Hypervalent iodine reactivity

General Considerations Introduction. A Note on Classes and Nomenclature. Bonding and Structure in Hypervalent Iodine. Reactivity Patterns. Practical Aspects. General References. 

Haloalkynes (R—C=C—X) react with ArSnBu3 and Cul to give R—C= C—Ar. Acetylene reacts with two equivalents of iodobenzene, in the presence of a palladium catalyst and Cul, to give 1,2-diphenylethyne. 1-Trialkylsilyl alkynes react with 1-haloalkynes, in the presence of a CuCl catalyst, to give diynes and with aryl triflates to give 1-aryl alkynes. Alkynes couple with alkyl halides in the presence of Sml2/Sm. Alkynes react with hypervalent iodine compounds " and with reactive alkanes such as adamantane in the presence of AIBN. ... 

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. 

In the search for less expensive and more easily accessible reagents, a new hypervalent iodine(III)-CF3 reagent has shown a promising reactivity in the mild and selective electrophilic trifluoromethylation of active methylene compounds and free thiols (Figure 2.38). Synthesis of this reagent is easy and scalable. ... 

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. 

The oxidation of phenols with hypervalent iodine compounds has been used frequently and nucleophilic additions can be performed as well as cyclization reactions using this technique. The resulting quinone derivatives show high reactivity and they have been used in a various subsequent reactions. Substituted phenols like 32 [78] or 34 [79] have been oxidized by hypervalent iodine reagents and, depending on the substitution pattern, cyclizations have taken place as shown in Scheme 16. Product 33 is unstable and undergoes subsequent... 

The oxidation of carbonyl compounds can be achieved with hypervalent iodine reagents quite easily. A general feature of these reactions is the electrophilic attack of the hypervalent iodine reagent at the a-carbon atom of a carbonyl group and a review on this chemistry has been published recently [6]. This leads to hypervalent iodine intermediates of type 55. These phenyliodinated intermediates are quite unstable and a variety of subsequent reactions are possible. Intermediates 55, Scheme 24, can be considered as umpoled substrates regarding the reactivity of the a-position of the initial carbonyl compounds. Major processes are the substitution by a nucleophile (see Sect. 3.5.1 Functionalization in the a-Position) or the introduction of a carbon-carbon double bond (see Sect. 3.5.2 Introduction of an a,/ -Unsaturation). 

Generally, hypervalent iodine reagents are often better than traditional reagents of similar reactivity, with respect to efficiency and chemoselectivity - sometimes even stereoselectivity. Unusual reactivity is another interesting feature which has often resulted in unexpected transformation. Examples of such reactions may be found in the oxidation of nitrogen-containing compounds, the Hofmann rearrangement in acidic conditions, the acetalization of carbonyl compounds in alkali, the remote functionalization of steroids, etc. Some unique transformations were effected in the... 

Using tetrafluoroboric acid, several unsaturated acids and nitriles were thus made reactive and were converted into acetoxy lactones [3]. Tosyloxy-, phosphoryloxy-and iodomethyl lactones as well as cyclic ethers resulting from analogous neighbouring group participation will be discussed in connection with other hypervalent iodine reagents. 

Such additions of nucleophiles to non-activated double bonds mediated by hypervalent iodine compounds are also possible in other cases (Section 3.5). This umpolung of reactivity is due to the formation of an adduct with hypervalent iodine which renders this intermediate highly electrophilic. In this way 6-propionylflavo-nols gave 1,2-dimethoxy-adducts in methanol-perchloric acid [10] ... 

As already discussed (Section 5.2.3), a-metallated ketones were converted by IOB into a-methoxyketones, in presence of methanol. Generally, various organometallic compounds react readily with hypervalent iodine reagents undergoing an umpolung of reactivity the intermediates formed need not be isolated, since they may react in situ with a variety of nucleophiles. A simple example illustrating the point is the... 

Diaryliodonium salts, with few exceptions, are stable compounds towards heat, oxygen and humidity they are mildly light-sensitive and should be stored in the dark, without refrigeration. Generally, their reactivity is less pronounced than that of other hypervalent iodine compounds. Indeed, in several of their reactions relatively drastic conditions may be necessary, especially for the least reactive heterocyclic iodonium salts. The search for optimum conditions is often desirable even for well-established reactions, by applying new findings concerning the use of specific... 

Vinyliodonium ions, 35 and 36, are hypervalent iodine species in which one or two alkenyl ligands are bound to a positively charged iodine(III) atom. Although they are reactive with nucleophilic reagents, they are less labile than alkynyliodonium ions, and stable halide salts of vinyliodonium ions can be prepared. The first vinyliodonium compounds [i.e. (a, / -dichlorovinyl)iodonium salts] were synthesized by the treatment of silver acetylide-silver chloride complexes with (dichloroiodo)arenes or l-(dichloroiodo)-2-chloroethene in the presence of water (equation 152). The early work was summarized by Willgerodt in 1914115. This is, of course, a limited and rather impractical synthetic method, and some time elapsed before the chemistry of vinyliodonium salts was developed. Contemporary synthetic approaches to vinyliodonium compounds include the treatment of (1) vinylsilanes and vinylstannanes with 23-iodanes, (2) terminal alkynes with x3-iodanes, (3) alkynyliodonium salts with nucleophilic reagents and (4) alkynyliodonium salts with dienes. 

The question as to whether the reactive intermediate is the phenol-metal/leaving group complex 21/22 or the free phenoxonium ion 17 has been studied in the particular case of hypervalent iodine. Pelter and co-workers presented permissive evidence in support of a mechanism involving the free oxonium species 17 (Scheme 7) Phl(OAc) is an extremely good nucleofuge, no transfer of chirality is observed when homochiral hypervalent iodine compounds are used, and calculations made on the cation species correctly predict the re-gioselectivity of the substitution reaction [32, 33]. 

De Munari, S., Frigerio, M., Santagostino, M. Hypervalent Iodine Oxidants Structure and Kinetics of the Reactive Intermediates in the Oxidation of Alcohols and 1,2-Diols by o-lodoxybenzoic Acid and Dess-Martin Periodinane. A Comparative 1H-NMR Study. J. Org. Chem. 1996, 61, 9272-9279. 

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... 

Molecular iodine can be considered as one of the ideal oxidants due to its many desirable properties like low cost, safe to handle/use, and easy availability. Because of the intrinsic low reactivity of I compared to the other highly reactive hypervalent iodine reagents, oxidation reactions with I required the concomitant use of activating agents. 

Today, the application of hypervalent iodine reagents still dominates the reaction landscape of electrophilic N-atom transfer processes, a testament to the unique reactivity of such oxidants. Nevertheless, the past decade has witnessed a flurry of activity aimed at the invention of new reagents and protocols that enable amine and amine derivative synthesis through selective C-H bond modification. We have attempted to highlight many of these recent discoveries, with apologies in advance... 

Recently, Ishihara and co-workers developed a more powerful hypervalent iodine catalyst, generated in situ from 2-iodobenzoic acid and furthermore demonstrated that its sulfonic acid analog 2 is more reactive as a precatalyst (Equation 10.3) [8]. They reported that it was not necessary to isolate hypervalent iodine compounds, which are potentially explosive oxidants, and furthermore that more powerful oxidants could be generated in situ. 

---