Arynes cycloaddition reactions

Buszek and coworkers next conducted additional studies to further understand the regioselectivity of these indole-aryne cycloaddition reactions [54], They chose to generate the indole-aryne systems either from the 4,5- or 5,6-ort/io-dibromo species 100c and 100b by treatment with n-BuLi (2.2 equiv) in toluene, or from the corresponding o-trimethylsilyl triflates 104 and 108 by treatment with tetrabuty-lammonium triphenyldifluorosilicate (TBAT, 2.5 equiv) in THF or CsF (3 equiv) in acetonitrile. It was observed that for either the 4,5- or 5,6- indolyne systems thus prepared, there are no regiochemical preferences in the cycloaddition reactions with t-butylfuran (105a) (Scheme 29). 

D. Perez, D. Pena, E. Guitian, Aryne cycloaddition reactions in the synthesis of large polycyclic aromatic compounds, Eur. J. Org. Chem. 

Grushin VV, Alper H (1999) Activation of Otherwise Unreactive C-Cl Bonds. 3 193-225 Guitian E, Perez D, Pena D (2005) Palladium-Catalyzed Cycloaddition Reactions of Arynes. 14 109-146... 

Four-membered carbocyclic ring systems are commonly formed by cycloaddition of electrophilic alkenes, ketenes and arynes to enamines. Since cycloaddition reactions of enamines are dealt with in Chapter 18 these reactions will only be mentioned briefly here. 

This chapter reviews thermal [2 + 2] cycloadditions of alkenes to form cyclobutanes, extending the coverage provided by earlier summaries of the literature.It docs not deal with [2 + 2] cycloadditions that are achieved photochemically, or that utilize allenes, arynes or ketenes, or that are deliberately catalyzed, or that result in heterocyclic four-membered rings, even though these other varieties of [2 + 2] cycloaddition reactions are important and of substantial interest. 

They are highly strained and have a singlet ground state.73,74 Because such intermediates have two reactive carbon centers they are attractive substrates for cycloaddition reactions. However, little consideration will be given to this important use of arynes and hetarynes because it is outside the scope of this article. Information dealing with the generation of new intermediates is included, although attempts have not yet been made to exploit them in syntheses. 

The [2 + 2 + 2] cydotrimerization of alkynes and its analogous arynes [134] leads directly to aromatic hydrocarbons and can be considered as special cases of [2 + 2 + 2] cycloaddition reactions of unsaturated compounds [135, 136]. Especially the catalyzed cydotrimerization reactions are often highly regio- and stereoselective and have been established as valuable methods for the syntheses of highly substituted benzenes, biphenylenes, triphenylenes, and in the approach towards natural products. 

Two interchangeable fluoride ion sources used in aryne generation from o-trimethylsily-laryl triflates are CsF and TBAF. Many henzannulated heterocycles are now conveniently prepared via cycloaddition reactions of arynes. 3-Indazolecarboxylic esters are accessible from such a reaction. ... 

The long-standing doubt over the existence of this hetaryne continues. The suggestion2 that it may be involved in some of the nucleophilic displacement reactions of 2- and 3-bromobenzo[b]thiophene has now been refuted.214 216 Heating bis(3-bromo-2-benzo[b]thienyl)mercury with tetra-phenylcyclopentadienone at 275°C produces 1,2,3,4-tetraphenyldibenzo-thiophene (54%).217 It is tempting to conclude that the reaction proceeds via the aryne. However, 3-bromobenzo[b]thiophene undergoes the same reaction, which might therefore proceed via a cycloaddition reaction of the... 

The arynes also undergo cycloaddition reactions very readily they even add to fullerenes. An excellent review of these reactions has appeared ... 

It should be noted that because of the extreme reactivity of arynes, other reactions such as 2+2 cycloaddition or the ene reaction may complete with the Diels-Alder mode of addition more frequently than is the case with less reactive dienophiles. This is especially true if the diene component is not conformationally predisposed to the 4+2 cycloaddition mode. Also, as with other dienophiles, Diels-Alder reactions of arynes are stereoselective. 

Intramolecular or partially intramolecular cycloaddition reactions are extremely useful tools in the synthesis of polycyclic molecules, since they can allow the construction of several rings in a single step. Preliminary studies indicate that this general principle also holds for partially intramolecular versions of the palladium-catalyzed cocycloaddition of arynes and alkynes. For example, benzo[fc]fluorenones 144a-d, which constitute the polycyclic skeleton of the kinamycin family of antitumour antibiotics, can be obtained by [2+2+2] cy-... 

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