Arynes ortho-benzyne

The triple bond in ortHo-benzyne can be stabilized by complexation with transition metals. Aryne-metal complexes were originally proposed as intermediates in the decomposition of various aryl derivatives of early transition metals, and the first fuUy characterized mononuclear ortho-benzyne complex, TaMe2(q -C5Me5) (q -CjH4), was prepared. Although this method does not appear general for all transition metals, various complexes of zirconium, rhenium, and niobium have been characterized. More recently, complexes of nickel and platinum have also been... 

In 1953, Robert s experiments on the conversion of C-labeled chlorobenzene with KNH2 into aniline gave strong support to the intermediacy of ortho-benzyne in this and related reactions. Additional direct evidence for the existence of ortho-benzyne was provided by the observation of its IR spectrum, sohd-state dipolar NMR spectrum, and NMR in a molecular container, and by UV photoelectron spectroscopy. Even at low temperatures, arynes are extraordinary reactive. The reactions of arynes can be divided into three groups (i) pericyclic reactions, (ii) nucleophilic additions, and (iii) transition-metal catalyzed reactions. The pericyclic reactions can be divided into several categories such as Diels-Alder reactions, [2-f2] cycloadditions, 1,3- and l,4-dipolar cycloadditions, and the ene reactions. Arynes react with practically aU kinds of nucleophiles. More recently, the transition-metal catalyzed reactions of arynes have been studied, in particular those involving palladium. 

Scheme 7.5 summarizes the common methods of aryne generation, although the examples are limited to ortho-benzyne. Because of their extreme reactivity, arynes must be generated in situ. When an unactivated aryl halide is treated with a very strong base, an elimination reaction is possible, generating aryne. 

There are many other reactions that possibly involve aryne intermediates. While some are of mechanistic curiosities, some have been studied in detail, although none are generally synthetically useful. Irradiation of 1,2-diiodobenzene can lead to ortho-benzyne, probably via an aryl radical intermediate resulting from cleavage of the weak C-1 bond (Scheme 7.19). Aryl cations, formed by the decomposition of diazonium salts are also possible intermediates to ortho-benzynes provided that a large ortho-substituent is present, loss of a proton to give an aryne becomes competitive with the normal nudeophihc addition to the cation. 

AU the examples discussed to date have involved ortho-benzyne itself, and have simply served to illustrate the range of nucleophiles that react. However, one needs to know what happens when unsymmetrical arynes are attacked by nucleophiles. 

Arynes with their reactive triple bond would be expected to participate readily in cycloaddition reactions. However, as demonstrated in the previous section, the addition of nucleophiles is extremely facile, and therefore reactions with non-nucleophilic reagents cannot usually be observed unless the aryne is generated in the absence of nucleophiles. In practice this usually means that routes involving the treatment of aryl halides with nucleophilic bases cannot be used. The first cycloaddition reaction of ortho-benzyne, the Diels-Alder reaction with furan was observed in 1955 by Wittig and used 2-fluorobromobenzene as the precursor. The cycloadduct was obtained in almost 90% yield, and the reaction has formed the basis for numerous synthetically useful Diels-Alder cycloadditions involving arynes. Tetrabromobenzene reacts with butyllithium to give the diaryne intermediate with furan to form a tetrahydroanthracene. The mixture of syn and anti conformers can be separated based on differences in methanol solubility (Scheme 7.26). 

Although the vast majority of stepwise polar additions to ortho-benzyne involve nucleophilic attack on the aryne, electrophilic attack is also possible provided that the aryne is generated by a method that does not involve strongly basic conditions. Few such additions are synthetically useful, with the exception of the formation of 1,2-dihalobenzenes by reactions of ortho-benzynes with halogens, although alternative mechanisms initiated by nucleophilic attack of halide may be envisaged. Radical reactions of ortHo-benzyne, on the other hand, are extremely rare. 

Also during the 1940s, the formation of biphenyl (24) from fluorobenzene (26) and phenyl hthium (25) in an uncatalyzed reaction (Scheme 1.9) led Wittig to propose a dehydrobenzene, specifically an ortho-benzyne, as intermediate [39, 40], the formation of which was confirmed by Roberts in 1953 [41]. Modem arylation methodologies based on arynes as key intermediates are reviewed by Yu Chen and Richard Larock in Chapter 12. 

Benzyne Mechanism. Two factors affect the position of the incoming group, the first being the direction in which the aryne forms. When there are groups ortho or para to the leaving group, there is no choice ... 

Liittringhaus et al. 68) have isolated many interesting substances from the byproducts ( 8%) of the Bayer process. The mechanism has been fully clarified and shown to be an aryne route. When chlorobenzene or diphenylether are treated with sodium phenyl, the products are ortho metalated derivatives and benzyne. These give the same products which are formed in the industrial phenol synthesis. The most interesting compounds are 2- and 4-hydroxy biphenyl, 2,6-diphenyl- and 2,4-diphenyl-phenol l). For similar syntheses see 69). 

Benzyne also reacts with compounds containing nucleophilic carbon atoms such as enolates and aryl anions. Intramolecular nucleophilic addition to an aryne by the ortho ring carbon atom of another benzene ring substituted... 

Arynes are formed when the loss of two mutually ortho substituents by an aromatic ring results in the formation of a triple bond [1-3]. Benzyne (1) is the parent member of a series that today comprises a huge number of substituted and unsubstituted monocyclic, polycyclic and heterocyclic compounds [2,3]. Figure 1 includes some illustrative examples of these structures 3-methoxy-... 

Interestingly, when the number of equivalents of t-butyllithium was reduced from 4.0 to 1.1, all three benzyne-furan cycloadducts (i.e., 97a, 102, and 103) resulting from the three possible dibromoindole starting materials (lOOa-c) were isolated in excellent yields (Scheme 28). It is noteworthy that while the ortho dichlOTO- and dibromo-substituted indoles (94, lOOa-c) resulted in clean formation of the aryne species, the ortho difluoro derivatives lOOd-f did not behave in the same way. The attempted Diels-Alder reactions with 4,5 and 6,7-difluoroindoles lOOe and lOOf resulted only in the recovery of starting material. However, in the case of 5,6-difluoroindole lOOd, the cycloaddition resulted in the formation of 103,... 

In cases where two possible arynes could be formed from a single precursor, the result wiU depend on the relative rates of the two steps involved in aryne generation. If the formation of the anion is rate determining then this will control which aryne is formed. For example, lithiation of 3-methoxy-l-bromobenzene occurs at the 2-position since it is directed by the oxygen substituent, and provided a single benzyne because the loss of bromide is faster (Scheme 7.12). Likewise, powerful ortho-directing substituents such as the oxazoline group can be used to control aryne formation. 

Benzyne is an extremely reactive species due to the nature of its triple bond. In normal acetylenic species, such as ethyne, the unhybridized p orbitals are parallel to each other above and below the molecular axis, and this facilitates maximum orbital overlap. In benzyne, however, the p orbitals are distorted to accommodate the triple bond within the ring system, thus reducing their effective overlap. Benzyne can also be drawn as a diradical, where the triple bond is drawn as a double bond with a single electron on each carbon. Benzyne can exist as either an ortho-, a meta- or a poro-benzyne, where the diradical can be a 1,2-, a 1,3- or a 1,4-diradical species, respectively. The 1,4-diradical species has been identified in the Bergman cychzation [3]. In this chapter, we will focus solely on the 1,2-dehydro-benzene (o-benzyne species). The term aryne here will be used to refer specifically to 1,2-dehydrobenzenes and derivatives. 

Mono- or di-arylaied products may be formed by a-arylation of -dicarbonyl compounds, such as malonamide esters, with arynes generated by reaction of fluoride with ortho-silylaryltriflates. A similar method of benzyne generation has been used in the a-arylation of -ketoamides in a procedure which may be modified to yield asymmettic products. The reaction of 2-haloacetanilides with arynes in the presence of a palladium catalyst may produceiV-acylcarbazoles such as (26). Possible pathways are initial formation of a palladacycle with aryne followed by oxidative addition of the haloacetanilide, or direct insertion of the palladium into the carbon-halogen bond of the acetanilide followed by carbopalladation of the aryne. ... 

This multicomponent reaction gives rise to a variety of ortho-functionalized arylamines 315 and thioethers 316 in good overall yields. The reaction can be extended to functionalized benzynes. Thus, the sulfonate 317 readily provides the expected aryne that adds regioselectively magnesium thiolate 318 providing the magnesium derivative 319. Its copper(I)-catalyzed trapping furnishes the tetrasub-stituted benzene 320 in 72% yield (Scheme 4.71) 171]. 

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