Phenylation, hypervalent iodine

Alkenyl(phenyl)iodonium salts have attracted a significant interest recently as stable and readily available powerful alkenylating reagents. Several convenient, general procedures for the stereoselective synthesis of alkenyliodonium salts from silylated or stannylated alkenes and the appropriate hypervalent iodine reagents are known [5]. The chemistry of alkenyliodonium salts has been extensively covered in several recent reviews [42 - 45]. 

AT-Substituted amidines 74 are transformed via the carbodiimide intermediate 75 into urea derivatives 76 as shown in Scheme 34 [141]. This reaction has been performed with a variety of aliphatic and aromatic substituents and in addition to (diacetoxyiodo)benzene 3 other hypervalent iodine compounds can also be used for this rearrangement. Phenyl substituted amidines 74 (R = Ph) can lead to cyclized products of type 77. 

Treatment of aryl-substituted alkenes with hypervalent iodine compounds can lead to the formation of phenyliodinated intermediates, which can be stabilized by the aryl substituent via the formation of phenonium ions. Subsequent nucleophilic attack might then lead to rearranged products. This behavior can be nicely seen by comparing the unsaturated carboxylic acids 78 in their reaction with (diacetoxyiodo)benzene 3. The substrate 78a without the phenyl substituent is cyclized to the phenyliodinated intermediate 79, which is then attacked by the acetate under the formation of lactone 81 [142]. Substrate 78b is, however, then stabilized by the formation of an intermediate phenonium ion 80 and attack by the acetate is accompanied by a 1,2-phenyl migration and 82 is generated, Scheme 35 [143]. 

A microwave-assisted one-pot approach towards 2,4,5-trisubstituted oxazoles employed a hypervalent iodine (III) catalyst to bring about the reaction of ketones, 1,3-diketones and /3-keto-carboxylic acid derivatives with amides [75]. Microwave dielectric heating was also successfully utilized in a solid-supported, solvent-free synthesis of 2-phenyl-oxazol-5-ones (azlac-tones) [76] as well as in a solution phase synthesis of isomeric 2-phenyl-oxazol-4-ones (oxalactims) [77]. 

Most known iodonium salts of this category have one phenyl and one aryl group. Various hypervalent iodine precursors can be used as effective electrophiles, notably the combination of (diacetoxyiodo)benzene with triflic acid. The reagent is formed in situ and is suitable for a range of activated to weakly deactivated arenes. The reactions proceed at room temperature and in some cases, e.g. with anisole, only the p-isomer was produced. Strongly deactivated arenes such as nitrobenzene did not react. 

Alkynyliodonium ions, 1 and 2, are hypervalent iodine species in which one or two alkynyl ligands are bound to a positively charged iodine(III) atom. They are sensitive to nucleophiles, especially at the /1-carbon atom(s) of the alkynyl ligand(s), and for that reason, the isolation of stable alkynyliodonium salts generally requires the incorporation of nucleofugic anions. A list of known alkynyliodonium compounds (i.e. as of 4/1/94), containing 134 iodonium salts derived from 103 iodonium ions, and references (5-45) to their preparation and characterization are presented in Table 1. Among these compounds, alkynyl(phenyl)iodonium sulfonates and tetrafluoroborates are the most common, while alkynyl(alkyl)iodonium salts of any kind are unknown. 

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

Selenazoles have been prepared by reactions using hypervalent iodine reagents. Condensation of a-tosyloxy-ketones with primary selenoamides affords 1,3-selenazoles in a one-pot process (Equation 7) <200081219, 2004CJI63>. Reactions of alkynyl(phenyl)iodonium salts with primary selenoamides give 1,3-selenazoles (Equation 8) <2001JHC503>. 

Benzyne is one of a group of reactive intermediates widely applicable to organic synthesis.2"5 The title hypervalent iodine-benzyne precursor, (phenyl)[2-(trimethylsilyl)phenyl]iodonium triflate 2,6 is prepared by only two steps from commercially available reagents. Products 1 and 2 are stable and easily purified. The hypervalent iodine-benzyne precursor 2 is obtained as a stable solid and handled without any precautions. More importantly, benzyne is generated by using... 

The synthesis of ( )-oxomaritidine (192) and a formal synthesis of (+)-maritidine (178) were achieved by intramolecular oxidative coupling of phenol derivatives using a hypervalent iodine reagent as a key step 143). 2-[(4-Hydroxy)phenyl]-A/ -[(3,4-dimethoxy)phenyl]-A -trifluoroacetyl-ethylamine was treated with phenyliodonium bis(trifluoroacetate) in... 

Recently, it has been found that hypervalent iodine reagents promote the conversion of ketones to a, (3-unsaturated ketones. For example, treatment of octyl phenyl... 

Hypervalent Iodine Chemistry. The formation of hyperva-lent iodine complexes is often promoted by TMSOTf. Thus, TMS-alkynes can be transformed with iodosobenzene and TMSOTf into phenyl iodonium triflates in moderate to good yields, which may be subsequently converted into alkyneamides (eq 102). ... 

A combination of a hypervalent iodine(III) reagent [phenyl-iodine(in) bis(trifluoroacetate)] and TMSOTf has shown great efficiency for the synthesis of pyrroloiminoquinones from 3-(azidoethyl)indole derivatives (eq 107). ... 

Processes involving a single-electron transfer (SET) step and cation-radical intermediates can occur in the reactions of X - or X -iodanes with electron-rich organic substrates in polar, non-nucleophilic solvents. Kita and coworkers first found that the reactions of p-substituted phenol ethers 29 with [bis(trifluoroacetoxy)iodo]benzene in the presence of some nucleophiles in fluoroalcohol solvents afford products of nucleophilic aromatic substitution 31 via a SET mechanism (Scheme 1.5) [212,213]. On the basis of detailed UV and ESR spectroscopic measurements, it was confirmed that this process involves the generation of cation-radicals 30 produced by SET oxidation through the charge-transfer complex of phenyl ethers with the hypervalent iodine reagent [213,214],... 

A very mild procedure for the Hofmann rearrangement of aromatic and aliphatic carboxamides 409 is based on the use of (tosylimino)phenyl-X. -iodane, PhINTs, as the oxidant (Scheme 3.165) [506]. Owing to the mild reaction conditions, this method is particularly useful for the Hofmann rearrangement of substituted benzamides 409 (R = aryl), which usually afford complex reaction mixtures with other hypervalent iodine oxidants. The mild reaction conditions and high selectivity in the reaction of carboxamides with PhINTs allow the isolation of the initially formed labile isocyanates 410, or their subsequent conversion into stable carbamates 411 by treatment with alcohols. Based on the previously reported mechanistic studies of the Hofmann rearrangement using other hypervalent iodine reagents [489,490,496], it is assumed that the reaction... 

Several mechanistic studies on the reactions of diaryliodonium salts with nucleophiles have been published. Ochiai and coworkers performed a mechanistic study on the phenylation of 3-keto ester enolates with diaryliodonium salts. An aryl radical trap was added to the reaction without affecting the outcome, which indicates that radical pathways are unlikely and the reaction occurs by direct coupling of the ligands on the hypervalent iodine center [889]. 

Kitamura et al. have developed (phenyl)[2-(trimethylsilyl)phenyl]iodomiim triflate (7) as an excellent benzyne precursor [13], possessing the hypervalent iodine group with a salient leaving ability ( 10 times greater than that of the OTf group). Treatment of 7, which is prepared in two steps from 1,2-dichlorobenzene, with TBAF efficiently generates benzyne (1) (Scheme 12.7). 

Similar direct arylations have been accomplished using hypervalent iodine reagents and the Herrmann-Beller catalyst 4 (Scheme 24.11) [ 15]. This method is applicable toward the phenylation of electron-neutral and electron-rich arene substrates and provides the products in modest to good yields. Increasing steric hindrance on the arene moiety leads to decreased product yields. An isomeric mixture of products is obtained, and the selectivity for phenylation of xylenes is similar to the transformations in Scheme 24.9. 

Stereoselective carbon-carbon bond formations with hypervalent iodine reagents are also prominently described in the literature. Direct asynunetric a-arylation reactions are not easy to perform. Ochiai et al. synthesized chiral diaryliodonium salts such as [l,l -binaphthalen]-2-yl(phenyl)iodonium tetrafluoroborate derivatives 21 via a BFs-catalyzed tin-X -iodane exchange reaction and developed the direct asymmetric a-phenylation of enolate anions derived from cyclic p-ketoesters (Scheme 7) [37]. A beautiful example of direct asymmetric a-arylation of cyclohexanones in the course of a natural product synthesis was presented through the desymmetrization of 4-substituted cyclohexanones using Simpkin s base, followed by coupling with diaryliodonium salts [38]. Other binaphthyl iodonium salts related to 21 have also been reported [39]. 

Also obtained by hypervalent iodine oxidation of l-(trimethylsilyloxy)-l-[2-(trimethylsilyloxy)-phenyl]ethene with iodosobenzene, boron trifluoride ether-ate and water. The mixture was stirred at -40 for 1 h, then the temperature was slowly (1 h) raised to r.t. and stirring was continued for 30 min (25%) [5058],... 

Papoutsis et al. and Malamidoli-Xenikaki and Spyroudis developed a method to transform 2-hydroxy-1,4-benzo-quinones, such as 132, into 2-cyclopentene-l,4-diones, like 124 112,113 rpjjg pjojocol is based on the thermolysis of a phenyl iodonium, such as 133, ° " which can be prepared treating a hydroxy quinine 132 with the commercially available hypervalent iodine reagent diacetoxy iodobenzene (PhI(OAc)2) (Scheme 18.29). 

A boron-iodine exchange between vinyl- and arylboronic acids or esters and hypervalent phenyliodanes gave vinyl-aquation (117)) and aryl(phenyl)iodonium salts (Equation (118)) with complete retention of configuration.556,557... 

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