkoxynaphthol 269 with [bis(trifluoroacetoxy)iodo]benzene in the presence of allylsilane affords 2,4-cyclohexadienone derivative 270 (Scheme 3.112) [342]. 

A significant improvement in the yield was also achieved in Takayama s concise synthesis of we.so-chimonanthine 121), via hypervalent iodine-mediated dimerization of a tryptamine precursor, giving we.so-chimonanthine in 30% yield over three steps (Scheme 12). This approach has also been applied by Takayama to the synthesis of chimonanthidine 108). A similar three-step procedure to we.so-chimonan-thine, albeit in lower overall yield, involving thallium trifluoroacetate-mediated oxidative coupling of the same tryptamine precursor has also been reported 122). 

Aziridines are key structural motifs present in natural products such as mitomycins and azinomycins and versatile building blocks which can undergo various useful transformations. Hypervalent iodine-mediated intramolecular aziridinations of allylic carbamates and reaction of A-tosyliminophenyliodinane (Phi = NTs) with double bonds have been reported to be efficient and practical routes to access these three-membered rings. Allylic carbamates 71 undergo enantioselective aziridine formation on oxidation with chiral binaphthyl hypervalent iodine compound 72 (Scheme 28) [86]. 

W. Liu, P. Zhou, C. Chen, Q. Zhang, Z. Zhu, Direct construction of 5-methyl-2-phenylisoxazol-3(2H)-ones via hypervalent iodine mediated sequential tandem oxidative cyclization of 3-oxo-N-phenylbutanamides catalyzed by zinc oxide, Org. Biomol. Chem. 11 (2013) 542-544. 

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]. 

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 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. 

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>... 

The L -iodane PhI(OAc)2 has been used extensively, most notably by Sanford, to oxygenate the C-H bonds of arenes and even alkanes in the presence of palladium catalysts." Interestingly, this reaction was likely mediated by a binuclear complex featuring two Pd(III) atoms joined by a palladium-palladium (Pd-Pd) bond however, this complex can disproportionate into a Pd(IV)-Pd(II) complex without a formal Pd-Pd bond, and this intricate interplay is often controlled by the presence and nature of hypervalent iodine oxidants." We discovered that this reaction manifold could be extended to include the amination of arene substrates heating 2-phenylindole 51 in the presence of the -iodane 49 and palladium acetate provided the ortho-aminated product 52 in a 19% yield however, switching the metal from palladium acetate... 

Canesi and coworkers have developed several synthetically useful tandem rearrangements on the basis of hypervalent iodine-promoted phenolic oxidation [328-331]. An oxidative Prins-pinacol tandem process mediated by a hypervalent iodine reagent allows the stereoselective tfansformation of simple phenols 261 into highly elaborate spirocyclic dienone cores 262 containing several quaternary carbon centers (Scheme 3.108). 

An oxidative /pio-rearrangement mediated by a hypervalent iodine reagent that enables rapid generation of a functionalized dienone system 266 containing a quaternary carbon center has been developed (Scheme 3.110) [330]. The process occurs through transfer of an aryl group from a silyl segment present on the lateral chain of the phenol derivative 265. This transformation has been utilized in a total synthesis of an alkaloid sceletenone [330],... 

Oxidative 1,2- and 1,3-alkyl shifts mediated by a hypervalent iodine reagent using simple and inexpensive phenol derivatives 267 enable rapid construction of highly functionalized scaffolds containing a prochiral... 

Hypervalent iodine species were demonstrated to have a pronounced catalytic effect on the metalloporphyrin-mediated oxygenations of aromatic hydrocarbons [93]. In particular, the oxidation of anthracene (114) to anthraquinone (115) with Oxone readily occurs at room temperature in aqueous acetonitrile in the presence of 5-20 mol% of iodobenzene and 5 mol% of a water-soluble iron(llI)-porphyrin complex (116) (Scheme 4.57) [93]. 2-ferf-Butylanthracene and phenanthrene also can be oxygenated under similar conditions in the presence of 50 mol% of iodobenzene. The oxidation of styrene in the presence of 20 mol% of iodobenzene leads to a mixture of products of epoxidation and cleavage of the double bond. Partially hydrogenated aromatic hydrocarbons (e.g., 9,10-dihydroanthracene, 1,2,3,4-tetrahydronaphthalene... 

De Mico A, Margarita R, Parlanti L, Vescovi A, Piancatelli G (1997) A versatile and highly selective hypervalent iodine (ni), 2,6,6-tetramethyl-l-piperidinyloxyl-mediated oxidation of alcohols to carbonyl compounds. J Org Chem 62 6974—6977... 

An oxidative Prins-pinacol tandem process mediated by hypervalent iodine reagent was recently established by the Canesi group [93] and it was used for the formal synthesis of (-)-platensimycin (Scheme 14) [94]. The strategy allowed rapid access to the highly functionahzed spirocyclic core present in the target natural product. 

This review is devoted to an overview of phenol dearomatization and its application in natural product synthesis through the use of a special class of phenolophile reagents that has attracted much attention in recent years, the hypervalent iodine reagents. These polyvalent iodine compounds, also called iodanes, are oxidizing electrophiles that can mediate a wide number of diverse chemical transformations not only of (hetero)aromatic compounds, but also of inter alia alkenes, alkynes, alcohols, sulfides, amines and amides, (enolizable) carbonyl... 

Hypervalent iodine(III) mediated/catalyzed intramolecular oxidative C-H bond functionalization of (hetero)arenes and alkenes has been widely applied in the synthesis of several biologically active heterocyclic scaffolds. This intramolecular oxidative C-H bond functionalization reaction leads to the formation of carbon-carbon and carbon-heteroatom bonds in an efficient manner. Of all bond formation reactions, C-N bond annulations have been exploited most and are of immense... 

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