Benzyne, intermediate in preparation

Benzyne, intermediate in preparation of phenyl t butyl ether, 46, 90 methods for generation of, 46, 112 trapping by tetraphenylcyclopenta-dienone, 46,112... 

Nesmeyanov and co-workers (1971) have found that thermolysis of tolane complex (XVII) gives diphenylindenone as the major product. Formation of this product was suggested to occur through a complexed benzyne intermediate. Attempted preparation of the corresponding lead complex gave only the indenone derivative in 58% yield. 

Preparation of phlorogluciaol or its monomethyl ether by reaction of a halogenated phenol with an alkaU metal hydroxide in an inert organic medium by means of a benzyne intermediate has been patented (142). For example, 4-chlororesorcinol reacts with excess potassium hydroxide under nitrogen in refluxing pseudocumene (1,2,4-trimethylbenzene) with the consequent formation of pure phlorogluciaol in 68% yield. In a version of this process, the solvent is omitted but a small amount of water is employed (143). 

Compounds of special interest whose preparation is described include 1,2,3-benzothiadiazole 1,1-dioxide (a benzyne precursor under exceptionally mild conditions), bis(l,3-diphenylimida-zolidinylidene-2) (whose chemistry is quite remarkable), 6- di-melhylamino)julvene (a useful intermediate for fused-ring non-benzenoid aromatic compounds), dipkenylcyclopropenone (the synthesis of which is a milestone in theoretical organic chemistry), ketene di(2-melhoxyethyl) acetal (the easiest ketene acetal to prepare), 2-methylcyclopenlane-l,3-dione (a useful intermediate in steroid synthesis), and 2-phenyl-5-oxazolone (an important intermediate in amino acid chemistry). 

Dibenzopyrrocolines have been prepared by intramolecular addition of benzyne intermediates and by nucleophilic substitutions, as shown in Scheme 6 with the synthesis of ( )-cryptowoline (2) and the related dehydro base 39 by Bennington and Morin (7). ( )-6 -Bromotetrahydroisoquinoline 37, prepared by standard procedures, when heated with copper powder in dimethylformamide afforded dibenzopyrrocoline 38 in low yield, and 39 was formed when 37 was allowed to react with potassium amide in liquid ammonia. Compound 39 was converted to ( )-cryptowoline iodide (2) by hydrogenolysis of O-benzyl ether 39 and quartemization with methyl iodide. 

It has been proved that the benzyne intermediate can be easily prepared from o-iodobenzoic acid and potassium peroxydisulfate in sulfuric acid. Water-soluble vicinal diols are converted into their corresponding aldehydes in the presence of Ag(I) catalyst. ... 

Cycloaddition of benzyne intermediates with aminothiazadienes provide access to substituted 2,4-diamino-4//-l,3-benzothiazines 196 in high yields. The benzynes are prepared by the treatment of (phenyl)[o-(trimethylsilyl)aryl]-iodonium triflates with 1.5 equiv of tetrabutylammonium fluoride (Scheme 20). Interestingly, 3-substituted-l,2-benzisothiazoles 197 are obtained when 4 equiv of tetrabutylammonium fluoride is used <2005H(65)1615>. 

In earlier chapters we revealed how some reactive intermediates can be prepared, usually under special conditions rather different from those of the reaction under study, as a reassurance that some of these unlikely looking species can have real existence. Intermediates of this kind include the carboca-tion in the S l reaction (Chapter 17), the cations and anions in electrophilic (Chapter 22) and nucleophilic (Chapter 23) aromatic substitutions, and the enols and enolates in various reactions of carbonyl compounds (Chapters 21 and 26-29). We have also used labelling in this chapter to show that symmetrical intermediates are probably involved in, for example, nucleophilic aromatic substitution with a benzyne intermediate (Chapter 23). 

In this context aryllithiums are also able to carbolithiate a benzyne moiety, and so we have also described the preparation of several phenantridine, dibenzopyran and diben-zothiopyran derivatives 383. In these cases y-functionalized organolithiums, derived from bromides 382, afford the corresponding and regiospecifically functionalized six-membered benzofused N-, O- or S-heterocycles through a 6-exo cyclization reaction onto a benzyne intermediate (Scheme 101)161b. 

The Kametani group has made considerable use of the intramolecular trapping of benzynes by pendant carbanion centers. The nitrile (133) is a key and versatile intermediate in many of the K etani studies, including the preparation of optically pure estradiol. The ester of the benzocyclobutenecarboxylic acid (134) was prepared by a similar benzyne cyclization. The acid (134) was converted via oxidative decarboxylation and HCl hydrolysis to the very labile tra/t5-2-arylbenzocyclobutenol (135), which was used in the preparation of p ophyllotoxin. ... 

Phosphorus-containing Ring Systems. - A range of new chiral oxazaphospholidine oxides 266 and 267 have been synthesised and used as catalysts in asymmetric reductions of ketones with diborane. Mannich-type cyclisation reactions of 5-amino-3-benzylthio-4-cyano(ethoxycarbonyl)pyrazoles with dichlorophenylphosphine and aromatic aldehydes in the presence of cation exchange resin have been used to prepare a number of 6-oxo-6-phospha-4,5,6-trihydroimidazolo[l,2-b]pyrazoles, e.g. 268. Some of these compounds have herbicidal activity and this report is typical of a number of similar ones in the Chinese literature. A number of metallocycles, e.g. 269, have been reported as products from reactions of transient zirconocene-benzyne intermediates with phosphaimines followed by sulfuration or selenation. ... 

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... 

While preparing benzonorbornadienes by the Diels-Alder cycloaddition of substituted benzyne intermediates with furan. Caster and coworkers discovered significantly differentregiochemistries be tween bromobenzene 121 and chlorobenzene 124 in the n-BuIi induced metallation step (Schemes 12.40 and 12.41) [72]. In the case of bromobenzene 121, benzyne intermediate 122 was generated via bromine-Uthium exchange, followed by elimination of UF trapping by furan then afforded 6-fluoro-9-oxabenzonorbornadiene (123). In contrast, aryne 125 was produced... 

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