Hypervalent Iodine Mediated

Pioneering work by Kita demonstrated that SET from electron-rich aromatic rings to phenyUodine(III) bis(trifluoroacetate) generates a radical cation which can be attacked by nucleophilic species with concomitant transfer of a second electron to the iodine species. Rearomatization by deprotonation yields the aromatic substitution prodnct. While this particular methodology does not fit the model for this review since the bond-forming event is ionic in nature, extensions and modifications do proceed through a radical-mediated C—H activation reaction and will be discussed below. 

Zhu and coworkers developed the cyclization of Al-arylamidines 55 and 56 mediated by phenyliodine(III) diacetate. Ligand substitution of the amidine for the acetate on the iodine center generates an Af-iodoimido intermediate. Homolysis gives an IV-centered radical which can undergo HAS. Formation of the N—C bond provides a resonance-stabilized radical. The iodine species accepts a second electron to form a cationic intermediate similar to EAS. Final rearomatization by deprotonation provides the benzimidazoles 57 and 58. 

The Yokoyama group found that irradiating 3-phenyl-l-propanol and its derivatives 59 and 60 with phenyliodine(III) diacetate and I2 formed a hypoiodite. Homolytic O—I bond cleavage results in an oxygen-centered radical which can undergo HAS to synthesize a chromane. Once formed, however, the now-activated electron-rich aromatic ring is primed for a classical EAS under tlie reaction conditions. AcOI acts as the electrophile for this tandem reaction to place an iodine substituent para to the new oxygen substituent in products 61 and 62.  

Diaryl-A, -iodanes (often referred to as diaryliodonium salts) such as [PhjIJOTf or derivatives can couple the phenyl group with another aromatic ring to form a 

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A limited number of hypervalent iodine-mediated synthesis of thiophenes and benzothiophenes have been reported. An indirect approach for the synthesis of thiophenes involves formation of 1,4-butanediones [85JC-S(CC)420 87JCS(P1)559 88TL3703 89JOC2605], followed by treatment with phosphorus pentasulfide. This approach is especially useful for the synthesis of 3,2 5, 3"-terthiophene (134) starting from 1,4-diketone 65 (85SC789). 

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

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... 

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]. 

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],... 

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). 

The hypervalent-iodine-mediated tandem reaction process, reported for preparation of benzodiazepinones, when applied to 2-hydroxy-AT-arylben-zamides 92 afforded dibenzo[d,/][l,3]oxazepin-6(7fi)-ones 93 (14AGE6216). 

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... 

A hypervalent iodine-mediated 1,3-DC exploiting phenyliodine bis(trifluoroacetate) (PIFA) as catalyst allowed the copper-free synthesis of a novel kind of bisfiinctional nitrogen heterocycle 3 containing both 1,2,3-triazole and isoxazole rings and applied in peptidomimetic synthesis (130BC1040). 

Abstract Recent progress in the area of hypervalent iodine-mediated and catalyzed amination reaction of hydrocarbons is reviewed. These reactions comprise processes under both intra and intermolecular control and include the functionalization of aromatic C-H bonds as well as conversion of sp-, sp -, and sp -hybridized carbon atoms. These developments demonstrate that hypervalent iodine(III) methodology has reached a high level in amination chemistry. The individual reactions are discussed with a focus on mechanistic details and emphasis is made to the underlying hypervalent iodine reagents, for which structural information is available. 

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. 

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. 

Silva LF Jr. Hypervalent iodine-mediated ring contraction reactions. Molecules 2006 11 421-434. 

Pouysegu L, Deffieux D, Quideau S. Hypervalent iodine-mediated phenol dearomatization in natural product synthesis. Tetrahedron 2010 66 2235-2261. 

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