Iodonium phenolates

The zwitterionic iodonium phenolate 253 is photochemically reactive and a variety of products can be obtained depending upon the substrate in which the reactions are carried out. The mechanism of formation of these products could be an electrophilic reaction of the iodonium species or could involve fission of the I—C bond to yield the phenolate zwitterion 254, which itself could undergo electrophilic reactions. Regardless of the route, addition of 254 to alkenes yields 255, to aUtynes gives 256 and to arenes produces the arylated products 257. Pyridine, thiourea, phenyliminobenzoxathiole and phenyl isocyanate also act as addends. ... 

The preparation of iodonium phenolates 410 was first reported in 1977 via a reaction of phenols 409 with (diacetoxyiodo)benzene followed by treatment with pyridine (Scheme 2.119) [553]. The system of an iodonium phenolate is stabilized by the presence of at least one electron-withdrawing substituent on the aromatic ring. Monosubstituted iodonium phenolates 410 are relatively unstable and easily rearrange to iodo ethers 411 under heating. Such a 1,4 aryl migration is a very common phenomenon for iodonium ylides of types 405-408 according to mechanistic and computational studies it is an intramolecular rearrangement via a concerted mechanism [554,555]. 

Iodosobenzene diacetate is used as a reagent for the preparation of glycol diacetates from olefins,9 for the oxidation of aromatic amines to corresponding azo compounds,10 for the ring acetylation of N-arylacetamides,11 for oxidation of some phenols to phenyl ethers,12 and as a coupling agent in the preparation of iodonium salts.13 Its hydrolysis to iodosobenzene constitutes the best synthesis of that compound.14... 

Levothyroxine is used to treat hypothyroidism (an underactive thyroid gland). Thyroid hormone can be made from beef and pork thyroid, but this lacks standardization and it is difficult to control dosage. The synthetic drug is more desirable. Levothyroxine is one of two important thyroid hormones. It is converted into the second important hormone, liothyronine, in the body. The key step in the synthesis of structures such as levothyroxine is the substitution of an iodonium salt by an iodinated phenol. Siql-like reactions on an aromatic ring are not common, but an iodonium salt provides a good leaving group. 

A very simple synthesis of coumestrol (228) has been described by Kappe and coworkers (Scheme 46) (74ZN(B)292). It is based upon dehydrogenation of 4-hydroxy-3-phenyl-coumarins to coumestans (720PP233). A number of 2 -hydroxy 3-phenylcoumarins were oxidized with lead tetraacetate to the corresponding coumestans 3-(l-acetoxy-4-methoxy-2-oxo-3,5-cyclohexadienyl)coumarins were obtained as by-products (76BCJ1955). Coumes-tan itself (226) has been obtained by photolysis of the phenol ether (232), which is in turn available from 4-hydroxycoumarin (229) and (diacetoxyiodo)benzene (Scheme 47) (78CB3857) via an iodonium ylide (231). 

Silyl ethers of aliphatic alcohols are inert towards strong bases, oxidants (ozone [81], Dess-Martin periodinane [605], iodonium salts [610,611], sulfur trioxide-pyridine complex [398]), and weak acids (e.g., 1 mol/L HC02H in DCM [605]), but can be selectively cleaved by treatment with HF in pyridine or with TBAF (Table 3.32). Phenols can also be linked to insoluble supports as silyl ethers, but these are less stable than alkyl silyl ethers and can even be cleaved by treatment with acyl halides under basic reaction conditions [595], Silyl ether attachment has been successfully used for the solid-phase synthesis of oligosaccharides [600,601,612,613] and peptides [614]. 

Barluenga et al.565 have reported the selective monoiodination of arenes with bis (pyridine)iodonium(I) tetrafluoroborate [I(py2)BF4] in excess superacids (2 equiv.) [Eq. (5.210)]. Comparable results were found for activated compounds with both HBF4 and triflic acid, whereas triflic acid was more effective in the iodination of deactivated aromatics. For example, nitrobenzene and methyl benzoate are unreactive in HBF4 but give the corresponding iodo derivatives in triflic acid (83% and 84% yields, respectively, in 14 h). Iodination of phenol required low temperature (-60°C). 

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. 

To a solution of phenol (235 mg, 2.5 mmol) in dichloromethane (25 ml) at - 30°C, under nitrogen, was added with stirring butyl lithium (1 ml of 2.5 M solution in hexane). The mixture was cooled to - 78°C and the iodonium salt (730 mg, 1 mmol) was added after 15 min of stirring at - 78°C the reaction mixture was allowed to warm to room temperature. The dark solution was filtered through silica gel (5 g) and the solvent evaporated. Column chromatography (silica gel, hexane) gave diphenyloxyacetylene (120 mg, 57%) as a colourless oil. 

Dinitro-6-phenyliodonium phenolate (146) is a stable iodonium zwitterion484. It reacts under photolytic conditions with various alkenes, alkynes and aromatic compounds to afford 2,3-dihydrobenzo[ ]furans, benzo[6]furans and 6-aryl-2,4-dinitrophenols. The mechanism involves hypervalent iodine compounds (iodinanes, 147) and is illustrated for the reaction with an aromatic compound (equation 127). Compounds 148 are the major products when ArH = PhH, PhOCH3 or 1,4-dimethoxybenzene. With furan and thiophene, 149 is the principal product. The reaction does not proceed with chlorobenzene and nitrobenzene. 

Among the reactions of diaryliodonium salts with inorganic compounds, their hydrolysis has been studied in detail.40.41,43,51-53 jhe hydrolysis reaction proceeds quite slowly in boiling water. However, in the presence of aqueous alkali, the hydrolysis takes place in a few days for diphenyl-iodonium bromide to afford a mixture of iodobenzene, bromobenzene and phenol. With weakly nucleophilic anions, the reaction affords iodobenzene, phenol and a small amount of diphenylether. The reaction was considered to involve an unstable hydroxydiaryliodane, which is likely to be in equilibrium with diaryliodonium hydroxide. Decomposition of the hydroxyiodane leads to the... 

The reaction of phenols with diaryliodonium salts leads to the diaryl ethers in modest to good yields, depending on the substrate and the reaction conditions.31 0>5l-i03 number of studies have dealt with this reaction as it was involved in the synthetic sequence towards diaryl ethers of biological importance, such as bisbenzylisoquinoline alkaloidsl04 or thyronine and tyrosine derivatives.105 The reaction requires relatively harsh conditions, as it is performed under reflux of the solvent. In the case of unsymmetrical diaryliodonium salts, the less electron-rich aryl group of the iodonium salt is preferentially transferred. 

A method of limited scope but involving mild conditions, introduced by Doskotch [161] and used also by us successfully [161] is the reaction of a phenolate anion with a diaryl iodonium salt (Scheme 59). ... 

Iodonium ylides derived from cyclic 1,3-dicarbonyl compounds, phenols, coumarin derivatives and hydrox-yquinones represent a particularly stable and synthetically important class of zwitterionic iodonium compounds [539,552], Several examples of these compounds are shown in Figure 2.15 in the major resonance form as enolate or phenolate zwitterionic structures 405-408. 

The O-arylation of appropriate phenols using symmetrical iodonium salts has been employed in the synthesis of hydroxylated and methoxylated polybrominated diphenyl ethers, some of which are related to natural products [872,873]. For example, several polybrominated diphenyl ethers 680 have been prepared by the reaction of iodonium salt 678 with phenols 679 in iV,iV-dimethylacetamide (DMAC) solution in the presence of base (Scheme 3.272) [872]. 

Thienyl(phenyl)iodonium salts and other heteroaryl(phenyl)iodonium salts can be used as the selective heteroaryl transfer agents in reactions with phenol ethers. These heteroarylations occur at room temperature in the hexafluoroisopropanol solution in the presence of trimethylsilyl triflate via a SET mechanism [876]. 

Three reviews have detailed progress in the formation of biaryl systems using metal-catalysed substitutions of carbon—hydrogen bonds. The preferential arylation at the para-position of phenol and aniline derivatives with diaryl iodonium salts has been achieved using copper catalysis. Under similar reaction conditions, a-arylacetamides are selectively arylated at the meta-position. A mechanistic study, including DFT calculations, suggests that the meta-selectivity in the copper-catalysed arylation of anilides derives from a Heck-like four-membered transition state involving a Cu(III)-phenyl species (47). 

Calculations indicate that the position of oxidation of substituted phenols by PIDA and phenyliodonium bis(trifluoroacetate) is in accord with the intervention of phen-oxenium ions as intermediates. The lack of induction of chirality observed in the reaction, whether using a preformed chiral iodonium reagent or a homochiral alcohol as the medium, also supports this hypothesis. ... 

---