Benzyne cycloaddition with

The catalysed macrocyclization of thietanes by metal carbonyl complexes has been reviewed <00ACR171>. Electronically stabilized thiones have been shown to undergo [2+2] cycloaddition with benzyne to give 27/-benzo[i>]thietes, for example 6 <00BCJ155>. 

Another important observation by Fields et al ° was that the acridizinium ion (25) will undergo cycloaddition with benzyne, affording... 

Although 1,2,5-thiadiazoles have been shown to undergo cycloaddition with benzyne <82CC299>, the predominant mode of attack is at sulfur. The result is extrusion of a nitrile and formation of a 1,2-benzisothiazole (22) (Scheme 4) <88JCS(Pl)2l4l>. 

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>. 

The AuCl-catalysed 4 + 2-cycloaddition of benzyne with o-alkynyl(oxo)benzenes produced anthracene derivatives having a ketone in the 9-position, in good to high yields under mild conditions.118 Hypervalent iodine compounds, [5-acyl-2-(trimethyl-silyl)]iodonium triflates, readily yielded acylbenzynes which could be trapped with furan.119 Both DMAD and benzyne reacted with borabenzene to yield substituted borabarrelenes and borabenzobarrelenes, respectively.120... 

The reaction of benzyne with aromatic aldehydes proceeds via nucleophilic attack of the carbonyl oxygen onto the benzyne to give the zwitterionic intermediate 172 followed by cyclization to the benzoxete intermediate. Cycloreversion then forms an ortho-quinone methide, which undergoes a [4+2] cycloaddition with a second molecule of the benzyne to form the xanthene (Scheme 56) <20040L4049>. 

Arylideneoxazolones 139a behaved as imines in [2+2] cycloaddition with benzyne, generated from benzenediazonium carboxylate, to afford mainly benzoxazepine-2-ones 144, through ring-opening of the cycloadduct 143, followed by water addition <03T6067>. 

The propensity of furans for benzyne cycloadditions is illustrated by its fourfold application to the four furan units of (495), providing the unusual macrocycle (496) in 84% yield in one synthetic operation (Scheme 115). The benzyne/furan adducts are also useful precursors for naphthalene derivatives. For example, adduct (489) (Scheme 114) was readily converted into a-naphthol (490) by treatment with acid. ... 

Using Ni(CO)4 as both reducing agent and cycloaddition mediator, o-diiodobenzene may be induced to serve as a benzyne equivalent in a cycloaddition with alkynes leading to indenones. Yields are consistently good and regioselectivity with terminal alkynes for the 2-substituted product excellent (equation... 

Cycloaddition reactions of benzyne with cyclic olejms, Benzyne reacts with cyclo-hexadiene to give, as the main products, hydrocarbons (l)-(4). The first (I) arises by 2 + 4 cycloaddition, (2) and (3) arise by ene cycloadditions, and (4) is a result of 2 + 2 cycloaddition. Addition of catalytic amounts of silver fluoroborate exerts a marked effect in this case (1) becomes almost the exclusive product. Silver ton, however. 

Cycloaddition reactions of the C(3)=N bond of azirines are common (Scheme 45) <71AHC(13)45, B-83MI 101-03,84CHEC-I(7)47>. Azirines can participate in [4 + 2] cycloadditions with dienes including cyclopentadienones, isobenzofurans, triazines, and tetrazines. They also participate in 1,3-dipolar cycloadditions with azomethine ylides, nitrile oxides, mesoionic compounds, and diazomethane. Cycloadditions with heterocumulenes, benzyne, and carbenes are known. Azirines also participate in other pericyclic reactions, such as ene reactions. 

Benzyne can be trapped in 1,3-dipolar cycloaddition reactions provided that the 1,3-dipolar species is sufficiently stable under the conditions necessary for benzyne generation. As an illustration of this, benzyne reacts with the nitrile oxide group in preference to the furan ring of compound 19, whereby adduct 20 is obtained.27 Benzyne and the nitrone 21 give adduct 22,28 and... 

A 1,6-cycloaddition was wrongly claimed to occur with benzyne and cyclo-heptatriene. The structure of the cycloadduct is reliably established as 25, and the isomer 26 derived from an ene reaction was also obtained.32 1,8-Cycloaddition of benzyne occurs with 8-cyanoheptafulvene (27) to give 28.3 3 It is clearly possible to envisage similar reactions occurring with heterocyclic compounds, although none has yet been reported. 

Furan also undergoes cycloadditions with allenes," " with benzyne" and with simpler dienophiles, like acrylonitrile and acrylate various Lewis acidic catalysts can assist" in some cases, zinc iodide is one such, hafnium tetrachloride another, and improved endo exo ratios are obtained in an ionic liquid as reaction solvent. Maleate and fumarate esters react if the addition is conducted under high pressure. This device can also be used to increase markedly the reactivity of 2-methoxyfuran and 2-acetoxyfuran towards dienophiles. At higher reaction temperatures alkynes and even electron-rich alkenes will add to furan. 3- or 5-Halo-furans react faster in these cycloadditions. ... 

Benzyne generation. As a fluoride source for initiating the generation of benz3fue from 2-trimethylsilylphenyl Inflate, the effectiveness of Bu4N(Ph3SiF2) is obvious. New possibilities for cycloaddition with enamides leading to indolines and isoquinohne derivatives have been explored. ... 

Cycloadditions with ynamines proceed readily at room temperature in carbon tetrachloride solution to yield a-pyrones (106) <77S252>. Likewise, a-pyrones (107) are also formed with cyclo-octyne <83TL1481>, whereas with benzyne the a-benzopyrone (108), produced initially, enters into a second [4 + 2] cycloaddition with benzyne to give ultimately the 9,10-disubstituted anthracene (109) (Scheme 12) <77S252>. 

Pyridazine JV-acetylimine reacts with benzyne to give 1 1 cycloadduct 70, which has been shown to be a precursor of a variety of heterocyclic compounds.194 The same JV-imine undergoes 1,3-dipolar cycloaddition with perhalocyclopropenes to give tricyclic adducts 71,195 the structure being established by X-ray crystallography. 

Compounds 64 and 65 act as 1,3-dipoles and undergo cycloaddition with arylisocyanates and benzyne. Addition of arylisocyanates yields arylaminoquinoxalinones, and addition of benzyne gives o-hydroxy-phenylquinoxalinones (Scheme 17). ... 

Hoye and co-workers (ref. 92) later reported the total synthesis of ancistrobrevine B (228), isolated from Ancistrocladus abbreviatus (ref. 93) and korupensamine C (229), isolated from Ancistrocladus korupensis. The approach to these natural products also utilised a benzyne cycloaddition to construct the naphthalene moiety. Thus, treatment of the amide 222 and bromide 230 with lithium cyclohexylisopropylamide furnished naphthalene 231 in low yield (Scheme 30). 

Dieh-Alder reactions with benzyne. Shepard has recently demonstrated that benzyne generated from chlorobenzene and LiTMP undergoes expected Diels-Alder cycloadditions with reactive dienes. The reaction with furane itself fails because of a base-promoted side reaction. 

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