Diels-Alder reaction with benzyne

Kuzuya M., Noguchi A. The Nature of Substituent Effects on Tautomeric Equilibria of 2-Pyridones and Their Reactions Trends Org. Chem. 1991 2 73-92 Keywords chemo- and regiochemistry of Diels-Alder reactions with benzyne,... 

Vinylbenzo[6]thiophene undergoes Diels-Alder reactions with benzyne,468 maleic anhydride,469 benzo[6]thiophene-1,1-dioxide,469 p-benzoquinone, and various 1,4-naphthaquinones.469,470 With quinones, the product depends on the reaction conditions. For... 

Oxazoles are anodier class of heteroaromatic dienes which readily undergo Diels-Alder reactions with benzynes. For example, slow, simultaneous injection of solutions of triazole (483) and lead tetraacetate to a solution of oxazole (515) in CH2CI2 at 0 C afforded cycloadduct (516) in essentially quantitative yield. The latter is a convenient source for the unstable isobenzofiiran (517), which can be trapped by [4 + 2] cycloaddition to a variety of dienophiles, e.g. by -methylmaleimide (Scheme 121). 

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

The molar ratio between benzyne and imidazole proved to have a critical influence on the direction of the reaction the benzyne/imidazole ratio was 1 3 in Yoshida s process, whereas a 1 1 ratio was employed by Xie and Zhang. The difference in substrate ratio apparently led to two entirely different reaction pathways. In Zhang s case, benzyne first underwent a Diels-Alder reaction with imidazole to produce the nitrogen-bridged isoquinoline intermediate 139. A subsequent retro Diels-Alder reaction led to intermediate 140 after the loss of hydrogen cyanide. This was followed by a second Diels-Alder reaction with benzyne to generate intermediate 141. Intermolecular nucleophilic addition of 138 to a third benzyne then gave rise to the final product arylamine 142. 

Indole-2,3-quinodimethane methodology has been utilized in the synthesis of the above groups of carbazoles 108). The N-sulphophenyl indole-2,3-quinodimethane anologue (136) undergoes the Diels-Alder reaction with benzyne generated from (137). In three steps (138-138B) it furnishes the simple benzo-b-carbazole (139). 

Chemical modiflcation of cahx[6]furan 41 by Diels-Alder reactions with benzyne and dimethyl acetylenedicarboxylate (DMAD) was studied by Kohnke et al. (Scheme 13) [53]. The reaction of 41 with benzyne afforded the adduct 95, which was converted to caUx[5]furan[l]naphthalene 96 by hydrogenation and subsequent dehydration. Two isomeric calix[4]furan[2]-naphthalenes 97 and 98 were obtained by similar chemical transformation starting from the corresponding bis-benzyne-adducts. Preparation of the tris-benzyne-adduct 99 was also reported. 

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 reaction of benzyne with furan was the first example of a Diels-Alder reaction of benzyne to be studied b. No authenticated examples of arynes are known which fail to give cyclo-adducts with furan i38>. The tetrahalogenobenzynes all form the expected adducts 103, X = F 6), Cl 57>i39)j gr 59) or i 59)). d0 other highly fluorinated arynes i40,i4i>. The isomeric adducts (104) and (105) have been detected by 19F n.m.r. spectroscopy when the dilithio-compound (12) was allowed to decompose in the presence of furan 28 103). 

Aromatic compounds can also behave as dienes.858 Benzene is very unreactive toward dienophiles very few dienophiles (one of them is benzyne) have been reported to give Diels-Alder adducts with it.859 Naphthalene and phenanthrene are also quite resistant, though naphthalene has given Diels-Alder addition at high pressures.860 However, anthracene and other compounds with at least three linear benzene rings give Diels-Alder reactions readily. The interesting compound triptycene can be prepared by a Diels-Alder reaction between benzyne and anthracene 861... 

I highly reactive triple bond of benzyne is a powerful dienophile. Predict the product of the Diels-Alder reaction of benzyne (from chlorobenzene and NaOH, heated) with cyclopentadiene. 

The reactive intermediate is benzyne, which undergoes a Diels Alder reaction with cyclopentadiene to yield the observed product. 

FIGURE 3.5 Halogen-metal exchange-mediated benzyne Diels-Alder reaction with cyclopentadiene. 

It has been reported that the furoindole (361) underwent Diels-Alder reactions with DMAD, N-phenylmaleimide and benzyne to give the expected products <84JOC45l8>. Treatment of 3-chloro-4-iodo-pyridine with t-butyllithium followed by addition of (361) led to a mixture of the isomeric Diels-Alder adducts (362) and (363) in 15% yield. Deoxygenation and desulfonylation of (362) and (363), gave a readily separable mixture of the pyridocarbazole alkaloids ellipticine (364), and isoellipticine (365), respectively (Scheme 14) <84JOC45l8,83TL5435>. 

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