Benzynes reactions with alcohols

Acid chloride 5 is readily available from the known benzylic alcohol 6,4e but intermediate 4 is still rather complex. It was recognized that compound 4 could conceivably be formed in one step from 2-methoxyfuran (9)10 and iodotriflate 10. The latter compound was designed with the expectation that it could be converted to benzyne 8," a highly reactive species that could be intercepted in an intermolecular Diels-Alder reaction with 2-methoxyfuran (9) to give 7. The intermediacy of 7 is expected to be brief, for it should undergo facile conversion to the aromatized isomer 4 either in situ or during workup. 

The tantalum-benzyne complex (130) is much less reactive than other early transition-metal aryne complexes. It shows no reaction with acetone, benzophenone, benzaldehyde, acetonitrile, 3-hexyne, or methanol. The lack of reactivity of 130 was attributed to nonlability of the PMe3 ligand. Indeed, no phosphine exchange was observed when 130 was mixed with an excess of PMe3-d9. Refluxing 129 in a mixture of methanol and toluene (3 10 v/v) leads to clean formation of 131. This presumably results from reaction of a 16-electron benzyne complex with the alcohol. 

Although the reactions between alkynes or alkenes and metal clusters are the main source of alkyne-substituted complexes, there are other reagents which can produce similar products. Two such reagents are tetraphenylcyclopentadienone, which in the reaction with Ru3(CO)i2 produces Ru3(CO)10(PhCCPh) (167), and dimethyl-vinylarsine, which has been made to react with several carbonyl clusters [Eq. (8)] (168, 169). In the reaction of M3(CO)12 (M = Ru, Os) with a number of tertiary phosphines and aromatic alcohols, an oxidative addition takes place and benzyne-triosmium compounds are obtained (170-176). The fact that Os3(CO)uPEt3 can be converted into an alkyne compound (177) suggests that the conversion goes through substituted intermediates. Carbene derivatives of clusters have also... 

O-Phenylation of tertiary alcohols can be realized through reaction with pentaphenylbismuth (4), a benzyne intermediate being involved. r rf-Butyl phenyl ether (80) was also obtained in rather low yields in the reaction of triphenylbismuth diacetate with rerr-butyl alcohol used as solvent in the presence of potassium carbonate or by reaction of triphenylbismuth dichloride with lithium ten-... 

Alkoxy-l, 3-benzodithioles (1). Carbon disulfide undergoes 1,3-dipolar cycloaddition to benzyne [generated from benzenediazonium-2-carboxylate (1,46)] to give 1,3-benzodithiole-2-carbene (a). This carbene reacts with alcohols to form (1) in 35-50% yields. The reaction can be carried out in one-step from anthranHic acid, since carbon disulfide is more reactive than alcohols toward benzyne. ... 

The reactions of benzyne complexes of zirconium " also occur by electrophilic attack at an M-C bond. The isolated phosphine adduct of a zironocraie-benzyne complex reacts with ketones to imdergo insertion into one of the M-C bonds and with alcohol to make an aryl alkoxo complex, as shown in Equation 12.67. An electron-rich ruthenium-benzyne complex also reacts with electrophiles, such as borzaldehyde or carbon dioxide, to form products from insertion, as shown at the top of Equation 12.68. It also reacts with weak acids, such as aniline, to form products from formal protonation at the Ru-C bond, as shown at the bottom of Equation 12.68. - This reaction with aniline could occur by initial protonation at the metal, followed by C-H bond-forming reductive elimination, or by direct protonation of the M-C bond. Initial protonation of the metal center was proposed. 

As mentioned in the introductory section, arynes behave as soft acids . Therefore, the relative reactivity of a nucleophile should be governed by basicity as well as polarizability. The following gradations, established through competitive reactions of arynes with different nucleophiles, are more or less in line with this expectation.1 (i) BuLi > PhSLi > PhNMeLi > PhGaCLi > ROLi > ArOLi, for 9,10-phe-nanthryne in ether (ii) PhS- > Ph3C > PhC=C > enolates > PhO- > RO" > I, CN, for benzyne in liquid ammonia (iii) I- > Br > Cl- > EtOH for benzyne in alcohol. 

Insertion of benzyne into tributyltin chloride forms an o-chlorophenyltin . In the presence of pyridine, neat, or in ethanol, Ph2SnBr2 and PhjSnBr react with allyl bromide and 3-bromocyclohex-l-ene to form the corresponding 1,2-addition products . The reaction is not general and, for example, allyl alcohols do not react. 

The preparation of indoles by the benzyne route is illustrated by the base-induced cyclization of the amino-alcohols (171 R = H or Me) to indole and 3-methylin-dole, respectively/ The photochemical reaction of o-bromo- or o-iodo-aniline with the enolates (172 R = H, Me, or PrO leads to indoles (173)/ The salt (174), generated by the action of lithium di-isopropylamide on o-tolyl isocyanide, serves as a source of diverse indole derivatives (i) it cyclizes spontaneously to 1-lithioindole, which forms 3-alkyl-indoles on treatment with alkyl halides in the presence of magnesium iodide, (ii) it reacts with allyl esters RC02CH2CH=CH2 (R = alkyl or aryl) to give the ketones (175), which cyclize... 

In solution, benzyne and its derivatives are strained, short-lived intermediates which react with a broad array of nucleophiles, including carbanions, amines, alcohols and their salts, water, and even ethers. They also undergo pericyclic reactions such as Diels-Alder cycloadditions, 1,3-dipolar cycloadditions or ene reactions. The instability of benzyne and its derivatives is due to the strain caused by the deformation of the linear geometry of the formal sp-hybridized carbons of the triple bond to the angles close to 120° imposed by the ring geometry [2,3]. 

Cheng and co-workers reported the synthesis of isochromenones and oxepines via Pd-catalyzed eascade cyclization of allq nes and benzynes in 2012. The reactions involve biscarbocyelization of allq nes and benzynes and C-H bond activation. Phenanthro[l,10-Z)c]-oxepine derivatives were prepared in good to excellent yields (Scheme 4.26a). They also developed the synthesis of seven-membered lactones via nickel- and zinc-catalyzed cyclization of 2-iodobenzyl alcohols with allq l propiolates (Scheme 4.26b). The catal) ic reaction involves an unusual ElZ isomerization of a earbon-carbon double bond prior to ring elosure and provides a convenient and unique method for the synthesis of seven-membered lactones. 

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